KCTD21

Chr 11

potassium channel tetramerization domain containing 21

Also known as: KCASH2

NCBI Gene: 283219 ENSG00000188997 UniProt: Q4G0X4 OMIM: 618790

Enables cullin family protein binding activity; histone deacetylase binding activity; and identical protein binding activity. Involved in negative regulation of smoothened signaling pathway and ubiquitin-dependent protein catabolic process. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.68

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.68LOEUF

pLI 0.003

Z-score 0.43

OE 0.79 (0.39–1.68)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.50Z-score

OE missense 0.89 (0.77–1.02)

138 obs / 155.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.39–1.68)

0≤0.351.4

Missense OE?0.89 (0.77–1.02)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 4 / 5.0Missense obs/exp: 138 / 155.7Syn Z: -0.28

Background carrier burden — how many people carry a rare variant somewhere in KCTD21?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

326 rare PASS variants

Rare truncating (LoF)

1 in 5,400

34 rare PASS variants

Rare synonymous (reference)

1 in 340

151 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KCTD21. 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 290	1 in 5,900
South Asian	~43k	1 in 140	1 in 2,100
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 7,500
European (Finnish)	~27k	1 in 360	1 in 4,400
Admixed American	~22k	1 in 280	≈ 1 in 5,600
African / African American	~21k	1 in 120	1 in 4,100
East Asian	~20k	1 in 190	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 420	none seen
Middle Eastern	~2,884	1 in 260	≈ 1 in 2,900

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.