HADHA
Chr 2hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha
Also known as: ECHA, GBP, LCEH, LCHAD, MLCL AT, MTPA, TP-ALPHA
This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. Mutations in this gene result in trifunctional protein deficiency or LCHAD deficiency. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. [provided by RefSeq, Jul 2008]
Definitive — sufficient evidence for diagnostic panels
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene — mechanism propensity
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
1213 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 | 78 | 1 | 12 | 0 | 91 |
Likely Pathogenic | 136 | 20 | 4 | 0 | 160 |
VUS | 4 | 232 | 41 | 11 | 288 |
Likely Benign | 0 | 6 | 262 | 293 | 561 |
Benign | 0 | 2 | 49 | 1 | 52 |
Conflicting | — | 40 | |||
| Total | 218 | 261 | 368 | 305 | 1,192 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →16 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap HADHA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
HADHA · 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