TTC39A
Chr 1tetratricopeptide repeat domain 39A
Also known as: C1orf34, DEME-6
TTC39A encodes a protein located in the centrosome, a cellular structure critical for cell division and cilia formation. Mutations in this gene cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, affecting the nervous system and brain development. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
94 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 5 | 0 | 5 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 59 | 4 | 0 | 63 |
Likely Benign | 0 | 2 | 0 | 2 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 61 | 12 | 2 | 75 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TTC39A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools