UniProtKB/Swiss-Prot Q9UHK6: Variant p.Ser52Pro

Alpha-methylacyl-CoA racemase
Gene: AMACR
Chromosomal location: 5p11-p13
Variant information

Variant position:  52
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Serine (S) to Proline (P) at position 52 (S52P, p.Ser52Pro).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from small size and polar (S) to medium size and hydrophobic (P)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In AMACRD and CBAS4; inactive enzyme.
Any additional useful information about the variant.



Sequence information

Variant position:  52
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  382
The length of the canonical sequence.

Location on the sequence:   VRVDRPGSRYDVSRLGRGKR  S LVLDLKQPRGAAVLRRLCKR
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         VRVDRPGSRYDVSRLGRGKRSLVLDLKQPRGAAVLRRLCKR

Mouse                         VRVNRLGSTGE-NFLARGKRSLALDLKRSQGVTVLRRMCAR

Rat                           VLVDRLGSVNHPSHLARGKRSLALDLKRSPGAAVLRRMCAR

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 2 – 382 Alpha-methylacyl-CoA racemase
Modified residue 58 – 58 N6-acetyllysine


Literature citations

Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy.
Ferdinandusse S.; Denis S.; Clayton P.T.; Graham A.; Rees J.E.; Allen J.T.; McLean B.N.; Brown A.Y.; Vreken P.; Waterham H.R.; Wanders R.J.A.;
Nat. Genet. 24:188-191(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT AMACRD PRO-52; VARIANT CBAS4 PRO-107; VARIANTS SER-201 AND LYS-277; CHARACTERIZATION OF VARIANT AMACRD PRO-52; CHARACTERIZATION OF VARIANT CBAS4 PRO-107;

Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy.
Setchell K.D.R.; Heubi J.E.; Bove K.E.; O'Connell N.C.; Brewsaugh T.; Steinberg S.J.; Moser A.; Squires R.H. Jr.;
Gastroenterology 124:217-232(2003)
Cited for: VARIANT CBAS4 PRO-52;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.