CHCHD4
Chr 3coiled-coil-helix-coiled-coil-helix domain containing 4
Also known as: MIA40, TIMM40
The CHCHD4 protein functions as a central component of mitochondrial intermembrane space import machinery, serving as a chaperone that catalyzes disulfide bond formation in substrate proteins required for respiratory chain complex biogenesis. Mutations in CHCHD4 cause autosomal recessive mitochondrial complex IV deficiency, nuclear type 11, which presents as a severe mitochondrial respiratory chain disorder. This gene follows autosomal recessive inheritance and affects mitochondrial energy metabolism through impaired assembly of cytochrome c oxidase and other respiratory complexes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CHCHD4 · 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