GABRG2 |
- 1
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- GABRG2 (HGNC:4087) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- gamma-aminobutyric acid type A receptor subunit gamma2
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- No aliases found
- %HI
- 11.88(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.74(Read more about gnomAD pLI score)
- LOEUF
- 0.4(Read more about gnomAD LOEUF score)
- Cytoband
- 5q34
- Genomic Coordinates
-
GRCh37/hg19: chr5:161494471-161582545 NCBI Ensembl UCSC GRCh38/hg38: chr5:162067465-162155539 NCBI Ensembl UCSC - MANE Select Transcript
- NM_198904.4 ENST00000639213.2 (Read more about MANE Select)
- Function
- Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:2538761, PubMed:29950725). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:23909897, PubMed:25489750, PubMed:27864268). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the ... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-34677
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency
(1)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
09/25/2018
Haploinsufficiency (HI) Score Details
HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence:
-
PUBMED:
12117362
Kananura et al. (2002): A total of 135 patients and 154 unrelated, ethnically matched controls were screened for mutations in GABRG2. An IVS6 + 2T-->G point mutation (HGVS c.769+2T>G) was found to cosegregate with the disease status in a family with childhood absence epilepsy and febrile convulsions. The mutation was predicted to produce a non-functional protein.
-
PUBMED:
19261880
Kang et al. (2009): A family with generalized epilepsy and febrile seizures was found to have a mutation that introduces a premature stop codon at Q351 (exon 9) of GABRB2. However, whether the mechanism was loss-of-function or a dominant negative effect, or a combination of both is not yet clear, at least for mutations in the 3' of the gene.
-
PUBMED:
24480790
Ishii et al. (2014): A heterozygous nonsense mutation (c.118C>T, p.Q40X) in GABRG2 was identified in dizygotic twin girls with Dravet syndrome and their apparently healthy father. The authors concluded that the phenotype was due to a dominant negative effect. This is at odds with an earlier publication (Huang et al., 2012 PMID 22750526], which found that the mutation was subject to nonsense mediated mRNA decay.
HI Evidence Comments:
Missense, splice and nonsense mutations in GABRG2 are associated with Dravet syndrome and idiopathic generalized epilepsy. The majority of mutations, nonsense and splice included, appear to have a dominant negative effect, causing severe epilepsy. However, some nonsense mutations are thought to result in haploinsufficiency, and these may be associated with a milder epilepsy phenotype (Kang and Macdonald, 2016 PMID:27367160 ).
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000005.9)
(NC_000005.10)