DYRK1ADual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Autism Reports / Total Reports
40 / 87Rare Variants / Common Variants
271 / 0Aliases
DYRK1A, DYRK, DYRK1, HP86, MNB, MNBH, MRD7Associated Syndromes
-Chromosome Band
21q22.13Associated Disorders
DD/NDD, ID, EP, EPS, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, FunctionalRelevance to Autism
Recurrent mutations in the DYRK1A gene have been identified in multiple individuals with ASD as described below. A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047). 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 DYRK1A as a gene reaching exome-wide significance (P < 2.5E-06).
Molecular Function
This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. It is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. Defects in DYRK1A are the cause of mental retardation autosomal dominant type 7 (MRD7) [MIM:614104].
External Links
SFARI Genomic Platforms
Reports related to DYRK1A (87 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly | Mller RS , et al. (2008) | No | Epilepsy, MR |
| 2 | Support | Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly | van Bon BW , et al. (2011) | No | Autistic features |
| 3 | Primary | Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations | O'Roak BJ , et al. (2012) | Yes | - |
| 4 | Support | De novo gene disruptions in children on the autistic spectrum | Iossifov I , et al. (2012) | Yes | - |
| 5 | Recent Recommendation | The DYRK1A gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy | Courcet JB , et al. (2012) | No | Epilepsy |
| 6 | Support | Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders | O'Roak BJ , et al. (2012) | Yes | - |
| 7 | Recent Recommendation | DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease | Barallobre MJ , et al. (2014) | No | - |
| 8 | Support | Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing | Redin C , et al. (2014) | No | - |
| 9 | Recent Recommendation | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 10 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 11 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | Yes | Microcephaly |
| 12 | Support | DYRK1A mutations in two unrelated patients | Ruaud L , et al. (2015) | No | Autistic features |
| 13 | Recent Recommendation | Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID | van Bon BW , et al. (2015) | Yes | Epilepsy/seizures, microcephaly |
| 14 | Recent Recommendation | Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A | Bronicki LM , et al. (2015) | Yes | Microcephaly |
| 15 | Recent Recommendation | DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies | Ji J , et al. (2015) | No | ASD, epilepsy/seizures |
| 16 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 17 | Support | Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities | Zhang Y , et al. (2015) | No | - |
| 18 | Support | Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly | Rump P , et al. (2016) | No | Microcephaly |
| 19 | Support | Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature | Luco SM , et al. (2016) | No | Epilepsy/seizures |
| 20 | Recent Recommendation | Phosphorylation of ?-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis | Ori-McKenney KM , et al. (2016) | No | - |
| 21 | Support | High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing | Martnez F , et al. (2016) | No | - |
| 22 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort | Wang T , et al. (2016) | Yes | - |
| 23 | Support | The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies | Redin C , et al. (2016) | No | Autistic features |
| 24 | Support | Clinical exome sequencing: results from 2819 samples reflecting 1000 families | Trujillano D , et al. (2016) | No | DD, ID, epilepsy/seizures |
| 25 | Support | Structural analysis of pathogenic mutations in the DYRK1A gene in patients with developmental disorders | Evers JM , et al. (2017) | No | - |
| 26 | Support | Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders | Reuter MS , et al. (2017) | No | - |
| 27 | Support | Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development | Dang T , et al. (2017) | Yes | - |
| 28 | Support | Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases | Stessman HA , et al. (2017) | Yes | - |
| 29 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
| 30 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | No | - |
| 31 | Support | Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders | Li J , et al. (2017) | Yes | - |
| 32 | Support | Clinical phenotype of ASD-associated DYRK1A haploinsufficiency | Earl RK , et al. (2017) | No | ASD |
| 33 | Recent Recommendation | Functional characterization of DYRK1A missense variants associated with a syndromic form of intellectual deficiency and autism | Widowati EW , et al. (2018) | No | - |
| 34 | Support | Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model | Guo H , et al. (2018) | Yes | - |
| 35 | Support | Impaired development of neocortical circuits contributes to the neurological alterations in DYRK1A haploinsufficiency syndrome | Arranz J , et al. (2019) | Yes | - |
| 36 | Support | Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly | Boonsawat P , et al. (2019) | No | DD, epilepsy/seizures |
| 37 | Support | Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes | Xiong J , et al. (2019) | Yes | ID |
| 38 | Support | The Body Size of Stimulus Conspecifics Affects Social Preference in a Binary Choice Task in Wild-Type, But Not in dyrk1aa Mutant, Zebrafish | Aslanzadeh M , et al. (2019) | No | - |
| 39 | Support | Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population | Monies D , et al. (2019) | Yes | - |
| 40 | Support | Characterization of intellectual disability and autism comorbidity through gene panel sequencing | Aspromonte MC , et al. (2019) | Yes | - |
| 41 | Support | DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract | Blackburn ATM , et al. (2019) | No | ASD, epilepsy/seizures, microcephaly |
| 42 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 43 | Support | Autism risk in offspring can be assessed through quantification of male sperm mosaicism | Breuss MW , et al. (2019) | Yes | - |
| 44 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 45 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use | Husson T , et al. (2020) | Yes | - |
| 46 | Support | Genetic landscape of autism spectrum disorder in Vietnamese children | Tran KT et al. (2020) | Yes | - |
| 47 | Support | The neurodevelopmental disorder risk gene DYRK1A is required for ciliogenesis and control of brain size in Xenopus embryos | Willsey HR et al. (2020) | No | - |
| 48 | Support | A novel de novo heterozygous DYRK1A mutation causes complete loss of DYRK1A function and developmental delay | Lee KS et al. (2020) | No | DD, epilepsy/seizures |
| 49 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | ID |
| 50 | Support | - | Méjécase C et al. (2021) | No | DD, ID, epilepsy/seizures |
| 51 | Support | - | Hiraide T et al. (2021) | No | - |
| 52 | Support | - | Chen JS et al. (2021) | Yes | - |
| 53 | Support | - | Okazaki T et al. (2021) | No | ASD, DD, epilepsy/seizures |
| 54 | Recent Recommendation | - | Courraud J et al. (2021) | No | ASD, stereotypy |
| 55 | Support | - | Valentino F et al. (2021) | No | Epilepsy/seizures, stereotypy |
| 56 | Support | - | Chau KK et al. (2021) | Yes | - |
| 57 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
| 58 | Support | - | Verberne EA et al. (2022) | No | - |
| 59 | Recent Recommendation | - | Fenster R et al. (2022) | No | ASD, epilepsy/seizures |
| 60 | Support | - | Hu C et al. (2022) | Yes | - |
| 61 | Support | - | Krgovic D et al. (2022) | Yes | DD, ID, epilepsy/seizures |
| 62 | Support | - | Durand B et al. (2022) | No | ASD |
| 63 | Support | - | Chen Y et al. (2021) | No | - |
| 64 | Support | - | Levchenko O et al. (2022) | No | Epilepsy/seizures |
| 65 | Support | - | Zhou X et al. (2022) | Yes | - |
| 66 | Support | - | Pijuan I et al. (2022) | No | - |
| 67 | Support | - | Obara K et al. (2023) | No | - |
| 68 | Support | - | Infantino I et al. (2023) | Yes | - |
| 69 | Recent Recommendation | - | Weinschutz Mendes H et al. (2023) | Yes | - |
| 70 | Recent Recommendation | - | Pintacuda G et al. (2023) | Yes | - |
| 71 | Support | - | Zhou C et al. (2023) | No | Autistic behavior |
| 72 | Support | - | Kurtz-Nelson EC et al. (2023) | Yes | - |
| 73 | Support | - | Sanchis-Juan A et al. (2023) | No | - |
| 74 | Support | - | Yu-Tzu Shih et al. (2023) | Yes | - |
| 75 | Support | - | Lucie Sedlackova et al. (2024) | No | - |
| 76 | Support | - | Erica Rosina et al. (2024) | No | - |
| 77 | Support | - | M Cecilia Poli et al. () | Yes | - |
| 78 | Support | - | Cheng Huang et al. (2023) | No | - |
| 79 | Support | - | Ãris Oliveira et al. (2024) | No | Stereotypy |
| 80 | Support | - | Marketa Wayhelova et al. (2024) | No | - |
| 81 | Support | - | Emily Neuhaus et al. (2024) | Yes | Attentional and depressive features |
| 82 | Support | - | Ruohao Wu et al. (2024) | No | - |
| 83 | Support | - | Alistair T Pagnamenta et al. (2024) | Yes | - |
| 84 | Support | - | Mehdi Agha Gholizadeh et al. () | Yes | DD, ID |
| 85 | Support | - | Tomoki T Nomakuchi et al. () | No | - |
| 86 | Support | - | Axel Schmidt et al. (2024) | No | ASD, epilepsy/seizures, stereotypy |
| 87 | Support | - | Fiona Whitaker et al. (2024) | No | - |
Rare Variants (271)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | inversion | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| - | - | translocation | De novo | - | - | 27841880 | Redin C , et al. (2016) | |
| - | - | translocation | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| - | - | copy_number_loss | Unknown | - | - | 35285131 | Fenster R et al. (2022) | |
| - | - | copy_number_loss | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| - | - | copy_number_loss | De novo | - | - | 21294719 | van Bon BW , et al. (2011) | |
| - | - | copy_number_loss | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| - | - | copy_number_loss | De novo | - | - | 25920557 | Bronicki LM , et al. (2015) | |
| - | - | copy_number_loss | De novo | - | Simplex | 37274198 | Zhou C et al. (2023) | |
| - | - | translocation | De novo | - | Simplex | 18405873 | Mller RS , et al. (2008) | |
| - | - | copy_number_loss | De novo | - | - | 39031459 | Tomoki T Nomakuchi et al. () | |
| - | - | copy_number_loss | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.232C>T | p.Gln78Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.208-1G>A | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| - | - | copy_number_loss | De novo | - | Simplex | 33624935 | Abe-Hatano C et al. (2021) | |
| c.349C>T | p.Arg117Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.367C>T | p.Gln123Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.763C>T | p.Arg255Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1071+1G>A | - | splice_site_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1072-2A>G | - | splice_site_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1099-2A>G | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1325C>G | p.Ser442Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.457G>T | p.Glu153Ter | stop_gained | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.613C>T | p.Arg205Ter | stop_gained | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.715G>T | p.Glu239Ter | stop_gained | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| - | - | inversion | De novo | - | Simplex | 38776926 | Alistair T Pagnamenta et al. (2024) | |
| c.214C>G | p.Pro72Ala | missense_variant | Unknown | - | - | 35741772 | Hu C et al. (2022) | |
| c.613C>T | p.Arg205Ter | stop_gained | De novo | - | - | 25641759 | Ruaud L , et al. (2015) | |
| c.763C>T | p.Arg255Ter | stop_gained | De novo | - | - | 29034068 | Earl RK , et al. (2017) | |
| c.665-1G>T | - | splice_site_variant | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.952-2A>G | - | splice_site_variant | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.328-2A>G | - | splice_site_variant | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 25944381 | Ji J , et al. (2015) | |
| c.763C>T | p.Arg255Ter | stop_gained | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.787C>T | p.Arg263Ter | stop_gained | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.349C>T | p.Arg117Ter | stop_gained | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.613C>T | p.Arg205Ter | stop_gained | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.657C>A | p.Tyr219Ter | stop_gained | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.691C>T | p.Arg231Ter | stop_gained | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.328-1G>T | - | splice_site_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.665-2A>G | - | splice_site_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.924+1G>C | - | splice_site_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1730T>A | p.Val577Asp | missense_variant | Unknown | - | - | 35741772 | Hu C et al. (2022) | |
| c.1282C>T | p.Arg428Ter | stop_gained | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.1309C>T | p.Arg437Ter | stop_gained | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.1035G>A | p.Met345Ile | stop_gained | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.1653C>A | p.Cys551Ter | stop_gained | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.322C>T | p.Arg108Ter | stop_gained | Unknown | - | - | 34345024 | Courraud J et al. (2021) | |
| c.349C>T | p.Arg117Ter | stop_gained | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.613C>T | p.Arg205Ter | stop_gained | Unknown | - | - | 34345024 | Courraud J et al. (2021) | |
| c.763C>T | p.Arg255Ter | stop_gained | Unknown | - | - | 34345024 | Courraud J et al. (2021) | |
| c.799C>T | p.Gln267Ter | stop_gained | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.936T>A | p.Cys312Ter | stop_gained | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1240-2A>G | - | splice_site_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.489+2T>C | - | splice_site_variant | De novo | - | - | 25707398 | van Bon BW , et al. (2015) | |
| c.1313G>A | p.Arg438His | missense_variant | De novo | - | - | 28831199 | Li J , et al. (2017) | |
| c.974G>A | p.Arg325His | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.982C>T | p.Arg328Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.924+4_924+7del | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.169T>C | p.Ser57Pro | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.183G>C | p.Gln61His | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.1309C>T | p.Arg437Ter | stop_gained | Unknown | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1399C>T | p.Arg467Ter | stop_gained | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.367C>T | p.Gln123Ter | stop_gained | De novo | - | - | 25707398 | van Bon BW , et al. (2015) | |
| c.1240-2A>G | - | splice_site_variant | De novo | - | - | 25707398 | van Bon BW , et al. (2015) | |
| c.312C>G | p.Tyr104Ter | stop_gained | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.613C>T | p.Arg205Ter | stop_gained | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.1031T>A | p.Met344Lys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1334C>T | p.Thr445Met | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1409C>T | p.Pro470Leu | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1852C>T | p.Arg618Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1879C>T | p.Arg627Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.355C>T | p.His119Tyr | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.376G>T | p.Asp126Tyr | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.398G>A | p.Arg133Gln | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.468G>A | p.Met156Ile | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.583G>A | p.Ala195Thr | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.777G>T | p.Leu259Phe | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| A>G | p.? | splice_site_variant | Familial | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
| c.1639C>T | p.Gln547Ter | stop_gained | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
| c.1669C>T | p.Gln557Ter | stop_gained | De novo | - | - | 34356170 | Valentino F et al. (2021) | |
| c.1399C>T | p.His467Tyr | stop_gained | Unknown | - | - | 35253369 | Verberne EA et al. (2022) | |
| c.586C>T | p.Arg196Ter | stop_gained | De novo | - | - | 25920557 | Bronicki LM , et al. (2015) | |
| c.736C>T | p.Arg246Ter | stop_gained | De novo | - | - | 25920557 | Bronicki LM , et al. (2015) | |
| c.691C>T | p.Arg231Ter | stop_gained | De novo | - | - | 28191889 | Stessman HA , et al. (2017) | |
| c.1071+1G>A | - | splice_site_variant | De novo | - | - | 28191889 | Stessman HA , et al. (2017) | |
| c.1399C>T | p.Arg467Ter | stop_gained | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.665-9_665-5del | - | splice_region_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.691C>T | p.Arg231Ter | stop_gained | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.586C>T | p.Arg196Ter | stop_gained | De novo | - | Simplex | 35873028 | Chen Y et al. (2021) | |
| c.1373G>T | p.Arg458Met | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.932C>T | p.Ser311Phe | missense_variant | De novo | - | - | 25641759 | Ruaud L , et al. (2015) | |
| c.883C>T | p.Leu295Phe | missense_variant | De novo | - | - | 29034068 | Earl RK , et al. (2017) | |
| c.638-8_638-3del | - | splice_site_variant | De novo | - | - | 29034068 | Earl RK , et al. (2017) | |
| c.1309C>T | p.Arg437Ter | stop_gained | Unknown | - | - | 25920557 | Bronicki LM , et al. (2015) | |
| c.1405C>T | p.Gln469Ter | stop_gained | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.208-1G>A | - | splice_site_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
| c.1399C>T | p.His467Tyr | stop_gained | De novo | - | Simplex | 35873028 | Chen Y et al. (2021) | |
| c.601C>T | p.Gln201Ter | stop_gained | De novo | - | Simplex | 32193494 | Tran KT et al. (2020) | |
| c.1178C>G | p.Thr393Ser | missense_variant | Unknown | - | - | 31031587 | Xiong J , et al. (2019) | |
| c.829G>C | p.Ala277Pro | missense_variant | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.848T>G | p.Ile283Ser | missense_variant | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| G>A | p.? | splice_site_variant | Familial | - | Multiplex | 28263302 | C Yuen RK et al. (2017) | |
| T>C | p.? | splice_site_variant | Familial | - | Multiplex | 28263302 | C Yuen RK et al. (2017) | |
| c.787C>T | p.Arg263Ter | stop_gained | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.1071+1G>A | - | splice_site_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.208-28G>A | - | splice_site_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
| c.586C>T | p.Arg196Ter | stop_gained | De novo | - | Simplex | 25167861 | Redin C , et al. (2014) | |
| c.946C>T | p.Gln316Ter | stop_gained | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.760C>T | p.Arg254Ter | stop_gained | De novo | - | Simplex | 26922654 | Luco SM , et al. (2016) | |
| c.1400G>A | p.Arg467Gln | missense_variant | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.272del | p.Leu91Ter | frameshift_variant | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.503G>A | p.Gly168Asp | missense_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.764G>A | p.Arg255Gln | missense_variant | Unknown | - | - | 34345024 | Courraud J et al. (2021) | |
| c.860A>T | p.Asp287Val | missense_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.914T>G | p.Ile305Arg | missense_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.972T>A | p.Ser324Arg | missense_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.924+4_924+7del | - | splice_site_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1282C>T | p.Arg428Ter | stop_gained | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.1309C>T | p.Arg437Ter | stop_gained | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.489+2T>C | - | splice_site_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.957C>G | p.Tyr319Ter | stop_gained | De novo | - | Simplex | 34253714 | Okazaki T et al. (2021) | |
| c.1240-2A>G | - | splice_site_variant | Unknown | - | Simplex | 31130284 | Monies D , et al. (2019) | |
| c.1098G>T | p.Glu366Asp | inframe_deletion | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1384T>C | p.Tyr462His | missense_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1400G>A | p.Arg467Gln | missense_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1457G>A | p.Gly486Asp | missense_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1519+1del | - | frameshift_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.638-9_638-5del | - | splice_site_variant | De novo | - | - | 25707398 | van Bon BW , et al. (2015) | |
| c.349C>T | p.Arg117Ter | stop_gained | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.361C>T | p.Gln121Ter | stop_gained | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.586C>T | p.Arg196Ter | stop_gained | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.613C>T | p.Arg205Ter | stop_gained | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.691C>T | p.Arg231Ter | stop_gained | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.763C>T | p.Arg255Ter | stop_gained | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.563A>T | p.Lys188Ile | missense_variant | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.734T>G | p.Leu245Arg | missense_variant | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.883C>T | p.Leu295Phe | missense_variant | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.477del | p.Tyr159Ter | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.638-9_638-5del | - | splice_region_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.691C>T | p.Arg231Ter | stop_gained | De novo | - | Simplex | 31873310 | Breuss MW , et al. (2019) | |
| c.1071+1G>A | - | splice_site_variant | De novo | - | Simplex | 22495309 | O'Roak BJ , et al. (2012) | |
| c.923T>C | p.Phe308Ser | missense_variant | Unknown | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.525G>A | p.Lys175= | missense_variant | De novo | - | - | 31209962 | Aspromonte MC , et al. (2019) | |
| c.1035G>A | p.Met345Ile | stop_gained | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1423C>T | p.Gln475Ter | stop_gained | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1036T>C | p.Ser346Pro | missense_variant | De novo | - | - | 25920557 | Bronicki LM , et al. (2015) | |
| c.665-4del | - | splice_site_variant | De novo | - | Simplex | 30842647 | Boonsawat P , et al. (2019) | |
| c.349C>T | p.Arg117Ter | stop_gained | Familial | Paternal | - | 34345024 | Courraud J et al. (2021) | |
| c.956G>A | p.Arg319Gln | splice_site_variant | De novo | - | - | 36741085 | Infantino I et al. (2023) | |
| c.208-1G>A | - | splice_site_variant | Familial | Maternal | - | 25707398 | van Bon BW , et al. (2015) | |
| c.1309C>T | p.Arg437Ter | stop_gained | De novo | - | Simplex | 38179410 | Cheng Huang et al. (2023) | |
| c.349C>T | p.Arg117Ter | stop_gained | De novo | - | Simplex | 38041506 | Erica Rosina et al. (2024) | |
| c.1040T>G | p.Leu347Arg | missense_variant | De novo | - | - | 27848944 | Trujillano D , et al. (2016) | |
| c.517G>T | p.Val173Phe | missense_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.317dup | p.Lys107GlufsTer13 | frameshift_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1028A>G | p.Asp343Gly | missense_variant | Unknown | - | Unknown | 33753861 | Chen JS et al. (2021) | |
| c.859G>T | p.Asp287Tyr | missense_variant | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.924+4_924+7del | - | splice_site_variant | De novo | - | Simplex | 26922654 | Luco SM , et al. (2016) | |
| c.451_466del | p.Glu151Ter | frameshift_variant | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| - | p.Gly4_Asn109del | copy_number_loss | De novo | - | Simplex | 38179410 | Cheng Huang et al. (2023) | |
| c.1282C>T | p.Arg428Ter | stop_gained | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1042G>A | p.Gly348Arg | missense_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.1400G>A | p.Arg467Gln | missense_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.1606C>T | p.Arg536Trp | missense_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
| c.33del | p.Lys11AsnfsTer38 | frameshift_variant | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.250dup | p.Leu84ProfsTer7 | frameshift_variant | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.719T>C | p.Leu240Pro | missense_variant | De novo | - | Simplex | 38764027 | Ruohao Wu et al. (2024) | |
| c.1159C>T | p.Gln387Ter | stop_gained | De novo | - | Multiplex | 38179410 | Cheng Huang et al. (2023) | |
| c.563_565del | p.Lys188del | inframe_deletion | Unknown | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.613C>T | p.Arg205Ter | stop_gained | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.395A>T | p.Asp132Val | missense_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.860A>T | p.Asp287Val | missense_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.878T>A | p.Ile293Asn | missense_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.883C>T | p.Leu295Phe | missense_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1595C>T | p.Thr532Met | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
| c.275del | p.Ile92ThrfsTer49 | frameshift_variant | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.887dup | p.Val297SerfsTer2 | frameshift_variant | De novo | - | - | 28053047 | Evers JM , et al. (2017) | |
| c.1046G>A | p.Cys349Tyr | missense_variant | De novo | - | Simplex | 33644862 | Hiraide T et al. (2021) | |
| c.208dup | p.Arg70LysfsTer9 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.2133C>A | p.Tyr711Ter | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1028A>C | p.Asp343Ala | missense_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1030A>T | p.Met344Leu | missense_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1028A>G | p.Asp343Gly | missense_variant | De novo | - | - | 38008000 | Lucie Sedlackova et al. (2024) | |
| c.1221del | p.Lys407AsnfsTer35 | frameshift_variant | De novo | - | - | 29034068 | Earl RK , et al. (2017) | |
| c.1400dup | p.His467GlnfsTer9 | frameshift_variant | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.1316del | p.Asp439AlafsTer3 | frameshift_variant | De novo | - | - | 35813072 | Krgovic D et al. (2022) | |
| c.1644+133T>G | - | intron_variant | Familial | Paternal | Simplex | 23160955 | O'Roak BJ , et al. (2012) | |
| c.799C>T | p.Gln267Ter | stop_gained | Unknown | Not maternal | - | 25707398 | van Bon BW , et al. (2015) | |
| c.1031_1037del | p.Met344ThrfsTer22 | frameshift_variant | Unknown | - | - | 35741772 | Hu C et al. (2022) | |
| c.775_776del | p.Leu259GlufsTer23 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.705_707delinsAC | p.Asn235LysfsTer6 | stop_gained | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.782del | p.Leu261GlnfsTer28 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1008dup | p.Pro337AlafsTer3 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1333dup | p.Thr445AsnfsTer4 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.473A>G | p.Lys158Arg | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.1536G>A | p.Ser512%3D | synonymous_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.1430_1431insA | p.Thr478TyrfsTer5 | missense_variant | Unknown | - | - | 28167836 | Dang T , et al. (2017) | |
| c.1406del | p.Phe469SerfsTer114 | frameshift_variant | Unknown | - | - | 35285131 | Fenster R et al. (2022) | |
| c.1033del | p.Trp345GlyfsTer23 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1270del | p.His424IlefsTer27 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1464del | p.Ala489ProfsTer94 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1978del | p.Ser660ProfsTer43 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.1541G>A | p.Ser514Asn | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.1763C>A | p.Thr588Asn | missense_variant | De novo | - | Simplex | 25920557 | Bronicki LM , et al. (2015) | |
| c.1522G>A | p.Gly508Ser | splice_site_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.434del | p.Lys145SerfsTer11 | frameshift_variant | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.1243_1244dup | p.Lys416ThrfsTer36 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.572_575del | p.Ala191GlyfsTer2 | frameshift_variant | De novo | - | - | 35285131 | Fenster R et al. (2022) | |
| c.263_264del | p.Ser88CysfsTer2 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.270_274del | p.Leu91GlnfsTer7 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.918dup | p.Gln307AlafsTer24 | frameshift_variant | De novo | - | - | 25920557 | Bronicki LM , et al. (2015) | |
| c.1764del | p.His590MetfsTer2 | stop_gained | De novo | - | Simplex | 38041506 | Erica Rosina et al. (2024) | |
| c.848dup | p.Asn283LysfsTer6 | frameshift_variant | De novo | - | Simplex | 36628390 | Obara K et al. (2023) | |
| c.208-28G>A | - | splice_site_variant | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.574_578del | p.Gln192ArgfsTer6 | frameshift_variant | De novo | - | - | 27620904 | Martnez F , et al. (2016) | |
| c.675_676del | p.Cys226PhefsTer4 | frameshift_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.263_264del | p.Ser88CysfsTer2 | frameshift_variant | De novo | - | - | 23099646 | Courcet JB , et al. (2012) | |
| c.1205dup | p.Arg404ThrfsTer10 | frameshift_variant | De novo | - | - | 25920557 | Bronicki LM , et al. (2015) | |
| c.1464del | p.Ala489ProfsTer94 | frameshift_variant | De novo | - | - | 28191889 | Stessman HA , et al. (2017) | |
| c.1309C>T | p.Arg437Ter | stop_gained | Unknown | Not maternal | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.474del | p.Gly159ValfsTer7 | frameshift_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.227dup | p.Met76IlefsTer12 | frameshift_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
| c.1634C>T | p.Ala545Val | missense_variant | Familial | Maternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.1643dup | p.Val549GlyfsTer15 | frameshift_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.1185dup | p.Lys398GlufsTer16 | frameshift_variant | De novo | - | Simplex | 32555303 | Lee KS et al. (2020) | |
| c.1190_1193del | p.Lys397ArgfsTer44 | frameshift_variant | De novo | - | - | 29034068 | Earl RK , et al. (2017) | |
| c.1374delinsGG | p.Ile459AspfsTer17 | frameshift_variant | De novo | - | - | 29034068 | Earl RK , et al. (2017) | |
| c.956_959del | p.Arg319LeufsTer39 | splice_site_variant | Unknown | - | - | 35285131 | Fenster R et al. (2022) | |
| c.763C>T | p.Arg255Ter | stop_gained | Unknown | Not maternal | Simplex | 32094338 | Husson T , et al. (2020) | |
| c.1451dup | p.Ser485IlefsTer79 | frameshift_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.398del | p.Asp133ValfsTer8 | frameshift_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.948_949insGG | p.Phe317GlyfsTer43 | frameshift_variant | Unknown | - | - | 38177409 | M Cecilia Poli et al. () | |
| c.797del | p.Phe266SerfsTer14 | frameshift_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1350dup | p.Leu451AlafsTer2 | frameshift_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1400dup | p.His467GlnfsTer9 | frameshift_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1074_1077del | p.Asp359ArgfsTer2 | frameshift_variant | De novo | - | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.714del | p.Phe238LeufsTer12 | frameshift_variant | De novo | - | Simplex | 28097321 | Reuter MS , et al. (2017) | |
| c.489_495del | p.Leu164AlafsTer9 | frameshift_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.1662_1663del | p.His554GlnfsTer45 | frameshift_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.817dup | p.Ser273LysfsTer6 | frameshift_variant | De novo | - | Simplex | 25920557 | Bronicki LM , et al. (2015) | |
| c.986_995del | p.Ser329CysfsTer36 | frameshift_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.143_144del | p.Ile48LysfsTer2 | frameshift_variant | De novo | - | Simplex | 23160955 | O'Roak BJ , et al. (2012) | |
| c.1464del | p.Ala489ProfsTer94 | frameshift_variant | De novo | - | Simplex | 22542183 | Iossifov I , et al. (2012) | |
| c.570_573del | p.Gln190HisfsTer3 | frameshift_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.572_575del | p.Ala191GlyfsTer2 | frameshift_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.425dup | p.Asn142LysfsTer12 | frameshift_variant | Unknown | Not maternal | - | 29034068 | Earl RK , et al. (2017) | |
| c.1217_1220del | p.Lys406ArgfsTer44 | frameshift_variant | De novo | - | - | 31263215 | Blackburn ATM , et al. (2019) | |
| TTTCTCTT>TTT | - | splice_site_variant | De novo | - | - | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.572_575del | p.Lys191ThrfsTer6 | frameshift_variant | De novo | - | Simplex | 35887114 | Levchenko O et al. (2022) | |
| c.594_597delinsGAA | p.Glu199AsnfsTer3 | frameshift_variant | De novo | - | - | 25920557 | Bronicki LM , et al. (2015) | |
| c.894del | p.Phe299LeufsTer60 | frameshift_variant | Unknown | - | Simplex | 38298296 | Ãris Oliveira et al. (2024) | |
| c.524del | p.Lys175ArgfsTer15 | frameshift_variant | Unknown | - | Unknown | 39109359 | Fiona Whitaker et al. (2024) | |
| c.914_919del | p.Leu305_Gln307delinsTer | inframe_indel | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.952_955del | p.Tyr318GlyfsTer40 | splice_site_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.1219_1222del | p.Lys407HisfsTer34 | frameshift_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.621_624delinsGA | p.Glu208ThrfsTer6 | frameshift_variant | De novo | - | Simplex | 25167861 | Redin C , et al. (2014) | |
| c.1004del | p.Gly335GlufsTer33 | frameshift_variant | Unknown | Not maternal | - | 34345024 | Courraud J et al. (2021) | |
| c.1135dup | p.Ala379GlyfsTer9 | frameshift_variant | Familial | Paternal | - | 31263215 | Blackburn ATM , et al. (2019) | |
| c.654_658del | p.Phe219ValfsTer10 | splice_region_variant | Unknown | - | - | 33562844 | Méjécase C et al. (2021) | |
| c.425dup | p.Asn142LysfsTer12 | frameshift_variant | Unknown | Not maternal | Simplex | 25944381 | Ji J , et al. (2015) | |
| c.539dup | p.Ile181AsnfsTer19 | frameshift_variant | De novo | - | Simplex | 38321498 | Marketa Wayhelova et al. (2024) | |
| c.1240-1_1240insTAA | p.Arg413_Glu414insTer | splice_site_variant | De novo | - | - | 34345024 | Courraud J et al. (2021) | |
| c.664C>T | p.Arg222Ter | stop_gained | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.1406del | p.Phe469SerfsTer114 | frameshift_variant | Unknown | Not maternal | Simplex | 26846091 | Rump P , et al. (2016) | |
| c.620T>C | p.Leu207Pro | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.860A>T | p.Asp287Val | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.1036T>C | p.Ser346Pro | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.-77+2T>C | p.? | 5_prime_UTR_variant | De novo (germline mosaicism) | - | Multiplex | 38976082 | Mehdi Agha Gholizadeh et al. () | |
| c.236del | p.Pro79GlnfsTer6 | frameshift_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.366_367dup | p.Glu123GlyfsTer19 | frameshift_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) |
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."
4/1/2021
Score remained at 1
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
1/1/2021
Score remained at 1
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
10/1/2020
Score remained at 1
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
7/1/2020
Score remained at 1
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
4/1/2020
Score remained at 1
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
1/1/2020
Score remained at 1
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
Reports Added
[Autism risk in offspring can be assessed through quantification of male sperm mosaicism.2019] [Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020] [Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use.2020]10/1/2019
Score remained at 1
New Scoring Scheme
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
Reports Added
[New Scoring Scheme]7/1/2019
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
Reports Added
[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019] [DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract.2019] [Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]4/1/2019
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
Reports Added
[Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly.2019] [Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.2019] [The Body Size of Stimulus Conspecifics Affects Social Preference in a Binary Choice Task in Wild-Type, But Not in dyrk1aa Mutant, Zebrafish.2019]1/1/2019
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
10/1/2017
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 De Rubeis et al., 2014 identified DYRK1A as a gene meeting high statistical significance with a FDR ? 0.01, meaning that this gene had a ? 99% 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). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD in van Bon et al., 2016 identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Furthermore, phenotypic comparison of 15 cases with DYRK1A disruptions in this report identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features (PMID 28053047).
4/1/2017
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 DYRK1A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Phenotypic comparison of 15 cases with DYRK1A disruptions in PMID 25707398 identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. 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). Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features.
Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID.2015] [Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly.2008] [DYRK1A mutations in two unrelated patients.2015] [The DYRK1A gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy.2012] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly.2011] [DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease.2014] [Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A.2015] [DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly.2016] [Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature.2016] [Phosphorylation of -Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis.2016] [High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.2017] [Structural analysis of pathogenic mutations in the DYRK1A gene in patients with developmental disorders.2017] [Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development.2017] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]1/1/2017
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 DYRK1A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Phenotypic comparison of 15 cases with DYRK1A disruptions in PMID 25707398 identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. 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). Evers et al., 2017 reported additional de novo DYRK1A variants identified in individuals from the Deciphering Developmental Disorders study presenting with intellectual disability and other features.
Reports Added
[Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.2017] [Structural analysis of pathogenic mutations in the DYRK1A gene in patients with developmental disorders.2017] [Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development.2017] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017]10/1/2016
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 DYRK1A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Phenotypic comparison of 15 cases with DYRK1A disruptions in PMID 25707398 identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. 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
[High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016]4/1/2016
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 DYRK1A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Phenotypic comparison of 15 cases with DYRK1A disruptions in PMID 25707398 identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. 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
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID.2015] [Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly.2008] [DYRK1A mutations in two unrelated patients.2015] [The DYRK1A gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy.2012] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly.2011] [DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease.2014] [Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A.2015] [DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly.2016] [Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature.2016] [Phosphorylation of -Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis.2016]1/1/2016
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 DYRK1A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Phenotypic comparison of 15 cases with DYRK1A disruptions in PMID 25707398 identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes. 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
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID.2015] [Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly.2008] [DYRK1A mutations in two unrelated patients.2015] [The DYRK1A gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy.2012] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly.2011] [DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease.2014] [Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A.2015] [DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly.2016] [Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature.2016]4/1/2015
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 DYRK1A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Phenotypic comparison of 15 cases with DYRK1A disruptions in PMID 25707398 identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes.
1/1/2015
Score remained at 1S
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 DYRK1A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). Resequencing of the DYRK1A gene in 4716 new cases with DD/ID or ASD identified five novel truncating variants, three of which were confirmed de novo and were observed in cases with ASD and intellectual disability; no truncating variants in DYRK1A were observed in 6503 individuals from NHLBI or in 2193 unaffected SSC siblings (PMID 25707398). Phenotypic comparison of 15 cases with DYRK1A disruptions in PMID 25707398 identified a syndromic disorder characterized by ASD, intellectual disability, microcephaly and other shared phenotypes.
Reports Added
[Large-scale discovery of novel genetic causes of developmental disorders.2014] [Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID.2015] [DYRK1A mutations in two unrelated patients.2015] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014]10/1/2014
Decreased from 2 to 1
Description
A total of four de novo LoF variants in the DYRK1A gene were identified in ASD probands from the Simons Simplex Collection (PMIDs 22495309, 22542183, 23160955, 25363768). 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 DYRK1A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).
7/1/2014
Increased from No data to 2
Description
Likely gene-disruptive de novo variants in the DYRK1A gene in autistic probands from simplex families have been identified in three separate reports. In the first report, 1 of ~200 de novo protein-altering variants was found in the DYRK1A gene (PMID 22495309). In the second report, 1 of 343 likely gene-disrupting (frameshift) variants was found in the DYRK1A gene (PMID 22542183). In the third report, MLPA screening of 44 candidate genes in 2446 ASD probands identified additional DYRK1A variation (PMID 23160955). No controls; many missense changes in controls in EGV.
Reports Added
[Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly.2008] [Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly.2011] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [The DYRK1A gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease.2014]4/1/2014
Increased from No data to 2
Description
Likely gene-disruptive de novo variants in the DYRK1A gene in autistic probands from simplex families have been identified in three separate reports. In the first report, 1 of ~200 de novo protein-altering variants was found in the DYRK1A gene (PMID 22495309). In the second report, 1 of 343 likely gene-disrupting (frameshift) variants was found in the DYRK1A gene (PMID 22542183). In the third report, MLPA screening of 44 candidate genes in 2446 ASD probands identified additional DYRK1A variation (PMID 23160955). No controls; many missense changes in controls in EGV.
Krishnan Probability Score
Score 0.57879561121083
Ranking 602/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99958454172665
Ranking 895/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.99
Ranking 26/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 1.9918805103288E-6
Ranking 6/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 77
Ranking 16/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.13355028307668
Ranking 5486/20870 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 |
|---|---|---|---|---|---|
| ABLIM1 | actin binding LIM protein 1 | Human | Protein Modification | 3983 | O14639 |
| C10ORF71 | Uncharacterized protein C10orf71 | Human | Protein Binding | 118461 | Q711Q0-3 |
| CAPN1 | Calpain-1 catalytic subunit | Human | Protein Binding | 823 | P07384 |
| DCHS1 | dachsous 1 (Drosophila) | Human | Protein Binding | 8642 | Q96JQ0 |
| FAM53C | family with sequence similarity 53, member C | Human | Protein Binding | 51307 | Q9NYF3 |
| GLCCI1 | glucocorticoid induced transcript 1 | Human | Protein Binding | 113263 | Q86VQ1 |
| GluN2A | Glutamate receptor ionotropic, NMDA 2A | Rat | Protein Modification | 24409 | Q00959 |
| HISTIH2B3 | histone cluster 1, H3a | Human | Protein Modification | 8350 | P68431 |
| histone H3 | Histone H3.1 | Human | Protein Modification | 8350 | P68431 |
| IFI44 | Interferon-induced protein 44 | Human | DNA Binding | 10561 | Q8TCB0 |
| IL1a | interleukin 1, alpha | Human | DNA Binding | 3552 | P01583 |
| IL6 | interleukin 6 (interferon, beta 2) | Human | DNA Binding | 3569 | B4DVM1 |
| IL8 | interleukin 8 | Human | DNA Binding | 3576 | P10145 |
| LRCH3 | leucine-rich repeats and calponin homology (CH) domain containing 3 | Human | Protein Binding | 84859 | Q96II8 |
| LZTS3 | leucine zipper, putative tumor suppressor family member 3 | Human | Protein Binding | 9762 | O60299 |
| NFATC1 | nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 | Human | Protein Modification | 4772 | B5B2M8 |
| RCAN1 | regulator of calcineurin 1 | Human | Protein Modification | 1827 | P53805 |
| RFPL2 | Ret finger protein-like 2 | Human | Protein Binding | 10739 | O75678-2 |
| RNF169 | ring finger protein 169 | Human | Protein Binding | 254225 | Q8NCN4 |
| SNAP91 | synaptosomal-associated protein 91 | Rat | Protein Modification | 65178 | Q05140 |
| Synj | synaptojanin | Fruit Fly | Protein Binding | 37517 | Q5U0V7 |
| Synj1 | synaptojanin 1 | Rat | Protein Modification | 85238 | Q62910 |
| TNFa | Tumor necrosis factor, membrane form | Human | DNA Binding | 7124 | P01375 |
| TNFAIP6 | Tumor necrosis factor-inducible gene 6 protein | Human | DNA Binding | 7130 | P98066 |
| TRMT61B | tRNA methyltransferase 61 homolog B (S. cerevisiae) | Human | Protein Binding | 55006 | Q9BVS5 |
| TROAP | trophinin associated protein | Human | Protein Binding | 10024 | Q12815 |