KCNK2

protein-coding

potassium two pore domain channel subfamily K member 2, the group of Potassium two pore domain channel subfamily K

Gene summary

This gene encodes one of the members of the two-pore-domain background potassium channel protein family. This type of potassium channel is formed by two homodimers that create a channel that leaks potassium out of the cell to control resting membrane potential. The channel can be opened, however, by certain anesthetics, membrane stretching, intracellular acidosis, and heat. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001017425.3

Inheritance

—

ClinVar variants

U:33B:1

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr1:215,005,775-215,237,090

External References & Databases

Ensembl (ENSG00000082482)

Transcript & Mutation Effects

hg38 • Region Span ~231.3 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 KCNK2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 27

not providedTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001017425.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			29 clinvar			29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	33	1	0	34

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001017425.3	RefSeq	NP_001017425.2	7	MANE Select
ENST00000444842.7	Ensembl	ENSP00000394033.2	7	MANE Select
NM_001017424.3	RefSeq	NP_001017424.1	7	Standard
NM_014217.4	RefSeq	NP_055032.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cortisol synthesis and secretion - Homo sapiens (human)
Cushing,s syndrome - Homo sapiens (human)
Gastric acid secretion - Homo sapiens (human)
Neuronal System
Phase 4 - resting membrane potential

Biological Process

cardiac ventricle development
G protein-coupled receptor signaling pathway
memory
response to mechanical stimulus
positive regulation of cell death

Molecular Function

outward rectifier potassium channel activity
potassium ion leak channel activity

Cellular Component

nucleus
endoplasmic reticulum membrane
plasma membrane
integral component of plasma membrane
voltage-gated potassium channel complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000444842
Coding exons: 7
Length: 231319
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125748
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.31	147	250	0.589	0.0000139	2752
Missense (PolyPhen)		46	103.82	0.44307		1150
Synonymous	0.758	92	102	0.904	0.00000646	882
Loss of Function	2.54	6	17.5	0.343	8.24e-7	209

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ion channel that contributes to passive transmembrane potassium transport (PubMed:23169818). Reversibly converts between a voltage-insensitive potassium leak channel and a voltage- dependent outward rectifying potassium channel in a phosphorylation-dependent manner (PubMed:11319556). In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2. 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). {ECO:0000250|UniProtKB:P97438, ECO:0000269|PubMed:10784345, ECO:0000269|PubMed:11319556, ECO:0000269|PubMed:23169818}.;

Intolerance Scores

LoFtool: 0.480
RVIS EVS: -0.45
RVIS percentile EVS: 24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium