HADH

Protein identityUniProt · HPA

UniProt accession

Q16836

Gene

HADH

Ensembl

ENSG00000138796

Chromosome

4

Canonical length

314 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene is a member of the 3-hydroxyacyl-CoA dehydrogenase gene family. The encoded protein functions in the mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the beta-oxidation pathway. Its enzymatic activity is highest with medium-chain-length fatty acids. Mutations in this gene cause one form of familial hyperinsulinemic hypoglycemia. The human genome contains a related pseudogene of this gene on chromosome 15. [provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

314 residues, UniProt reviewed canonical sequence.

>Q16836|HADH
     1  MAFVTRQFMR SVSSSSTASA SAKKIIVKHV TVIGGGLMGA GIAQVAAATG HTVVLVDQTE
    61  DILAKSKKGI EESLRKVAKK KFAENLKAGD EFVEKTLSTI ATSTDAASVV HSTDLVVEAI
   121  VENLKVKNEL FKRLDKFAAE HTIFASNTSS LQITSIANAT TRQDRFAGLH FFNPVPVMKL
   181  VEVIKTPMTS QKTFESLVDF SKALGKHPVS CKDTPGFIVN RLLVPYLMEA IRLYERGDAS
   241  KEDIDTAMKL GAGYPMGPFE LLDYVGLDTT KFIVDGWHEM DAENPLHQPS PSLNKLVAEN
   301  KFGKKTGEGF YKYK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HADH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

262 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HADH.

Disease | AllUniProt

Conditions HADH is implicated in, by any mechanism.

• 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency (HADH deficiency) MIM:231530
• Hyperinsulinemic hypoglycemia, familial, 4 (HHF4) MIM:609975

Disease | GeneticClinVar

33 pathogenic / likely-pathogenic of 390 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Deficiency of 3-hydroxyacyl-CoA dehydrogenase
• Hyperinsulinemic hypoglycemia, familial, 4
• Hyperinsulinemic hypoglycemia
• Familial hyperinsulinism

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1

gnomAD pLI

0

gnomAD missense Z

0.53

DepMap mean gene effect

-0.1

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell differentiation
• fatty acid beta-oxidation
• negative regulation of insulin secretion
• positive regulation of cold-induced thermogenesis
• regulation of insulin secretion
• response to activity
• response to insulin
• response to xenobiotic stimulus
• spermatogenesis

Molecular functions

• (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
• identical protein binding
• NAD+ binding
• transferase activity

Cellular components

• cytoplasm
• mitochondrial matrix
• mitochondrion
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• 3-hydroxyacyl-CoA dehydrogenase, C-terminal
• 3-hydroxyacyl-CoA dehydrogenase, NAD binding
• 3-hydroxyacyl-CoA dehydrogenase, conserved site
• 6-phosphogluconate dehydrogenase-like, C-terminal domain superfamily
• 6-phosphogluconate dehydrogenase, domain 2
• 3-hydroxyacyl-CoA dehydrogenase
• NAD(P)-binding domain superfamily
• 3-hydroxyacyl-CoA dehydrogenase, C-terminal domain
• 3-hydroxyacyl-CoA dehydrogenase, NAD binding domain
• Mitochondrial 3-hydroxyacyl-CoA dehydrogenase

KeywordsUniProt

• Acetylation
• Differentiation
• Fatty acid metabolism
• Hydroxylation
• Lipid metabolism
• Mitochondrion
• NAD
• Oxidoreductase
• Spermatogenesis
• Transferase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of HADH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GLUD1