KCNK5

Chr 6

potassium two pore domain channel subfamily K member 5

Also known as: K2p5.1, KCNK5b, TASK-2, TASK2

NCBI Gene: 8645ENSG00000164626UniProt: O95279

This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The message for this gene is mainly expressed in the cortical distal tubules and collecting ducts of the kidney. The protein is highly sensitive to external pH and this, in combination with its expression pattern, suggests it may play an important role in renal potassium transport. [provided by RefSeq, Jul 2008]

74
ClinVar variants
6
Pathogenic / LP
0.33
pLI score
0
Active trials
Clinical Summary— KCNK5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 59 VUS of 74 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.325
Z-score 2.95
OE 0.23 (0.11–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.97Z-score
OE missense 0.68 (0.60–0.76)
203 obs / 298.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.23 (0.11–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.60–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 4 / 17.2Missense obs/exp: 203 / 298.6Syn Z: -0.28

ClinVar Variant Classifications

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS59
Likely Benign7
Benign2
6
Pathogenic
59
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
57
2
0
59
Likely Benign
0
3
1
3
7
Benign
0
2
0
0
2
Total0629374

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KCNK5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura.
Bjornsdottir G et al.·Nat Genet
2023Functional
Dominant-Negative Effect of a Missense Variant in the TASK-2 (KCNK5) K+ Channel Associated with Balkan Endemic Nephropathy.
Reed AP et al.·PLoS One
2016
Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5.
Gray AT et al.·Anesthesiology
2000
A SWI/SNF complex-related genes signature predicts prognosis and immune infiltration in ccRCC with KCNK5 as a novel biomarker.
Xu K et al.·Sci Rep
2025
In Silico Establishment and Validation of Novel Lipid Metabolism-Related Gene Signature in Bladder Cancer.
Sun X et al.·Oxid Med Cell Longev
2022
Genetic screening of hypertensive patients with aldosterone hypersecretion under conditions of stress.
Mourtzi N et al.·Hormones (Athens)
2022Cohort
Genetic, cellular, and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore.
Trofimenko E et al.·Elife
2021
A genome-wide screen for variants influencing certolizumab pegol response in a moderate to severe rheumatoid arthritis population.
White IR et al.·PLoS One
2022
Two-pore-domain potassium channels support anion secretion from human airway Calu-3 epithelial cells.
Davis KA et al.·Pflugers Arch
2006
Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants.
Winsvold BS et al.·PLoS One
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools