GABRA6

protein-coding

gamma-aminobutyric acid type A receptor subunit alpha6, the group of Gamma-aminobutyric acid type A receptor subunits

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_000811.3

Inheritance

ClinVar variants

U:50B:23

Top phenotype

Childhood absence epilepsy

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr5:161,547,063-161,702,593

External References & Databases

Ensembl (ENSG00000145863)

Transcript & Mutation Effects

hg38 • Region Span ~155.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epilepsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005027

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GABRA6 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 15

Childhood absence epilepsyTotal: 15

GABRA6-related disorderTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000811.3. 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				10 clinvar	3 clinvar	13
missense			46 clinvar	8 clinvar	2 clinvar	56
nonsense						0
start loss			1 clinvar			1
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	18	5	73

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000811.3	RefSeq	NP_000802.2	9	MANE Select
ENST00000274545.10	Ensembl	ENSP00000274545.5	9	MANE Select
ENST00000517823.5	Ensembl	ENSP00000430212.1	5	Standard
ENST00000520000.5	Ensembl	ENSP00000429943.1	5	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
benzodiazepine receptor activity

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: ENST00000274545
Coding exons: 9
Length: 155531
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 62
Defined: 125748
p: 0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.409	257	239	1.07	0.0000128	2969
Missense (PolyPhen)		166	151.77	1.0938		1892
Synonymous	-1.47	107	89.3	1.20	0.00000541	882
Loss of Function	0.253	19	20.2	0.939	9.40e-7	254

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	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: 0.160

Intolerance Scores

LoFtool: 0.505
RVIS EVS: 0.22
RVIS percentile EVS: 68.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.203

Gene Damage Prediction

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