UniProtKB/SwissProt variant VAR

Variant information

Variant position:

241

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 Aspartate (D) to Asparagine (N) at position 241 (D241N, p.Asp241Asn).

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 acidic (D) to medium size and polar (N)

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:

Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) [MIM:607944]: A disease characterized by vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone. {ECO:0000269|PubMed:21217752, ECO:0000269|PubMed:21217755}. Note=The disease is caused by mutations affecting the gene represented in this entry. ACP5 inactivating mutations result in a functional excess of phosphorylated osteopontin causing deregulation of osteopontin signaling and consequential autoimmune disease.

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 SPENCDI.

Any additional useful information about the variant.

Sequence information

Variant position:

241

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

Protein sequence length:

325

The length of the canonical sequence.

Location on the sequence:

VKQLRPLLATYGVTAYLCGH D HNLQYLQDENGVGYVLSGAG

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                         VKQLRPLLATYGV----TAYLCGHDHNLQYLQDENGVGYVLSGAG-------------

Mouse                         VKNLRPLLATYGV----TAYLCGHDHNLQYLQDENGVGYVL

Rat                           VKNLRPLLAAYGV----TAYLCGHDHNLQYLQDENGVGYVL

Pig                           VKQLLPLLTTHKV----TAYLCGHDHNLQYLQDENGLGFVL

Rabbit                        VKKLQPLLVKYGV----TAYLCGHDHNLQYLQDENGVGYVL

Baker's yeast                 IKSVGSNLFNASVKLLKQSEIQDQKVWLSFTHDTDILNF-L

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	22 – 325	Tartrate-resistant acid phosphatase type 5
Metal binding	240 – 240	Iron 2
Metal binding	242 – 242	Iron 1
Beta strand	240 – 248

Literature citations

Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature.
Briggs T.A.; Rice G.I.; Daly S.; Urquhart J.; Gornall H.; Bader-Meunier B.; Baskar K.; Baskar S.; Baudouin V.; Beresford M.W.; Black G.C.; Dearman R.J.; de Zegher F.; Foster E.S.; Frances C.; Hayman A.R.; Hilton E.; Job-Deslandre C.; Kulkarni M.L.; Le Merrer M.; Linglart A.; Lovell S.C.; Maurer K.; Musset L.; Navarro V.; Picard C.; Puel A.; Rieux-Laucat F.; Roifman C.M.; Scholl-Burgi S.; Smith N.; Szynkiewicz M.; Wiedeman A.; Wouters C.; Zeef L.A.; Casanova J.L.; Elkon K.B.; Janckila A.; Lebon P.; Crow Y.J.;
Nat. Genet. 43:127-131(2011)
Cited for: VARIANTS SPENCDI ILE-89; ARG-215; ASN-241 AND LYS-264;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P13686: Variant p.Asp241Asn