HADH
Chr 4ARhydroxyacyl-CoA dehydrogenase
Also known as: HAD, HADH1, HADHSC, HCDH, HHF4, MSCHAD, SCHAD
The protein catalyzes the third step of mitochondrial fatty acid beta-oxidation, specifically oxidizing medium and short-chain 3-hydroxy fatty acyl-CoAs, and also inhibits glutamate dehydrogenase to help regulate insulin secretion. Mutations cause 3-hydroxyacyl-CoA dehydrogenase deficiency and familial hyperinsulinemic hypoglycemia type 4, inherited in an autosomal recessive pattern. The gene shows extremely low constraint against loss-of-function variants (pLI 0.00007, LOEUF 0.998), indicating tolerance to complete protein loss.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
300 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 | 10 | 0 | 7 | 0 | 17 |
Likely Pathogenic | 13 | 1 | 1 | 0 | 15 |
VUS | 1 | 78 | 3 | 2 | 84 |
Likely Benign | 0 | 1 | 84 | 73 | 158 |
Benign | 0 | 0 | 19 | 0 | 19 |
Conflicting | — | 2 | |||
| Total | 24 | 80 | 114 | 75 | 295 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HADH · 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
External Resources
Links to major genomics databases and tools