UniProtKB/SwissProt variant VAR

Variant information

Variant position:

72

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 Histidine (H) to Leucine (L) at position 72 (H72L, p.His72Leu).

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 (H) to medium size and hydrophobic (L)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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; type II.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs387906261 [ dbSNP | Ensembl ]

Sequence information

Variant position:

72

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:

YETCPTVQPNMLNVHLLPHT H DDVGWLKTVDQYFYGIKNDI

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                         YETCPTVQPNMLNVHLLPHTHDDVGWLKTVDQYFYGIKNDI

Mouse                         YKTCPPTKPGMLNVHLLPHTHDDVGWLKTVDQYYYGILSDV

Bovine                        YKTCPKVKPDMLNVHLVPHTHDDVGWLKTVDQYFYGIYNNI

Cat                           YETCPMVHPDMLNVHLVAHTHDDVGWLKTVDQYFYGIHNDV

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.

Type	Positions	Description
Chain	50 – 1011	Lysosomal alpha-mannosidase
Chain	50 – 345	Lysosomal alpha-mannosidase A peptide
Metal binding	72 – 72	Zinc
Metal binding	74 – 74	Zinc
Disulfide bond	55 – 358

Literature citations

Alpha-mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected siblings.
Nilssen O.; Berg T.; Riise H.M.F.; Ramachandran U.; Evjen G.; Hansen G.M.; Malm D.; Tranebjaerg L.; Tollersrud O.-K.;
Hum. Mol. Genet. 6:717-726(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); PARTIAL PROTEIN SEQUENCE; VARIANT MANSA LEU-72;

Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.
Gotoda Y.; Wakamatsu N.; Kawai H.; Nishida Y.; Matsumoto T.;
Am. J. Hum. Genet. 63:1015-1024(1998)
Cited for: VARIANTS MANSA LEU-72; ARG-356 AND TRP-750;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O00754: Variant p.His72Leu