KCTD13

Chr 16

potassium channel tetramerization domain containing 13

Also known as: BACURD1, FKSG86, PDIP1, POLDIP1, hBACURD1

NCBI Gene: 253980 ENSG00000174943 UniProt: Q8WZ19

The protein functions as a substrate-specific adapter in a BCR E3 ubiquitin ligase complex that degrades RHOA to regulate the actin cytoskeleton and promote synaptic transmission. Mutations cause neurodevelopmental disorders including intellectual disability, autism spectrum disorder, and developmental delay, typically with autosomal dominant inheritance. This gene is not highly constrained against loss-of-function variants, suggesting that both loss and gain of function may contribute to pathogenicity in different contexts.

ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity and small GTPase binding activity. Contributes to ubiquitin-protein transferase activity. Involved in several processes, including negative regulation of Rho protein signal transduction; proteasome-mediated ubiquitin-dependent protein catabolic process; and stress fiber assembly. Located in nuclear body. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.95

Clinical Summary— KCTD13

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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

42 VUS of 56 total submissions

Explore recent and relevant literature in Research Assistant →

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?

0.95LOEUF

pLI 0.001

Z-score 1.71

OE 0.51 (0.29–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.92Z-score

OE missense 0.63 (0.55–0.73)

138 obs / 217.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.29–0.95)

0≤0.351.4

Missense OE?0.63 (0.55–0.73)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 7 / 13.9Missense obs/exp: 138 / 217.7Syn Z: 0.52

This gene — mechanism propensity

0.6745th %ile

GOF

0.6150th %ile

LOF

0.3745th %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

56 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	41	0	0	42
Likely Benign	0	0	1	2	3
Benign	0	0	0	0	0
Total	1	41	1	2	45

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

View in ClinVar →

282 pathogenic / likely-pathogenic (of 303) ClinVar copy-number / structural variants overlap KCTD13 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →