KCNK6

protein-coding

potassium two pore domain channel subfamily K member 6, the group of Potassium two pore domain channel subfamily K

Gene summary

This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. This channel protein, considered an open rectifier, is widely expressed. It is stimulated by arachidonic acid, and inhibited by internal acidification and volatile anaesthetics. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004823.3

Inheritance

—

ClinVar variants

U:74B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr19:38,319,845-38,332,076

External References & Databases

Ensembl (ENSG00000099337)

Transcript & Mutation Effects

hg38 • Region Span ~12.2 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 KCNK6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004823.3. 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			3 clinvar	2 clinvar		5
missense			69 clinvar	3 clinvar		72
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	74	5	0	79

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004823.3	RefSeq	NP_004814.1	3	MANE Select
ENST00000263372.5	Ensembl	ENSP00000263372.2	3	MANE Select
ENST00000884216.1	Ensembl	ENSP00000554275.1	2	Standard
ENST00000884216.2	Ensembl	ENSP00000554275.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuronal System
Phase 4 - resting membrane potential
Cardiac conduction
Muscle contraction
Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK)

Biological Process

negative regulation of systemic arterial blood pressure
potassium ion transport
stabilization of membrane potential
regulation of ion transmembrane transport
regulation of resting membrane potential

Molecular Function

inward rectifier potassium channel activity
potassium channel activity
potassium ion leak channel activity

Cellular Component

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: ENST00000263372
Coding exons: 3
Length: 9177
Individuals with no LoFs: 125611
Homozygous LoFs: 0
Heterozygous LoFs: 105
Defined: 125716
p: 0.000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0263	183	184	0.995	0.0000114	1917
Missense (PolyPhen)		65	61.719	1.0532		688
Synonymous	-0.0421	94	93.5	1.01	0.00000638	740
Loss of Function	0.931	5	7.81	0.640	3.36e-7	84

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0029	0.0029	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00031	0.00030	rare
South Asian	0.00037	0.00036	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Exhibits outward rectification in a physiological K(+) gradient and mild inward rectification in symmetrical K(+) conditions.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.604
RVIS EVS: -0.11
RVIS percentile EVS: 45.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.241

Gene Damage Prediction

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