AMACR

Chr 5AR

alpha-methylacyl-CoA racemase

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).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.752 OMIM phenotypes
Clinical SummaryAMACR
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Gene-Disease Validity (ClinGen)
alpha-methylacyl-CoA racemase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.75LOEUF
pLI 0.027
Z-score 2.24
OE 0.36 (0.180.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.56Z-score
OE missense 0.90 (0.801.01)
207 obs / 230.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.180.75)
00.351.4
Missense OE0.90 (0.801.01)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 5 / 14.1Missense obs/exp: 207 / 230.8Syn Z: 1.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAMACR-related alpha-methylacyl-CoA racemase deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7036th %ile
GOF
0.5954th %ile
LOF
0.2680th %ile

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AMACR · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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