KCNK7

Chr 11

potassium two pore domain channel subfamily K member 7

Also known as: K2p7.1, TWIK3

NCBI Gene: 10089 ENSG00000173338 UniProt: Q9Y2U2

This protein is a probable potassium channel subunit that requires association with unknown partner proteins to reach the plasma membrane and function properly. Mutations cause autosomal recessive progressive myoclonus epilepsy with ataxia and sensorineural hearing loss. The gene shows no constraint against loss-of-function variants in the general population.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the superfamily of potassium channel proteins containing two pore-forming P domains. The product of this gene has not been shown to be a functional channel; however, it may require other non-pore-forming proteins for activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.67

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.67LOEUF

pLI 0.000

Z-score 0.19

OE 0.92 (0.52–1.67)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.99 (0.87–1.12)

168 obs / 170.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.52–1.67)

0≤0.351.4

Missense OE?0.99 (0.87–1.12)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 7 / 7.6Missense obs/exp: 168 / 170.3Syn Z: -0.71

Background carrier burden — how many people carry a rare variant somewhere in KCNK7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

458 rare PASS variants

Rare truncating (LoF)

1 in 1,000

85 rare PASS variants

Rare synonymous (reference)

1 in 170

220 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KCNK7. 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 1,600
South Asian	~43k	1 in 150	1 in 1,600
Remaining (unassigned)	~30k	1 in 130	1 in 670
European (Finnish)	~27k	1 in 530	1 in 760
Admixed American	~22k	1 in 110	1 in 960
African / African American	~21k	1 in 93	1 in 700
East Asian	~20k	1 in 120	1 in 800
Ashkenazi Jewish	~13k	1 in 1,500	≈ 1 in 3,000
Middle Eastern	~2,884	1 in 220	1 in 530

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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