Human Gene Module / Chromosome 15 / GABRB3

GABRB3gamma-aminobutyric acid (GABA) A receptor, beta 3

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
28 / 52
Rare Variants / Common Variants
109 / 31
Aliases
GABRB3, MGC9051
Associated Syndromes
-
Chromosome Band
15q12
Associated Disorders
DD/NDD, ADHD, ID, ASD
Relevance to Autism

Rare variants in the GABRB3 gene have been identified with autism (e.g. Cook et al., 1998) and genetic association has been found between GABRB3 and childhood absence epilepsy (CAE) (Urak et al., 2006). As well, a number of studies have found genetic association between the GABRB3 gene and autism (including one that enriched for savant skills). Populations studied include Caucasian, African-American, Hispanic, as well as AGRE, SARC and CLSA cohorts. However, other studies found no genetic association between the GABRB3 gene and autism in IMGSAC and other cohorts.

Molecular Function

The encoded protein is a subunit of GABA-A receptor. Neurotransmission is predominantly mediated by a gated chloride channel activity intrinsic to the receptor.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
Fruit fly
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GABRB3 (52 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Negative Association Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium Maestrini E , et al. (1999) Yes -
2 Negative Association Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism Salmon B , et al. (1999) Yes -
3 Positive Association Association between a GABRB3 polymorphism and autism Buxbaum JD , et al. (2002) Yes -
4 Positive Association Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder Menold MM , et al. (2002) Yes -
5 Positive Association Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13 Nurmi EL , et al. (2003) Yes -
6 Positive Association A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism McCauley JL , et al. (2004) Yes -
7 Positive Association An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum disorder Curran S , et al. (2005) Yes -
8 Positive Association An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as risk factors for autistic disorder Ashley-Koch AE , et al. (2006) Yes -
9 Recent Recommendation A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity Urak L , et al. (2006) No -
10 Recent Recommendation Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: a potential model of autism spectrum disorder DeLorey TM , et al. (2007) No -
11 Positive Association Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism Delahanty RJ , et al. (2009) Yes -
12 Recent Recommendation Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3 DeLorey TM , et al. (2010) No -
13 Recent Recommendation Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3 Jiang YH , et al. (2010) No -
14 Support De novo gene disruptions in children on the autistic spectrum Iossifov I , et al. (2012) Yes -
15 Recent Recommendation Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children Tavassoli T , et al. (2012) No -
16 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder Girirajan S , et al. (2013) Yes -
17 Positive Association De novo mutations in epileptic encephalopathies Epi4K Consortium , et al. (2013) No IS, LGS, DD, ID, ASD, ADHD
18 Positive Association Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism Warrier V , et al. (2013) Yes ALTs
19 Negative Association Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders Chen CH , et al. (2014) Yes -
20 Support De novo mutations in moderate or severe intellectual disability Hamdan FF , et al. (2014) No Autistic features
21 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
22 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
23 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
24 Recent Recommendation Incorporating Functional Information in Tests of Excess De Novo Mutational Load Jiang Y , et al. (2015) No -
25 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
26 Support Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities Zhang Y , et al. (2015) No -
27 Recent Recommendation Compromising the phosphodependent regulation of the GABAAR ?3 subunit reproduces the core phenotypes of autism spectrum disorders Vien TN , et al. (2015) No -
28 Recent Recommendation Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease Johnson MR , et al. (2015) No -
29 Support Comprehensive molecular testing in patients with high functioning autism spectrum disorder Alvarez-Mora MI , et al. (2016) Yes -
