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UniProtKB/Swiss-Prot O00754: Variant p.Cys501Ser

Lysosomal alpha-mannosidase
Gene: MAN2B1
Chromosomal location: 19cen-q13.1
Variant information

Variant position:  501
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Cysteine (C) to Serine (S) at position 501 (C501S, p.Cys501Ser).
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 medium size and polar (C) to small size and polar (S)
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:  Mannosidosis, alpha B, lysosomal (MANSA) [MIM:248500]: A lysosomal storage disease characterized by accumulation of unbranched oligosaccharide chains. This accumulation is expressed histologically as cytoplasmic vacuolation predominantly in the CNS and parenchymatous organs. Depending on the clinical findings at the age of onset, a severe infantile (type I) and a mild juvenile (type II) form of alpha-mannosidosis are recognized. There is considerable variation in the clinical expression with mental retardation, recurrent infections, impaired hearing and Hurler-like skeletal changes being the most consistent abnormalities. {ECO:0000269|PubMed:12718372, ECO:0000269|PubMed:15712269, ECO:0000269|PubMed:22161967, ECO:0000269|PubMed:9158146, ECO:0000269|PubMed:9758606, ECO:0000269|PubMed:9915946}. 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 MANSA; reduced enzyme activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  501
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1011
The length of the canonical sequence.

Location on the sequence:   ARLRGFKDHFTFCQQLNISI  C PLSQTAARFQVIVYNPLGRK
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                         ARLRGFKDHFTFCQQLNISICPLSQTAARFQVIVYNPLGRK

Mouse                         ARLSHYKQNFSFCRELNISICPVSQTSERFQVTLYNPLGRK

Bovine                        AHLSGLKEDFAFCRKLNISICPLTQTAERFQVIVYNPLGRK

Cat                           ARLSGSKEDFTYCRNLNVSVCPLSQTAKNFQVTIYNPLGRK

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 50 – 1011 Lysosomal alpha-mannosidase
Chain 430 – 601 Lysosomal alpha-mannosidase C peptide
Glycosylation 497 – 497 N-linked (GlcNAc...) asparagine
Disulfide bond 493 – 501


Literature citations

Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.
Riise Stensland H.M.; Klenow H.B.; Van Nguyen L.; Hansen G.M.; Malm D.; Nilssen O.;
Hum. Mutat. 33:511-520(2012)
Cited for: VARIANTS MANSA PHE-55; GLU-74; PRO-95; HIS-99; ASN-159; ARG-197; ASN-200; LEU-200; PRO-202; TRP-229; LEU-263; LEU-318; 339-VAL--GLN-342 DEL; PRO-352; LEU-379; CYS-390; LYS-402; VAL-420; TYR-445; CYS-451; TYR-453; PHE-453; GLU-457; SER-501; PRO-565; ARG-745; ARG-800; TRP-800; HIS-ARG-815 INS; ARG-891; PRO-892; CYS-916; HIS-916; PRO-950; ARG-956 AND SER-1000; VARIANTS LEU-248; VAL-278; SER-282; ILE-312; GLN-337; SER-413; SER-481 AND LEU-669; CHARACTERIZATION OF VARIANTS MANSA PHE-55; GLU-74; PRO-95; HIS-99; ASN-159; ARG-197; ASN-200; LEU-200; PRO-202; TRP-229; LEU-263; LEU-318; PRO-352; LEU-379; CYS-390; LYS-402; VAL-420; TYR-445; CYS-451; TYR-453; PHE-453; GLU-457; SER-501; PRO-565; ARG-745; ARG-800; TRP-800; HIS-ARG-815 INS; ARG-891; PRO-892; CYS-916; HIS-916; PRO-950; ARG-956 AND SER-1000;

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.