GABRA5
protein-codinggamma-aminobutyric acid type A receptor subunit alpha5, 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. Transcript variants utilizing three different alternative non-coding first exons have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0018614
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0032813
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0032813
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0032813
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GABRA5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000810.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 36 | 3 | 39 | |||
| missense | 2 | 4 | 72 | 6 | 1 | 85 |
| nonsense | 4 | 4 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 2 | 4 | 80 | 42 | 4 | 132 |
Highest pathogenic variant AF is 7.116556e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000801.1 | 9 | MANE Select | |
| Ensembl | ENSP00000335592.5 | 9 | MANE Select | |
| RefSeq | NP_001158509.1 | 9 | Standard | |
| Ensembl | ENSP00000347557.5 | 9 | Standard |
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
- behavioral fear response
- signal transduction
- gamma-aminobutyric acid signaling pathway
- chemical synaptic transmission
- brain development
Molecular Function
- GABA-A receptor activity
- transporter activity
- extracellular ligand-gated ion channel activity
- inhibitory extracellular ligand-gated ion channel activity
- chloride channel activity
Cellular Component
- nucleoplasm
- cytosol
- plasma membrane
- integral component of plasma membrane
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000335625
- Coding exons
- 9
- Length
- 82845
- Individuals with no LoFs
- 124653
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 124659
- p
- 0.0000241
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.23 | 127 | 279 | 0.456 | 0.0000170 | 3027 |
| Missense (PolyPhen) | 54 | 151.91 | 0.35548 | 1655 | ||
| Synonymous | -0.248 | 120 | 117 | 1.03 | 0.00000868 | 882 |
| Loss of Function | 3.62 | 3 | 20.8 | 0.144 | 0.00000105 | 235 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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
- 0.194
Intolerance Scores
- LoFtool
- 0.131
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 29.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.478
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |