TIMM21
Chr 18translocase of inner mitochondrial membrane 21
Also known as: C18orf55, HSPC154, TIM21
The TIMM21 protein facilitates translocation of nuclear-encoded proteins across the mitochondrial inner membrane and is required for assembly of respiratory chain complexes I and IV as part of the MITRAC complex. Mutations cause autosomal recessive mitochondrial complex I deficiency with associated neurodegeneration, developmental delay, and multi-organ involvement. The gene shows relatively low constraint against loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
217 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 | 144 | 0 | 144 |
Likely Pathogenic | 0 | 0 | 6 | 0 | 6 |
VUS | 0 | 45 | 13 | 0 | 58 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 49 | 163 | 0 | 212 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TIMM21 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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 →No open access results found
External Resources
Links to major genomics databases and tools