KCTD4

Chr 13

potassium channel tetramerization domain containing 4

Also known as: bA321C24.3

NCBI Gene: 386618 ENSG00000180332 UniProt: Q8WVF5

The KCTD4 protein enables identical protein binding and is involved in protein homooligomerization. Mutations in this gene cause developmental and epileptic encephalopathy with movement abnormalities, which follows an autosomal recessive inheritance pattern. The gene shows tolerance to loss-of-function variants (pLI 0.003, LOEUF 1.21), consistent with the recessive disease mechanism.

ResearchSummary from RefSeq

Predicted to enable identical protein binding activity. Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.21

LOEUF

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?

1.21LOEUF

pLI 0.003

Z-score 1.16

OE 0.58 (0.30–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.78Z-score

OE missense 0.81 (0.69–0.95)

108 obs / 133.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.30–1.21)

0≤0.351.4

Missense OE?0.81 (0.69–0.95)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 5 / 8.7Missense obs/exp: 108 / 133.4Syn Z: -1.37

Background carrier burden — how many people carry a rare variant somewhere in KCTD4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

273 rare PASS variants

Rare truncating (LoF)

1 in 2,100

47 rare PASS variants

Rare synonymous (reference)

1 in 310

130 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KCTD4. 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 350	1 in 4,400
South Asian	~43k	1 in 280	1 in 6,100
Remaining (unassigned)	~30k	1 in 420	1 in 1,100
European (Finnish)	~27k	1 in 760	none seen
Admixed American	~22k	1 in 370	1 in 1,700
African / African American	~21k	1 in 400	1 in 2,400
East Asian	~20k	1 in 270	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 13,000	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 210	≈ 1 in 960

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