Human Gene Module / Chromosome 16 / ANKRD11

ANKRD11ankyrin repeat domain 11

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
22 / 76
Rare Variants / Common Variants
231 / 0
EAGLE Score
22.6
Strong Learn More
Aliases
ANKRD11, T13,  LZ16,  ANCO-1
Associated Syndromes
KBG syndrome, Cornelia de Lange syndrome, KBG syndrome, DD, KBG syndrome, DD, ID, KBG syndrome, epilepsy/seizures, KBG syndrome, ADHD, ID
Chromosome Band
16q24.3
Associated Disorders
DD/NDD, ADHD, ID, EPS, ASD
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance to Autism

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder. Two additional de novo likely gene-disruptive variants in ANKRD11 were observed in ASD probands from the Autism Sequencing Consortium in Satterstrom et al., 2020; subsequent TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in this report identified ANKRD11 as a candidate gene with a false discovery rate (FDR) 0.01. 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 ANKRD11 as a gene reaching exome-wide significance (P < 2.5E-06).

Molecular Function

This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ANKRD11 (76 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators Zhang A , et al. (2004) No -
2 Recent Recommendation Subcellular localization of ankyrin repeats cofactor-1 regulates its corepressor activity Zhang A , et al. (2007) No -
3 Primary Structural variation of chromosomes in autism spectrum disorder Marshall CR , et al. (2008) Yes -
4 Recent Recommendation Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function Li CW , et al. (2008) No -
5 Recent Recommendation Identification of ANKRD11 as a p53 coactivator Neilsen PM , et al. (2008) No -
6 Support Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome Willemsen MH , et al. (2009) Yes -
7 Support Haploinsufficiency of ANKRD11 causes mild cognitive impairment, short stature and minor dysmorphisms Isrie M , et al. (2011) No ADHD
8 Support Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia Sirmaci A , et al. (2011) No ID
9 Support Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel Brett M , et al. (2014) Yes MCA
10 Support Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism Ansari M , et al. (2014) No -
11 Support Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing Redin C , et al. (2014) No -
12 Support De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder Dong S , et al. (2014) No -
13 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
14 Recent Recommendation Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations Ockeloen CW , et al. (2014) No ASD, ID, ADHD, epilepsy
15 Support Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders Soden SE , et al. (2014) No -
16 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) Yes -
17 Recent Recommendation Ankrd11 is a chromatin regulator involved in autism that is essential for neural development Gallagher D , et al. (2015) No -
18 Support Whole exome sequencing in females with autism implicates novel and candidate genes Butler MG , et al. (2015) Yes -
19 Support Broadening of cohesinopathies: exome sequencing identifies mutations in ANKRD11 in two patients with Cornelia de Lange-overlapping phenotype Parenti I , et al. (2015) No -
20 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
21 Support Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate Charng WL , et al. (2016) No -
22 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
23 Support Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11 Goldenberg A , et al. (2016) No -
24 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing Martnez F , et al. (2016) No ID, autistic behavior, stereotypic behavior
25 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
26 Support Clinical and genetic aspects of KBG syndrome Low K , et al. (2016) No -
27 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
28 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families Trujillano D , et al. (2016) No -
29 Support KBG syndrome involving a single-nucleotide duplication in ANKRD11 Kleyner R , et al. (2016) No ASD, ID, epilepsy/seizures
30 Support ANKRD11 variants cause variable clinical features associated with KBG syndrome and Coffin-Siris-like syndrome Miyatake S , et al. (2017) No -
31 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
32 Support A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology Vissers LE , et al. (2017) No -
33 Support Genomic diagnosis for children with intellectual disability and/or developmental delay Bowling KM , et al. (2017) Yes -
34 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 -
