KCTD17

Chr 22AD

potassium channel tetramerization domain containing 17

NCBI Gene: 79734ENSG00000100379UniProt: Q8N5Z5

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]

Primary Disease Associations & Inheritance

Dystonia 26, myoclonicMIM #616398
AD
210
ClinVar variants
22
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— KCTD17
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 86 VUS of 210 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.81LOEUF
pLI 0.018
Z-score 2.04
OE 0.39 (0.20–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.58Z-score
OE missense 0.64 (0.54–0.76)
99 obs / 154.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.20–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.54–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 5 / 12.9Missense obs/exp: 99 / 154.3Syn Z: -0.13

ClinVar Variant Classifications

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS86
Likely Benign79
Benign18
Conflicting5
20
Pathogenic
2
Likely Pathogenic
86
VUS
79
Likely Benign
18
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
17
0
20
Likely Pathogenic
1
0
1
0
2
VUS
1
72
12
1
86
Likely Benign
0
7
39
33
79
Benign
0
2
13
3
18
Conflicting
—5
Total4828237210

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

View in ClinVar →

Protein Context — Lollipop Plot

KCTD17 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dystonia 26, myoclonic

MIM #616398

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KCTD17-mediated Ras stabilization promotes hepatocellular carcinoma progression.
Jung YH et al.·Clin Mol Hepatol
2024
Combined dystonias: clinical and genetic updates.
Weissbach A et al.·J Neural Transm (Vienna)
2021Review
Routine Diagnostics Confirm Novel Neurodevelopmental Disorders.
Jauss RT et al.·Genes (Basel)
2022
KCTD17-related myoclonus-dystonia syndrome: clinical and electrophysiological findings of a patient with atypical late onset.
Todisco M et al.·Parkinsonism Relat Disord
2020Case report
Genetic Dystonias: Update on Classification and New Genetic Discoveries.
Keller Sarmiento IJ et al.·Curr Neurol Neurosci Rep
2021Review
A missense mutation in KCTD17 causes autosomal dominant myoclonus-dystonia.
Mencacci NE et al.·Am J Hum Genet
2015Case report
Novel Dystonia Genes: Clues on Disease Mechanisms and the Complexities of High-Throughput Sequencing.
Domingo A et al.·Mov Disord
2016Review
Childhood onset myoclonus-dystonia associated with a novel KCTD17 variant in an Indian patient.
Garg D et al.·Parkinsonism Relat Disord
2023
Rare functional missense variants in CACNA1H: What can we learn from Writer's cramp?
Huang M et al.·Mol Brain
2021Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools