KCNK3

Chr 2

potassium two pore domain channel subfamily K member 3

Also known as: DDSA, K2p3.1, OAT1, PPH4, TASK, TASK-1, TASK1, TBAK1

NCBI Gene: 3777 ENSG00000171303 UniProt: O14649

This gene encodes a pH-sensitive potassium channel that conducts outward rectifying currents and is involved in regulating neuronal excitability, respiratory chemoreflexes, and vascular tone. Mutations cause autosomal dominant developmental delay with sleep apnea and primary pulmonary hypertension, affecting respiratory and cardiovascular systems. The gene has an associated GeneReviews entry indicating its clinical significance in pediatric practice.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the superfamily of potassium channel proteins that contain two pore-forming P domains. The encoded protein is an outwardly rectifying channel that is sensitive to changes in extracellular pH and is inhibited by extracellular acidification. Also referred to as an acid-sensitive potassium channel, it is activated by the anesthetics halothane and isoflurane. Although three transcripts are detected in northern blots, there is currently no sequence available to confirm transcript variants for this gene. [provided by RefSeq, Aug 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPulmonary hypertension, primary, 4

UniProtDevelopmental delay with sleep apnea

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · pulmonary arterial hypertension · AD · ClinGen 2021

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.40

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — KCNK3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.40LOEUF

pLI 0.900

Z-score 2.92

OE 0.08 (0.03–0.40)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.55Z-score

OE missense 0.39 (0.33–0.46)

103 obs / 266.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.40)

0≤0.351.4

Missense OE?0.39 (0.33–0.46)

0≤0.61.4

Synonymous OE?0.62

0≤1.21.6

LoF obs/exp: 1 / 11.8Missense obs/exp: 103 / 266.1Syn Z: 3.49

Background carrier burden — how many people carry a rare variant somewhere in KCNK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

436 rare PASS variants

Rare truncating (LoF)

1 in 18,000

28 rare PASS variants

Rare synonymous (reference)

1 in 260

295 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KCNK3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 220	1 in 34,000
South Asian	~43k	1 in 150	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 160	≈ 1 in 9,800
European (Finnish)	~27k	1 in 560	none seen
Admixed American	~22k	1 in 450	≈ 1 in 7,200
African / African American	~21k	1 in 170	≈ 1 in 8,300
East Asian	~20k	1 in 300	1 in 2,000
Ashkenazi Jewish	~13k	1 in 490	≈ 1 in 5,400
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