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 en... See more...

Aliases for GABRA4 Gene

Aliases for GABRA4 Gene

  • Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha4 2 3 5
  • Gamma-Aminobutyric Acid (GABA) A Receptor, Alpha 4 2 3
  • Gamma-Aminobutyric Acid Receptor Subunit Alpha-4 3 4
  • GABA(A) Receptor, Alpha 4 2 3
  • Gamma-Aminobutyric Acid Type A Receptor Alpha4 Subunit 3
  • Gamma-Aminobutyric Acid A Receptor Alpha 4 3
  • GABA(A) Receptor Subunit Alpha-4 4
  • GABRA4 5

External Ids for GABRA4 Gene

Previous GeneCards Identifiers for GABRA4 Gene

  • GC04M047001
  • GC04M047239
  • GC04M046778
  • GC04M046761
  • GC04M046615
  • GC04M046239

Summaries for GABRA4 Gene

Entrez Gene Summary for GABRA4 Gene

  • 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]

GeneCards Summary for GABRA4 Gene

GABRA4 (Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha4) is a Protein Coding gene. Diseases associated with GABRA4 include Status Epilepticus and Autism. Among its related pathways are Nicotine addiction and Sweet Taste Signaling. Gene Ontology (GO) annotations related to this gene include chloride channel activity and GABA-A receptor activity. An important paralog of this gene is GABRA6.

UniProtKB/Swiss-Prot Summary for GABRA4 Gene

  • 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.

Tocris Summary for GABRA4 Gene

  • GABAA receptors are members of the Cys-loop family of ligand-gated ion channels and, along with GABAB receptors, are responsible for mediating the inhibitory effects of GABA. They are pentameric proteins, consisting of five subunits belonging to different families.

Gene Wiki entry for GABRA4 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GABRA4 Gene

Genomics for GABRA4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GABRA4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J046993 Promoter 1 EPDnew Ensembl 606.8 -0.1 -120 1.4 PRDM1 POLR2A EZH2 RAD21 DPF2 BHLHE40 MLLT1 ZBTB33 GABRA4 GABRB1 COX7B2 HSALNG0034230 COMMD8
GH04J047641 Enhancer 0.9 FANTOM5 Ensembl ENCODE 7.4 -649.2 -649220 3.2 GTF2F1 JUND RAD51 USF1 POLR2A BHLHE40 TOE1 SMARCA4 USF2 CBFA2T2 GABRA4 LOC105374443 MIR8053 ATP10D CORIN
GH04J046981 Enhancer 0.3 Ensembl 5.9 +12.5 12480 0.2 SPI1 GABRA4 GABRB1 piR-48325-116 COX7B2
GH04J047031 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE CraniofacialAtlas 0.3 -38.3 -38320 2.6 GATAD2A CTCF RFX5 RAD21 TRIM22 YY1 SCRT2 NRF1 ZBTB20 ZSCAN29 GABRB1 ENSG00000260918 HSALNG0034230 GABRA4 LOC105374442 COMMD8
GH04J046720 Enhancer 0.2 FANTOM5 1.6 +272.5 272498 0.2 GABRA4 piR-56925-001 piR-50129-178 COX7B2 GABRA2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GABRA4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GABRA4

Top Transcription factor binding sites by QIAGEN in the GABRA4 gene promoter:
  • aMEF-2
  • c-Ets-1
  • Lhx3a
  • LHX3b
  • MEF-2
  • MEF-2A
  • Pax-4a
  • POU2F1
  • POU2F1a

Genomic Locations for GABRA4 Gene

Genomic Locations for GABRA4 Gene
chr4:46,918,900-46,993,581
(GRCh38/hg38)
Size:
74,682 bases
Orientation:
Minus strand
chr4:46,920,917-46,996,424
(GRCh37/hg19)
Size:
75,508 bases
Orientation:
Minus strand

Genomic View for GABRA4 Gene

Genes around GABRA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GABRA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GABRA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GABRA4 Gene

Proteins for GABRA4 Gene

  • Protein details for GABRA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P48169-GBRA4_HUMAN
    Recommended name:
    Gamma-aminobutyric acid receptor subunit alpha-4
    Protein Accession:
    P48169
    Secondary Accessions:
    • Q8IYR7

    Protein attributes for GABRA4 Gene

    Size:
    554 amino acids
    Molecular mass:
    61623 Da
    Quaternary structure:
    • Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.

neXtProt entry for GABRA4 Gene

Post-translational modifications for GABRA4 Gene

  • Glycosylation at Asn47, Asn144, and Asn157
  • Modification sites at PhosphoSitePlus

Other Protein References for GABRA4 Gene

No data available for DME Specific Peptides for GABRA4 Gene

Domains & Families for GABRA4 Gene

Gene Families for GABRA4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • FDA approved drug targets
  • Predicted membrane proteins

Protein Domains for GABRA4 Gene

InterPro:
Blocks:
  • Neurotransmitter-gated ion-channel
  • Gamma-aminobutyric-acid A receptor alpha subunit signature
  • Gamma-aminobutyric-acid A receptor alpha 4 subunit signature
  • Gamma-aminobutyric acid A (GABAA) receptor signature
ProtoNet:

Suggested Antigen Peptide Sequences for GABRA4 Gene

GenScript: Design optimal peptide antigens:
  • GABA(A) receptor subunit alpha-4 (GBRA4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P48169

UniProtKB/Swiss-Prot:

GBRA4_HUMAN :
  • Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA4 sub-subfamily.
Family:
  • Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA4 sub-subfamily.
genes like me logo Genes that share domains with GABRA4: view

Function for GABRA4 Gene

Molecular function for GABRA4 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction:
The alpha4 beta2 gamma 2L receptor is not repressed by diazepam.
GENATLAS Biochemistry:
gamma-aminobutyric acid (GABA) A receptor,ionotropic,alpha 4,subunit,component of a pentameric receptor mediating inhibitory neurotransmission

Phenotypes From GWAS Catalog for GABRA4 Gene

Gene Ontology (GO) - Molecular Function for GABRA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004888 transmembrane signaling receptor activity IEA --
GO:0004890 contributes_to GABA-A receptor activity IBA 21873635
GO:0005216 ion channel activity IEA --
GO:0005230 extracellular ligand-gated ion channel activity IEA --
GO:0005237 inhibitory extracellular ligand-gated ion channel activity IBA 21873635
genes like me logo Genes that share ontologies with GABRA4: view
genes like me logo Genes that share phenotypes with GABRA4: view

Animal Models for GABRA4 Gene

MGI Knock Outs for GABRA4:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GABRA4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GABRA4 Gene

Localization for GABRA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GABRA4 Gene

Cell junction, synapse, postsynaptic cell membrane. Multi-pass membrane protein. Cell membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GABRA4 gene
Compartment Confidence
plasma membrane 5
extracellular 1
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 0

Gene Ontology (GO) - Cellular Components for GABRA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS,IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0030054 cell junction IEA --
genes like me logo Genes that share ontologies with GABRA4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GABRA4 Gene

Pathways & Interactions for GABRA4 Gene

genes like me logo Genes that share pathways with GABRA4: view

Pathways by source for GABRA4 Gene

1 Tocris pathway for GABRA4 Gene
2 Qiagen pathways for GABRA4 Gene
  • Akt Signaling
  • Sperm Motility

Gene Ontology (GO) - Biological Process for GABRA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006821 chloride transport IEA --
GO:0007165 signal transduction IBA 21873635
GO:0007214 gamma-aminobutyric acid signaling pathway TAS,IBA 21873635
GO:0007268 chemical synaptic transmission IBA 21873635
genes like me logo Genes that share ontologies with GABRA4: view

No data available for SIGNOR curated interactions for GABRA4 Gene

Drugs & Compounds for GABRA4 Gene

(114) Drugs for GABRA4 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, HMDB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Bromazepam Approved, Illicit, Investigational Pharma Target, positive allosteric modulator, binder 3
Butabarbital Approved, Illicit Pharma Target, positive allosteric modulator, antagonist 0
Butalbital Approved, Illicit Pharma Target, Target, potentiator, positive allosteric modulator, antagonist 0
Butethal Approved, Illicit Pharma Target, potentiator, antagonist 0
Chlordiazepoxide Approved, Illicit, Investigational Pharma Target, positive allosteric modulator, agonist 5

(5) Additional Compounds for GABRA4 Gene - From: HMDB, IUPHAR, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
gaba
56-12-2
Ro154513
Allosteric regulator, Inverse agonist, Full agonist
THIP
Agonist, Full agonist, Antagonist
3'-Hydroxyhexobarbital
  • 3'-Hydroxyhexobarbital, (R-(r*,s*))-isomer
  • 3'-Hydroxyhexobarbital, (r*,s*)-(+-)-isomer
  • 3'-Hydroxyhexobarbital, (S-(r*,r*))-isomer
  • 3'-Hydroxyhexobarbital, (S-(r*,s*))-isomer
  • 3'-Hydroxyhexobarbitone
427-29-2
Alpha-hydroxyalprazolam
37115-43-8

(4) Tocris Compounds for GABRA4 Gene

Compound Action Cas Number
Acamprosate calcium GABA agonist and glutamatergic modulator 77337-73-6
GABA Endogenous agonist 56-12-2
TACA GABAA agonist. Also GABA-T substrate and GABA uptake inhibitor 38090-53-8
ZAPA sulfate Agonist at 'low affinity' GABAA receptor. More potent than GABA/muscimol 371962-01-5

(3) ApexBio Compounds for GABRA4 Gene

Compound Action Cas Number
(+)-Bicuculline GABAA receptor antagonist,competitve and classical 485-49-4
ARN-509 Androgen receptor inhibitor 956104-40-8
Bemegride 64-65-3
genes like me logo Genes that share compounds with GABRA4: view

Drug Products

Transcripts for GABRA4 Gene

mRNA/cDNA for GABRA4 Gene

3 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GABRA4

Alternative Splicing Database (ASD) splice patterns (SP) for GABRA4 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9
SP1: -
SP2: - -
SP3: - - -
SP4:

Relevant External Links for GABRA4 Gene

GeneLoc Exon Structure for
GABRA4

Expression for GABRA4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GABRA4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GABRA4 Gene

This gene is overexpressed in Brain - Nucleus accumbens (basal ganglia) (x8.6), Brain - Caudate (basal ganglia) (x7.4), Brain - Putamen (basal ganglia) (x6.9), Brain - Frontal Cortex (BA9) (x5.8), Brain - Anterior cingulate cortex (BA24) (x5.3), and Brain - Cortex (x4.1).

Protein differential expression in normal tissues from HIPED for GABRA4 Gene

This gene is overexpressed in Frontal cortex (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GABRA4 Gene



Protein tissue co-expression partners for GABRA4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GABRA4

SOURCE GeneReport for Unigene cluster for GABRA4 Gene:

Hs.248112

Evidence on tissue expression from TISSUES for GABRA4 Gene

  • Nervous system(4.7)
genes like me logo Genes that share expression patterns with GABRA4: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for GABRA4 Gene

Orthologs for GABRA4 Gene

This gene was present in the common ancestor of animals.

Orthologs for GABRA4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia GABRA4 30 31
  • 99.58 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia GABRA4 30 31
  • 92.06 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia GABRA4 30 31
  • 91.37 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Gabra4 30 17 31
  • 87.3 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Gabra4 30
  • 86.45 (n)
Oppossum
(Monodelphis domestica)
Mammalia GABRA4 31
  • 85 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia GABRA4 31
  • 54 (a)
OneToOne
Chicken
(Gallus gallus)
Aves GABRA4 30 31
  • 78.68 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia GABRA4 31
  • 87 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii GABRA4 31
  • 85 (a)
OneToOne
zgc:110204 30
  • 67.17 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Grd 32
  • 50 (a)
CG8916 32
  • 42 (a)
Species where no ortholog for GABRA4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for GABRA4 Gene

ENSEMBL:
Gene Tree for GABRA4 (if available)
TreeFam:
Gene Tree for GABRA4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GABRA4: view image

Paralogs for GABRA4 Gene

Variants for GABRA4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GABRA4 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
724381 Benign: not provided 46,965,099(-) G/A SYNONYMOUS_VARIANT
728659 Benign: not provided 46,928,459(-) G/A SYNONYMOUS_VARIANT
734596 Likely Benign: not provided 46,977,529(-) C/T SYNONYMOUS_VARIANT
737522 Likely Benign: not provided 46,965,129(-) G/C SYNONYMOUS_VARIANT
757568 Likely Benign: not provided 46,979,024(-) T/C INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for GABRA4 Gene

Structural Variations from Database of Genomic Variants (DGV) for GABRA4 Gene

Variant ID Type Subtype PubMed ID
nsv1161081 CNV duplication 26073780
nsv470031 CNV gain 18288195

Variation tolerance for GABRA4 Gene

Residual Variation Intolerance Score: 13% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.30; 90.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GABRA4 Gene

Human Gene Mutation Database (HGMD)
GABRA4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GABRA4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GABRA4 Gene

Disorders for GABRA4 Gene

MalaCards: The human disease database

(7) MalaCards diseases for GABRA4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
status epilepticus
  • grand mal status
autism
  • autistic disorder
restless legs syndrome
  • ekbom syndrome
essential tremor
  • tremor, hereditary essential, 1
alcohol dependence
  • alcoholism
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for GABRA4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with GABRA4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GABRA4 Gene

Publications for GABRA4 Gene

  1. Pathway-based association analysis of genome-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia. (PMID: 18334916) Inada T … Arinami T (Pharmacogenetics and genomics 2008) 3 23 41
  2. Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism. (PMID: 16080114) Ma DQ … Pericak-Vance MA (American journal of human genetics 2005) 3 23 41
  3. Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster. (PMID: 7607683) McLean PJ … Russek SJ (Genomics 1995) 2 3 4
  4. Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol? (PMID: 20602615) Ruaño G … Wu AH (Pharmacogenomics 2010) 3 41
  5. Association study of 182 candidate genes in anorexia nervosa. (PMID: 20468064) Pinheiro AP … Woodside DB (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 41

Products for GABRA4 Gene

  • Signalway Proteins for GABRA4

Sources for GABRA4 Gene