GeneBe

GABRA2

protein-coding

gamma-aminobutyric acid type A receptor subunit alpha2, the group of Gamma-aminobutyric acid type A receptor subunits

Gene summary

GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

MANE transcript

NM_000807.4

Inheritance

AD

ClinVar variants

P:24U:138B:99

Top phenotype

Developmental and epileptic encephalopathy 78

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr4:46,243,548-46,475,230

External References & Databases

Ensembl (ENSG00000151834)NCBI Gene (2555)OMIM (137140)HGNC:4076GenCCUniProt (P47869)AlphaFoldClinVar (GABRA2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~231.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 78STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032812

Submitter: G2P

undetermined early-onset epileptic encephalopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018614

Submitter: Orphanet

developmental and epileptic encephalopathy, 78STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032812

Submitter: PanelApp Australia

developmental and epileptic encephalopathy, 78MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032812

Submitter: Ambry Genetics

developmental and epileptic encephalopathy, 78STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032812

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 78AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29422393; 29961870; 31032849Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GABRA2 variants in ClinVar

10 Conditions Cataloged
not providedTotal: 330
Inborn genetic diseasesTotal: 33
Developmental and epileptic encephalopathy, 78Total: 30
GABRA2-related disorderTotal: 11
not specifiedTotal: 4
Alcohol dependenceTotal: 2
EpilepsyTotal: 1
Developmental and epileptic encephalopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000807.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
72
clinvar
 75
missense
3
clinvar
18
clinvar
117
clinvar
25
clinvar
2
clinvar
 165
nonsense
1
clinvar
5
clinvar
 6
start loss
0
frameshift
2
clinvar
8
clinvar
 10
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total519138972261

Highest pathogenic variant AF is 0.000002000248

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000807.4RefSeqNP_000798.29MANE Select
ENST00000381620.9EnsemblENSP00000371033.49MANE Select
NM_001114175.3RefSeqNP_001107647.19Standard
NM_001286827.3RefSeqNP_001273756.18Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
gabra2aDanio rerio

Structure: third ventricle

Quality: apoptotic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Retrograde endocannabinoid signaling - Homo sapiens (human)
  • GABAergic synapse - Homo sapiens (human)
  • Nicotine addiction - Homo sapiens (human)
  • Neuroactive ligand-receptor interaction - Homo sapiens (human)
  • Taste transduction - Homo sapiens (human)

Biological Process

  • regulation of neurotransmitter levels
  • neurotransmitter transport
  • signal transduction
  • gamma-aminobutyric acid signaling pathway
  • chemical synaptic transmission

Molecular Function

  • GABA-A receptor activity
  • extracellular ligand-gated ion channel activity
  • inhibitory extracellular ligand-gated ion channel activity
  • chloride channel activity
  • benzodiazepine receptor activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • cell junction
  • integral component of synaptic vesicle membrane
  • dendrite membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000510861
Coding exons
9
Length
226804
Individuals with no LoFs
125657
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125661
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.13972310.4200.00001102970
Missense (PolyPhen)17107.670.157881427
Synonymous0.4937782.70.9310.00000414858
Loss of Function4.01120.70.04839.94e-7259

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000360.000035rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.;

Recessive Scores

pRec
0.135

Intolerance Scores

LoFtool
0.167
RVIS EVS
-0.27
RVIS percentile EVS
33.97

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.164

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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