35 Support High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies Hamdan FF , et al. (2017) No DD/ID
36 Support Exome Pool-Seq in neurodevelopmental disorders Popp B , et al. (2017) No Microcephaly
37 Support Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice Tumien B , et al. (2017) No Specific learning disability
38 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
39 Recent Recommendation Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement Kline AD , et al. (2018) No -
40 Support Prominent and elongated coccyx, a new manifestation of KBG syndrome associated with novel mutation in ANKRD11 De Bernardi ML , et al. (2018) No -
41 Support The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders Jiao Q , et al. (2019) No -
42 Support Characterization of intellectual disability and autism comorbidity through gene panel sequencing Aspromonte MC , et al. (2019) Yes -
43 Support Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder Munnich A , 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 16q24.3 Microduplication in a Patient With Developmental Delay, Intellectual Disability, Short Stature, and Nonspecific Dysmorphic Features: Case Report and Review of the Literature Bucerzan S et al. (2020) No ASD, DD, ID, epilepsy/seizures
47 Support - Kim SJ et al. (2020) No DD, ID/learning disability, ADHD, autistic feature
48 Support - Brunet T et al. (2021) Yes -
49 Support - Abe-Hatano C et al. (2021) No -
50 Support - Hiraide T et al. (2021) No -
51 Support - Chen JS et al. (2021) No -
52 Support - Kutkowska-Kaźmierczak A et al. (2021) No ASD, ADHD, ID, epilepsy/seizures
53 Support - Pode-Shakked B et al. (2021) Yes -
54 Support - Ho S et al. (2022) No ASD, ADHD
55 Support - Álvarez-Mora MI et al. (2022) No -
56 Support - Brea-Fernández AJ et al. (2022) No ADHD
57 Support - Gao F et al. (2022) No ID, epilepsy/seizures
58 Support - Murphy MJ et al. (2022) No -
59 Recent Recommendation - de Boer E et al. (2022) No ASD or autistic features, ADHD, epilepsy/seizures
60 Support - N.Y.) (07/2) No -
61 Support - Zhou X et al. (2022) Yes -
62 Support - Martinez-Cayuelas E et al. (2022) No ASD, ADHD, DD, ID, epilepsy/seizures
63 Support - Choi Y et al. (2022) No ADHD, ID, epilepsy/seizures
64 Support - Borja N et al. (2023) No -
65 Support - More RP et al. (2023) Yes -
66 Support - Chaves LD et al. (2023) No -
67 Support - Spataro N et al. (2023) No ASD or autistic features, ADHD, dyslexia
68 Support - Wang J et al. (2023) Yes -
69 Support - Sanchis-Juan A et al. (2023) No DD
70 Support - Amerh S Alqahtani et al. (2023) No -
71 Support - Erica Rosina et al. (2024) No Epilepsy/seizures
72 Support - Omri Bar et al. (2024) Yes OCD, learning disability, epilepsy/seizures
73 Support - Eoin P Donnellan et al. (2024) No Stereotypy
74 Support - Adelaide Carrara et al. () No -
75 Support - Tamam Khalaf et al. (2024) No -
76 Support - Axel Schmidt et al. (2024) No Cognitive impairment, stereotypy
Rare Variants   (231)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 35174959 Ho S et al. (2022)
- - copy_number_loss De novo - - 36564961 Choi Y et al. (2022)
- - copy_number_loss De novo - - 19920853 Willemsen MH , et al. (2009)
- - copy_number_loss De novo - Simplex 36628575 Borja N et al. (2023)
- - copy_number_loss De novo - Simplex 21654729 Isrie M , et al. (2011)
- - copy_number_gain Unknown - Simplex 32760686 Bucerzan S et al. (2020)
c.2014A>G p.Ile672Val missense_variant De novo - - 35901164 N.Y.) (07/2)
c.226+1G>A - splice_site_variant De novo - - 36564961 Choi Y et al. (2022)
c.397+1G>A - splice_site_variant De novo - - 36564961 Choi Y et al. (2022)
- - copy_number_loss De novo - Simplex 18252227 Marshall CR , et al. (2008)
- - copy_number_loss De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
- - copy_number_loss Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.4140C>A p.Tyr1380Ter stop_gained De novo - - 35174959 Ho S et al. (2022)
c.4750G>T p.Glu1584Ter stop_gained De novo - - 35174959 Ho S et al. (2022)
c.1801C>T p.Arg601Ter stop_gained De novo - - 35330407 Gao F et al. (2022)
c.-60+24969del - intron_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.3562C>T p.Arg1188Ter stop_gained De novo - - 35330407 Gao F et al. (2022)
c.5659C>T p.Gln1887Ter stop_gained Unknown - - 35330407 Gao F et al. (2022)
c.602-1G>A - splice_site_variant De novo - - 36980980 Spataro N et al. (2023)
c.6623C>A p.Ser2208Ter stop_gained De novo - - 30945278 Jiao Q , et al. (2019)
c.2512C>T p.Arg838Ter stop_gained De novo - - 36980980 Spataro N et al. (2023)
c.7534C>T p.Arg2512Trp missense_variant De novo - - 35174959 Ho S et al. (2022)
c.331C>A p.Leu111Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.7519C>T p.Gln2507Ter stop_gained De novo - - 36943625 Chaves LD et al. (2023)
c.2512C>T p.Arg838Ter stop_gained Unknown - - 28771251 Lionel AC , et al. (2017)
c.7832A>T p.His2611Leu missense_variant De novo - - 35330407 Gao F et al. (2022)
c.1356T>G p.Asn452Lys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1457C>T p.Ser486Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_gain Unknown - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
- - copy_number_loss De novo - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
- - copy_number_loss Unknown - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.5156T>G p.Met1719Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5636C>T p.Pro1879Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5950C>T p.Pro1984Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.6187G>T p.Glu2063Ter stop_gained De novo - - 28250421 Miyatake S , et al. (2017)
c.6472G>T p.Glu2158Ter stop_gained De novo - - 28554332 Bowling KM , et al. (2017)
c.2751dup p.Glu918Ter stop_gained De novo - - 25424714 Ockeloen CW , et al. (2014)
c.2716C>T p.Arg906Ter stop_gained De novo - - 39039281 Axel Schmidt et al. (2024)
c.7570-2A>G - splice_site_variant De novo - - 27848944 Trujillano D , et al. (2016)
c.1893A>G p.Lys631%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.2454dup p.Asn819Ter frameshift_variant De novo - - 36564961 Choi Y et al. (2022)
c.6220G>T p.Glu2074Ter stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.1200G>C p.Lys400Asn missense_variant De novo - - 35833929 de Boer E et al. (2022)
c.1222T>A p.Ser408Thr missense_variant Unknown - - 35833929 de Boer E et al. (2022)
c.1526T>C p.Leu509Pro missense_variant De novo - - 35833929 de Boer E et al. (2022)
c.2075A>G p.Asp692Gly missense_variant De novo - - 35833929 de Boer E et al. (2022)
c.2704G>T p.Glu902Ter stop_gained De novo - Simplex 33619735 Brunet T et al. (2021)
c.3277G>A p.Gly1093Arg missense_variant De novo - - 35833929 de Boer E et al. (2022)
c.6049G>A p.Ala2017Thr missense_variant De novo - - 35833929 de Boer E et al. (2022)
c.6532G>T p.Asp2178Tyr missense_variant Unknown - - 35833929 de Boer E et al. (2022)
c.7567C>T p.Arg2523Trp missense_variant De novo - - 35833929 de Boer E et al. (2022)
c.7753C>T p.Arg2585Cys missense_variant De novo - - 35833929 de Boer E et al. (2022)
c.276del p.Lys93ArgfsTer31 frameshift_variant De novo - - 35174959 Ho S et al. (2022)
c.1909A>T p.Lys637Ter stop_gained De novo - Simplex 33644862 Hiraide T et al. (2021)
c.2512C>T p.Arg838Ter stop_gained De novo - Simplex 29100083 Hamdan FF , et al. (2017)
c.2083A>G p.Lys695Glu missense_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.226+1G>A - splice_site_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.7189C>T p.Gln2397Ter stop_gained De novo - Simplex 21782149 Sirmaci A , et al. (2011)
c.5317G>T p.Glu1773Ter stop_gained De novo - Simplex 27435318 Charng WL , et al. (2016)
c.7534C>T p.Arg2512Trp missense_variant De novo - - 39039281 Axel Schmidt et al. (2024)
c.520C>T p.Arg174Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.866dup p.Tyr289Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.2262dup p.Glu755ArgfsTer27 frameshift_variant De novo - - 35330407 Gao F et al. (2022)
c.2983A>G p.Lys995Glu missense_variant Unknown - - 31209962 Aspromonte MC , et al. (2019)
c.1731dup p.Asp578Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.1846G>T p.Glu616Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.2197C>T p.Arg733Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.5397dup p.Glu1800ArgfsTer150 frameshift_variant De novo - - 35174959 Ho S et al. (2022)
c.5519C>T p.Ala1840Val missense_variant Familial Maternal - 35330407 Gao F et al. (2022)
c.6122T>G p.Val2041Gly missense_variant Familial Paternal - 35330407 Gao F et al. (2022)
c.4911del p.Pro1638LeufsTer48 frameshift_variant De novo - - 35330407 Gao F et al. (2022)
c.2161del p.Ile721SerfsTer28 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.3309dup p.Asp1104ArgfsTer2 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.3623dup p.Lys1209GlufsTer3 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.2308A>G p.Lys770Glu missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.389A>G p.Asn130Ser missense_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.3193A>T p.Lys1065Ter stop_gained Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.3448C>T p.Gln1150Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.3931C>T p.Arg1311Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.4171C>T p.Gln1391Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.5790C>A p.Tyr1930Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.6628G>T p.Glu2210Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.7180C>T p.Gln2394Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.7407C>G p.Tyr2469Ter stop_gained De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.7068G>A p.Glu2356%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1523del p.Val508GlyfsTer2 frameshift_variant De novo - - 36980980 Spataro N et al. (2023)
c.7595A>C p.Gln2532Pro missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.7388C>A p.Pro2463His missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7535G>A p.Arg2512Gln missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7564G>A p.Glu2522Lys missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7606C>T p.Arg2536Trp missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7607G>C p.Arg2536Pro missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7735C>T p.Arg2579Cys missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7736G>A p.Arg2579His missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7741C>T p.Arg2581Cys missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7753C>T p.Arg2585Cys missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.7814T>G p.Leu2605Arg missense_variant De novo - Simplex 35833929 de Boer E et al. (2022)
c.895_896del p.Ser299LeufsTer49 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.4093C>T p.Arg1365Ter stop_gained Familial Maternal Simplex 36564961 Choi Y et al. (2022)
c.6176C>A p.Pro2059His missense_variant Familial - Multiplex 36702863 More RP et al. (2023)
c.6868C>T p.Pro2290Ser missense_variant Familial Maternal - 24690944 Brett M , et al. (2014)
c.3770_3771del p.Lys1257ArgfsTer25 frameshift_variant De novo - - 35174959 Ho S et al. (2022)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant De novo - - 35330407 Gao F et al. (2022)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant Unknown - - 35330407 Gao F et al. (2022)
c.2398_2401del p.Glu800AsnfsTer62 frameshift_variant De novo - - 35330407 Gao F et al. (2022)
c.6528_6538del p.Gly2177HisfsTer5 frameshift_variant De novo - - 35330407 Gao F et al. (2022)
c.5162C>T p.Thr1721Met missense_variant Unknown - Multiplex 35833929 de Boer E et al. (2022)
c.1382C>G p.Thr461Arg missense_variant Unknown - Multiplex 25574603 Butler MG , et al. (2015)
c.(601+1_602-1)_(7713+1_7714-1)del - copy_number_loss De novo - - 36564961 Choi Y et al. (2022)
c.745-599_745-595del - frameshift_variant De novo - Simplex 28250421 Miyatake S , et al. (2017)
c.7534C>T p.Arg2512Trp missense_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.7753C>T p.Arg2585Cys missense_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant De novo - - 29158550 Popp B , et al. (2017)
c.554_557del p.Lys185SerfsTer42 frameshift_variant De novo - - 25473036 Soden SE , et al. (2014)
c.6793del p.Ala2265ProfsTer72 frameshift_variant De novo - - 28554332 Bowling KM , et al. (2017)
c.1489G>C p.Gly497Arg missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2395A>T p.Lys799Ter stop_gained De novo - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.5494_5495del p.Arg1832GlyfsTer117 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.5889del p.Ile1963MetfsTer9 frameshift_variant De novo - Simplex 33262785 Kim SJ et al. (2020)
c.3301dup p.Glu1101GlyfsTer5 frameshift_variant Unknown - Unknown 33262785 Kim SJ et al. (2020)
c.7570-1G>C - splice_site_variant Familial Paternal Multiplex 21782149 Sirmaci A , et al. (2011)
c.6184del p.Leu2062TrpfsTer25 frameshift_variant De novo - - 25424714 Ockeloen CW , et al. (2014)
c.6513dup p.Gly2172ArgfsTer14 frameshift_variant De novo - - 25424714 Ockeloen CW , et al. (2014)
c.4965del p.Glu1656SerfsTer30 frameshift_variant De novo - - 27479843 Lelieveld SH et al. (2016)
c.6340C>T p.Gln2114Ter stop_gained De novo - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.7552C>T p.Gln2518Ter stop_gained Unknown - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.4432del p.Asp1478ThrfsTer53 frameshift_variant Familial Maternal - 35174959 Ho S et al. (2022)
c.1318C>T p.Arg440Ter stop_gained Familial Maternal Simplex 25424714 Ockeloen CW , et al. (2014)
c.2647del p.Glu883ArgfsTer94 frameshift_variant Familial Maternal - 36564961 Choi Y et al. (2022)
c.5648dup p.Ser1884LeufsTer66 frameshift_variant Unknown - Unknown 33753861 Chen JS et al. (2021)
c.7834G>T p.Glu2612Ter stop_gained Familial Maternal - 36446582 Martinez-Cayuelas E et al. (2022)
c.5620dup p.Thr1874AsnfsTer76 frameshift_variant De novo - Simplex 38256266 Omri Bar et al. (2024)
c.6882_6883del p.Glu2295GlyfsTer236 frameshift_variant De novo - - 36980980 Spataro N et al. (2023)
c.5174dup p.Ser1726ValfsTer6 frameshift_variant Unknown - Simplex 28263302 C Yuen RK et al. (2017)
c.2305del p.Ser769GlnfsTer8 frameshift_variant De novo - Simplex 21782149 Sirmaci A , et al. (2011)
c.2092_2096del p.Glu698ThrfsTer2 frameshift_variant De novo - - 27479843 Lelieveld SH et al. (2016)
c.7570_7572del p.Glu2524del inframe_deletion De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.4374del p.Lys1459ArgfsTer72 frameshift_variant Unknown - Simplex 28263302 C Yuen RK et al. (2017)
c.3460dup p.Glu1154GlyfsTer16 frameshift_variant De novo - Simplex 32094338 Husson T , et al. (2020)
c.4964_4965del p.Lys1655ArgfsTer12 frameshift_variant De novo - - 28333917 Vissers LE , et al. (2017)
c.1460_1463del p.Glu487ValfsTer22 frameshift_variant Unknown - - 25424714 Ockeloen CW , et al. (2014)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant De novo - - 25424714 Ockeloen CW , et al. (2014)
c.2398_2401del p.Glu800AsnfsTer62 frameshift_variant De novo - - 27479843 Lelieveld SH et al. (2016)
c.2404_2407del p.Leu802LysfsTer60 frameshift_variant De novo - - 38334877 Adelaide Carrara et al. ()
c.6792del p.Ala2265ProfsTer72 frameshift_variant De novo - - 38317675 Eoin P Donnellan et al. (2024)
c.831del p.Thr278ArgfsTer3 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.4621_4624del p.Glu1541ArgfsTer5 frameshift_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.4083C>A p.His1361Gln missense_variant Familial Maternal Multiplex 25167861 Redin C , et al. (2014)
c.6015dup p.Gly2006ArgfsTer26 frameshift_variant De novo - Simplex 27900361 Kleyner R , et al. (2016)
c.3224_3227del p.Glu1075GlyfsTer242 frameshift_variant De novo - - 28250421 Miyatake S , et al. (2017)
c.3382_3383del p.Asp1128GlnfsTer41 frameshift_variant De novo - - 25424714 Ockeloen CW , et al. (2014)
c.4391_4392del p.Lys1464ThrfsTer89 frameshift_variant De novo - - 25424714 Ockeloen CW , et al. (2014)
c.4389_4390del p.Lys1464ThrfsTer89 frameshift_variant Unknown - - 38438125 Tamam Khalaf et al. (2024)
c.3704_3707del p.Lys1235ArgfsTer82 frameshift_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.7607G>A p.Arg2536Gln missense_variant De novo - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.2175_2178del p.Asn725LysfsTer23 frameshift_variant De novo - Simplex 25284784 Dong S , et al. (2014)
c.6416C>T p.Pro2139Leu missense_variant Familial Maternal Simplex 28250421 Miyatake S , et al. (2017)
c.3123_3126del p.Ile1042TrpfsTer275 frameshift_variant De novo - - 25424714 Ockeloen CW , et al. (2014)
c.2367del p.Glu790ArgfsTer73 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.2593dup p.Tyr865LeufsTer51 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.3309dup p.Asp1104ArgfsTer2 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.6792dup p.Ala2265ArgfsTer8 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.6792dup p.Ala2265ArgfsTer8 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.7047_7049delinsTT p.Lys2349AsnfsTer52 frameshift_variant De novo - - 36980980 Spataro N et al. (2023)
c.7535G>T p.Arg2512Leu missense_variant Unknown Not maternal Simplex 35833929 de Boer E et al. (2022)
c.7736G>A p.Arg2579His missense_variant Familial - Multi-generational 35833929 de Boer E et al. (2022)
c.6812_6813del p.Pro2271ArgfsTer24 frameshift_variant Unknown - - 31209962 Aspromonte MC , et al. (2019)
c.4384dup p.Arg1462LysfsTer92 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.4529dup p.Pro1511AlafsTer43 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.6691dup p.Ala2231GlyfsTer29 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.7083del p.Thr2362ProfsTer39 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.6792dup p.Ala2265ArgfsTer8 frameshift_variant De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.6968_6975del p.Ala2323GlyfsTer206 frameshift_variant De novo - - 31209962 Aspromonte MC , et al. (2019)
c.3309dup p.Asp1104ArgfsTer2 frameshift_variant De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
c.3309dup p.Asp1104ArgfsTer2 frameshift_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.3046del p.Asp1016IlefsTer302 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.3334del p.Ser1112AlafsTer206 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.6682del p.Glu2228LysfsTer109 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.6701del p.Asp2234ValfsTer103 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.6071_6084del p.Pro2024ArgfsTer3 frameshift_variant De novo - Simplex 21782149 Sirmaci A , et al. (2011)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.7234del p.Gln2412SerfsTer79 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.4384dup p.Arg1462LysfsTer92 frameshift_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.548_551del p.Arg183ProfsTer44 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.5953_5954del p.Gln1985GlufsTer46 frameshift_variant De novo - Simplex 21782149 Sirmaci A , et al. (2011)
c.2408_2412del p.Lys803ArgfsTer5 frameshift_variant De novo - Simplex 38041506 Erica Rosina et al. (2024)
c.2329_2332del p.Glu777ArgfsTer5 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.2408_2412del p.Lys803ArgfsTer5 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.2765_2766del p.Glu922AlafsTer6 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant De novo - Simplex 38041506 Erica Rosina et al. (2024)
c.2366_2369del p.Lys789ArgfsTer73 frameshift_variant De novo - Simplex 38041506 Erica Rosina et al. (2024)
c.1367_1370del p.Lys456SerfsTer53 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.1381_1384del p.Glu461GlnfsTer48 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.2398_2401del p.Glu800AsnfsTer62 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.3905_3906del p.Glu1302GlyfsTer4 frameshift_variant Unknown - - 36446582 Martinez-Cayuelas E et al. (2022)
c.3704_3707del p.Lys1235ArgfsTer82 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.6938_6941dup p.Ala2315SerfsTer218 frameshift_variant De novo - Simplex 38041506 Erica Rosina et al. (2024)
c.2615_2616del p.Ser872CysfsTer43 frameshift_variant De novo - Multiplex 33624935 Abe-Hatano C et al. (2021)
c.3832A>T p.Lys1278Ter stop_gained Familial Maternal Extended multiplex 25424714 Ockeloen CW , et al. (2014)
c.1722_1725del p.Glu576LeufsTer13 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.6968_6975del p.Ala2323GlyfsTer206 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.1389dup p.Gly464ArgfsTer29 frameshift_variant De novo - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.1801C>T p.Arg601Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1940_1941delinsT p.Ser647LeufsTer6 frameshift_variant De novo - - 36446582 Martinez-Cayuelas E et al. (2022)
c.3771dup p.Glu1258ArgfsTer25 frameshift_variant Unknown - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.4558del p.Asp1520ThrfsTer11 frameshift_variant De novo - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.4528_4529del p.Pro1510AlafsTer43 frameshift_variant De novo - Simplex 30088855 De Bernardi ML , et al. (2018)
c.6792dup p.Ala2265ArgfsTer8 frameshift_variant Familial Maternal - 36446582 Martinez-Cayuelas E et al. (2022)
c.1381_1384del p.Glu461GlnfsTer48 frameshift_variant Unknown - Unknown 37799141 Amerh S Alqahtani et al. (2023)
c.7571A>G p.Glu2524Gly missense_variant De novo - Multiplex (monozygotic twins) 35573061 Murphy MJ et al. (2022)
c.7481dup p.Pro2495SerfsTer37 frameshift_variant Familial Maternal Multiplex 25424714 Ockeloen CW , et al. (2014)
c.1385_1388del p.Thr462LysfsTer47 frameshift_variant Unknown - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant Unknown - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.2828_2829del p.Glu943ValfsTer74 frameshift_variant Unknown - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.3295_3296del p.Phe1099LeufsTer2 frameshift_variant De novo - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.6053_6057del p.Pro2018ArgfsTer12 frameshift_variant Unknown - - 34440431 Kutkowska-Kaźmierczak A et al. (2021)
c.3369_3372del p.Ser1123ArgfsTer194 frameshift_variant Familial Paternal Simplex 27620904 Martnez F , et al. (2016)
c.1940_1941delinsT p.Ser647LeufsTer6 frameshift_variant De novo - Simplex 35183220 Álvarez-Mora MI et al. (2022)
c.3590_3594del p.Lys1197ArgfsTer5 frameshift_variant Familial Maternal - 36446582 Martinez-Cayuelas E et al. (2022)
NM_013275:c.3542_3543ins23 p.Arg1182AlafsTer144 frameshift_variant De novo - Simplex 31406558 Munnich A , et al. (2019)
c.3582del p.Arg1195GlufsTer123 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.2408_2412del p.Lys803ArgfsTer5 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1903_1907del p.Lys635GlnfsTer26 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.3437_3462del p.Thr1146ArgfsTer15 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.3704_3707del p.Lys1235ArgfsTer82 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.4103_4104del p.Lys1368ArgfsTer17 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.4475_4476insTCCTGCGGCATCACAGGGACGAGC p.Leu1492_Leu1493insProAlaAlaSerGlnGlyArgAla inframe_insertion De novo - - 29286531 Tumien B , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 Genes

We 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.

S

Syndromic

See all Category S Genes

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
1
icon
1

Score remained at 1

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder.

Reports Added
[Comorbidities associated with genetic abnormalities in children with intellectual disability2021]
1/1/2021
1
icon
1

Score remained at 1

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder.

Reports Added
[Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review2020] [De novo variants in neurodevelopmental disorders-experiences from a tertiary care center2021] [Whole genome sequencing of 45 Japanese patients with intellectual disability2021] [Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing2021]
7/1/2020
1
icon
1

Score remained at 1

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder.

Reports Added
[16q24.3 Microduplication in a Patient With Developmental Delay, Intellectual Disability, Short Stature, and Nonspecific Dysmorphic Features: Case Report and Review of the Literature2020]
1/1/2020
1
icon
1

Score remained at 1

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder.

Reports Added
[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
2S
icon
1

Decreased from 2S to 1

New Scoring Scheme
Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder.

Reports Added
[New Scoring Scheme]
7/1/2019
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder.

Reports Added
[Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019] [Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.2019]
4/1/2019
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder.

Reports Added
[The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.2019]
7/1/2018
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features. De novo variants in the ANKRD11 gene have been reported in individuals with a non-classic Cornelia de Lange phenotype (Ansari et al., 2014; Parenti et al., 2016). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with ANKRD11 mutations presented with autism spectrum disorder.

Reports Added
[Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism.2014] [Broadening of cohesinopathies: exome sequencing identifies mutations in ANKRD11 in two patients with Cornelia de Lange-overlapping phenotype.2015] [Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement.2018] [Prominent and elongated coccyx, a new manifestation of KBG syndrome associated with novel mutation in ANKRD11.2018]
10/1/2017
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features.

Reports Added
[High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.2017] [Exome Pool-Seq in neurodevelopmental disorders.2017]
7/1/2017
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features.

Reports Added
[Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.2017]
4/1/2017
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features.

Reports Added
[Structural variation of chromosomes in autism spectrum disorder.2008] [Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome.2009] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Whole exome sequencing in females with autism implicates novel and candidate genes.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Haploinsufficiency of ANKRD11 causes mild cognitive impairment, short stature and minor dysmorphisms.2011] [Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia.2011] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations.2014] [Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators.2004] [Subcellular localization of ankyrin repeats cofactor-1 regulates its corepressor activity.2007] [Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function.2008] [Identification of ANKRD11 as a p53 coactivator.2008] [Haploinsufficiency of ANKRD11 causes mild cognitive impairment, short stature and minor dysmorphisms.2011] [De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.2014] [Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.2014] [Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11.2016] [Clinical and genetic aspects of KBG syndrome.2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [KBG syndrome involving a single-nucleotide duplication in ANKRD11.2016] [ANKRD11 variants cause variable clinical features associated with KBG syndrome and Coffin-Siris-like syndrome.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]
1/1/2017
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features.

Reports Added
[KBG syndrome involving a single-nucleotide duplication in ANKRD11.2016]
10/1/2016
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability. Clinical evaluation of 32 patients with KBG syndrome in Low et al., 2016 found that 8 out of 32 cases (25%) had a formal diagnosis of ASD, with an additional case presenting with some autistic features.

Reports Added
[High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11.2016] [Clinical and genetic aspects of KBG syndrome.2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016]
7/1/2016
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability.

Reports Added
[Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016]
4/1/2016
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability.

Reports Added
[Structural variation of chromosomes in autism spectrum disorder.2008] [Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome.2009] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Whole exome sequencing in females with autism implicates novel and candidate genes.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Haploinsufficiency of ANKRD11 causes mild cognitive impairment, short stature and minor dysmorphisms.2011] [Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia.2011] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations.2014] [Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators.2004] [Subcellular localization of ankyrin repeats cofactor-1 regulates its corepressor activity.2007] [Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function.2008] [Identification of ANKRD11 as a p53 coactivator.2008] [Haploinsufficiency of ANKRD11 causes mild cognitive impairment, short stature and minor dysmorphisms.2011] [De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.2014] [Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.2014]
1/1/2016
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability.

Reports Added
[Structural variation of chromosomes in autism spectrum disorder.2008] [Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome.2009] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Whole exome sequencing in females with autism implicates novel and candidate genes.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Haploinsufficiency of ANKRD11 causes mild cognitive impairment, short stature and minor dysmorphisms.2011] [Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia.2011] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations.2014] [Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators.2004] [Subcellular localization of ankyrin repeats cofactor-1 regulates its corepressor activity.2007] [Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function.2008] [Identification of ANKRD11 as a p53 coactivator.2008] [Haploinsufficiency of ANKRD11 causes mild cognitive impairment, short stature and minor dysmorphisms.2011] [De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.2014] [Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015]
1/1/2015
2S
icon
2S

Decreased from 2S to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability.

Reports Added
[Whole exome sequencing in females with autism implicates novel and candidate genes.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.2015]
10/1/2014
4
icon
2S

Decreased from 4 to 2S

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008). Two de novo LoF variants in the ANKRD11 gene (both frameshift) have been identified in ASD probands from the Simons Simplex Collection (PMIDs 25284784, 25363768). Mutations in ANKRD11 are also responsible for KBG syndrome (OMIM 148050), which is characterized by developmental delay/intellectual disability and, in some cases, autism (PMID 21782149, 19597979). A comprehensive clinical and genetic evaluation of 20 patients with KBG syndrome from 13 families published in 2014 found that many patients displayed behavioral abnormalities such as ASD (PMID 25424714). In this report, de novo LoF variants in ANKRD11 were observed in three KBG patients that also presented with ASD (two frameshift, one nonsense), while another frameshift variant in ANKRD11 segregated with disease in a multi-generational pedigree in which a mother with intellectual disability and autistic features transmitted this variant to four affected children, all of whom presented with ASD and intellectual disability.

Reports Added
[De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations.2014]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

ANKRD11 is in an ASD-associated multi-genic CNV on chromosome 16q24.3 (Willemsen et al., 2010; Marshall et al., 2008).

Reports Added
[Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014]
Krishnan Probability Score

Score 0.49683458187312

Ranking 2497/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99999982163224

Ranking 214/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Iossifov Probability Score

Score 1

Ranking 1/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.40237920709992

Ranking 282/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 70

Ranking 19/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.18451936412407

Ranking 4526/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
BZRAP1 benzodiazapine receptor (peripheral) associated protein 1 Human Protein Binding 9256 O95153
CDCA7L cell division cycle associated 7-like Human Protein Binding 55536 Q96GN5
Fzd3 frizzled homolog 3 (Drosophila) Mouse Direct Regulation 14365 Q61086
GPS2 G protein pathway suppressor 2 Human Protein Binding 2874 Q13227
HDAC3 Histone deacetylase 3 Human Protein Binding 8841 O15379
HDAC4 histone deacetylase 4 Human Protein Binding 9759 P56524
HDAC5 Histone deacetylase 5 Human Protein Binding 10014 Q9UQL6
HOOK2 hook homolog 2 (Drosophila) Human Protein Binding 29911 Q96ED9
IKZF1 IKAROS family zinc finger 1 (Ikaros) Human Protein Binding 10320 Q13422
KIAA1712 centrosomal protein 44kDa Human Protein Binding NM_001040157 Q9C0F1
Kmt2e lysine (K)-specific methyltransferase 2E Mouse Direct Regulation 69188 Q3UG20
MKRN3 makorin ring finger protein 3 Human Protein Binding 7681 Q13064
NCOA2 nuclear receptor coactivator 2 Human Protein Binding 10499 Q15596
NCOA3 nuclear receptor coactivator 3 Human Protein Binding 8202 Q9Y6Q9
Ncor1 nuclear receptor co-repressor 1 Mouse Direct Regulation 20185 Q60974
Notch1 notch 1 Mouse Direct Regulation 18128 Q01705
PDE4DIP phosphodiesterase 4D interacting protein Human Protein Binding 9659 Q5VU43
Slc1a2 solute carrier family 1 (glial high affinity glutamate transporter), member 2 Mouse Direct Regulation 20511 P43006
Sox6 SRY-box containing gene 6 Mouse Direct Regulation 20679 P40645
TADA3 transcriptional adaptor 3 Human Protein Binding 10474 O75528
TFIP11 tuftelin interacting protein 11 Human Protein Binding 24144 Q9UBB9
TRIM37 tripartite motif containing 37 Human Protein Binding NM_015294 A8K0V9
Submit New Gene

Report an Error