HACD4
Chr 9AR3-hydroxyacyl-CoA dehydratase 4
Also known as: PTPLAD2
HACD4 encodes a very-long-chain 3-hydroxyacyl-CoA dehydratase that catalyzes the third step in the fatty acid elongation cycle within the endoplasmic reticulum, essential for producing very long-chain fatty acids used in membrane lipids and signaling molecules. Mutations cause congenital myopathy with excess autophagy, an autosomal recessive disorder presenting in infancy with muscle weakness and distinctive muscle biopsy findings of excessive autophagic vacuoles. The gene shows low constraint to loss-of-function variants, consistent with its recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HACD4 · 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