KCTD11

Chr 17

potassium channel tetramerization domain containing 11

Also known as: C17orf36, KCASH1, REN, REN/KCTD11

NCBI Gene: 147040 ENSG00000213859 UniProt: Q693B1 OMIM: 609848

KCTD11 encodes a protein that regulates neuronal differentiation and acts as a tumor suppressor by promoting apoptosis, growth arrest, and antagonizing the Hedgehog signaling pathway in cerebellar granule cells. Mutations cause autosomal dominant microcephaly, intellectual disability, and seizures with onset in infancy or early childhood. The gene shows tolerance to loss-of-function variants, suggesting that clinical phenotypes may result from complex mutational mechanisms.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Predicted to be involved in positive regulation of neuron differentiation. Predicted to act upstream of or within negative regulation of neuroblast proliferation; negative regulation of smoothened signaling pathway; and nervous system development. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.47

Clinical Summary— KCTD11

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 VUS of 35 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.47LOEUF

pLI 0.005

Z-score 0.79

OE 0.65 (0.32–1.47)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.23Z-score

OE missense 0.72 (0.62–0.85)

115 obs / 158.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.32–1.47)

0≤0.351.4

Missense OE?0.72 (0.62–0.85)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 4 / 6.1Missense obs/exp: 115 / 158.6Syn Z: 1.38

This gene — mechanism propensity

0.6452th %ile

GOF

0.6346th %ile

LOF

0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

35 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	34	34
Likely Benign	0	0
Benign	1	1
Total	35	35

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap KCTD11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →