AMACR: Alpha-Methylacyl-CoA Racemase
Key Enzyme in Bile Acid Synthesis and Peroxisomal Fatty Acid Metabolism; Implicated in Metabolic Disorders and Cancer
Gene Information Card
| Symbol | AMACR |
|---|---|
| Full Name | Alpha-Methylacyl-CoA Racemase |
| Gene Type | Protein coding |
| Chromosomal Location | 5p13.2-q11.1 |
| NCBI Gene ID | 23600 ncbi.nlm.nih.gov/gene/23600 |
| Ensembl ID | ENSG00000115414 |
| UniProt ID | Q9UHK6 |
| OMIM ID | 604489 |
| HGNC ID | 451 |
| Aliases | AMACRD, CBAS4, RACE |
Description
The AMACR gene encodes alpha-methylacyl-CoA racemase, a peroxisomal and mitochondrial enzyme that catalyzes the conversion of (R)-alpha-methyl-branched-chain fatty acyl-CoAs to their (S)-stereoisomers. This racemization is essential for the beta-oxidation of dietary branched-chain fatty acids (e.g., phytanic acid) and for bile acid synthesis from cholesterol intermediates. Mutations in AMACR cause a peroxisomal disorder characterized by adult-onset sensorimotor neuropathy and bile acid abnormalities. Overexpression of AMACR is a well-established biomarker for prostate cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alpha-methylacyl-CoA racemase deficiency (AMACR deficiency) | Loss-of-function mutations impair peroxisomal beta-oxidation of branched-chain fatty acids and bile acid intermediates, leading to accumulation of pristanic acid and C27-bile acid intermediates. | OMIM #614307; ClinVar |
| Prostate cancer | AMACR is consistently overexpressed in prostate adenocarcinoma compared to benign tissue, likely due to altered fatty acid metabolism in cancer cells. | NCBI Gene; COSMIC; multiple studies |
| Colorectal cancer | Elevated AMACR expression has been reported in colorectal adenocarcinomas, suggesting a role in cancer metabolism. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Prostate | 7.1 | Medium |
| Small intestine | 6.9 | Medium |
| Heart | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LNCaP (prostate cancer) | 15.2 | High expression; used as biomarker |
| PC-3 (prostate cancer) | 10.8 | Moderate expression |
| HepG2 (liver cancer) | 9.5 | Moderate expression |
| MCF7 (breast cancer) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.154T>C (p.Ser52Pro) | Missense | Rare | Loss of function; associated with AMACR deficiency |
| c.359C>T (p.Thr120Met) | Missense | Rare | Loss of function; associated with AMACR deficiency |
| c.682C>T (p.Arg228Trp) | Missense | Rare | Loss of function; associated with AMACR deficiency |
| c.875A>G (p.Tyr292Cys) | Missense | Rare | Loss of function; associated with AMACR deficiency |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Ser52Pro, p.Thr120Met) reduce or abolish enzyme activity, leading to accumulation of branched-chain fatty acids and bile acid intermediates, causing AMACR deficiency.
Gain of Function (GOF)
Not reported; AMACR overexpression in cancer is due to transcriptional upregulation, not activating mutations.
Dominant Negative (DN)
Not reported; AMACR deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0008111 - alpha-methylacyl-CoA racemase activity | • GO:0005777 - peroxisome |
| • GO:0005739 - mitochondrion | • GO:0006635 - fatty acid beta-oxidation |
| • GO:0008206 - bile acid metabolic process |
Pathways
• Peroxisomal beta-oxidation of branched-chain fatty acids
• Bile acid biosynthesis (classic and alternative pathways)
Protein Summary
Alpha-methylacyl-CoA racemase (AMACR) is a 42 kDa enzyme localized to peroxisomes and mitochondria. It catalyzes the racemization of (R)-alpha-methylacyl-CoAs to their (S)-forms, a prerequisite for beta-oxidation of branched-chain fatty acids such as phytanic and pristanic acid, and for the conversion of dihydroxycholestanoic acid (DHCA) and trihydroxycholestanoic acid (THCA) to their CoA esters for bile acid synthesis. The protein is highly expressed in liver, kidney, and prostate. AMACR is a clinically useful immunohistochemical marker for prostate cancer, where it is consistently overexpressed.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AMACR Knockout HEK293 Cell Line | EDJ-KQ51120 | Human | 23600 | Details Get a Quote |
| AMACR Knockout HeLa Cell Line | EDJ-KQ55779 | Human | 23600 | Details Get a Quote |
| AMACR Knockout A-549 Cell Line | EDJ-KQ64274 | Human | 23600 | Details Get a Quote |
| AMACR Knockout HCT 116 Cell Line | EDJ-KQ72720 | Human | 23600 | Details Get a Quote |
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