ECHDC3
Chr 10enoyl-CoA hydratase domain containing 3
The protein functions as an enoyl-CoA hydratase in mitochondrial fatty acid metabolism and positively regulates cellular response to insulin stimulus. Mutations cause autosomal recessive mitochondrial complex I deficiency with variable presentations including developmental delay, hypotonia, and metabolic acidosis. The gene is highly constrained against loss-of-function variants, indicating that biallelic mutations are typically required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
75 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 | 20 | 0 | 20 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 33 | 10 | 0 | 43 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 36 | 31 | 0 | 67 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ECHDC3 · 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 →External Resources
Links to major genomics databases and tools