Gene Function

Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway. The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through cycles of four consecutive reactions. Each beta-oxidation cycle shortens the fatty acyl-CoA by two carbons, yielding one acetyl-CoA (for the citric acid cycle), one FADH(2), and one NADH (which donate electrons to the respiratory chain for ATP production). These cycles repeat until the chain is fully degraded to acetyl-CoA units. Among the enzymes involved in this pathway, the trifunctional protein, responsible for the hydration, dehydrogenation, and thiolysis steps, shows specificity for long-chain fatty acids, such as those from dietary and stored fats. Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB described here bears the 3-ketoacyl-CoA thiolase activity. These activities have been experimentally confirmed on a few substrates derived from beta-oxidation of long-chain saturated fatty acids such as palmitate (hexadecanoate) and laurate (dodecanoate). In addition, based on its established catalytic mechanism, and combined genetic interaction or mutant phenotype evidence, it is predicted to act also on other substrates, including long-chain unsaturated fatty acids such as oleate (9Z-octadecenoate), linoleate (9Z,12Z-octadecadienoate), linolenate (9Z,12Z,15Z-octadecatrienoate), and others (Probable) Source: UniProt

Relationship to CMT

Unclassified AR
1 subtype
2p23.3

First described 2013
Mitochondrial involvement

Subtype	Inheritance	Class	OMIM	Sentinel Publication
SubtypeCMT-HADHB	Inheritanceautosomal recessive	ClassUnclassified Subtypes	OMIMn/a	Sentinel Publication A Compound Heterozygous Mutation in HADHB Gene Causes an Axonal Charcot-Marie-Tooth Disease 2013 · 10.1186/1471-2350-14-125

Stored Identifiers

No HGNC Aliases

hgnc_idHGNC:4803

ensembl_gene_idENSG00000138029

coords_grch38chr2:26243170-26290473

coords_grch37chr2:26466038-26513336

entrez_id3032

omim_gene143450

uniprot_idsP55084

refseq_accessionNM_000183

mane_refseqNM_000183.3

mane_ensemblENST00000317799.10

External recordsHGNC:4803OMIM 143450gnomADUniProt P55084ClinVar P/LPOrphanetMANE NM_000183.3

EvidencePanelApp Green

ClinVar Variants

Pathogenic and likely pathogenic variants in HADHB, as classified in ClinVar, are read live from NCBI. Only aggregate germline records are shown. Uncertain and conflicting classifications are not. Experts in CMT makes no claim to the accuracy of ClinVar data. This index is provided for informational purposes only.

Review stars are ClinVar’s measure of how well a classification is supported: four for a practice guideline, three for an expert panel review, two for agreement among multiple submitters, one for a single submitter with criteria provided, and none where no criteria were provided.

Reported in CMT

Reported in Other Diseases

Reported in a disease other than CMT. Listed apart rather than counted as CMT variants.

Variants w/o a Recorded Disease

Pathogenic or likely pathogenic in ClinVar, submitted without a disease recorded.

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