GABRE

protein-coding

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

Gene summary

The product of this gene belongs to the ligand-gated ionic channel (TC 1.A.9) family. It encodes the gamma-aminobutyric acid (GABA) A receptor which is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes an epsilon subunit. It is mapped to chromosome Xq28 in a cluster comprised of genes encoding alpha 3, beta 4 and theta subunits of the same receptor. Alternatively spliced transcript variants have been identified, but only one is thought to encode a protein. [provided by RefSeq, Oct 2008]

MANE transcript

NM_004961.4

Inheritance

—

ClinVar variants

P:1U:126B:14

Top phenotype

GABRE-related disorder

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chrX:151,953,124-151,974,680

External References & Databases

Ensembl (ENSG00000102287)

Transcript & Mutation Effects

hg38 • Region Span ~21.6 kb

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GenCC 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 GABRE variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 18

GABRE-related disorderTotal: 3

Short statureTotal: 1

GABRE-related epilepsyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004961.4. 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			8 clinvar	3 clinvar	2 clinvar	13
missense			105 clinvar	7 clinvar	2 clinvar	114
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	1	0	126	10	4	141

Highest pathogenic variant AF is 0.000024801608

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_004961.4	RefSeq	NP_004952.2	9	MANE Select
ENST00000370328.4	Ensembl	ENSP00000359353.3	9	MANE Select
ENST00000417300.1	Ensembl	ENSP00000397335.1	2	Standard
ENST00000441219.5	Ensembl	ENSP00000389384.1	2	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: ENST00000370328
Coding exons: 9
Length: 21557
Individuals with no LoFs: 125732
Homozygous LoFs: 7
Heterozygous LoFs: 7
Defined: 125746
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0720	211	208	1.01	0.0000172	3322
Missense (PolyPhen)		65	87.903	0.73945		1349
Synonymous	0.605	70	76.7	0.912	0.00000620	982
Loss of Function	1.51	8	14.1	0.567	9.55e-7	254

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00023	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00014	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.000079	rare
South Asian	0	0.0	absent
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: 0.135

Intolerance Scores

LoFtool: 0.188
RVIS EVS: 1.82
RVIS percentile EVS: 97.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.254

Gene Damage Prediction

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