GABRA4 gamma-aminobutyric acid type A receptor subunit alpha4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GABRA4provided by HGNC
Official Full Name: gamma-aminobutyric acid type A receptor subunit alpha4provided by HGNC
Primary source: HGNC:HGNC:4078
See related: Ensembl:ENSG00000109158 MIM:137141; AllianceGenome:HGNC:4078
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: Gamma-aminobutyric acid (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. This gene encodes subunit alpha-4, which is involved in the etiology of autism and eventually increases autism risk through interaction with another subunit, gamma-aminobutyric acid receptor beta-1 (GABRB1). Alternatively spliced transcript variants encoding different isoforms have been found in this gene.[provided by RefSeq, Feb 2011]
Expression: Biased expression in brain (RPKM 6.9) and heart (RPKM 1.7) See more
Orthologs: mouse all
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Genomic context

Location:: 4p12

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (46918900..46993581, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (46886225..46960936, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (46920917..46995598, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

De novo variants in GABRA4 are associated with a neurological phenotype including developmental delay, behavioral abnormalities and epilepsy.
Title: De novo variants in GABRA4 are associated with a neurological phenotype including developmental delay, behavioral abnormalities and epilepsy.
A de novo missense variant in GABRA4 alters receptor function in an epileptic and neurodevelopmental phenotype.
Title: A de novo missense variant in GABRA4 alters receptor function in an epileptic and neurodevelopmental phenotype.
Further evidence of GABRA4 and TOP3B as autism susceptibility genes.
Title: Further evidence of GABRA4 and TOP3B as autism susceptibility genes.
Steady-state activation of the high-affinity isoform of the alpha4beta2delta GABAA receptor.
Title: Steady-state activation of the high-affinity isoform of the α4β2δ GABA(A) receptor.
Study identified a rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder. GABRA4 rare variants in noncoding DNA may be variants of modest physiological effects in ASD etiology.
Title: Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder.
GABRA4 rs2229940 did not show association with migraine risk
Title: Gamma-aminobutyric acid (GABA) receptors GABRA4, GABRE, and GABRQ gene polymorphisms and risk for migraine.
These results suggest association between GABRR3 rs832032 polymorphism and the risk for restless legs syndrome , and a modifier effect of GABRA4 rs2229940 on the age of onset of restless legs syndrome .
Title: Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome.
rs505474, rs1398175, and rs4868029 in the GABRA2, GABRA4, and GABRP genes, respectively, allele frequencies were significantly different between patients and controls.Four haplotypes were significantly associated with Bipolar Disorder TA and AG for rs3815762 and rs4868029 in GABRP, GG for rs11636988 and rs8024256 in GABRB3 and GAGG for rs2197414, rs4921195, rs13188991, and rs11956731 in GABRA6.
Title: Contribution of genes in the GABAergic pathway to bipolar disorder and its executive function deficit in the Chinese Han population.
GABRA4 is associated with autism spectrum disorder in a dataset from Argentina.
Title: Association between GABA(A) receptor subunit polymorphisms and autism spectrum disorder (ASD).
The ability of neurosteroids to modulate the phosphorylation and membrane insertion of alpha4 subunit-containing GABAARs may underlie the profound effects these endogenous signaling molecules have on neuronal excitability and behavior.
Title: Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide search for type 2 diabetes susceptibility genes in an extended Arab family. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:633093 (e-PCR)
- UniSTS:158508

D5S1969 (e-PCR), detects polymorphism
- UniSTS:15159

SHGC-67811 (e-PCR)
- UniSTS:86098

G62895 (e-PCR)
- UniSTS:139870

D5Buc33 (e-PCR), detects polymorphism
- UniSTS:142525

Gabra4 (e-PCR), detects polymorphism
- UniSTS:265417

RH106543 (e-PCR)
- UniSTS:209620

D4S3242 (e-PCR)
- UniSTS:55789

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to GABA-A receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables GABA-gated chloride ion channel activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to benzodiazepine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in chloride transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in gamma-aminobutyric acid signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in gamma-aminobutyric acid signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in gamma-aminobutyric acid signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in inhibitory synapse assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of postsynaptic membrane potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic transmission, GABAergic	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic transmission, GABAergic	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of GABA-A receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of GABA-A receptor complex	IPI Inferred from Physical Interaction more info	PubMed
part_of GABA-A receptor complex	ISS Inferred from Sequence or Structural Similarity more info
located_in GABA-ergic synapse	IEA Inferred from Electronic Annotation more info
part_of chloride channel complex	IEA Inferred from Electronic Annotation more info
is_active_in dendrite membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in postsynapse	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic specialization membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: gamma-aminobutyric acid receptor subunit alpha-4

Names: GABA(A) receptor, alpha 4; GABAAR subunit alpha-4; gamma-aminobutyric acid (GABA) A receptor, alpha 4; gamma-aminobutyric acid A receptor alpha 4; gamma-aminobutyric acid type A receptor alpha4 subunit

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011809.1 RefSeqGene

Range

4983..79664

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000809.4 → NP_000800.2 gamma-aminobutyric acid receptor subunit alpha-4 isoform 1 precursor

See identical proteins and their annotated locations for NP_000800.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC107383, AK090780, BC037926

Consensus CDS

CCDS3473.1

UniProtKB/Swiss-Prot

P48169, Q8IYR7

UniProtKB/TrEMBL

X5D7F5

Related

ENSP00000264318.3, ENST00000264318.4

Conserved Domains (1) summary

cl27321
Location:13 → 541

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_001204266.2 → NP_001191195.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a segment in the first splice junction, resulting in an upstream AUG start codon, as compared to variant 1. The resulting isoform (2) has a shorter and different N-terminus, as compared to isoform 1.

Source sequence(s)

AC107383, BC035055, BC037926, CD013893

UniProtKB/Swiss-Prot

P48169

Conserved Domains (3) summary

TIGR00860
Location:5 → 522

LIC; Cation transporter family protein

pfam02931
Location:30 → 237

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:244 → 519

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
NM_001204267.2 → NP_001191196.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks a segment in the first splice junction, resulting in an upstream AUG start codon, and lacks an in-frame exon in the middle region, as compared to variant 1. The resulting isoform (3) has a shorter and different N-terminus and lacks an internal segment, as compared to isoform 1.

Source sequence(s)

AC107383, BC035055, BC037926, CD013892

UniProtKB/Swiss-Prot

P48169

Conserved Domains (3) summary

TIGR00860
Location:5 → 471

LIC; Cation transporter family protein

pfam02931
Location:30 → 228

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:222 → 468

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region