KCTD18

Chr 2

potassium channel tetramerization domain containing 18

Also known as: 6530404F10Rik

NCBI Gene: 130535 ENSG00000155729 UniProt: Q6PI47

The KCTD18 protein is predicted to enable identical protein binding and participate in ion transport across cell membranes and protein complex formation. Mutations cause neurodevelopmental disorders with intellectual disability and seizures, inherited in an autosomal recessive pattern. This gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance where both copies must be affected to cause disease.

ResearchSummary from RefSeq

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

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.42

Clinical Summary— KCTD18

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

73 VUS of 105 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.41

OE 0.88 (0.56–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.37Z-score

OE missense 0.94 (0.84–1.04)

251 obs / 268.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.56–1.42)

0≤0.351.4

Missense OE?0.94 (0.84–1.04)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 12 / 13.6Missense obs/exp: 251 / 268.1Syn Z: 0.00

This gene — mechanism propensity

0.6161th %ile

GOF

0.5661th %ile

LOF

0.4529th %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

105 submitted variants in ClinVar

ClinVar

Classification Summary

VUS73

Likely Benign11

Benign11

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	73	0	73
Likely Benign	0	5	6	11
Benign	1	7	3	11
Total	1	85	9	95

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap KCTD18 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →