UniProtKB/SwissProt variant VAR

Variant information

Variant position:

383

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 Arginine (R) to Histidine (H) at position 383 (R383H, p.Arg383His).

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 large size and basic (R) to medium size and polar (H)

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

BLOSUM score:

0

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:

Mucopolysaccharidosis 1S (MPS1S) [MIM:607016]: A mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding. {ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:25256405, ECO:0000269|PubMed:7550232, ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:8213840}. 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 MPS1S; 2-3% of normal activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs754949360 [ dbSNP | Ensembl ]

Sequence information

Variant position:

383

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

Protein sequence length:

653

The length of the canonical sequence.

Location on the sequence:

RTLTARFQVNNTRPPHVQLL R KPVLTAMGLLALLDEEQLWA

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                         RTLTARFQVNNTRPPHVQLLRKPVLTAMGLLALLDEEQLWA

                              RTLTARFQVNDTEPPHVQLLRKPVLTAMALLALLDGRQLWA

Mouse                         RTLTARFQVNNTHPPHVQLLRKPVLTVMGLMALLDGEQLWA

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	28 – 653	Alpha-L-iduronidase
Binding site	363 – 363	Substrate
Glycosylation	372 – 372	N-linked (GlcNAc...) asparagine
Beta strand	378 – 383

Literature citations

Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene.
Bunge S.; Kleijer W.J.; Steglich C.; Beck M.; Schwinger E.; Gal A.;
Hum. Mutat. 6:91-94(1995)
Cited for: VARIANTS MPS1S TRP-89 AND HIS-383; VARIANT MPS1H 349-ASP-ASN-350 DEL; VARIANTS MPS1H/S THR-504 AND ARG-626;

Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients.
Matte U.; Yogalingam G.; Brooks D.; Leistner S.; Schwartz I.; Lima L.; Norato D.Y.; Brum J.M.; Beesley C.; Winchester B.; Giugliani R.; Hopwood J.J.;
Mol. Genet. Metab. 78:37-43(2003)
Cited for: VARIANTS MPS1H ILE-133; LYS-182; ASP-208; TYR-349 AND ARG-533; VARIANTS MPS1H/S PHE-260; PRO-327; ARG-380 AND PRO-628; VARIANTS MPS1S GLN-89; ILE-350; HIS-383 AND ASP-445 DEL;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35475: Variant p.Arg383His