KCNK16

Chr 6

potassium two pore domain channel subfamily K member 16

Also known as: K2p16.1, TALK-1, TALK1

NCBI Gene: 83795ENSG00000095981UniProt: Q96T55

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 expressed predominantly in the pancreas and is activated at alkaline pH. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

50
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KCNK16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 37 VUS of 50 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.42LOEUF
pLI 0.000
Z-score 0.68
OE 0.76 (0.43–1.42)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.91Z-score
OE missense 0.81 (0.70–0.93)
140 obs / 173.9 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.0.76 (0.43–1.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.70–0.93)
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.0.93
0≤1.21.6
LoF obs/exp: 7 / 9.2Missense obs/exp: 140 / 173.9Syn Z: 0.46

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS37
Likely Benign5
Benign2
6
Pathogenic
37
VUS
5
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
34
3
0
37
Likely Benign
0
2
2
1
5
Benign
0
1
1
0
2
Total03712150

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

View in ClinVar →

Protein Context — Lollipop Plot

KCNK16 · 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
Genetic Susceptibility Determines β-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76).
Carayol J et al.·Diabetes Care
2020Cohort
A KCNK16 mutation causing TALK-1 gain of function is associated with maturity-onset diabetes of the young.
Graff SM et al.·JCI Insight
2021
Genetic Variants in SDC3, KCNA2, KCNK1, KCNK16, and Heat Shock Transcription Factor-1 Genes: An Exploratory Analysis Supporting the Piezo2 Channelopathy Hypothesis in Amyotrophic Lateral Sclerosis Onset.
Sonkodi B et al.·Int J Mol Sci
2025
Osteopontin activates the diabetes-associated potassium channel TALK-1 in pancreatic β-cells.
Dickerson MT et al.·PLoS One
2017
Genetic screening of hypertensive patients with aldosterone hypersecretion under conditions of stress.
Mourtzi N et al.·Hormones (Athens)
2022Cohort
Genetics of type 2 diabetes and coronary artery disease and their associations with twelve cardiometabolic traits in the United Arab Emirates population.
Osman W et al.·Gene
2020
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