TTC39C

Chr 18

tetratricopeptide repeat domain 39C

Also known as: C18orf17, HsT2697

NCBI Gene: 125488ENSG00000168234UniProt: Q8N584

The TTC39C protein is predicted to be involved in cilium assembly and otolith morphogenesis. Mutations in this gene have not been definitively associated with human disease. The gene shows relatively low constraint against loss-of-function variants, suggesting it may be more tolerant to complete loss of function.

Summary from RefSeq
Research Assistant →
0
Active trials
4
Pubs (1 yr)
37
P/LP submissions
0%
P/LP missense
0.58
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— TTC39C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 68 VUS of 125 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.000
Z-score 3.47
OE 0.36 (0.23–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.43Z-score
OE missense 0.77 (0.69–0.85)
226 obs / 295.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.23–0.58)
0≤0.351.4
Missense OE0.77 (0.69–0.85)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 12 / 33.8Missense obs/exp: 226 / 295.1Syn Z: 0.61
DN
0.6454th %ile
GOF
0.6735th %ile
LOF
0.3164th %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

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic1
VUS68
34
Pathogenic
1
Likely Pathogenic
68
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
1
0
1
VUS
0
62
6
0
68
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total062410103

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

View in ClinVar →

Protein Context — Lollipop Plot

TTC39C · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Integrative causal inference illuminates gene-environment interactions linking endocrine disruptors to female infertility.
Hong Y et al.·Ecotoxicol Environ Saf
2025
Whole genome and transcriptome analyses in dairy goats identify genetic markers associated with high milk yield.
Zhao J et al.·Int J Biol Macromol
2024
Development and validation of a diagnostic machine learning model for gastric cancer risk based on double-negative T cell-related features
Yin Z et al.·Cancer Cell Int
2026Functional
Genome-wide association study of growth and reproductive traits based on low-coverage whole-genome sequencing in a Chubao black-head goat population.
Shangguan A et al.·Gene
2024
Development of a Prognostic Alternative Splicing Signature Associated With Tumor Microenvironment Immune Profiles in Lung Adenocarcinoma
Bao G et al.·Front Oncol
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients