KCNK10

protein-coding

potassium two pore domain channel subfamily K member 10, the group of Protein phosphatase 1 regulatory subunits|Potassium two pore domain channel subfamily K

Gene summary

The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

MANE transcript

NM_138317.3

Inheritance

—

ClinVar variants

U:67B:5

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr14:88,180,103-88,326,907

External References & Databases

Ensembl (ENSG00000100433)

Transcript & Mutation Effects

hg38 • Region Span ~146.8 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 KCNK10 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 2

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

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138317.3. 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			4 clinvar	3 clinvar		7
missense			62 clinvar	2 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	67	5	0	72

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138317.3	RefSeq	NP_612190.1	7	MANE Select
ENST00000319231.10	Ensembl	ENSP00000312811.5	7	MANE Select
NM_021161.5	RefSeq	NP_066984.1	7	Standard
NM_138318.3	RefSeq	NP_612191.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gastric acid secretion - Homo sapiens (human)
Ectoderm Differentiation
Neuronal System
Phase 4 - resting membrane potential
Cardiac conduction

Biological Process

signal transduction
memory
stabilization of membrane potential
regulation of ion transmembrane transport
potassium ion transmembrane transport

Molecular Function

voltage-gated ion channel activity
potassium channel activity
potassium ion leak channel activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000319231
Coding exons: 7
Length: 144139
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.32	273	342	0.799	0.0000220	3543
Missense (PolyPhen)		68	121.18	0.56115		1304
Synonymous	-0.970	157	142	1.10	0.00000995	1099
Loss of Function	2.69	8	21.4	0.373	0.00000115	244

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.0019	0.0019	notable
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Outward rectifying potassium channel. Produces rapidly activating and non-inactivating outward rectifier K(+) currents. Activated by arachidonic acid and other naturally occurring unsaturated free fatty acids.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.0713
RVIS EVS: -0.38
RVIS percentile EVS: 28.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0583

Gene Damage Prediction

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