AMACR

Chr 5AR

alpha-methylacyl-CoA racemase

ENSG00000242110 UniProt: Q9UHK6 OMIM: 604489

The protein is a racemase that catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters, including pristanoyl-CoA and bile acid intermediates, which is necessary for their degradation by peroxisomal beta-oxidation. Mutations cause autosomal recessive alpha-methylacyl-CoA racemase deficiency, presenting with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. The gene shows moderate tolerance to loss-of-function variation (LOEUF 0.747).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:10655068, PubMed:11060359, PubMed:11893780, PubMed:7649182). Acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), and arylpropionic acids like the anti-inflammatory drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but neither 3-methyl-branched nor linear-chain acyl-CoAs (PubMed:10655068, PubMed:11060359, PubMed:7649182)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Alpha-methylacyl-CoA racemase deficiencyMIM #614307

Bile acid synthesis defect, congenital, 4MIM #214950

UniProtCongenital bile acid synthesis defect 4

Clinical highlights

Gene-disease validity (ClinGen)

alpha-methylacyl-CoA racemase 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.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.75

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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