GABRG1

protein-coding

gamma-aminobutyric acid type A receptor subunit gamma1, the group of Gamma-aminobutyric acid type A receptor subunits

Gene summary

The protein encoded by this gene belongs to the ligand-gated ionic channel family. It is an integral membrane protein and plays an important role in inhibiting neurotransmission by binding to the benzodiazepine receptor and opening an integral chloride channel. This gene is clustered with three other family members on chromosome 4. [provided by RefSeq, Jul 2008]

MANE transcript

NM_173536.4

Inheritance

ClinVar variants

U:61B:1

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr4:46,035,769-46,124,054

External References & Databases

Ensembl (ENSG00000163285)

Transcript & Mutation Effects

hg38 • Region Span ~88.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

genetic developmental and epileptic encephalopathyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100062

Submitter: PanelApp Australia

genetic developmental and epileptic encephalopathyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100062

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GABRG1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 2

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173536.4. 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			1 clinvar	1 clinvar		2
missense			59 clinvar			59
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	61	1	0	62

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173536.4	RefSeq	NP_775807.2	9	MANE Select
ENST00000295452.5	Ensembl	ENSP00000295452.4	9	MANE Select
ENST00000964875.1	Ensembl	ENSP00000634934.1	7	Standard
ENST00000964875.2	Ensembl	ENSP00000634934.1	7	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

integral component of plasma membrane
cell junction
dendrite membrane
chloride channel complex
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295452
Coding exons: 9
Length: 88313
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125741
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.519	220	243	0.906	0.0000120	3052
Missense (PolyPhen)		82	100.12	0.81898		1283
Synonymous	-1.46	100	83.1	1.20	0.00000407	867
Loss of Function	2.22	10	21.0	0.476	0.00000105	273

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000090	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

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: 0.0896

Intolerance Scores

LoFtool: 0.332
RVIS EVS: -0.8
RVIS percentile EVS: 12.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.177

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium