GABRG3
protein-codinggamma-aminobutyric acid type A receptor subunit gamma3, the group of Gamma-aminobutyric acid type A receptor subunits
Gene summary
This gene encodes a gamma-aminobutyric acid (GABA) receptor. 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. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~570.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GABRG3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_033223.5. 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 | 1 | 1 | 3 | 5 | ||
| missense | 40 | 4 | 44 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 1 | 0 | 44 | 4 | 3 | 52 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_150092.2 | 10 | MANE Select | |
| Ensembl | ENSP00000479113.1 | 10 | MANE Select | |
| RefSeq | NP_001257802.1 | 6 | Standard | |
| Ensembl | ENSP00000331912.7 | 6 | 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)
- Morphine addiction - Homo sapiens (human)
Biological Process
- signal transduction
- gamma-aminobutyric acid signaling pathway
- chemical synaptic transmission
- ion transmembrane transport
- regulation of membrane potential
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
- dendrite membrane
- chloride channel complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000333743
- Coding exons
- 10
- Length
- 561945
- Individuals with no LoFs
- 124641
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 124650
- p
- 0.0000361
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.52 | 145 | 259 | 0.560 | 0.0000147 | 3021 |
| Missense (PolyPhen) | 62 | 136.63 | 0.45376 | 1538 | ||
| Synonymous | -0.175 | 106 | 104 | 1.02 | 0.00000653 | 871 |
| Loss of Function | 3.76 | 4 | 23.8 | 0.168 | 0.00000116 | 297 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000051 | 0.000044 | rare |
| South Asian | 0.000037 | 0.000033 | rare |
| 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
- 0.102
Intolerance Scores
- LoFtool
- 0.196
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 46.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.205
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |