HADHA Gene: Hydroxyacyl-CoA Dehydrogenase Trifunctional Multienzyme Complex Subunit Alpha
HADHA: A key mitochondrial enzyme in fatty acid beta-oxidation and its role in LCHAD deficiency and related disorders.
Gene Information Card
| Symbol | HADHA |
|---|---|
| Full Name | Hydroxyacyl-CoA Dehydrogenase Trifunctional Multienzyme Complex Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 2p23.3 |
| NCBI Gene ID | 3030 ncbi.nlm.nih.gov/gene/3030 |
| Ensembl ID | ENSG00000184730 |
| UniProt ID | P40939 |
| OMIM ID | 600890 |
| HGNC ID | 4801 |
| Aliases | LCHAD, MTPA, GBP, HADH, LCEH, ECHA |
Description
The HADHA gene encodes the alpha subunit of the mitochondrial trifunctional protein (MTP), which catalyzes the last three steps of long-chain fatty acid beta-oxidation. The alpha subunit possesses long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activities. Mutations in HADHA cause LCHAD deficiency and mitochondrial trifunctional protein deficiency, leading to impaired fatty acid oxidation, hypoglycemia, cardiomyopathy, and liver dysfunction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency | Loss-of-function mutations in HADHA impair the LCHAD activity of the alpha subunit, leading to accumulation of toxic long-chain 3-hydroxyacyl metabolites and energy deficiency during fasting. | ClinVar, OMIM |
| Mitochondrial trifunctional protein (MTP) deficiency | Biallelic mutations in HADHA disrupt the entire trifunctional protein complex, causing severe neonatal or infantile onset of cardiomyopathy, hypoglycemia, and early death. | ClinVar, OMIM |
| Acute fatty liver of pregnancy (AFLP) | Heterozygous HADHA mutations in the fetus can cause maternal liver dysfunction during pregnancy due to impaired fetal fatty acid oxidation. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 42.3 | High |
| Heart | 38.1 | High |
| Skeletal muscle | 35.7 | High |
| Kidney | 28.9 | Medium |
| Adipose tissue | 22.5 | Medium |
| Brain | 8.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 45.6 | High expression |
| HeLa (cervical) | 30.2 | Medium expression |
| K562 (leukemia) | 18.4 | Low expression |
| SH-SY5Y (neuroblastoma) | 12.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1528G>C (p.Glu510Gln) | Missense | Common in LCHAD deficiency | Reduces LCHAD enzyme activity |
| c.1678C>T (p.Arg560*) | Nonsense | Rare | Complete loss of alpha subunit function |
| c.209+1G>A | Splice site | Rare | Exon skipping, frameshift, protein truncation |
| c.274delC (p.Leu92Trpfs*12) | Frameshift | Rare | Loss of all enzymatic activities |
Mutation functional classification
Loss of Function (LOF)
Most HADHA mutations are loss-of-function, leading to reduced or absent LCHAD and hydratase activities, causing fatty acid oxidation defects.
Gain of Function (GOF)
No gain-of-function mutations are reported for HADHA.
Dominant Negative (DN)
Dominant-negative effects are not typical; disease is autosomal recessive, though heterozygous carriers may have mild biochemical abnormalities.
View complete mutation data：
Gene Ontology (GO)
| • 3-hydroxyacyl-CoA dehydrogenase activity (GO:0003854) | • enoyl-CoA hydratase activity (GO:0004300) |
| • fatty acid beta-oxidation (GO:0006635) | • mitochondrion (GO:0005739) |
| • acetyl-CoA C-acetyltransferase activity (GO:0003985) |
Pathways
• Fatty acid beta-oxidation (mitochondrial)
• Metabolic pathways
• PPAR signaling pathway
Protein Summary
The HADHA protein (UniProt P40939) is a 763-amino acid mitochondrial enzyme that forms a heterotetramer (alpha2beta2) with the HADHB subunit. The alpha subunit contains two catalytic domains: N-terminal enoyl-CoA hydratase and C-terminal 3-hydroxyacyl-CoA dehydrogenase. It is essential for the metabolism of long-chain fatty acids, providing energy during fasting and stress. Defects cause severe metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HADHA Knockout HEK293 Cell Line | EDJ-KQ2238 | Human | 3030 | Details Get a Quote |
| HADHA Knockout A-549 Cell Line | EDJ-KQ22530 | Human | 3030 | Details Get a Quote |
| HADHA Knockout HCT 116 Cell Line | EDJ-KQ22531 | Human | 3030 | Details Get a Quote |
| HADHA Knockout HeLa Cell Line | EDJ-KQ22532 | Human | 3030 | Details Get a Quote |
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