KCNK1

protein-coding

potassium two pore domain channel subfamily K member 1, the group of Potassium two pore domain channel subfamily K |MicroRNA protein coding host genes

Gene summary

This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The product of this gene has not been shown to be a functional channel, however, it may require other non-pore-forming proteins for activity. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002245.4

Inheritance

—

ClinVar variants

U:45B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr1:233,614,106-233,672,514

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~58.4 kb
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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCNK1 variants in ClinVar

1 Conditions Cataloged
not specifiedTotal: 46

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002245.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
0
missense
45
clinvar
1
clinvar
46
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00451046
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002245.4RefSeqNP_002236.13MANE Select
ENST00000366621.8EnsemblENSP00000355580.33MANE Select
ENST00000446915.1EnsemblENSP00000409626.13Standard
ENST00000918244.1EnsemblENSP00000588303.13Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
kcnk1bDanio rerio

Structure: post-vent region

Quality: increased curvature

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Antiarrhythmic Pathway, Pharmacodynamics
  • Disopyramide Action Pathway
  • Procainamide (Antiarrhythmic) Action Pathway
  • Phenytoin (Antiarrhythmic) Action Pathway
  • Fosphenytoin (Antiarrhythmic) Action Pathway

Biological Process

  • potassium ion transport
  • stabilization of membrane potential
  • response to nicotine
  • sodium ion transmembrane transport
  • regulation of resting membrane potential

Molecular Function

  • inward rectifier potassium channel activity
  • voltage-gated potassium channel activity
  • potassium channel activity
  • sodium channel activity
  • protein binding

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • voltage-gated potassium channel complex
  • integral component of membrane
  • apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000366621
Coding exons
3
Length
58509
Individuals with no LoFs
125739
Homozygous LoFs
0
Heterozygous LoFs
8
Defined
125747
p
0.0000318
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7221641920.8530.000009972169
Missense (PolyPhen)4472.3190.60841856
Synonymous-0.2239188.31.030.00000494692
Loss of Function1.78410.10.3964.27e-7123

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000460.000044rare
South Asian0.0000330.000033rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMed:15820677, PubMed:21653227). Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel is selective for K(+) ions at physiological potassium concentrations and at neutral pH, but becomes permeable to Na(+) at subphysiological K(+) levels and upon acidification of the extracellular medium (PubMed:21653227, PubMed:22431633). The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (PubMed:8605869, PubMed:8978667, PubMed:15820677, PubMed:21653227, PubMed:22431633, PubMed:23169818, PubMed:25001086). Channel activity is modulated by activation of serotonin receptors (By similarity). Heterodimeric channels containing KCNK1 and KCNK2 have much higher activity, and may represent the predominant form in astrocytes (By similarity). Heterodimeric channels containing KCNK1 and KCNK3 or KCNK9 have much higher activity (PubMed:23169818). Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane- sensitive currents (PubMed:23169818). Mediates outward rectifying potassium currents in dentate gyrus granule cells and contributes to the regulation of their resting membrane potential (By similarity). Contributes to the regulation of action potential firing in dentate gyrus granule cells and down-regulates their intrinsic excitability (By similarity). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (By similarity). Required for normal ion and water transport in the kidney (By similarity). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (By similarity). The low channel activity of homodimeric KCNK1 may be due to sumoylation (PubMed:15820677, PubMed:20498050, PubMed:23169818). The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (PubMed:19959478). {ECO:0000250|UniProtKB:O08581, ECO:0000250|UniProtKB:Q9Z2T2, ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:19959478, ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22282804, ECO:0000269|PubMed:22431633, ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:25001086, ECO:0000269|PubMed:8605869, ECO:0000269|PubMed:8978667}.;

Recessive Scores

pRec
0.148

Intolerance Scores

LoFtool
0.352
RVIS EVS
-0.27
RVIS percentile EVS
34.32

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.655

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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