GABRR2
protein-codinggamma-aminobutyric acid type A receptor subunit rho2, the group of Gamma-aminobutyric acid type A receptor subunits
Gene summary
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.8 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 GABRR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002043.5. 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 | 2 | 2 | 5 | ||
| missense | 78 | 3 | 1 | 82 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 81 | 5 | 3 | 89 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002034.3 | 9 | MANE Select | |
| Ensembl | ENSP00000386029.4 | 9 | MANE Select | |
| RefSeq | XP_011534016.1 | 6 | Standard | |
| RefSeq | XP_011534017.1 | 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
- visual perception
- ion transmembrane transport
Molecular Function
- GABA-A receptor activity
- extracellular ligand-gated ion channel activity
- chloride channel activity
- protein domain specific binding
- transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell junction
- chloride channel complex
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000402938
- Coding exons
- 9
- Length
- 58092
- Individuals with no LoFs
- 125693
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 55
- Defined
- 125748
- p
- 0.000219
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.296 | 268 | 282 | 0.950 | 0.0000166 | 3082 |
| Missense (PolyPhen) | 132 | 142.95 | 0.92343 | 1578 | ||
| Synonymous | 0.250 | 111 | 114 | 0.970 | 0.00000742 | 878 |
| Loss of Function | 1.93 | 11 | 20.4 | 0.540 | 9.46e-7 | 247 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0.0016 | 0.0016 | notable |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00026 | 0.00026 | 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. Rho-2 GABA receptor could play a role in retinal neurotransmission.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- RVIS EVS
- 0.07
- RVIS percentile EVS
- 59.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.141
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |