KCTD3

Chr 1

potassium channel tetramerization domain containing 3

Also known as: NY-REN-45

KCTD3 encodes an accessory subunit that regulates hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) by increasing its cell surface expression and current density. Mutations cause neuronal migration disorders and developmental delays with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants, indicating that complete loss of KCTD3 function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.41
Clinical SummaryKCTD3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.101
Z-score 4.63
OE 0.25 (0.160.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.76Z-score
OE missense 0.62 (0.560.69)
263 obs / 422.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.25 (0.160.41)
00.351.4
Missense OE0.62 (0.560.69)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 11 / 44.2Missense obs/exp: 263 / 422.5Syn Z: 1.37

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KCTD3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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