KCNJ2 potassium inwardly-rectifying channel, subfamily J, member 2 [Homo sapiens] - Gene

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Summary

Official Symbol: KCNJ2provided by HGNC
Official Full Name: potassium inwardly-rectifying channel, subfamily J, member 2provided by HGNC
Primary source: HGNC:6263
See related: Ensembl:ENSG00000123700; HPRD:02815; MIM:600681
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: IRK1; LQT7; SQT3; ATFB9; HHIRK1; KIR2.1; HHBIRK1
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, probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Mutations in this gene have been associated with Andersen syndrome, which is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 17q24.3

Sequence :: Chromosome: 17; NC_000017.10 (68165676..68176185)

See KCNJ2 in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

The C-terminal region is a vital motif of phosphatidylinositol-4,5-bisphosphate (PIP2) binding and channel trafficking, and defects in PIP2 binding have been reported to constitute a pathogenic mechanism in ATS.5
Title: KCNJ2 variant of unknown significance reclassified as long QT syndrome causing ventricular fibrillation.
bacterial Kir channels (KirBac1.1 and KirBac3.1) and human Kir2.1 are all inhibited by cholesterol, most likely by locking the channels into prolonged closed states, whereas the enantiomer, ent-cholesterol, does not inhibit these channels
Title: Enantioselective protein-sterol interactions mediate regulation of both prokaryotic and eukaryotic inward rectifier K+ channels by cholesterol.
tetrad complex shows the close association of the Kir2.1 cytoplasmic domains and the influence of PSD-95 mediated self-assembly on the clustering of these channels
Title: Self-directed assembly and clustering of the cytoplasmic domains of inwardly rectifying Kir2.1 potassium channels on association with PSD-95.
Data report a novel nonsense KCNJ2 mutation, S369X, in a patient with a prominent QU prolongation and mild Andersen-Tawil syndrome phenotype.
Title: A novel KCNJ2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil syndrome.
The identification of a trafficking signal in the tertiary structure of Kir2.1 reveals a quality control step that couples protein conformation to Golgi export and provides molecular insight into how mutations in Kir2.1 arrest the channels at the Golgi.
Title: Golgi export of the Kir2.1 channel is driven by a trafficking signal located within its tertiary structure.
hKir2.1 channels are down-regulated by protein tyrosine kinase inhibition.
Title: Genistein and tyrphostin AG556 inhibit inwardly-rectifying Kir2.1 channels expressed in HEK 293 cells via protein tyrosine kinase inhibition.
AMPK is a potent regulator of Kir2.1.
Title: Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase.
Data suggest that the regulation of K+ permeation by [K+]o as a new mechanism for the [K+]o-dependence of outward Kir2.1.
Title: Extracellular K+ elevates outward currents through Kir2.1 channels by increasing single-channel conductance.
A novel de novo KCNJ2 mutation associated with classic phenotypic features of Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry, is reported.
Title: Biophysical and molecular characterization of a novel de novo KCNJ2 mutation associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry.
Kir2.1 and Kir2.2 have two distinct lipid requirements for activity.
Title: Dual-mode phospholipid regulation of human inward rectifying potassium channels.

Submit: New GeneRIF Correction See all (61)

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Atrial fibrillation, familial, 9

MIM: 613980

Common variants at ten loci modulate the QT interval duration in the QTSCD Study.

Genome-wide association study reveals multiple loci associated with primary tooth development during infancy.

Andersen-Tawil syndrome (referred to as ATS in this entry) is characterized by a triad of episodic flaccid muscle weakness (i.e., periodic paralysis), ventricular arrhythmias and prolonged QT interval, and anomalies such as low-set ears, ocular hypertelorism, small mandible, fifth-digit clinodactyly, syndactyly, short stature, and scoliosis. Affected individuals present in the first or second decade with either cardiac symptoms (palpitations and/or syncope) or weakness that occurs spontaneously following prolonged rest or following rest after exertion. Mild permanent weakness is common. Mild learning difficulties and a distinct neurocognitive phenotype (i.e., deficits in executive function and abstract reasoning) have been described.

Diagnosis Testing

The diagnosis of ATS is suspected in an individual with characteristic clinical and ECG findings. KCNJ2, encoding the inward rectifier potassium channel 2 protein (Kir2.1), is the only gene known to be associated with ATS. Approximately 60% of individuals with ATS have a detectable mutation in KCNJ2. Such testing is clinically available. The presence of a pathogenic KCNJ2 mutation confirms the diagnosis.

Genetic Counseling

ATS is inherited in an autosomal dominant manner. At least 50% of individuals diagnosed with ATS have an affected parent. Up to 50% of cases are caused by de novo mutations. Each child of an individual with ATS has a 50% chance of inheriting the disorder. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutation has been identified in an affected family member.

References

PMID: 20301441

Short QT syndrome-3

MIM: 609622

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
P63252	P24588	AKAP5	HPRD	PubMed
P63252	O14936	CASK	HPRD	PubMed
P63252	Q12959	DLG1	HPRD	PubMed
P63252	Q15700	DLG2	HPRD	PubMed
P63252	Q92796	DLG3	HPRD	PubMed
P63252	P78352	DLG4	HPRD	PubMed
P63252	P21333	FLNA	HPRD	PubMed
P63252	Q14005	IL16	HPRD	PubMed
P63252	Q8NI35	INADL	HPRD	PubMed
P63252	Q14654	KCNJ11	HPRD	PubMed
P63252	Q9NPI9	KCNJ16	HPRD	PubMed
P63252	P48050	KCNJ4	HPRD	PubMed
P63252	Q15842	KCNJ8	HPRD	PubMed
P63252	O60296	TRAK2	HPRD	PubMed
BioGRID:109961	BioGRID:108083	DLG1	BioGRID	PubMed	Reconstituted Complex
BioGRID:109961	BioGRID:108086	DLG4	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:109961	BioGRID:109816	IL16	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:109961	BioGRID:122452	TRAK2	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid

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General gene information

Markers

RH48445 (e-PCR)
- UniSTS:48390

KCNJ2_1577 (e-PCR)
- UniSTS:277423

KCNJ2_v544 (e-PCR)
- UniSTS:277423

NoName (e-PCR)
- UniSTS:482479

KCNJ2 (e-PCR)
- UniSTS:480220

RH98566 (e-PCR)
- UniSTS:83965

Genotypes

See KCNJ2 SNP Geneview Report
See KCNJ2 SNP Genotype Report
See KCNJ2 SNP Variation Viewer Report

Homology

Homologs of the KCNJ2 gene: The KCNJ2 gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

Activation of G protein gated Potassium channels, organism-specific biosystem (from REACTOME)
Activation of G protein gated Potassium channels, organism-specific biosystemActivation of Kir 3 channels occurs after binding of G beta gamma subunits of GPCR. Activation of Kir3/GIRK leads to K+ efflux. The dissociation of GPCR into G alpha and G beta gamma subunits is acti...
Activation of GABAB receptors, organism-specific biosystem (from REACTOME)
Activation of GABAB receptors, organism-specific biosystemGABA B receptors are metabotropic receptors that are functionally linked to C type G protein coupled receptors.? GABA B receptors are activated upon ligand binding. The GABA B1 subunit binds ligand a...
Cholinergic synapse, organism-specific biosystem (from KEGG)
Cholinergic synapse, organism-specific biosystemAcetylcholine (ACh) is a neurotransmitter widely distributed in the central (and also peripheral, autonomic and enteric) nervous system (CNS). In the CNS, ACh facilitates many functions, such as lear...
Classical Kir channels, organism-specific biosystem (from REACTOME)
Classical Kir channels, organism-specific biosystemClassical Kir channels are inwardly rectifying K+ channels with strong inwardly rectifying currents that contribute to highly negative resting membrane potential, prolonged action potential plateau a...
G protein gated Potassium channels, organism-specific biosystem (from REACTOME)
G protein gated Potassium channels, organism-specific biosystemInwardly rectifying G protein activated K+ channels (GIRK) are tetrameric assemblies of Ki3 3 family subunits (Kir 3.1, 3.2 3.3 and 3.4). The activation of G protein coupled receptor by ligand result...
GABA B receptor activation, organism-specific biosystem (from REACTOME)
GABA B receptor activation, organism-specific biosystemFunctional GABA B receptors are heteromers of GABA B1 and B2 subunits, complexed with G protein alpha-i, 0, beta, and gamma subunits. They function as metabotropic receptors. When GABA is bound to th...
GABA receptor activation, organism-specific biosystem (from REACTOME)
GABA receptor activation, organism-specific biosystemGamma aminobutyric acid (GABA) receptors are the major inhibitory receptors in human synapses. They are of two types. GABA A receptors are fast-acting ligand gated chloride ion channels that mediate ...
Gastric acid secretion, organism-specific biosystem (from KEGG)
Gastric acid secretion, organism-specific biosystemGastric acid is a key factor in normal upper gastrointestinal functions, including protein digestion and calcium and iron absorption, as well as providing some protection against bacterial infections...
Gastric acid secretion, conserved biosystem (from KEGG)
Gastric acid secretion, conserved biosystemGastric acid is a key factor in normal upper gastrointestinal functions, including protein digestion and calcium and iron absorption, as well as providing some protection against bacterial infections...
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits, organism-specific biosystem (from REACTOME)
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits, organism-specific biosystemGABA B receptors are coupled to Gproteins and function by increasing the K+ and decreasing the Ca2+ inside the cell. The increase in K+ increases the negative membrane potential of the cell thereby h...
Inwardly rectifying K+ channels, organism-specific biosystem (from REACTOME)
Inwardly rectifying K+ channels, organism-specific biosystemInwardly rectifying K+ channels (Kir channels) show an inward rather than outward (like the voltage gated K+ channels) flow of K+ thereby contributing to maintenance of resting membrane potential an...
Neuronal System, organism-specific biosystem (from REACTOME)
Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell, organism-specific biosystem (from REACTOME)
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell, organism-specific biosystemThe neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein cou...
Potassium Channels, organism-specific biosystem (from REACTOME)
Potassium Channels, organism-specific biosystemPotassium channels are tetrameric ion channels that are widely distributed and are found in all cell types. Potassium channels control resting membrane potential in neurons, contribute to regulation ...
Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
inward rectifier potassium channel activity	TAS Traceable Author Statement more info
voltage-gated ion channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
ion transport	IEA Inferred from Electronic Annotation more info
potassium ion transport	IEA Inferred from Electronic Annotation more info
synaptic transmission	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

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General protein information

Preferred Names: inward rectifier potassium channel 2

Names: inward rectifier potassium channel 2; IRK-1; hIRK1; inward rectifier K+ channel KIR2.1; cardiac inward rectifier potassium channel

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NCBI Reference Sequences (RefSeq)

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

NG_008798.1 RefSeqGene

Range

5001..15510

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_328

mRNA and Protein(s)

NM_000891.2 → NP_000882.1 inward rectifier potassium channel 2

Status: REVIEWED

Source sequence(s)

AF153820

Consensus CDS

CCDS11688.1

UniProtKB/Swiss-Prot

P63252

Related

ENSP00000243457, ENST00000243457

Conserved Domains (2) summary

pfam08466
Location:1 – 47
Blast Score: 233

IRK_N; Inward rectifier potassium channel N-terminal

cl11596
Location:48 – 379
Blast Score: 1645

Ion_trans_2; Ion channel

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000017.10 Reference GRCh37.p5 Primary Assembly

Range

68165676..68176185

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

63551441..63561946

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC005242.1 (23519..34028)	None
genomic	AF153818.1 (9..175)	None
genomic	AF153819.1	AAF73242.1
genomic	CH471099.1	EAW89092.1
genomic	CS173015.1	CAJ33689.1
mRNA	AF011904.1	AAC39555.1
mRNA	AF021139.1	AAB88797.1
mRNA	AF153820.1	AAF73241.1
mRNA	U12507.1	AAC50072.1
mRNA	U16861.1	AAA91781.1
mRNA	U22413.1	AAA64282.1
mRNA	U24055.1	AAB50277.1
other-genetic	BC152811.1	AAI52812.1