KCNJ3 potassium inwardly rectifying channel subfamily J member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNJ3provided by HGNC
Official Full Name: potassium inwardly rectifying channel subfamily J member 3provided by HGNC
Primary source: HGNC:HGNC:6264
See related: Ensembl:ENSG00000162989 MIM:601534; AllianceGenome:HGNC:6264
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
Also known as: KGA; GIRK1; KIR3.1
Summary: Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex that also couples to neurotransmitter receptors in the brain and whereby channel activation can inhibit action potential firing by hyperpolarizing the plasma membrane. These multimeric G-protein-gated inwardly-rectifying potassium (GIRK) channels may play a role in the pathophysiology of epilepsy, addiction, Down's syndrome, ataxia, and Parkinson's disease. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, May 2012]
Expression: Biased expression in brain (RPKM 10.3), heart (RPKM 5.7) and 8 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q24.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (154698695..154858354)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (155151671..155311378)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (155555207..155714866)

Chromosome 2 - NC_000002.12 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: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

GIRK1 triggers multiple cancer-related pathways in the benign mammary epithelial cell line MCF10A.
Title: GIRK1 triggers multiple cancer-related pathways in the benign mammary epithelial cell line MCF10A.
A constricted opening in Kir channels does not impede potassium conduction.
Title: A constricted opening in Kir channels does not impede potassium conduction.
Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation.
Title: Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation.
Gi/o-coupled muscarinic receptors co-localize with GIRK channel for efficient channel activation
Title: Gi/o-coupled muscarinic receptors co-localize with GIRK channel for efficient channel activation.
these data suggest that patients with estrogen receptor positive breast cancer might be stratified into high risk and low risk groups based on the KCNJ3 levels in the tumor
Title: KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients.
Results clearly corroborate that overexpression of GIRK1 protein exerts profound effects on wound healing, chemoinvasion and cellular motility in the MCF-7 breast cancer cell line suggesting a role to promote invasion and metastasis.
Title: Overexpression of KCNJ3 gene splice variants affects vital parameters of the malignant breast cancer cell line MCF-7 in an opposing manner.
GIRK1/GIRK4 hetero-tetramers are not activated by Na+, but rather are in a permanent state of high responsiveness to G proteins beta-gamma, suggesting that the GIRK1 subunit functions like a GIRK4 subunit with Na+ permanently bound.
Title: The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers.
The findings of this study suggest that variations in KCNJ3 genes are associated with both mild and severe persistent breast pain after breast cancer surgery.
Title: Variations in potassium channel genes are associated with distinct trajectories of persistent breast pain after breast cancer surgery.
For KCNJ3 rs7574878, individuals who were heterozygous or homozygous for the rare G allele (TT versus TG+ GG) had a 48% reduction in the odds of reporting preoperative breast pain.
Title: Variations in potassium channel genes are associated with breast pain in women prior to breast cancer surgery.
we show that Kir3.1, in the absence of trafficking partner subunits, can exit the endoplasmic reticulum (ER) and reach the Golgi (though not the plasma membrane)
Title: A novel, radiolabel-free pulse chase strategy to study Kir3 channel ontogeny.

Submit: New GeneRIF Correction See all GeneRIFs (24)

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
GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region. 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

D10S275 (e-PCR)
- UniSTS:147992

D8S2279 (e-PCR)
- UniSTS:473907

SGC31664 (e-PCR)
- UniSTS:6983

GDB:375307 (e-PCR)
- UniSTS:157022

D11S3114 (e-PCR)
- UniSTS:152207

KCNJ3_340 (e-PCR)
- UniSTS:277424

D2S2105E (e-PCR)
- UniSTS:154034

SHGC-106069 (e-PCR)
- UniSTS:169656

D2S2106E (e-PCR)
- UniSTS:154043

SHGC-31309 (e-PCR)
- UniSTS:74182

RH70622 (e-PCR)
- UniSTS:50635

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G-protein activated inward rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to inward rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-4,5-bisphosphate binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
enables voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization	IC Inferred by Curator more info	PubMed
enables voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization	IC Inferred by Curator more info	PubMed

Process	Evidence Code	Pubs
involved_in membrane repolarization during atrial cardiac muscle cell action potential	IC Inferred by Curator more info	PubMed
involved_in membrane repolarization during ventricular cardiac muscle cell action potential	IEA Inferred from Electronic Annotation more info
involved_in potassium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion transmembrane transport	NAS Non-traceable Author Statement more info	PubMed
involved_in potassium ion transport	TAS Traceable Author Statement more info	PubMed
involved_in regulation of heart rate by cardiac conduction	IC Inferred by Curator more info	PubMed
involved_in regulation of monoatomic ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in response to electrical stimulus	IEA Inferred from Electronic Annotation more info
involved_in ventricular cardiac muscle cell membrane repolarization	IC Inferred by Curator more info	PubMed

Component	Evidence Code	Pubs
part_of I(KACh) inward rectifier potassium channel complex	ISO Inferred from Sequence Orthology more info
located_in T-tubule	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in parallel fiber to Purkinje cell synapse	IEA Inferred from Electronic Annotation 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
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info
part_of voltage-gated potassium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: G protein-activated inward rectifier potassium channel 1

Names: GIRK-1; inward rectifier K(+) channel Kir3.1; inward rectifier K+ channel KIR3.1; potassium channel, inwardly rectifying subfamily J member 3; potassium voltage-gated channel subfamily J member 3

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_001260508.2 → NP_001247437.1 G protein-activated inward rectifier potassium channel 1 isoform 2

See identical proteins and their annotated locations for NP_001247437.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region, compared to variant 1. This difference results in a frameshift and a protein (isoform 2; also known as GIRK1d) with a truncated C-terminus, compared to isoform 1.

Source sequence(s)

AC093633, AK293824, U50964

Consensus CDS

CCDS58733.1

UniProtKB/Swiss-Prot

P48549

Related

ENSP00000438410.1, ENST00000544049.2

Conserved Domains (2) summary

pfam01007
Location:47 → 187

IRK; Inward rectifier potassium channel

pfam17655
Location:194 → 234

IRK_C; Inward rectifier potassium channel C-terminal domain
NM_001260509.2 → NP_001247438.1 G protein-activated inward rectifier potassium channel 1 isoform 3

See identical proteins and their annotated locations for NP_001247438.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks the 3' terminal exon and uses an alternate splice site in the upstream coding region, compared to variant 1. These differences result in a protein (isoform 3; also known as GIRK1c) with a truncated and novel C-terminus, compared to isoform 1.

Source sequence(s)

GU068048, U50964

UniProtKB/TrEMBL

D2X9V0

Conserved Domains (1) summary

cl21560
Location:47 → 307

Ion_trans_2; Ion channel
NM_001260510.2 → NP_001247439.1 G protein-activated inward rectifier potassium channel 1 isoform 4

See identical proteins and their annotated locations for NP_001247439.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks multiple 3' terminal exons and contains an additional coding segment, compared to variant 1. These differences result in a protein (isoform 4; also known as GIRK1e) with a truncated and novel C-terminus, compared to isoform 1.

Source sequence(s)

GU074516, U50964

UniProtKB/TrEMBL

D2XBF0

Conserved Domains (1) summary

cl21560
Location:47 → 234

Ion_trans_2; Ion channel
NM_002239.4 → NP_002230.1 G protein-activated inward rectifier potassium channel 1 isoform 1

See identical proteins and their annotated locations for NP_002230.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1; also known as GIRK1a).

Source sequence(s)

AC093633, U50964

Consensus CDS

CCDS2200.1

UniProtKB/Swiss-Prot

B4DEW7, P48549, Q8TBI0

Related

ENSP00000295101.2, ENST00000295101.3

Conserved Domains (2) summary

pfam01007
Location:47 → 187

IRK; Inward rectifier potassium channel

pfam17655
Location:194 → 364

IRK_C; Inward rectifier potassium channel C-terminal domain