GABRA3

protein-coding

gamma-aminobutyric acid type A receptor subunit alpha3, the group of Gamma-aminobutyric acid type A receptor subunits|MicroRNA protein coding host genes

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000808.4

Inheritance

ClinVar variants

P:4U:89B:12

Top phenotype

epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chrX:152,166,234-152,451,315

External References & Databases

Ensembl (ENSG00000011677)

Transcript & Mutation Effects

hg38 • Region Span ~285.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic featuresDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0859564

Submitter: Illumina

epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic featuresSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0859564

Submitter: Labcorp Genetics (formerly Invitae)

epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic featuresSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0859564

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GABRA3 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 37

Inborn genetic diseasesTotal: 25

Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic featuresTotal: 16

GABRA3-related disorderTotal: 9

not specifiedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000808.4. 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			6 clinvar	6 clinvar	1 clinvar	13
missense	3 clinvar	1 clinvar	71 clinvar	5 clinvar		80
nonsense			5 clinvar			5
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	3	1	89	11	1	105

Highest pathogenic variant AF is 0.000005464426

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000808.4	RefSeq	NP_000799.1	9	MANE Select
ENST00000370314.9	Ensembl	ENSP00000359337.4	9	MANE Select
ENST00000535043.1	Ensembl	ENSP00000443527.1	9	Standard
ENST00000862742.1	Ensembl	ENSP00000532801.1	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

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
protein binding

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370314
Coding exons: 9
Length: 285125
Individuals with no LoFs: 125147
Homozygous LoFs: 1
Heterozygous LoFs: 74
Defined: 125222
p: 0.000300

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.53	97	197	0.493	0.0000153	3230
Missense (PolyPhen)		27	98.177	0.27501		1624
Synonymous	0.684	68	75.6	0.900	0.00000605	985
Loss of Function	2.40	5	15.0	0.333	0.00000118	253

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.0031	0.0022	notable
European (Non-Finnish)	0.00029	0.00020	rare
South Asian	0.000057	0.000033	rare
Other	0.00047	0.00033	rare

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: 0.216

Intolerance Scores

LoFtool: 0.253
RVIS EVS: -0.05
RVIS percentile EVS: 49.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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