GABRB3
Homo sapiens
Gene Name: gamma-aminobutyric acid (GABA) A receptor, beta 3
Aliases: MGC9051
Chromosome No: 15
Chromosome Band: 15q12
Genetic Category: Genetic Association--Rare single gene variant-Multigenic CNV-Genetic association/rare single gene variant-Functional-Rare single gene variant/Functional-Genetic association/Functional-Rare Single Gene variant, Genetic Association
Aliases: MGC9051
Chromosome No: 15
Chromosome Band: 15q12
Genetic Category: Genetic Association--Rare single gene variant-Multigenic CNV-Genetic association/rare single gene variant-Functional-Rare single gene variant/Functional-Genetic association/Functional-Rare Single Gene variant, Genetic Association
Summary Statistics:
ASD Reports: 52
Recent Reports: 11
Annotated variants: 148
Associated CNVs: 15
Evidence score: 4
ASD Reports: 52
Recent Reports: 11
Annotated variants: 148
Associated CNVs: 15
Evidence score: 4
| Associated Disorders: |
|
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
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.
ASD
Positive Association
Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism.
ASD
ALTs
Positive Association
Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder.
ASD
Positive Association
De novo mutations in epileptic encephalopathies.
Epilepsy
IS, LGS, DD, ID, ASD, ADHD
Positive Association
Association between a GABRB3 polymorphism and autism.
ASD
Positive Association
Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism.
ASD
Positive Association
An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as ris...
ASD
Positive Association
An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum di...
ASD
Positive Association
A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism.
ASD
Positive Association
GABAA receptor subunit gene polymorphisms predict symptom-based and developmental deficits in Chinese Han children and adolescents with autistic sp...
ASD subphenotypes (CARS and ABC)
Positive Association
Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.
ASD
Negative Association
Meta-analysis of GABRB3 Gene Polymorphisms and Susceptibility to Autism Spectrum Disorder.
ASD
Negative Association
Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders.
ASD
Negative Association
Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.
ASD
Negative Association
Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the ...
ASD
Support
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
ASD
Support
Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex
ASD
Support
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.
DD, ID, epilepsy/seizures
Support
Mutations in GABRB3: From febrile seizures to epileptic encephalopathies
Epilepsy/seizures
ASD or autistic features, ID
Support
Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.
Epilepsy/seizures
Microcephaly
Support
Gabrb3 endothelial cell-specific knockout mice display abnormal blood flow
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD, epilepsy
Support
De novo genic mutations among a Chinese autism spectrum disorder cohort.
ASD
Support
GABRB3-related epilepsy: novel variants, clinical features and therapeutic implications
DD, epilepsy/seizures
Autistic features
Support
De novo mutations in moderate or severe intellectual disability.
DD, epilepsy/seizures
Autistic features
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
ID
Support
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
DD, ID, epilepsy/seizures
Support
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
ASD
Support
De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies.
Epilepsy/seizures
Support
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
ASD, DD
Support
Comprehensive molecular testing in patients with high functioning autism spectrum disorder.
ASD
Highly Cited
GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.
Recent Recommendation
A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity.
CAE
Recent Recommendation
Incorporating Functional Information in Tests of Excess De Novo Mutational Load.
Recent Recommendation
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Recent Recommendation
Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children.
Recent Recommendation
Gain-of-function and loss-of-function GABRB3 variants lead to distinct clinical phenotypes in patients with developmental and epileptic encephalopathies
Developmental and epileptic encephalopathy 43
ASD
Recent Recommendation
Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.
Recent Recommendation
Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.
Recent Recommendation
Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3.
Recent Recommendation
Compromising the phosphodependent regulation of the GABAAR 3 subunit reproduces the core phenotypes of autism spectrum disorders.
Recent Recommendation
Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar verm...
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN101R012
2KB_upstream_variant
NM_021912.4:c.-1442G>A
Unknown
Not maternal
Multiplex
GEN101R013
2KB_upstream_variant
NM_021912.5:c.-1437T>G
Familial
Paternal
Simplex
GEN101R014
2KB_upstream_variant
NM_021912.4:c.-1090G>A
Familial
Paternal
Simplex
GEN101R015
2KB_upstream_variant
NM_021912.4:c.-541C>T
Familial
Paternal
Simplex
GEN101R016
2KB_upstream_variant
NM_021912.4:c.-541C>T
Familial
Paternal
Simplex
GEN101R017
2KB_upstream_variant
NM_001278631.1:c.-232G>T
Familial
Paternal
Simplex
GEN101R019
2KB_upstream_variant
NM_000814.6:c.-142G>T
Familial
Paternal
Simplex
GEN101R020a
2KB_upstream_variant
NM_000814.6:c.-142G>T
Familial
Maternal
Simplex
GEN101R020b
2KB_upstream_variant
NM_021912.4:c.-140A>T
Familial
Paternal
Simplex
GEN101R025
frameshift_variant
c.1295del
p.Ser432PhefsTer11
De novo
Simplex
GEN101R028
missense_variant
c.662T>C
p.Ile221Thr
De novo
Simplex
GEN101R032
missense_variant
c.31C>T
p.Pro11Ser
Familial
Paternal
Simplex
GEN101R033
missense_variant
c.358G>A
p.Asp120Asn
De novo
GEN101R034
missense_variant
c.470C>T
p.Thr157Met
Familial
Maternal
GEN101R035
missense_variant
c.545A>T
p.Tyr182Phe
De novo
GEN101R036
missense_variant
c.745C>A
p.Gln249Lys
De novo
GEN101R037
missense_variant
c.767T>A
p.Leu256Gln
De novo
GEN101R038
missense_variant
c.878T>A
p.Leu293His
Unknown
GEN101R039
missense_variant
c.913G>A
p.Ala305Thr
De novo
GEN101R046
inframe_insertion
c.413_414insACC
p.Asn138delinsLysPro
De novo
Simplex
GEN101R080
frameshift_variant
c.1376_1377del
p.Thr459IlefsTer14
Familial
Paternal
GEN101R082
missense_variant
c.1286G>A
p.Arg429Gln
Familial
Maternal
Multiplex
Common
Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
GEN101C001
intron_variant
N/A
N/A
Caucasian, African-American, Hispanic
Discovery
GEN101C006
intron_variant
rs1432007
c.835+2039T>C;c.580+2039T>C;c.622+2039T>C
A/G
98% Caucasian
Discovery
GEN101C008
intron_variant
rs4542636
c.241-1250G>A;c.-15-1250G>A;c.28-1250G>A
T/C
98% Caucasian
Discovery
GEN101C009
intron_variant
rs878960
c.241-62255G>A;c.-16+32825G>A;c.-111-41261G>A
C/T
98% Caucasian
Discovery
GEN101C011
intron_variant
rs890317
c.241-55520T>G;c.-16+39560T>G;c.-111-34526T>G
N/A
Caucasian
Discovery
GEN101C013
2KB_upstream_variant
rs4243768
c.-1852G>A;c.-2203G>A;c.-1090G>A
G/A
Discovery
GEN101C014
2KB_upstream_variant
rs4906902
c.-1659T>C;c.-2010T>C;c.-897T>C
T/C
Discovery
GEN101C015
2KB_upstream_variant
rs8179184
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
Discovery
GEN101C016
2KB_upstream_variant
rs7171660
c.-1303C>T;c.-1654C>T;c.-541C>T
T/C
Discovery
GEN101C018
2KB_upstream_variant
rs4906901
c.-931G>T;c.-1282G>T;c.-169G>T
T/G
Discovery
GEN101C019
2KB_upstream_variant
rs20317
c.-828C>G;c.-1179C>G;c.-66C>G
G/C
Discovery
GEN101C020
missense_variant, 2_KB_upstream_variant
rs25409
c.-732C>T;c.-1083C>T;c.31C>T
p.Pro11Ser
Discovery
GEN101C021
synonymous_variant, 2KB_upstream_variant
rs20318
c.-688C>T;c.-1039C>T;c.75C>T
p.(=)
Discovery
GEN101C025
intron_variant
rs7180158
c.240+39311C>T;c.-112+39311C>T
A/G
Cases: 118 individuals with a DSM-IV or ICD-10 diagnosis of Asperger syndrome; controls: 412 individuals with an Autism Spectrum Quotient score below 24. All individuals of Caucasian ancestry.
Discovery
GEN101C026
intron_variant
rs7165604
c.240+23093A>G;c.-112+23093A>G
C/T
Cases: 118 individuals with a DSM-IV or ICD-10 diagnosis of Asperger syndrome; controls: 412 individuals with an Autism Spectrum Quotient score below 24. All individuals of Caucasian ancestry.
Discovery
GEN101C027
intron_variant
rs12593579
c.240+29417T>G;c.-112+29417T>G
C/A
Cases: 118 individuals with a DSM-IV or ICD-10 diagnosis of Asperger syndrome; controls: 412 individuals with an Autism Spectrum Quotient score below 24. All individuals of Caucasian ancestry.
Discovery
GEN101C028
intron_variant
rs11636966
c.241-26347G>A;c.-15-26347G>A;c.-111-5353G>A
T/C
413 individuals of Caucasian ancestry without a clinical diagnosis of Asperger syndrome
Discovery
GEN101C029
intron_variant
rs9806546
c.241-26705C>T;c.-15-26705C>T;c.-111-5711C>T
A/G
413 individuals of Caucasian ancestry without a clinical diagnosis of Asperger syndrome
Discovery
GEN101C030
intron_variant
rs2081648
c.1081-4918A>G;c.826-4918A>G;c.868-4918A>G;c.904-4918A>G
99 Han Chinese ASD children and adolescents (79 male, 20 female; age 8.53 ± 0.42 years; 82 with autism, 17 with PDD-NOS)
Discovery
GEN101C031
intron_variant
rs7180158
c.240+39311C>T;c.-112+39311C>T
316 Indo-Caucasoid ASD probands (262 male, 54 female; mean age 5.96 +/- 3.31 years) from West Bengal recruited from Manovikas Kendra Rehabilitation and Research Institute of the Handicapped (MRIH), Kolkata, India, and 227 healthy controls (124 male, 103 female; mean age 8.9 +/- 6.8 years) recruited from different regions around Kolkata.
Replication
GEN101C032
intron_variant
rs2081648
c.1081-4918A>G;c.826-4918A>G;c.868-4918A>G;c.904-4918A>G
316 Indo-Caucasoid ASD probands (262 male, 54 female; mean age 5.96 +/- 3.31 years) from West Bengal and their families recruited from Manovikas Kendra Rehabilitation and Research Institute of the Handicapped (MRIH), Kolkata, India.
Replication
