KCTD17

Chr 22AD

potassium channel tetramerization domain containing 17

NCBI Gene: 79734 ENSG00000100379 UniProt: Q8N5Z5 OMIM: 616386

This protein functions as a substrate adaptor for cullin3-based ubiquitin ligase and targets trichoplein for degradation during ciliogenesis. Mutations cause autosomal dominant myoclonic dystonia through a gain-of-function mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that belongs to a conserved family of potassium channel tetramerization domain (KCTD)-containing proteins. The encoded protein functions in ciliogenesis by acting as a substrate adaptor for the cullin3-based ubiquitin-conjugating enzyme E3 ligase, and targets trichoplein, a keratin-binding protein, for degradation via polyubiquitinylation. A mutation in this gene is associated with autosomal dominant myoclonic dystonia 26. [provided by RefSeq, Nov 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 0.811 OMIM phenotype

Clinical Summary— KCTD17

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 84 VUS of 199 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?

0.81LOEUF

pLI 0.018

Z-score 2.04

OE 0.39 (0.20–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.58Z-score

OE missense 0.64 (0.54–0.76)

99 obs / 154.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.20–0.81)

0≤0.351.4

Missense OE?0.64 (0.54–0.76)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 5 / 12.9Missense obs/exp: 99 / 154.3Syn Z: -0.13

This gene — mechanism propensity

0.6356th %ile

GOF

0.7125th %ile

LOF

0.3841th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

199 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic2

VUS84

Likely Benign79

Benign18

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	0	2
Likely Pathogenic	1	1	0	0	2
VUS	2	73	8	1	84
Likely Benign	1	7	39	32	79
Benign	0	2	13	3	18
Conflicting	—				4
Total	5	84	60	36	189

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap KCTD17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →