TIMMDC1
Chr 3ARtranslocase of inner mitochondrial membrane domain containing 1
Also known as: C3orf1, MC1DN31
TIMMDC1 encodes a chaperone protein that assembles mitochondrial complex I (NADH:ubiquinone oxidoreductase), specifically participating in construction of the membrane arm of this respiratory chain complex. Mutations cause mitochondrial complex I deficiency, nuclear type 31, inherited in an autosomal recessive pattern. This gene shows minimal constraint against loss-of-function variants (very low pLI score), which is consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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
173 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 | 1 | 0 | 15 | 0 | 16 |
Likely Pathogenic | 6 | 1 | 0 | 0 | 7 |
VUS | 5 | 72 | 9 | 1 | 87 |
Likely Benign | 0 | 3 | 13 | 14 | 30 |
Benign | 0 | 3 | 7 | 2 | 12 |
Conflicting | — | 3 | |||
| Total | 12 | 79 | 44 | 17 | 155 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TIMMDC1 · 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