PTENphosphatase and tensin homolog (mutated in multiple advanced cancers 1)
Autism Reports / Total Reports
48 / 108Rare Variants / Common Variants
178 / 0Aliases
PTEN, BZS, MHAM, TEP1, MMAC1, PTEN1, MGC11227Associated Syndromes
Cowden syndrome, Macrocephaly/autism syndrome, PTEN hamartoma tumor syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (PHTS), Cowden syndrome, ASD, Cowden syndrome 1, ASD, DDChromosome Band
10q23.31Associated Disorders
DD/NDD, ADHD, ID, EPS, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, FunctionalRelevance to Autism
Recurrent mutations in the PTEN gene have been identified in multiple individuals with ASD as described below. Deleterious variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified PTEN as a gene reaching exome-wide significance (P < 2.5E-06). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
Molecular Function
The protein encoded this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases.
External Links
SFARI Genomic Platforms
Reports related to PTEN (108 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | PTEN mutation in a family with Cowden syndrome and autism | Goffin A , et al. (2001) | No | ASD |
| 2 | Positive Association | Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations | Butler MG , et al. (2005) | Yes | ASD, macrocephaly |
| 3 | Support | - | Valiente M , et al. (2005) | No | - |
| 4 | Recent Recommendation | Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN | Zhao M , et al. (2006) | No | - |
| 5 | Recent Recommendation | Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase | Wang XL , et al. (2006) | No | - |
| 6 | Support | Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly | Buxbaum JD , et al. (2007) | Yes | - |
| 7 | Support | Novel PTEN mutations in neurodevelopmental disorders and macrocephaly | Orrico A , et al. (2008) | Yes | DD, ID |
| 8 | Support | The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly | Varga EA , et al. (2009) | Yes | - |
| 9 | Support | Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly | McBride KL , et al. (2010) | Yes | - |
| 10 | Recent Recommendation | PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression | Jurado S , et al. (2010) | No | - |
| 11 | Support | A mutant form of PTEN linked to autism | Redfern RE , et al. (2010) | No | - |
| 12 | Support | Autistic spectrum disorder in a 9-year-old girl with macrocephaly | Stein MT , et al. (2010) | Yes | - |
| 13 | Support | Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders | Schaaf CP , et al. (2011) | Yes | - |
| 14 | Support | Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations | O'Roak BJ , et al. (2012) | Yes | - |
| 15 | Support | Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling | Busa T , et al. (2012) | No | ID |
| 16 | Support | Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders | O'Roak BJ , et al. (2012) | Yes | - |
| 17 | Support | Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly | Hobert JA , et al. (2013) | Yes | DD, epilepsy |
| 18 | Recent Recommendation | A secreted PTEN phosphatase that enters cells to alter signaling and survival | Hopkins BD , et al. (2013) | No | - |
| 19 | Positive Association | De novo mutations in epileptic encephalopathies | Epi4K Consortium , et al. (2013) | No | IS, LGS, DD, ID, ASD, ADHD |
| 20 | Recent Recommendation | PTEN knockdown alters dendritic spine/protrusion morphology, not density | Haws ME , et al. (2013) | No | - |
| 21 | Recent Recommendation | Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations | Vanderver A , et al. (2014) | No | - |
| 22 | Recent Recommendation | Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures | Weston MC , et al. (2014) | No | - |
| 23 | Support | Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening | Marchese M , et al. (2014) | Yes | ID, epilepsy |
| 24 | Recent Recommendation | PTEN interacts with histone H1 and controls chromatin condensation | Chen ZH , et al. (2014) | No | - |
| 25 | Recent Recommendation | Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism | Frazier TW , et al. (2014) | No | - |
| 26 | Recent Recommendation | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 27 | Support | Recurrent de novo mutations implicate novel genes underlying simplex autism risk | O'Roak BJ , et al. (2014) | Yes | - |
| 28 | Recent Recommendation | Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes | Spinelli L , et al. (2014) | No | - |
| 29 | Recent Recommendation | Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders | Johnston SB and Raines RT (2015) | No | - |
| 30 | Recent Recommendation | Neural transcriptome of constitutional Pten dysfunction in mice and its relevance to human idiopathic autism spectrum disorder | Tilot AK , et al. (2015) | No | - |
| 31 | Recent Recommendation | The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles | Vogt D , et al. (2015) | No | - |
| 32 | Support | Excess of rare, inherited truncating mutations in autism | Krumm N , et al. (2015) | Yes | - |
| 33 | Support | Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders | Codina-Sol M , et al. (2015) | Yes | - |
| 34 | Support | Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder | Tammimies K , et al. (2015) | No | - |
| 35 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 36 | Support | A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome | Schwerd T , et al. (2015) | No | - |
| 37 | Recent Recommendation | Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice | Cupolillo D , et al. (2015) | No | - |
| 38 | Support | Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits | He X , et al. (2015) | No | - |
| 39 | Support | Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms | D'Gama AM , et al. (2015) | Yes | - |
| 40 | Recent Recommendation | A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons | Williams MR , et al. (2016) | No | - |
| 41 | Support | Altered proliferation and networks in neural cells derived from idiopathic autistic individuals | Marchetto MC , et al. (2016) | Yes | - |
| 42 | Support | A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly | Negishi Y , et al. (2017) | No | - |
| 43 | Support | Prevalence of four Mendelian disorders associated with autism in 2392 affected families | Saskin A , et al. (2017) | Yes | - |
| 44 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
| 45 | Support | PTEN Loss Increases the Connectivity of Fast Synaptic Motifs and Functional Connectivity in a Developing Hippocampal Network | Barrows CM , et al. (2017) | No | - |
| 46 | Support | Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test | Lionel AC , et al. (2017) | No | - |
| 47 | Support | Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands | Jin SC , et al. (2017) | No | Neurodevelopmental disorders (NDD) |
| 48 | Support | Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism | Yeung KS , et al. (2018) | No | ASD |
| 49 | Recent Recommendation | Nuclear Excluded Autism-Associated Phosphatase and Tensin Homolog Mutations Dysregulate Neuronal Growth | Fricano-Kugler CJ , et al. (2018) | No | - |
| 50 | Support | Identification of a PTEN mutation with reduced protein stability, phosphatase activity, and nuclear localization in Hong Kong patients with autistic features, neurodevelopmental delays, and macrocephaly | Wong CW , et al. (2018) | No | ASD or autistic features, DD, macrocephaly |
| 51 | Support | A family with PTEN mutations with malignancy and an unusually high number of offspring with autism spectrum disorder: a case report | Gruhl SL , et al. (2018) | No | ASD, macrocephaly |
| 52 | Support | Clinical spectrum of PTEN mutation in pediatric patients. A bicenter experience | Ciaccio C , et al. (2018) | No | DD, ASD |
| 53 | Support | Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder | Du X , et al. (2018) | No | Autistic features |
| 54 | Support | Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations | Zhou WZ , et al. (2019) | Yes | - |
| 55 | Support | Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population | Monies D , et al. (2019) | No | ASD |
| 56 | Support | A novel missense PTEN mutation identified in a patient with macrocephaly and developmental delay | Ueno Y , et al. (2019) | No | Macrocephaly |
| 57 | Support | Characterization of intellectual disability and autism comorbidity through gene panel sequencing | Aspromonte MC , et al. (2019) | Yes | - |
| 58 | Support | Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans | Wong WR , et al. (2019) | Yes | - |
| 59 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 60 | Support | Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort | Wu H , et al. (2019) | Yes | Macrocephaly |
| 61 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 62 | Support | Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy | Lee J et al. (2020) | Yes | - |
| 63 | Support | Polymicrogyria is Associated With Pathogenic Variants in PTEN | Shao DD et al. (2020) | No | - |
| 64 | Support | - | Abe-Hatano C et al. (2021) | No | - |
| 65 | Support | - | Kaymakcalan H et al. (2021) | Yes | ADHD, ID |
| 66 | Support | - | Chai AP et al. (2021) | Yes | - |
| 67 | Support | - | Dhaliwal N et al. (2021) | No | - |
| 68 | Support | - | Cummings K et al. (2022) | No | ASD |
| 69 | Support | - | Getz SA et al. (2022) | No | - |
| 70 | Support | - | Clipperton-Allen AE et al. (2022) | No | - |
| 71 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
| 72 | Support | - | Yehia L et al. (2022) | No | ASD, DD |
| 73 | Support | - | Verberne EA et al. (2022) | No | - |
| 74 | Support | - | Ledderose JMT et al. (2022) | No | - |
| 75 | Support | - | Hu C et al. (2022) | Yes | - |
| 76 | Support | - | Levchenko O et al. (2022) | No | - |
| 77 | Support | - | Zhou X et al. (2022) | Yes | - |
| 78 | Support | - | Hendricks LAJ et al. (2022) | No | DD |
| 79 | Support | - | Ermakova G et al. (2022) | Yes | - |
| 80 | Support | - | Zhou X et al. (2022) | Yes | - |
| 81 | Support | - | Busch RM et al. (2023) | No | - |
| 82 | Support | - | Kagan M et al. (2023) | Yes | - |
| 83 | Support | - | Yuan B et al. (2023) | Yes | - |
| 84 | Recent Recommendation | - | Pintacuda G et al. (2023) | Yes | - |
| 85 | Support | - | Spataro N et al. (2023) | No | Autistic features |
| 86 | Support | - | Hu C et al. (2023) | Yes | - |
| 87 | Support | - | Zhang Y et al. (2023) | Yes | DD, ID |
| 88 | Recent Recommendation | - | Fu S et al. (2023) | Yes | - |
| 89 | Support | - | Pigoni M et al. (2023) | Yes | - |
| 90 | Support | - | Wang J et al. (2023) | Yes | - |
| 91 | Support | - | Balasar et al. (2023) | No | - |
| 92 | Support | - | Sanchis-Juan A et al. (2023) | No | - |
| 93 | Support | - | Masahiro Hitomi et al. (2023) | No | ASD |
| 94 | Recent Recommendation | - | Shin Chung Kang et al. () | Yes | - |
| 95 | Support | - | Erica Rosina et al. (2024) | No | - |
| 96 | Support | - | Lena H Nguyen et al. (2024) | No | - |
| 97 | Support | - | Tamam Khalaf et al. (2024) | No | - |
| 98 | Support | - | Andrew Dhawan et al. (2024) | No | ASD, epilepsy/seizures |
| 99 | Support | - | Gemma Molinaro et al. (2024) | Yes | Epilepsy/seizures |
| 100 | Support | - | Kakha Bregvadze et al. (2024) | Yes | - |
| 101 | Support | - | Navroop K Dhaliwal et al. (2024) | No | - |
| 102 | Support | - | Ruohao Wu et al. (2024) | Yes | - |
| 103 | Support | - | Axel Schmidt et al. (2024) | No | - |
| 104 | Support | - | Katilynne Croom et al. (2024) | Yes | - |
| 105 | Support | - | Karen Lob et al. () | Yes | DD |
| 106 | Highly Cited | PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer | Li J , et al. (1997) | No | - |
| 107 | Highly Cited | The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate | Maehama T and Dixon JE (1998) | No | - |
| 108 | Highly Cited | Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN | Stambolic V , et al. (1998) | No | - |
Rare Variants (178)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | Unknown | - | - | 39136901 | Karen Lob et al. () | |
| C>G | - | intron_variant | De novo | - | - | 19265751 | Varga EA , et al. (2009) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| G>A | - | splice_site_variant | Unknown | - | - | 19265751 | Varga EA , et al. (2009) | |
| c.-903G>A | - | 5_prime_UTR_variant | - | - | - | 17427195 | Buxbaum JD , et al. (2007) | |
| - | - | copy_number_loss | Unknown | - | Simplex | 21624971 | Schaaf CP , et al. (2011) | |
| c.-1088C>T | - | 5_prime_UTR_variant | - | - | - | 17427195 | Buxbaum JD , et al. (2007) | |
| c.697C>T | p.Arg233Ter | stop_gained | Unknown | - | - | 35741772 | Hu C et al. (2022) | |
| c.249C>A | p.Cys83Ter | stop_gained | Unknown | - | - | 32477112 | Lee J et al. (2020) | |
| c.-132C>T | - | stop_gained | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.259C>T | p.Gln87Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.165-2A>G | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.253+1G>A | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.87T>G | p.Tyr29Ter | stop_gained | De novo | - | - | 28991257 | Jin SC , et al. (2017) | |
| c.388C>T | p.Gln130Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.388C>T | p.Arg130Ter | stop_gained | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
| T>C | - | intron_variant | Familial | Maternal | - | 17427195 | Buxbaum JD , et al. (2007) | |
| c.23T>A | p.Ile8Asn | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.-478del | - | frameshift_variant | Unknown | - | - | 24580998 | Marchese M , et al. (2014) | |
| c.1003C>T | p.Arg335Ter | stop_gained | De novo | - | - | 29608813 | Wong CW , et al. (2018) | |
| c.634+2T>G | - | splice_site_variant | De novo | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| - | - | 2KB_upstream_variant | Familial | Maternal | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.734A>C | p.Gln245Pro | missense_variant | Unknown | - | - | 39136901 | Karen Lob et al. () | |
| c.149T>C | p.Ile50Thr | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1003C>T | p.Arg335Ter | stop_gained | De novo | - | - | 20814261 | Stein MT , et al. (2010) | |
| c.697C>T | p.Arg233Ter | stop_gained | De novo | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.697C>T | p.Arg233Ter | stop_gained | Unknown | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.-479_-477del | - | inframe_deletion | Unknown | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.-835C>T | - | 5_prime_UTR_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
| c.*10del | - | 3_prime_UTR_variant | Unknown | - | - | 34268892 | Kaymakcalan H et al. (2021) | |
| c.403A>C | p.Ile135Leu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.424C>T | p.Arg142Trp | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.479C>T | p.Pro160Leu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.514A>G | p.Arg172Gly | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.626G>T | p.Gly209Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.820T>G | p.Trp274Gly | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1003C>T | p.Arg335Ter | stop_gained | De novo | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.493-2A>G | - | splice_site_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.27dup | p.Ser10Ter | frameshift_variant | De novo | - | - | 37035742 | Zhang Y et al. (2023) | |
| c.77C>T | p.Thr26Ile | missense_variant | De novo | - | - | 36980980 | Spataro N et al. (2023) | |
| c.1003C>T | p.Arg335Ter | stop_gained | Unknown | - | - | 35253369 | Verberne EA et al. (2022) | |
| c.164+1G>A | - | splice_site_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.209+5G>A | - | splice_site_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.303T>C | p.Ile101Thr | missense_variant | De novo | - | - | 29608813 | Wong CW , et al. (2018) | |
| c.204A>G | p.Tyr68Cys | missense_variant | De novo | - | - | 29296277 | Yeung KS , et al. (2018) | |
| c.102C>T | p.Ala34Val | missense_variant | Unknown | - | - | 31130284 | Monies D , et al. (2019) | |
| c.44G>T | p.Arg15Ile | missense_variant | De novo | - | - | 28771251 | Lionel AC , et al. (2017) | |
| c.75G>T | p.Leu25Phe | missense_variant | Unknown | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.7_9del | p.Ala3del | inframe_deletion | De novo | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.1008C>G | p.Tyr336Ter | stop_gained | Familial | Maternal | - | 37007974 | Hu C et al. (2023) | |
| c.388C>T | p.Gln130Ter | stop_gained | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.686C>A | p.Ser229Ter | stop_gained | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.1027-1G>A | - | splice_site_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.353A>C | p.His118Pro | missense_variant | De novo | - | - | 18759867 | Orrico A , et al. (2008) | |
| c.527A>G | p.Tyr176Cys | missense_variant | De novo | - | - | 18759867 | Orrico A , et al. (2008) | |
| c.827A>G | p.Asn276Ser | missense_variant | De novo | - | - | 18759867 | Orrico A , et al. (2008) | |
| c.605C>T | p.Thr202Ile | missense_variant | De novo | - | - | 19265751 | Varga EA , et al. (2009) | |
| c.315G>T | p.Cys105Phe | missense_variant | De novo | - | - | 29296277 | Yeung KS , et al. (2018) | |
| c.510G>C | p.Ser170Thr | missense_variant | De novo | - | - | 29296277 | Yeung KS , et al. (2018) | |
| c.-115dup | - | frameshift_variant | De novo | - | Simplex | 23160955 | O'Roak BJ , et al. (2012) | |
| c.1027-2A>G | - | splice_site_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.302T>C | p.Ile101Thr | missense_variant | De novo | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.389G>C | p.Arg130Pro | missense_variant | De novo | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.801G>T | p.Lys267Asn | missense_variant | De novo | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.388C>T | p.Arg130Ter | stop_gained | De novo | - | - | 38585419 | Kakha Bregvadze et al. (2024) | |
| c.97A>G | p.Asn33Asp | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.80-1G>A | - | splice_site_variant | Familial | Maternal | - | 28250423 | Saskin A , et al. (2017) | |
| c.445C>T | p.Gln149Ter | stop_gained | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
| c.195C>A | p.Cys65Ter | stop_gained | Unknown | - | Unknown | 26637798 | D'Gama AM , et al. (2015) | |
| c.209+5G>A | - | splice_site_variant | Unknown | - | Unknown | 23695273 | Hobert JA , et al. (2013) | |
| c.976G>A | p.Asp326Asn | missense_variant | De novo | - | - | 17427195 | Buxbaum JD , et al. (2007) | |
| c.278A>G | p.His93Arg | missense_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
| c.714C>A | p.Tyr238Ter | stop_gained | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.737C>T | p.Pro246Leu | missense_variant | De novo | - | Simplex | 30555518 | Du X , et al. (2018) | |
| c.810T>A | p.Met270Lys | missense_variant | De novo | - | Simplex | 31674007 | Wu H , et al. (2019) | |
| c.220A>G | p.Arg74Gly | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| A>G | - | splice_site_variant | Familial | Paternal | Simplex | 19265751 | Varga EA , et al. (2009) | |
| c.494G>T | p.Gly165Val | missense_variant | De novo | - | - | 26325558 | Tammimies K , et al. (2015) | |
| c.370T>A | p.Cys124Ser | missense_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.253+1dup | - | frameshift_variant | De novo | - | Simplex | 33624935 | Abe-Hatano C et al. (2021) | |
| c.235G>A | p.Ala79Thr | missense_variant | Unknown | - | - | 34268892 | Kaymakcalan H et al. (2021) | |
| c.302T>C | p.Ile101Thr | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.320A>T | p.Lys107Met | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.723T>G | p.Phe241Leu | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.466G>A | p.Gly156Arg | missense_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.518G>T | p.Arg173Leu | missense_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.534T>G | p.Tyr178Ter | stop_gained | Familial | Maternal | - | 11496368 | Goffin A , et al. (2001) | |
| c.1003C>T | p.Arg335Ter | stop_gained | Unknown | - | Unknown | 23695273 | Hobert JA , et al. (2013) | |
| c.388C>T | p.Gln130Ter | stop_gained | Unknown | - | Unknown | 35887114 | Levchenko O et al. (2022) | |
| - | - | 5_prime_UTR_variant | Familial | Maternal | Multiplex | 17427195 | Buxbaum JD , et al. (2007) | |
| c.493-1G>A | - | splice_site_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.403A>C | p.Ile135Leu | missense_variant | Unknown | - | - | 27378147 | Marchetto MC , et al. (2016) | |
| c.239-21G>C | - | inframe_insertion | De novo | - | Simplex | 25969726 | Codina-Sol M , et al. (2015) | |
| c.19G>T | p.Glu7Ter | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.960T>C | p.Leu320Ser | missense_variant | De novo | - | Simplex | 31149344 | Ueno Y , et al. (2019) | |
| c.323T>C | p.Leu108Pro | missense_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.380G>C | p.Gly127Ala | missense_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.389G>A | p.Arg130Gln | missense_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.406T>C | p.Cys136Arg | missense_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.464A>C | p.Tyr155Ser | missense_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.521A>G | p.Tyr174Cys | missense_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.737C>T | p.Pro246Leu | missense_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.274G>A | p.Asp92Asn | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
| c.38A>G | p.Lys13Glu | missense_variant | Unknown | - | Unknown | 31130284 | Monies D , et al. (2019) | |
| c.697C>T | p.Arg233Ter | stop_gained | Familial | Paternal | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.-1026C>A | - | 5_prime_UTR_variant | Familial | Maternal | - | 17427195 | Buxbaum JD , et al. (2007) | |
| c.389G>A | p.Arg130Gln | missense_variant | Unknown | - | Simplex | 37524782 | Balasar et al. (2023) | |
| c.131G>A | p.Gly44Asp | missense_variant | Unknown | - | Unknown | 19265751 | Varga EA , et al. (2009) | |
| c.182C>T | p.His61Tyr | missense_variant | Unknown | - | Unknown | 31130284 | Monies D , et al. (2019) | |
| c.697C>T | p.Arg233Ter | stop_gained | De novo | - | Simplex | 34268892 | Kaymakcalan H et al. (2021) | |
| c.54_56del | p.Gly19del | inframe_deletion | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.723T>G | p.Phe241Leu | missense_variant | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
| c.737C>T | p.Pro246Leu | missense_variant | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
| c.464A>G | p.Tyr155Cys | missense_variant | De novo | - | Simplex | 38764027 | Ruohao Wu et al. (2024) | |
| c.278A>G | p.His93Arg | missense_variant | De novo | - | Simplex | 15805158 | Butler MG , et al. (2005) | |
| c.232A>G | p.Thr78Ala | missense_variant | De novo | - | Simplex | 21624971 | Schaaf CP , et al. (2011) | |
| c.208C>G | p.Pro70Ala | missense_variant | Unknown | - | Unknown | 23695273 | Hobert JA , et al. (2013) | |
| c.1027del | p.Val343Ter | frameshift_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.329dup | p.Gln110ProfsTer5 | frameshift_variant | Familial | - | - | 29608813 | Wong CW , et al. (2018) | |
| c.149T>C | p.Ile50Thr | missense_variant | Familial | Maternal | - | 28250423 | Saskin A , et al. (2017) | |
| c.520dup | p.Tyr174LeufsTer6 | frameshift_variant | De novo | - | - | 19265751 | Varga EA , et al. (2009) | |
| c.722T>C | p.Phe241Ser | missense_variant | De novo | - | Simplex | 15805158 | Butler MG , et al. (2005) | |
| c.755A>G | p.Asp252Gly | missense_variant | De novo | - | Simplex | 15805158 | Butler MG , et al. (2005) | |
| c.618C>G | p.Phe206Leu | missense_variant | Unknown | - | Simplex | 21624971 | Schaaf CP , et al. (2011) | |
| c.500C>A | p.Thr167Asn | missense_variant | De novo | - | Simplex | 22495309 | O'Roak BJ , et al. (2012) | |
| c.392C>T | p.Ala131Val | missense_variant | De novo | - | Simplex | 23160955 | O'Roak BJ , et al. (2012) | |
| c.320A>T | p.Lys107Met | missense_variant | De novo | - | Simplex | 25418537 | O'Roak BJ , et al. (2014) | |
| c.741T>C | p.Leu247Ser | missense_variant | De novo | - | Simplex | 28086757 | Negishi Y , et al. (2017) | |
| c.737C>T | p.Pro246Leu | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.397G>A | p.Ala133Thr | missense_variant | Familial | Maternal | - | 28250423 | Saskin A , et al. (2017) | |
| c.549del | p.Lys183ArgfsTer16 | frameshift_variant | De novo | - | - | 29296277 | Yeung KS , et al. (2018) | |
| c.302T>C | p.Ile101Thr | missense_variant | De novo | - | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.3G>T | p.Leu1? | initiator_codon_variant | Unknown | - | Unknown | 23695273 | Hobert JA , et al. (2013) | |
| c.369C>G | p.Tyr123Ter | missense_variant | Unknown | - | Unknown | 20533527 | McBride KL , et al. (2010) | |
| c.737C>T | p.Pro246Leu | missense_variant | Unknown | - | Unknown | 35887114 | Levchenko O et al. (2022) | |
| c.502_503del | p.Ser168ProfsTer15 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.510T>A | p.Ser170Arg | missense_variant | Familial | Maternal | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.400A>T | p.Met134Leu | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.-1034_-1030dupGCCCT | - | 2KB_upstream_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.388C>T | p.Arg130Ter | stop_gained | Familial | Paternal | Simplex | 19265751 | Varga EA , et al. (2009) | |
| c.416T>A | p.Leu139Ter | stop_gained | Familial | Paternal | Simplex | 19265751 | Varga EA , et al. (2009) | |
| c.611C>T | p.Pro204Leu | missense_variant | De novo | - | Simplex | 34268892 | Kaymakcalan H et al. (2021) | |
| c.1013del | p.Ser338LeufsTer6 | frameshift_variant | De novo | - | Simplex | 31674007 | Wu H , et al. (2019) | |
| c.27del | p.Ser10AlafsTer14 | frameshift_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.640C>T | p.Gln214Ter | stop_gained | Familial | Maternal | Simplex | 23160955 | O'Roak BJ , et al. (2012) | |
| c.302T>C | p.Ile101Thr | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.449A>G | p.Glu150Gly | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.821G>T | p.Trp274Leu | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.389G>A | p.Arg130Gln | missense_variant | Unknown | Not maternal | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.235G>A | p.Ala79Thr | missense_variant | Familial | Maternal | - | 31209962 | Aspromonte MC , et al. (2019) | |
| c.752G>A | p.Gly251Asp | missense_variant | Familial | Maternal | Simplex | 36699461 | Kagan M et al. (2023) | |
| c.611del | p.Pro204GlnfsTer17 | frameshift_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.955insA | p.Thr319AsnfsTer6 | frameshift_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.1176del | p.Phe392LeufsTer24 | frameshift_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.640C>T | p.Gln214Ter | stop_gained | Unknown | Not maternal | Simplex | 28086757 | Negishi Y , et al. (2017) | |
| c.402G>C | p.Glu134Asp | missense_variant | Familial | Maternal | Multiplex | 23124040 | Busa T , et al. (2012) | |
| c.697C>T | p.Arg233Ter | stop_gained | Unknown | Not paternal | Multiplex | 19265751 | Varga EA , et al. (2009) | |
| NM_000314.5:c.1006C>G | p.Tyr336Ter | stop_gained | De novo | - | Simplex | 28086757 | Negishi Y , et al. (2017) | |
| c.405dup | p.Cys136MetfsTer44 | frameshift_variant | Familial | Paternal | - | 30763456 | Zhou WZ , et al. (2019) | |
| c.462dup | p.Tyr155LeufsTer25 | frameshift_variant | Familial | Maternal | - | 30763456 | Zhou WZ , et al. (2019) | |
| NM_001304717.3:c.1011+2T>G | - | splice_site_variant | Unknown | - | Simplex | 31130284 | Monies D , et al. (2019) | |
| c.225_226del | p.His75LeufsTer2 | frameshift_variant | De novo | - | Simplex | 31130284 | Monies D , et al. (2019) | |
| c.518G>A | p.Arg173His | missense_variant | Familial | Paternal | Simplex | 20533527 | McBride KL , et al. (2010) | |
| c.66C>G | p.Asp22Glu | missense_variant | Familial | Paternal | Multiplex | 17427195 | Buxbaum JD , et al. (2007) | |
| c.100del | p.Ala34LeufsTer20 | frameshift_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.512_513insACA | p.Leu171_Pro172insHis | inframe_insertion | De novo | - | - | 30528446 | Ciaccio C , et al. (2018) | |
| c.176C>G | p.Pro59Arg | stop_gained | Familial | Paternal | Multi-generational | 30482242 | Gruhl SL , et al. (2018) | |
| c.548del | p.Lys183ArgfsTer16 | frameshift_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.420_421insA | p.Ala141SerfsTer43 | frameshift_variant | Unknown | - | Unknown | 23695273 | Hobert JA , et al. (2013) | |
| c.545T>C | p.Val182Ala | missense_variant | Familial | Both parents | Multiplex | 26443266 | Schwerd T , et al. (2015) | |
| c.361_362dup | p.Ser121ArgfsTer55 | frameshift_variant | De novo | - | Simplex | 38041506 | Erica Rosina et al. (2024) | |
| c.525_526dup | p.Tyr176CysfsTer8 | frameshift_variant | De novo | - | Simplex | 34268892 | Kaymakcalan H et al. (2021) | |
| c.1110_1111insATAGT | p.Asp371IlefsTer47 | frameshift_variant | Unknown | - | Unknown | 32959437 | Shao DD et al. (2020) | |
| c.518G>A | p.Arg173His | missense_variant | Familial | Maternal | Multi-generational | 19265751 | Varga EA , et al. (2009) | |
| c.493G>T | p.Lys164Asn | missense_variant | Familial | Maternal | Multi-generational | 29296277 | Yeung KS , et al. (2018) | |
| c.470A>G | p.Gln157Arg | missense_variant | De novo | - | Multiplex (identical twins) | 19265751 | Varga EA , et al. (2009) | |
| c.401T>C | p.Met134Thr | missense_variant | Familial | Maternal | Multi-generational | 20533527 | McBride KL , et al. (2010) | |
| c.821G>T | p.Trp274Leu | missense_variant | Familial | Maternal | Multi-generational | 20533527 | McBride KL , et al. (2010) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence, Syndromic
Score Delta: Score remained at 1S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
1/1/2021
Score remained at 1
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
10/1/2020
Score remained at 1
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
4/1/2020
Score remained at 1
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
1/1/2020
Score remained at 1
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
10/1/2019
Score remained at 1
New Scoring Scheme
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
7/1/2019
Score remained at 1S
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
Reports Added
[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [A novel missense PTEN mutation identified in a patient with macrocephaly and developmental delay.2019] [Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019] [Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans.2019] [Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]1/1/2019
Score remained at 1S
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
Reports Added
[Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder.2018] [Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype c...2019]10/1/2018
Score remained at 1S
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
Reports Added
[Recurrent de novo mutations implicate novel genes underlying simplex autism risk.2014] [Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autis...2015] [A family with PTEN mutations with malignancy and an unusually high number of offspring with autism spectrum disorder: a case report.2018] [Clinical spectrum of PTEN mutation in pediatric patients. A bicenter experience.2018]10/1/2017
Score remained at 1S
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR ? 0.05, meaning that this gene had a ? 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
7/1/2017
Score remained at 1S
Description
Variants in PTEN have been identified in individuals presenting with ASD and macrocephaly in multiple studies (PMIDs 15805158, 18759867, 19265751, 20533527). Two de novo deleterious events in the PTEN gene were identified in exome sequencing studies in simplex ASD cases in 2012: a missense variant (p.Thr167Asn) that was classified as "severe" in O'Roak et al. Nature 2012 (PMID 22495309); and a frameshift variant (p.Cys136MetfsX44) in O'Roak et al. Science 2012 (PMID 23160955). A detailed examination of ASD cases with heterozygous PTEN mutations in Frazier et al., 2015 found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). An additional de novo loss-of-function variant in the PTEN gene was subsequently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report furthermore identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR ? 0.05, meaning that this gene had a ? 95% chance of being a true autism gene. This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). PTEN has also been designated as a syndromic ASD gene, as mutations in the PTEN gene are causative for Cowden syndrome, a disorder in which a subpopulation of individuals with the syndrome develop autism (PMID 11496368).
4/1/2017
Score remained at 1S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LoF events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified." A de novo LoF variant in the PTEN gene was recently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A detailed examination of ASD cases with heterozygous PTEN mutations found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified PTEN as a gene meeting high statistical significance with a 0.01< FDR ?0.05, meaning that this gene had a ?95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).
Reports Added
[Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.2007] [Autistic spectrum disorder in a 9-year-old girl with macrocephaly.2010] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly.2013] [Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Novel PTEN mutations in neurodevelopmental disorders and macrocephaly.2008] [The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.2009] [Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly.2010] [PTEN mutation in a family with Cowden syndrome and autism.2001] [De novo mutations in epileptic encephalopathies.2013] [Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.2005] [Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling.2012] [PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.1997] [The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.1998] [Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.1998] [Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.2006] [Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase.2006] [PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.2010] [A secreted PTEN phosphatase that enters cells to alter signaling and survival.2013] [PTEN knockdown alters dendritic spine/protrusion morphology, not density.2013] [Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations.2014] [Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.2014] [Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes.2014] [PTEN interacts with histone H1 and controls chromatin condensation.2014] [Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.2014] [Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders.2015] [A mutant form of PTEN linked to autism.2010] [Neural transcriptome of constitutional Pten dysfunction in mice and its relevance to human idiopathic autism spectrum disorder.2015] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome.2015] [Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons.2016] [A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Prevalence of four Mendelian disorders associated with autism in 2392 affected families.2017]1/1/2017
Score remained at 1S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LoF events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified." A de novo LoF variant in the PTEN gene was recently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A detailed examination of ASD cases with heterozygous PTEN mutations found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified PTEN as a gene meeting high statistical significance with a 0.01 < FDR ?0.05, meaning that this gene had a ?95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).
4/1/2016
Score remained at 1S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LoF events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified." A de novo LoF variant in the PTEN gene was recently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A detailed examination of ASD cases with heterozygous PTEN mutations found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified PTEN as a gene meeting high statistical significance with a 0.01
Reports Added
[Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.2007] [Autistic spectrum disorder in a 9-year-old girl with macrocephaly.2010] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly.2013] [Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Novel PTEN mutations in neurodevelopmental disorders and macrocephaly.2008] [The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.2009] [Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly.2010] [PTEN mutation in a family with Cowden syndrome and autism.2001] [De novo mutations in epileptic encephalopathies.2013] [Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.2005] [Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling.2012] [PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.1997] [The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.1998] [Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.1998] [Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.2006] [Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase.2006] [PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.2010] [A secreted PTEN phosphatase that enters cells to alter signaling and survival.2013] [PTEN knockdown alters dendritic spine/protrusion morphology, not density.2013] [Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations.2014] [Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.2014] [Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes.2014] [PTEN interacts with histone H1 and controls chromatin condensation.2014] [Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.2014] [Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders.2015] [A mutant form of PTEN linked to autism.2010] [Neural transcriptome of constitutional Pten dysfunction in mice and its relevance to human idiopathic autism spectrum disorder.2015] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome.2015] [Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons.2016]1/1/2016
Score remained at 1S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LoF events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified." A de novo LoF variant in the PTEN gene was recently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A detailed examination of ASD cases with heterozygous PTEN mutations found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified PTEN as a gene meeting high statistical significance with a 0.01
Reports Added
[Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.2007] [Autistic spectrum disorder in a 9-year-old girl with macrocephaly.2010] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly.2013] [Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Novel PTEN mutations in neurodevelopmental disorders and macrocephaly.2008] [The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.2009] [Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly.2010] [PTEN mutation in a family with Cowden syndrome and autism.2001] [De novo mutations in epileptic encephalopathies.2013] [Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.2005] [Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling.2012] [PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.1997] [The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.1998] [Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.1998] [Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.2006] [Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase.2006] [PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.2010] [A secreted PTEN phosphatase that enters cells to alter signaling and survival.2013] [PTEN knockdown alters dendritic spine/protrusion morphology, not density.2013] [Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations.2014] [Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.2014] [Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes.2014] [PTEN interacts with histone H1 and controls chromatin condensation.2014] [Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.2014] [Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders.2015] [A mutant form of PTEN linked to autism.2010] [Neural transcriptome of constitutional Pten dysfunction in mice and its relevance to human idiopathic autism spectrum disorder.2015] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome.2015] [Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015]7/1/2015
Score remained at 1S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LoF events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified." A de novo LoF variant in the PTEN gene was recently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A detailed examination of ASD cases with heterozygous PTEN mutations found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified PTEN as a gene meeting high statistical significance with a 0.01
Reports Added
[Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.2007] [Autistic spectrum disorder in a 9-year-old girl with macrocephaly.2010] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly.2013] [Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Novel PTEN mutations in neurodevelopmental disorders and macrocephaly.2008] [The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.2009] [Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly.2010] [PTEN mutation in a family with Cowden syndrome and autism.2001] [De novo mutations in epileptic encephalopathies.2013] [Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.2005] [Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling.2012] [PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.1997] [The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.1998] [Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.1998] [Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.2006] [Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase.2006] [PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.2010] [A secreted PTEN phosphatase that enters cells to alter signaling and survival.2013] [PTEN knockdown alters dendritic spine/protrusion morphology, not density.2013] [Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations.2014] [Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.2014] [Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes.2014] [PTEN interacts with histone H1 and controls chromatin condensation.2014] [Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.2014] [Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders.2015] [A mutant form of PTEN linked to autism.2010] [Neural transcriptome of constitutional Pten dysfunction in mice and its relevance to human idiopathic autism spectrum disorder.2015] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015]4/1/2015
Score remained at 1S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LoF events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified." A de novo LoF variant in the PTEN gene was recently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A detailed examination of ASD cases with heterozygous PTEN mutations found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified PTEN as a gene meeting high statistical significance with a 0.01
Reports Added
[Neural transcriptome of constitutional Pten dysfunction in mice and its relevance to human idiopathic autism spectrum disorder.2015] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles.2015] [Excess of rare, inherited truncating mutations in autism.2015]1/1/2015
Score remained at 1S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LGD events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified." A de novo LoF variant in the PTEN gene was recently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A detailed examination of ASD cases with heterozygous PTEN mutations found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified PTEN as a gene meeting high statistical significance with a 0.01
Reports Added
[Novel PTEN mutations in neurodevelopmental disorders and macrocephaly.2008] [The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.2009] [Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly.2010] [Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes.2014] [Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders.2015] [A mutant form of PTEN linked to autism.2010]10/1/2014
Decreased from 2S to 1S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LGD events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified." A de novo LoF variant in the PTEN gene was recently identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A detailed examination of ASD cases with heterozygous PTEN mutations found that these cases had a high proportion of missense variants, showed reduced PTEN protein levels, and exhibited prominent white-matter and cognitive abnormalities compared to other groups (PMID 25288137). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified PTEN as a gene meeting high statistical significance with a 0.01
7/1/2014
Increased from No data to 2S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LGD events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified."
Reports Added
[PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.1997] [The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.1998] [Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.1998] [PTEN mutation in a family with Cowden syndrome and autism.2001] [Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.2005] [Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.2006] [Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase.2006] [Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.2007] [PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.2010] [Autistic spectrum disorder in a 9-year-old girl with macrocephaly.2010] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly.2013] [A secreted PTEN phosphatase that enters cells to alter signaling and survival.2013] [De novo mutations in epileptic encephalopathies.2013] [PTEN knockdown alters dendritic spine/protrusion morphology, not density.2013] [Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations.2014] [Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.2014] [Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.2014] [PTEN interacts with histone H1 and controls chromatin condensation.2014]4/1/2014
Increased from No data to 2S
Description
Syndromic because of causative mutations in Cowden syndrome. Two de novo LGD events in PTEN from recent exome sequencing studies in simplex ASD cases: from O'Roak et al. Nature 2012 (PMID 22495309) a de novo missense variant (p.Thr167Asn) that was ranked severe"; and from O'Roak et al. Science 2012 (PMID 23160955) a de novo frameshift insertion (p.Cys136MetfsX44) was also identified."
Krishnan Probability Score
Score 0.49831091848158
Ranking 2260/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.97550686584803
Ranking 2246/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.973
Ranking 52/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.00071064664987682
Ranking 18/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 82
Ranking 13/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.24988226958981
Ranking 3481/20870 scored genes
[Show Scoring Methodology]
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| Beclin-1 | Beclin-1 | Human | Direct Regulation | 8678 | Q14457 |
| BMP9 | Growth/differentiation factor 2 | Mouse | Protein Binding | 12165 | Q9WV56 |
| C19orf29OS | chromosome 19 open reading frame 29 opposite strand | Human | Protein Binding | 404665 | Q8N1I8 |
| CHGB | chromogranin B (secretogranin 1) | Human | Protein Binding | 1114 | P05060 |
| cyclin D1 | G1/S-specific cyclin-D1 | Human | Protein Binding | 595 | P24385 |
| DJ1 | Protein deglycase DJ-1 | Human | Protein Modification | 11315 | Q99497 |
| FRK | fyn-related kinase | Human | Protein Modification | 2444 | P42685 |
| GFRA2 | GDNF family receptor alpha 2 | Human | Protein Binding | 2675 | E9PD47 |
| GPR113 | G protein-coupled receptor 113 | Human | Protein Binding | 165082 | Q8IZF5 |
| HBA1 | hemoglobin, alpha 1 | Human | Protein Binding | 3039 | P69905 |
| Histone H1.2 | Histone H1.2 | Human | Protein Binding | 3006 | P16403 |
| HP1 alpha | Chromobox protein homolog 5 | Human | Protein Binding | 23468 | P45973 |
| LEPREL4 | leprecan-like 4 | Human | Protein Binding | 10609 | Q92791 |
| lncRNA-BGL3 | beta globin locus transcript 3 (non-protein coding) | Human | RNA Binding | 103344929 | N/A |
| miR-106b | microRNA 106b | Human | RNA Binding | 406900 | N/A |
| miR-130b | microRNA 130b | Human | RNA Binding | 406920 | N/A |
| miR-21 | microRNA 21 | Human | RNA Binding | 406991 | N/A |
| miR-221 | microRNA 221 | Human | RNA Binding | 407006 | |
| miR-29a | microRNA mir-29a | Rat | RNA Binding | 100314230 | N/A |
| miR-518c | microRNA 518c | Human | RNA Binding | 574477 | N/A |
| miR-638 | microRNA 638 | Human | RNA Binding | 693223 | N/A |
| miR-7 | leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 1 | Human | RNA Binding | 10859 | Q8NHL6 |
| miR-802 | microRNA 802 | Human | RNA Binding | 768219 | N/A |
| miR-92a | microRNA 29a | Human | Direct Regulation | 407021 | N/A |
| miR-BART7 | ebv-mir-BART7 (MI0003729) | HHV-4 | RNA Binding | N/A | N/A |
| miR1297 | microRNA 1297 | Human | RNA Binding | 100302187 | N/A |
| miR20b | microRNA 20b | Human | RNA Binding | 574032 | N/A |
| miR214 | microRNA 214 | Human | RNA Binding | 406996 | N/A |
| MIR221 | microRNA 221 | Human | RNA Binding | 407006 | N/A |
| miR26a | microRNA 26a-1 | Human | RNA Binding | 407015 | N/A |
| MIR29C | microRNA 29c | Human | RNA Binding | 407026 | N/A |
| p21 | cyclin-dependent kinase inhibitor 1A (p21, Cip1) | Human | Protein Binding | 1026 | P38936 |
| PTPN6 | protein tyrosine phosphatase, non-receptor type 6 | Human | Protein Modification | 5777 | P29350 |
| PTPRZ1 | N/A | Pig | Protein Modification | 100511294 | N/A |
| QRFPR | pyroglutamylated RFamide peptide receptor | Human | Protein Binding | 84109 | Q96P65 |
| SLUG | Zinc finger protein SNAI2 | Human | DNA Binding | 6591 | O43623 |
| TCEB3C | transcription elongation factor B polypeptide 3C (elongin A3) | Human | Protein Binding | 162699 | Q8NG57 |
| TNKS1 | Tankyrase-1 | Human | Protein Modification | 8658 | O95271 |