AMACR

alpha-methylacyl-CoA racemase

Basic information

Region (hg38): 5:33986164-34008104

Links

ENSG00000242110 ∙ NCBI:23600 ∙ OMIM:604489 ∙ HGNC:451 ∙ Uniprot:Q9UHK6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital bile acid synthesis defect 4 (Supportive), mode of inheritance: AR
• alpha-methylacyl-CoA racemase deficiency (Definitive), mode of inheritance: AR
• alpha-methylacyl-CoA racemase deficiency (Strong), mode of inheritance: AR
• alpha-methylacyl-CoA racemase deficiency (Moderate), mode of inheritance: AR
• alpha-methylacyl-CoA racemase deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bile acid synthesis defect, congenital, 4; Alpha-methylacyl-CoA racemase deficiency	AR	Biochemical; Gastrointestinal; Hematologic	Individuals with Bile acid synthesis defect, congenital, 4 may present with manifestations of hepatic disease, and medical therapy (eg, with oral cholic acid, and Vitamin K for bleeding) has been reported as beneficial; In Alpha-methylacyl-CoA Racemase deficiency, early diagnosis may allow potentially benefical dietary/medical therapy (eg, restriction of dietary phytanic acid and pristanic acid)	Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	9584266; 10655068; 11473573; 12512044; 15249642; 18032455; 20821052; 21576695; 23286897

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AMACR gene.

• Alpha-methylacyl-CoA racemase deficiency (322 variants)
• not provided (73 variants)
• not specified (19 variants)
• Inborn genetic diseases (14 variants)
• Oculocutaneous albinism (9 variants)
• Congenital bile acid synthesis defect 4 (7 variants)
• AMACR-related condition (4 variants)
• Congenital bile acid synthesis defect 4;Alpha-methylacyl-CoA racemase deficiency (4 variants)
• Spastic ataxia (1 variants)
• Alpha-methylacyl-CoA racemase deficiency;Congenital bile acid synthesis defect 4 (1 variants)
• Mitochondrial complex I deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMACR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	40		43
missense		1	161	10	8	180
nonsense			6	1		7
start loss			1			1
frameshift			6			6
inframe indel			2			2
splice donor/acceptor (+/-2bp)			2			2
splice region			10	6		16
non coding			25	42	12	79
Total	0	1	206	93	20

Variants in AMACR

This is a list of pathogenic ClinVar variants found in the AMACR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-33987000-T-C		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987005-T-A		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 12, 2018)
5-33987049-G-T		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 12, 2018)
5-33987108-C-T		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987132-C-T		Alpha-methylacyl-CoA racemase deficiency • Oculocutaneous albinism	Likely benign (Jun 14, 2016)
5-33987148-T-C		Alpha-methylacyl-CoA racemase deficiency	Likely benign (Jun 14, 2016)
5-33987151-G-A		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987162-C-G		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 12, 2018)
5-33987165-A-G		Alpha-methylacyl-CoA racemase deficiency	Likely benign (Jan 13, 2018)
5-33987218-G-A		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 12, 2018)
5-33987231-G-A		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987240-C-T		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987241-G-A		Alpha-methylacyl-CoA racemase deficiency	Benign (Jan 12, 2018)
5-33987289-C-A		Alpha-methylacyl-CoA racemase deficiency	Likely benign (Jun 14, 2016)
5-33987329-T-G		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987366-C-A		Alpha-methylacyl-CoA racemase deficiency	Benign (Jan 13, 2018)
5-33987450-A-G		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987471-A-G		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jun 14, 2016)
5-33987533-C-T		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 12, 2018)
5-33987726-A-G		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987727-T-C		Alpha-methylacyl-CoA racemase deficiency	Likely benign (Jan 13, 2018)
5-33987740-C-T		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)
5-33987890-T-C		Alpha-methylacyl-CoA racemase deficiency	Likely benign (Jan 12, 2018)
5-33987912-C-T		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 12, 2018)
5-33987915-C-T		Alpha-methylacyl-CoA racemase deficiency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMACR	protein_coding	protein_coding	ENST00000382085	6	21938

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0274	0.962	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.557	207	231	0.897	0.0000121	2539
Missense in Polyphen		66	73.939	0.89263		820
Synonymous	1.17	75	89.1	0.842	0.00000485	791
Loss of Function	2.24	5	14.1	0.355	6.59e-7	173

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000243	0.000242
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000801	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.0000334	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Racemization of 2-methyl-branched fatty acid CoA esters. Responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers.
• Disease: DISEASE: Alpha-methylacyl-CoA racemase deficiency (AMACRD) [MIM:614307]: A rare autosomal recessive peroxisomal disorder characterized by elevated plasma concentrations of pristanic acid C27-bile-acid intermediates, and adult onset of variable neurodegenerative symptoms affecting the central and peripheral nervous systems. Features may include seizures, visual failure, sensorimotor neuropathy, spasticity, migraine, and white matter hyperintensities on brain imaging. {ECO:0000269|PubMed:10655068}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Congenital bile acid synthesis defect 4 (CBAS4) [MIM:214950]: A disorder characterized by the presence of trihydroxycoprostanic acid in the bile and absence of cholic acid. Patients manifest neonatal jaundice, intrahepatic cholestasis and bile duct deficiency. {ECO:0000269|PubMed:10655068, ECO:0000269|PubMed:12512044}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Peroxisome - Homo sapiens (human);Primary bile acid biosynthesis - Homo sapiens (human);Ibuprofen Pathway, Pharmacokinetics;27-Hydroxylase Deficiency;Bile Acid Biosynthesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Metabolism of lipids;Metabolism of proteins;Tyrosine metabolism;Beta-oxidation of pristanoyl-CoA;Trihydroxycoprostanoyl-CoA beta-oxidation;Peroxisomal lipid metabolism;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts via 24-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Peroxisomal protein import;Fatty acid metabolism;Metabolism of steroids;Dimethyl-branched-chain fatty acid mitochondrial beta-oxidation;Phytanic acid peroxisomal oxidation;Vitamin E metabolism;bile acid biosynthesis, neutral pathway (Consensus)

Recessive Scores

• pRec: 0.314

Intolerance Scores

• loftool: 0.661
• rvis_EVS: 1.42
• rvis_percentile_EVS: 94.89

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.255

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.315

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: Amacr
• Phenotype: liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: protein targeting to peroxisome;bile acid biosynthetic process;bile acid metabolic process;fatty acid beta-oxidation using acyl-CoA oxidase
• Cellular component: cytoplasm;mitochondrion;peroxisome;peroxisomal matrix;cytosol;plasma membrane;intracellular membrane-bounded organelle
• Molecular function: signaling receptor binding;alpha-methylacyl-CoA racemase activity