Human Gene GABRA4 (uc021xnz.1)
  Description: Homo sapiens gamma-aminobutyric acid (GABA) A receptor, alpha 4 (GABRA4), transcript variant 2, mRNA.
RefSeq Summary (NM_001204266): 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].
Transcript (Including UTRs)
   Position: hg19 chr4:46,920,917-46,995,522 Size: 74,606 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg19 chr4:46,930,242-46,995,452 Size: 65,211 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:46,920,917-46,995,522)mRNA (may differ from genome)Protein (535 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
H-INVHGNCHPRDHuman Cortex Gene ExpressionLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GBRA4_HUMAN
DESCRIPTION: RecName: Full=Gamma-aminobutyric acid receptor subunit alpha-4; AltName: Full=GABA(A) receptor subunit alpha-4; Flags: Precursor;
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.
SUBUNIT: Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.
SUBCELLULAR LOCATION: Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.
INDUCTION: The alpha4 beta2 gamma 2L receptor is not repressed by diazepam.
SIMILARITY: 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.
WEB RESOURCE: Name=Protein Spotlight; Note=Forbidden fruit - Issue 56 of March 2005; URL="http://web.expasy.org/spotlight/back_issues/sptlt056.shtml";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GABRA4
CDC HuGE Published Literature: GABRA4
Positive Disease Associations: Iron
Related Studies:
  1. Iron
    , , . [PubMed 0]

-  MalaCards Disease Associations
  MalaCards Gene Search: GABRA4
Diseases sorted by gene-association score: status epilepticus (6), autism spectrum disorder (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.08 RPKM in Brain - Nucleus accumbens (basal ganglia)
Total median expression: 38.36 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -20.4070-0.291 Picture PostScript Text
3' UTR -2270.479325-0.243 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006028 - GABAA_rcpt
IPR001390 - GABAAa_rcpt
IPR005434 - GABBAa4_rcpt
IPR006202 - Neur_chan_lig-bd
IPR006201 - Neur_channel
IPR006029 - Neurotrans-gated_channel_TM
IPR018000 - Neurotransmitter_ion_chnl_CS

Pfam Domains:
PF02931 - Neurotransmitter-gated ion-channel ligand binding domain
PF02932 - Neurotransmitter-gated ion-channel transmembrane region

SCOP Domains:
63712 - Nicotinic receptor ligand binding domain-like
90112 - Neurotransmitter-gated ion-channel transmembrane pore

ModBase Predicted Comparative 3D Structure on P48169
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004888 transmembrane signaling receptor activity
GO:0004890 GABA-A receptor activity
GO:0005216 ion channel activity
GO:0005230 extracellular ligand-gated ion channel activity
GO:0005254 chloride channel activity
GO:0008503 benzodiazepine receptor activity

Biological Process:
GO:0006811 ion transport
GO:0006821 chloride transport
GO:0007214 gamma-aminobutyric acid signaling pathway
GO:0007417 central nervous system development
GO:0034220 ion transmembrane transport
GO:1902476 chloride transmembrane transport
GO:2001023 regulation of response to drug

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030054 cell junction
GO:0034707 chloride channel complex
GO:0045202 synapse
GO:0045211 postsynaptic membrane
GO:1902711 GABA-A receptor complex


-  Descriptions from all associated GenBank mRNAs
  BC036474 - Homo sapiens gamma-aminobutyric acid (GABA) A receptor, alpha 4, mRNA (cDNA clone IMAGE:5259163).
BC042117 - Homo sapiens gamma-aminobutyric acid (GABA) A receptor, alpha 4, mRNA (cDNA clone IMAGE:4794716).
AF238869 - Homo sapiens clone GLSH-2 similar to gliadin mRNA sequence.
BC037926 - Homo sapiens gamma-aminobutyric acid (GABA) A receptor, alpha 4, mRNA (cDNA clone IMAGE:5284531).
JD559607 - Sequence 540631 from Patent EP1572962.
JD294882 - Sequence 275906 from Patent EP1572962.
JD506785 - Sequence 487809 from Patent EP1572962.
JD084533 - Sequence 65557 from Patent EP1572962.
JD241130 - Sequence 222154 from Patent EP1572962.
JD091759 - Sequence 72783 from Patent EP1572962.
JD358861 - Sequence 339885 from Patent EP1572962.
JD359712 - Sequence 340736 from Patent EP1572962.
JD163587 - Sequence 144611 from Patent EP1572962.
JD566743 - Sequence 547767 from Patent EP1572962.
JD374690 - Sequence 355714 from Patent EP1572962.
JD327811 - Sequence 308835 from Patent EP1572962.
JD503663 - Sequence 484687 from Patent EP1572962.
JD367866 - Sequence 348890 from Patent EP1572962.
JD181830 - Sequence 162854 from Patent EP1572962.
JD378138 - Sequence 359162 from Patent EP1572962.
JD292865 - Sequence 273889 from Patent EP1572962.
JD139533 - Sequence 120557 from Patent EP1572962.
JD227498 - Sequence 208522 from Patent EP1572962.
JD562812 - Sequence 543836 from Patent EP1572962.
JD236208 - Sequence 217232 from Patent EP1572962.
JD092958 - Sequence 73982 from Patent EP1572962.
JD428724 - Sequence 409748 from Patent EP1572962.
JD313211 - Sequence 294235 from Patent EP1572962.
JD326071 - Sequence 307095 from Patent EP1572962.
JD552908 - Sequence 533932 from Patent EP1572962.
JD563816 - Sequence 544840 from Patent EP1572962.
JD039357 - Sequence 20381 from Patent EP1572962.
JD550105 - Sequence 531129 from Patent EP1572962.
JD093216 - Sequence 74240 from Patent EP1572962.
JD422576 - Sequence 403600 from Patent EP1572962.
JD237739 - Sequence 218763 from Patent EP1572962.
JD243065 - Sequence 224089 from Patent EP1572962.
JD298482 - Sequence 279506 from Patent EP1572962.
JD226053 - Sequence 207077 from Patent EP1572962.
JD063735 - Sequence 44759 from Patent EP1572962.
JD433702 - Sequence 414726 from Patent EP1572962.
JD071801 - Sequence 52825 from Patent EP1572962.
JD516315 - Sequence 497339 from Patent EP1572962.
JD083051 - Sequence 64075 from Patent EP1572962.
JD315742 - Sequence 296766 from Patent EP1572962.
JD302834 - Sequence 283858 from Patent EP1572962.
JD315547 - Sequence 296571 from Patent EP1572962.
JD559768 - Sequence 540792 from Patent EP1572962.
JD285977 - Sequence 267001 from Patent EP1572962.
JD326072 - Sequence 307096 from Patent EP1572962.
JD301020 - Sequence 282044 from Patent EP1572962.
JD235134 - Sequence 216158 from Patent EP1572962.
JD235131 - Sequence 216155 from Patent EP1572962.
JD101381 - Sequence 82405 from Patent EP1572962.
JD506723 - Sequence 487747 from Patent EP1572962.
JD551102 - Sequence 532126 from Patent EP1572962.
JD552920 - Sequence 533944 from Patent EP1572962.
BC035055 - Homo sapiens gamma-aminobutyric acid (GABA) A receptor, alpha 4, mRNA (cDNA clone MGC:41866 IMAGE:5259426), complete cds.
JD047070 - Sequence 28094 from Patent EP1572962.
JD164749 - Sequence 145773 from Patent EP1572962.
JD359463 - Sequence 340487 from Patent EP1572962.
AK090780 - Homo sapiens cDNA FLJ33461 fis, clone BRAMY2000946, highly similar to Gamma-aminobutyric-acid receptor alpha-4 subunit precursor.
U30461 - Human GABAA receptor subunit alpha4 mRNA, complete cds.
DQ891679 - Synthetic construct clone IMAGE:100004309; FLH179217.01X; RZPDo839E01130D gamma-aminobutyric acid (GABA) A receptor, alpha 4 (GABRA4) gene, encodes complete protein.
KJ896846 - Synthetic construct Homo sapiens clone ccsbBroadEn_06240 GABRA4 gene, encodes complete protein.
DQ894864 - Synthetic construct Homo sapiens clone IMAGE:100009324; FLH179213.01L; RZPDo839E01129D gamma-aminobutyric acid (GABA) A receptor, alpha 4 (GABRA4) gene, encodes complete protein.
EU176605 - Synthetic construct Homo sapiens clone IMAGE:100011576; FLH263603.01L; RZPDo839F04254D gamma-aminobutyric acid (GABA) A receptor, alpha 4 (GABRA4) gene, encodes complete protein.
KJ534840 - Homo sapiens clone GABRA4_iso-A_adult-A01 gamma-aminobutyric acid A receptor alpha 4 isoform A (GABRA4) mRNA, partial cds, alternatively spliced.
KJ535037 - Homo sapiens clone GABRA4_iso-B_fetal-F04 gamma-aminobutyric acid A receptor alpha 4 isoform B (GABRA4) mRNA, complete cds, alternatively spliced.
CU690038 - Synthetic construct Homo sapiens gateway clone IMAGE:100019854 5' read GABRA4 mRNA.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction

BioCarta from NCI Cancer Genome Anatomy Project
h_flumazenilPathway - Cardiac Protection Against ROS
h_gabaPathway - Gamma-aminobutyric Acid Receptor Life Cycle

Reactome (by CSHL, EBI, and GO)

Protein P48169 (Reactome details) participates in the following event(s):

R-HSA-8856398 NPTN binds GABA A receptors
R-HSA-975340 GABR heteropentamers:GABA transport Cl- from extracellular region to cytosol
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315 Transmission across Chemical Synapses
R-HSA-977441 GABA A receptor activation
R-HSA-112316 Neuronal System
R-HSA-977443 GABA receptor activation

-  Other Names for This Gene
  Alternate Gene Symbols: GBRA4_HUMAN, NM_001204266, NP_001191195, P48169, Q8IYR7
UCSC ID: uc021xnz.1
RefSeq Accession: NM_001204266
Protein: P48169 (aka GBRA4_HUMAN or GAA4_HUMAN)
CCDS: CCDS3473.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001204266.1
exon count: 9CDS single in 3' UTR: no RNA size: 11017
ORF size: 1608CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3411.00frame shift in genome: no % Coverage: 99.87
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.