HADHA

Chr 2

hydroxyacyl-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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMitochondrial trifunctional protein deficiency 1
UniProtLong-chain 3-hydroxyl-CoA dehydrogenase deficiency
UniProtMaternal acute fatty liver of pregnancy

Clinical highlights

Gene-disease validity (ClinGen)
long chain 3-hydroxyacyl-CoA dehydrogenase deficiency · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
69
Pubs (1 yr)
P/LP submissions
P/LP missense
0.62
LOEUF
LOF
Mechanism· G2P
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GeneReview available — HADHA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.62LOEUF
pLI 0.000
Z-score 3.43
OE 0.41 (0.280.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.82Z-score
OE missense 0.88 (0.810.97)
355 obs / 401.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.41 (0.280.62)
00.351.4
Missense OE?0.88 (0.810.97)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 16 / 39.1Missense obs/exp: 355 / 401.3Syn Z: -0.58

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HADHA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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