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

Gene ID: 2557, updated on 11-Apr-2024

Summary

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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
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Genomic context

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See GABRA4 in Genome Data Viewer
Location:
4p12
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (46918900..46993581, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (46886225..46960936, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (46920917..46995598, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:46725989-46726490 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:46726491-46726990 Neighboring gene Rac family small GTPase 1 pseudogene 2 Neighboring gene cytochrome c oxidase subunit 7B2 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:46889421-46889608 Neighboring gene Sharpr-MPRA regulatory region 10756 Neighboring gene Sharpr-MPRA regulatory region 8016 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21529 Neighboring gene gamma-aminobutyric acid type A receptor subunit beta1 Neighboring gene small nucleolar RNA U13 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:47379937-47380444 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15398 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:47416165-47416745 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:47432124-47432333 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15399 Neighboring gene COMM domain containing 8

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A de novo missense variant in GABRA4 alters receptor function in an epileptic and neurodevelopmental phenotype. Vogel FD, et al. Epilepsia, 2022 Apr. PMID 35152403, Free PMC Article
  2. Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder. Griswold AJ, et al. Neurogenetics, 2018 Jan. PMID 29151244, Free PMC Article
  3. How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity. Dick DM, et al. Twin Res Hum Genet, 2013 Jun. PMID 23561058, Free PMC Article
  4. Alternative splicing of the GABA(A) receptor alpha 4 subunit creates a severely truncated mRNA. Mu W, et al. Brain Res Bull, 2002 Sep 15. PMID 12242096
  5. Human genome search in celiac disease using gliadin cDNA as probe. Kumar R, et al. J Mol Biol, 2000 Jul 28. PMID 10903861

See all (46) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. Further evidence of GABRA4 and TOP3B as autism susceptibility genes.
    Title: Further evidence of GABRA4 and TOP3B as autism susceptibility genes.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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).
  9. 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.
  10. Transgenic mice with the alpha4betadelta GABAA receptor subunit deletion show increased conditioned place preference, but not from delta-deficient or alpha4-deficient knockout mice.
    Title: Tonic inhibition of accumbal spiny neurons by extrasynaptic α4βδ GABAA receptors modulates the actions of psychostimulants.
Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 chloride transmembrane transport ISS
Inferred from Sequence or Structural Similarity
more info
  
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
  
is_active_in neuron projection IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma 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
  
is_active_in synapse IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of transmembrane transporter complex IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
gamma-aminobutyric acid receptor subunit alpha-4
Names
GABA(A) receptor, 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

  1. NG_011809.1 RefSeqGene

    Range
    4983..79664
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    46918900..46993581 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    46886225..46960936 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P48169.2 GenPept UniProtKB/Swiss-Prot:P48169

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