KCNK17

protein-coding

potassium two pore domain channel subfamily K member 17, the group of 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. This gene is activated at alkaline pH. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

MANE transcript

NM_031460.4

Inheritance

—

ClinVar variants

P:1U:56B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr6:39,299,001-39,314,461

External References & Databases

Ensembl (ENSG00000124780)

Transcript & Mutation Effects

hg38 • Region Span ~15.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

heart conduction diseaseLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0000992

Submitter: Genomics England PanelApp

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCNK17 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031460.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense		1 clinvar	53 clinvar	4 clinvar	1 clinvar	59
nonsense			1 clinvar			1
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	0	1	56	6	1	64

Highest pathogenic variant AF is 0.000029427638

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031460.4	RefSeq	NP_113648.2	5	MANE Select
ENST00000373231.9	Ensembl	ENSP00000362328.4	5	MANE Select
NM_001135111.2	RefSeq	NP_001128583.1	5	Standard
ENST00000453413.2	Ensembl	ENSP00000401271.2	5	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
TWIK-related alkaline pH activated K+ channel (TALK)

Biological Process

potassium ion transport
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: ENST00000373231
Coding exons: 5
Length: 15553
Individuals with no LoFs: 125643
Homozygous LoFs: 0
Heterozygous LoFs: 105
Defined: 125748
p: 0.000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.200	180	188	0.959	0.0000103	2118
Missense (PolyPhen)		58	62.086	0.93418		707
Synonymous	1.02	72	83.8	0.859	0.00000489	686
Loss of Function	0.453	9	10.6	0.850	5.41e-7	101

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0031	0.0031	notable
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00049	0.00049	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.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.911
RVIS EVS: -0.07
RVIS percentile EVS: 48.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0925

Gene Damage Prediction

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