Gabra4 gamma-aminobutyric acid (GABA) A receptor, subunit alpha 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Gabra4provided by MGI
Official Full Name: gamma-aminobutyric acid (GABA) A receptor, subunit alpha 4provided by MGI
Primary source: MGI:MGI:95616
See related: Ensembl:ENSMUSG00000029211 AllianceGenome:MGI:95616
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Gabra-4
Summary: Predicted to enable GABA-gated chloride ion channel activity; inhibitory extracellular ligand-gated ion channel activity; and transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential. Predicted to contribute to GABA-A receptor activity; benzodiazepine receptor activity; and chloride channel activity. Acts upstream of or within central nervous system development. Predicted to be located in postsynaptic membrane. Predicted to be integral component of membrane. Predicted to be part of GABA-A receptor complex. Predicted to be active in dendrite membrane and postsynapse. Predicted to be integral component of plasma membrane. Is expressed in several structures, including alimentary system; brain; eye; genitourinary system; and spinal cord. Human ortholog(s) of this gene implicated in autistic disorder. Orthologous to human GABRA4 (gamma-aminobutyric acid type A receptor subunit alpha4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in cortex adult (RPKM 12.0), frontal lobe adult (RPKM 10.2) and 5 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5; 5 C3.2

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (71727077..71815651, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (71569734..71658308, complement)

Chromosome 5 - NC_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

These data suggest that pubertal synaptic pruning requires alpha4betadelta GABA-A receptors.
Title: Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines.
Gabra4 KO CD4(+) cells produced increased cytokines.
Title: GABA(A) receptor α(4)-subunit knockout enhances lung inflammation and airway reactivity in a murine asthma model.
Rindings suggest that knock-out of the GABAR alpha4 subunit restores synaptic plasticity and spatial learning at puberty and is consistent with the concept that the dendritic alpha4betadelta GABARs which emerge at puberty selectively impair central nervous system plasticity.
Title: Role of α4-containing GABA(A) receptors in limiting synaptic plasticity and spatial learning of female mice during the pubertal period.
This study addressed the effects of AW on changes in the expression of Gabra4 and related genes that encode other subunits of GABAARs
Title: Downregulation of Gabra4 expression during alcohol withdrawal is mediated by specific microRNAs in cultured mouse cortical neurons.
The alpha4 subunit-containing GABA A-receptors are required for the low dose, locomotor stimulatory effect of anesthetics.
Title: GABAA-R α4 subunits are required for the low dose locomotor stimulatory effect of alphaxalone, but not for several other behavioral responses to alphaxalone, etomidate or propofol.
GABAA receptors in the mediodorsal thalamic nucleus (MD) modulate fear extinction.
Title: Extrasynaptic GABAA receptors in mediodorsal thalamic nucleus modulate fear extinction learning.
Increase in GABRA4 activity promotes hippocampal neurogenesis via nuclear factor of activated T cell (NFATc)4.
Title: Modulation of GABAA receptor signaling increases neurogenesis and suppresses anxiety through NFATc4.
This study demonistrated that alpha4-GABAARs contribute to nRT burst-mediated inhibition and that activity-dependent recruitment of eGABAARs dynamically influences the ventrobasal neuron tonic conductance during nRT tonic spike trains.
Title: Extrasynaptic GABA(A) receptors couple presynaptic activity to postsynaptic inhibition in the somatosensory thalamus.
alpha4 subunit expression strongly influences the pubertal increase of delta subunits at the plasma membrane, and that genetic deletion of alpha4 serves as a functional knock-down of delta-containing GABARs.
Title: Knockout of the γ-aminobutyric acid receptor subunit α4 reduces functional δ-containing extrasynaptic receptors in hippocampal pyramidal cells at the onset of puberty.
Data suggest that the availability of distinct GABA(A) R subtypes (Gabra2, -4, and Gabrd) provides a molecular mechanism endowing spatiotemporal specificity to GABAergic control of neuronal maturation in adult brain.
Title: Spatiotemporal specificity of GABAA receptor-mediated regulation of adult hippocampal neurogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (3) 1 citation
Endonuclease-mediated (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Gabra4 (e-PCR), detects polymorphism
- UniSTS:166217

Gabra4 (e-PCR), detects polymorphism
- UniSTS:525650

Gabra4 (e-PCR), detects polymorphism
- UniSTS:495990

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

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

Homology

Homologs of the Gabra4 gene: The Gabra4 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, and zebrafish.
Orthologs from Annotation Pipeline: 457 organisms have orthologs with human gene Gabra4
Orthologs

Gene Ontology Provided by MGI

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

Process	Evidence Code	Pubs
acts_upstream_of_or_within central nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chloride transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acts_upstream_of_or_within chloride transport	IEA Inferred from Electronic Annotation more info
involved_in chloride transport	IEA Inferred from Electronic Annotation more info
involved_in gamma-aminobutyric acid signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in nervous system process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of postsynaptic membrane potential	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in synaptic transmission, GABAergic	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
part_of GABA-A receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
is_active_in GABA-ergic synapse	ISO Inferred from Sequence Orthology 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	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in postsynapse	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
is_active_in postsynaptic specialization membrane	ISO Inferred from Sequence Orthology more info
is_active_in synapse	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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

Names: GABA(A) receptor subunit alpha-4

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.

mRNA and Protein(s)

NM_001359041.1 → NP_001345970.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 1 precursor

Status: VALIDATED

Description

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

Source sequence(s)

AC163437, AK139970

Consensus CDS

CCDS89927.1

UniProtKB/TrEMBL

Q3USX9

Related

ENSMUSP00000143675.2, ENSMUST00000199357.2

Conserved Domains (1) summary

cl27321
Location:13 → 565

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_001359043.1 → NP_001345972.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 3

Status: VALIDATED

Source sequence(s)

AC163437

Conserved Domains (1) summary

cl27321
Location:13 → 460

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_001359044.1 → NP_001345973.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 4 precursor

Status: VALIDATED

Source sequence(s)

AC163437
NM_001359045.1 → NP_001345974.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 5 precursor

Status: VALIDATED

Source sequence(s)

AC163437

Conserved Domains (1) summary

cl27321
Location:13 → 314

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_001359046.1 → NP_001345975.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 6 precursor

Status: VALIDATED

Source sequence(s)

AC163437

Conserved Domains (1) summary

cl27321
Location:13 → 288

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_001359047.1 → NP_001345976.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 7 precursor

Status: VALIDATED

Source sequence(s)

AC163437
NM_001359048.1 → NP_001345977.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 8 precursor

Status: VALIDATED

Source sequence(s)

AC163437

Conserved Domains (1) summary

cl27321
Location:13 → 296

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_001359050.1 → NP_001345979.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 9 precursor

Status: VALIDATED

Source sequence(s)

AC163437

Consensus CDS

CCDS89928.1

UniProtKB/TrEMBL

A0A0G2JDR1

Related

ENSMUSP00000142466.2, ENSMUST00000198138.2

Conserved Domains (1) summary

cl27321
Location:13 → 68

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_010251.2 → NP_034381.1 gamma-aminobutyric acid receptor subunit alpha-4 isoform 2 precursor

See identical proteins and their annotated locations for NP_034381.1

Status: VALIDATED

Source sequence(s)

AC114826, AK013727

Consensus CDS

CCDS39107.1

UniProtKB/Swiss-Prot

Q9D6F4

UniProtKB/TrEMBL

Q543Z0

Related

ENSMUSP00000031121.6, ENSMUST00000031121.10

Conserved Domains (3) summary

TIGR00860
Location:13 → 539

LIC; Cation transporter family protein

pfam02931
Location:49 → 256

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:263 → 536

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region