30 Support De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016) No -
31 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
32 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
33 Support Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes Parrini E , et al. (2016) No Microcephaly
34 Support - Møller RS et al. (2017) No ASD or autistic features, ID
35 Positive Association GABA A receptor subunit gene polymorphisms predict symptom-based and developmental deficits in Chinese Han children and adolescents with autistic spectrum disorders Yang S , et al. (2017) Yes -
36 Negative Association Meta-analysis of GABRB3 Gene Polymorphisms and Susceptibility to Autism Spectrum Disorder Noroozi R , et al. (2018) Yes -
37 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
38 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
39 Support - Pode-Shakked B et al. (2021) No -
40 Support - Yang Y et al. (2021) No Autistic features
41 Support - Agrud A et al. (2022) No -
42 Recent Recommendation - Absalom NL et al. (2022) No ASD
43 Support - Zhou X et al. (2022) Yes -
44 Support - Babij R et al. (2022) Yes -
45 Positive Association - Adak P et al. (2023) Yes -
46 Support - Hu C et al. (2023) Yes -
47 Support - Du Y et al. (2023) No -
48 Support - Sanchis-Juan A et al. (2023) No -
49 Support - Aniqa Tasnim et al. (2024) Yes Somatosensory behaviors
50 Support - Luigi Vetri et al. (2024) No -
51 Highly Cited GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits Fritschy JM and Mohler H (1995) No -
52 Primary Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers Cook EH Jr , et al. (1998) Yes -
Rare Variants   (109)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 35383156 Absalom NL et al. (2022)
- - copy_number_gain De novo - - 28053010 Møller RS et al. (2017)
- - copy_number_gain Familial Maternal - 9545402 Cook EH Jr , et al. (1998)
- - copy_number_gain De novo - Simplex 23375656 Girirajan S , et al. (2013)
c.753T>G p.Tyr251Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.1240C>T p.Arg414Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
- p.Arg166Ser missense_variant De novo - - 35383156 Absalom NL et al. (2022)
c.3G>A p.Met1? initiator_codon_variant De novo - - 37007974 Hu C et al. (2023)
c.358G>A p.Asp120Asn missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.425G>A p.Arg142His missense_variant De novo - - 35982159 Zhou X et al. (2022)
insA - frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1057C>T p.Arg353Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1058G>C p.Arg353Pro missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.5G>A p.Trp2Ter stop_gained Familial Maternal - 27824329 Wang T , et al. (2016)
c.5G>A p.Trp2Ter stop_gained Familial Paternal - 27824329 Wang T , et al. (2016)
c.844C>T p.Arg282Cys missense_variant Familial - - 27824329 Wang T , et al. (2016)
c.544+3G>A - splice_region_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.241-2710C>T - missense_variant De novo - Simplex 26544041 Zhang Y , et al. (2015)
c.241-3248T>G - missense_variant De novo - Simplex 26544041 Zhang Y , et al. (2015)
- - 2KB_upstream_variant Familial Maternal Simplex 24999380 Chen CH , et al. (2014)
c.239T>C p.Met80Thr missense_variant De novo - - 35383156 Absalom NL et al. (2022)
c.372A>C p.Leu124Phe missense_variant De novo - - 27864847 Parrini E , et al. (2016)
c.761C>T p.Ser254Phe missense_variant De novo - - 27864847 Parrini E , et al. (2016)
c.372A>C p.Leu124Phe missense_variant De novo - - 35383156 Absalom NL et al. (2022)
c.630G>T p.Gln210His missense_variant De novo - - 35383156 Absalom NL et al. (2022)
c.733T>C p.Tyr245His missense_variant Unknown - - 35383156 Absalom NL et al. (2022)
c.913G>A p.Ala305Thr missense_variant De novo - - 35383156 Absalom NL et al. (2022)
c.953T>C p.Phe318Ser missense_variant De novo - - 35383156 Absalom NL et al. (2022)
c.911A>G p.Lys304Arg missense_variant De novo - - 38256219 Luigi Vetri et al. (2024)
c.205G>A p.Ala69Thr missense_variant Unknown - - 28053010 Møller RS et al. (2017)
c.227C>G p.Ser76Cys missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.125A>G p.Asp42Gly missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.154C>G p.Leu52Val missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.232G>C p.Val78Leu missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.238A>T p.Met80Leu missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.372A>C p.Leu124Phe missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.380A>G p.Lys127Arg missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.550T>C p.Tyr184His missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.554C>T p.Thr185Ile missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.695G>A p.Arg232Gln missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.758C>T p.Pro253Leu missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.761C>T p.Ser254Phe missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.902C>T p.Pro301Leu missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.905A>G p.Tyr302Cys missense_variant De novo - - 28053010 Møller RS et al. (2017)
c.70G>T p.Glu24Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.31C>T p.Pro11Ser missense_variant Familial - - 19935738 Delahanty RJ , et al. (2009)
c.358G>A p.Asp120Asn missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.372A>C p.Leu124Phe missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.487A>G p.Met163Val missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.509T>G p.Leu170Arg missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.554C>T p.Thr185Ile missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.695G>A p.Arg232Gln missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.733T>C p.Tyr245His missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.747G>C p.Gln249His missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.757C>T p.Pro253Ser missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.761C>T p.Ser254Phe missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.832C>T p.Leu278Phe missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.842C>T p.Thr281Ile missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.860C>T p.Thr287Ile missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.863C>A p.Thr288Asn missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.863C>T p.Thr288Ile missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.905C>G p.Tyr302Cys missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.913G>A p.Ala305Thr missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.914C>T p.Ala305Val missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.962T>C p.Leu321Pro missense_variant De novo - Simplex 34698933 Yang Y et al. (2021)
c.1412A>G p.Tyr471Cys missense_variant De novo - - 27479843 Lelieveld SH et al. (2016)
c.461+5271T>C - intron_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.232G>A p.Val78Ile missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
- - 2KB_upstream_variant Unknown Not maternal Multiplex 24999380 Chen CH , et al. (2014)
- - indel, 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
c.331C>T p.Arg111Ter stop_gained Familial Maternal - 28053010 Møller RS et al. (2017)
c.694C>T p.Arg232Ter stop_gained Familial Paternal - 28053010 Møller RS et al. (2017)
c.-53G>T - 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
c.8del p.Gly3AlafsTer26 frameshift_variant Unknown - - 28053010 Møller RS et al. (2017)
c.328A>C p.Asn110His missense_variant De novo - - 23934111 Epi4K Consortium , et al. (2013)
c.358G>A p.Asp120Asn missense_variant De novo - - 23934111 Epi4K Consortium , et al. (2013)
c.539A>G p.Glu180Gly missense_variant De novo - - 23934111 Epi4K Consortium , et al. (2013)
c.905A>G p.Tyr302Cys missense_variant De novo - - 23934111 Epi4K Consortium , et al. (2013)
c.-169G>T - 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
c.489G>A p.Met163Ile missense_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.425G>T p.Arg142Leu missense_variant Familial Maternal - 28053010 Møller RS et al. (2017)
c.675C>G p.Phe225Leu missense_variant De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
c.851T>G p.Leu284Arg missense_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.557C>T p.Thr186Met missense_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
c.942C>T p.Phe314= synonymous_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
c.1006C>T p.Pro336Ser missense_variant Familial Maternal Simplex 24999380 Chen CH , et al. (2014)
c.1295del p.Ser432PhefsTer11 frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.110T>G p.Val37Gly missense_variant Familial Paternal Multiplex 28053010 Møller RS et al. (2017)
c.287_288delinsTC p.Arg96Ile missense_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.1376_1377del p.Thr459IlefsTer14 frameshift_variant Familial Paternal - 34698933 Yang Y et al. (2021)
NM_000814.6:c.-142G>T - 2KB_upstream_variant Familial Maternal Simplex 24999380 Chen CH , et al. (2014)
NM_000814.6:c.-142G>T - 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
NM_021912.4:c.-140A>T - 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
NM_021912.4:c.-541C>T - 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
c.31C>T p.Pro11Ser missense_variant Familial Paternal Simplex 26845707 Alvarez-Mora MI , et al. (2016)
NM_021912.4:c.-1090G>A - 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
NM_021912.5:c.-1437T>G - 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
c.1286G>A p.Arg429Gln missense_variant Familial Maternal Multiplex 28053010 Møller RS et al. (2017)
NM_001278631.1:c.-232G>T - 2KB_upstream_variant Familial Paternal Simplex 24999380 Chen CH , et al. (2014)
c.413_414insACC p.Asn138delinsLysPro inframe_insertion De novo - Simplex 25356899 Hamdan FF , et al. (2014)
NM_021912.4:c.-1442G>A - 2KB_upstream_variant Unknown Not maternal Multiplex 24999380 Chen CH , et al. (2014)
c.662T>C p.Ile221Thr missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.358G>A p.Asp120Asn missense_variant De novo - - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
c.545A>T p.Tyr182Phe missense_variant De novo - - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
c.745C>A p.Gln249Lys missense_variant De novo - - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
c.767T>A p.Leu256Gln missense_variant De novo - - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
c.878T>A p.Leu293His missense_variant Unknown - - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
c.913G>A p.Ala305Thr missense_variant De novo - - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
c.470C>T p.Thr157Met missense_variant Familial Maternal - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
Common Variants   (31)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.241-1250G>A;c.-15-1250G>A;c.28-1250G>A T/C intron_variant - - - 15389768 McCauley JL , et al. (2004)
c.835+2039T>C;c.580+2039T>C;c.622+2039T>C A/G intron_variant - - - 15389768 McCauley JL , et al. (2004)
c.241-26347G>A;c.-15-26347G>A;c.-111-5353G>A T/C intron_variant - - - 24321478 Warrier V , et al. (2013)
c.241-26705C>T;c.-15-26705C>T;c.-111-5711C>T A/G intron_variant - - - 24321478 Warrier V , et al. (2013)
c.241-62255G>A;c.-16+32825G>A;c.-111-41261G>A C/T intron_variant - - - 15389768 McCauley JL , et al. (2004)
c.1081-4918A>G;c.826-4918A>G;c.868-4918A>G;c.904-4918A>G - intron_variant - - - 36943547 Adak P et al. (2023)
c.1081-4918A>G;c.826-4918A>G;c.868-4918A>G;c.904-4918A>G - intron_variant - - - 28607477 Yang S , et al. (2017)
c.241-55520T>G;c.-16+39560T>G;c.-111-34526T>G N/A intron_variant - - - 16674551 Ashley-Koch AE , et al. (2006)
c.-688C>T;c.-1039C>T;c.75C>T p.(=) synonymous_variant, 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
c.-732C>T;c.-1083C>T;c.31C>T p.Pro11Ser missense_variant, 2_KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
c.-1493G>A;c.-1493G>C;c.-1493G>T;c.-1844G>A;c.-1844G>C;c.-1844G>T;c.-731G>A;c.-731G>C;c.-731G>T G/A 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
N/A N/A intron_variant - - - 9545402 Cook EH Jr , et al. (1998)
N/A N/A microsatellite - - - 15952184 Curran S , et al. (2005)
- T/C 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
- - intergenic_variant - - - 15389768 McCauley JL , et al. (2004)
N/A N/A intron_variant - - - 11920158 Buxbaum JD , et al. (2002)
C473A - 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
C662T - 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
c.241-728G>A - intron_variant - - - 15389768 McCauley JL , et al. (2004)
- - microsatellite, intron_variant - - - 12819446 Nurmi EL , et al. (2003)
c.-1437T>G T/G 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
c.240+12C>T;c.-112+12C>T - intron_variant - - - 16835263 Urak L , et al. (2006)
c.240+39311C>T;c.-112+39311C>T - intron_variant - - - 36943547 Adak P et al. (2023)
c.240+23093A>G;c.-112+23093A>G C/T intron_variant - - - 24321478 Warrier V , et al. (2013)
c.240+29417T>G;c.-112+29417T>G C/A intron_variant - - - 24321478 Warrier V , et al. (2013)
c.240+39311C>T;c.-112+39311C>T A/G intron_variant - - - 24321478 Warrier V , et al. (2013)
c.-828C>G;c.-1179C>G;c.-66C>G G/C 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
c.-931G>T;c.-1282G>T;c.-169G>T T/G 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
c.-1303C>T;c.-1654C>T;c.-541C>T T/C 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
c.-1659T>C;c.-2010T>C;c.-897T>C T/C 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
c.-1852G>A;c.-2203G>A;c.-1090G>A G/A 2KB_upstream_variant - - - 16835263 Urak L , et al. (2006)
SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

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.

4/1/2022
2
icon
1

Decreased from 2 to 1

10/1/2020
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
1/1/2020
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
2
icon
2

Decreased from 2 to 2

New Scoring Scheme
Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).

Reports Added
[New Scoring Scheme]
7/1/2018
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).

Reports Added
[Meta-analysis of GABRB3 Gene Polymorphisms and Susceptibility to Autism Spectrum Disorder.2018]
7/1/2017
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01 < FDR ? 0.05, meaning that this gene had a ? 95% chance of being a true autism gene (PMID 25363760).

Reports Added
[GABAA receptor subunit gene polymorphisms predict symptom-based and developmental deficits in Chinese Han children and adolescents with autistic sp...2017]
4/1/2017
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01< FDR ?0.05, meaning that this gene had a ?95% chance of being a true autism gene (PMID 25363760).

Reports Added
[Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.1998] [Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the ...1999] [Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.1999] [Association between a GABRB3 polymorphism and autism.2002] [Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder.2002] [Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.2003] [A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism.2004] [An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum di...2005] [An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as ris...2006] [Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism.2009] [De novo gene disruptions in children on the autistic spectrum.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism.2013] [Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity.2006] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [De novo mutations in epileptic encephalopathies.2013] [GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.1995] [Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar verm...2007] [Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3.2010] [Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.2010] [Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children.2012] [Excess of rare, inherited truncating mutations in autism.2015] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Compromising the phosphodependent regulation of the GABAAR 3 subunit reproduces the core phenotypes of autism spectrum disorders.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.2015] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [De novo mutations in moderate or severe intellectual disability.2014]
1/1/2017
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01 < FDR ?0.05, meaning that this gene had a ?95% chance of being a true autism gene (PMID 25363760).

Reports Added
[Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016]
10/1/2016
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01

Reports Added
[De novo genic mutations among a Chinese autism spectrum disorder cohort.2016]
7/1/2016
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01

Reports Added
[De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016]
1/1/2016
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01

Reports Added
[Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.1998] [Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the ...1999] [Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.1999] [Association between a GABRB3 polymorphism and autism.2002] [Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder.2002] [Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.2003] [A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism.2004] [An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum di...2005] [An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as ris...2006] [Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism.2009] [De novo gene disruptions in children on the autistic spectrum.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism.2013] [Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity.2006] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [De novo mutations in epileptic encephalopathies.2013] [GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.1995] [Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar verm...2007] [Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3.2010] [Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.2010] [Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children.2012] [Excess of rare, inherited truncating mutations in autism.2015] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Compromising the phosphodependent regulation of the GABAAR 3 subunit reproduces the core phenotypes of autism spectrum disorders.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.2015] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016]
7/1/2015
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01

Reports Added
[Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.1998] [Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the ...1999] [Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.1999] [Association between a GABRB3 polymorphism and autism.2002] [Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder.2002] [Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.2003] [A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism.2004] [An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum di...2005] [An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as ris...2006] [Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism.2009] [De novo gene disruptions in children on the autistic spectrum.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism.2013] [Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity.2006] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [De novo mutations in epileptic encephalopathies.2013] [GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.1995] [Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar verm...2007] [Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3.2010] [Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.2010] [Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children.2012] [Excess of rare, inherited truncating mutations in autism.2015] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015]
4/1/2015
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01

Reports Added
[Excess of rare, inherited truncating mutations in autism.2015]
1/1/2015
2
icon
2

Decreased from 2 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01

Reports Added
[Large-scale discovery of novel genetic causes of developmental disorders.2014]
10/1/2014
4
icon
2

Decreased from 4 to 2

Description

The gene lies within the 15q11-q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category S gene) causes decreased expression of GABRB3. A de novo LoF variant in the GABRB3 gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while a de novo likely damaging missense variant in this gene has been observed in an ASD case from the Simons Simplex Collection (PMID 22542183). 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 GABRB3 as a gene meeting high statistical significance with a 0.01

Reports Added
[Synaptic, transcriptional and chromatin genes disrupted in autism.2014]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

There is minimal evidence for the role of GABRB3 in autism. The gene lies within the 15q11q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category X gene), causes decreased expression of GABRB3.

Reports Added
[GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.1995] [Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.1998] [Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the ...1999] [Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.1999] [Association between a GABRB3 polymorphism and autism.2002] [Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder.2002] [Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.2003] [A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism.2004] [An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum di...2005] [An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as ris...2006] [A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity.2006] [Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar verm...2007] [Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism.2009] [Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3.2010] [Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.2010] [De novo gene disruptions in children on the autistic spectrum.2012] [Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [De novo mutations in epileptic encephalopathies.2013] [Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism.2013] [Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders.2014]
4/1/2014
No data
icon
4

Increased from No data to 4

Description

There is minimal evidence for the role of GABRB3 in autism. The gene lies within the 15q11q13 duplication that, when maternally inherited, causes autism. There have been multiple gene-based association studies with mixed results; the gene has not been implicated in genome-wide association studies, nor have any of the gene-based associations been replicated. Knockout mice show social deficits and cerebellar vermis hypoplasia, and deficiency of MECP2 (a category X gene), causes decreased expression of GABRB3.

Krishnan Probability Score

Score 0.76491725651352

Ranking 27/25841 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 0.99707396027166

Ranking 1358/18225 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 0.812

Ranking 223/239 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 0.04494292732921

Ranking 44/18665 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 85.5

Ranking 11/461 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 0.25275803209956

Ranking 3442/20870 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
ACCN4 Acid-sensing ion channel 4 Human Protein Binding 55515 Q96FT7-4
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