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UniProtKB/Swiss-Prot P35475: Variant p.Leu490Pro

Alpha-L-iduronidase
Gene: IDUA
Chromosomal location: 4p16.3
Variant information

Variant position:  490
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 Leucine (L) to Proline (P) at position 490 (L490P, p.Leu490Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Mucopolysaccharidosis 1H/S (MPS1H/S) [MIM:607015]: A form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility. {ECO:0000269|PubMed:10466419, ECO:0000269|PubMed:10735634, ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:7550232, ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:8401515}. 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:  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 MPS1H/S and MPS1S.
Any additional useful information about the variant.

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



Sequence information

Variant position:  490
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:   VYVTRYLDNGLCSPDGEWRR  L GRPVFPTAEQFRRMRAAEDP
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                         VYVTRYLDNGLCSPDGEWRRLGRPVFPTAEQFRRMRAAEDP

                              VYVTLALDNPRCSPHGEWQRLGRPVFPTAEEFRRMRAAEDP

Mouse                         VYIVLYLDNQLSSPYSAWQHMGQPVFPSAEQFRRMRMVEDP

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 28 – 653 Alpha-L-iduronidase


Literature citations

Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S).
Tieu P.T.; Bach G.; Matynia A.; Hwang M.; Neufeld E.F.;
Hum. Mutat. 6:55-59(1995)
Cited for: VARIANTS MPS1H/S PRO-490 AND LEU-496; VARIANT MPS1S PRO-492;

IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel alpha-L-iduronidase (IDUA) alleles.
Bertola F.; Filocamo M.; Casati G.; Mort M.; Rosano C.; Tylki-Szymanska A.; Tuysuz B.; Gabrielli O.; Grossi S.; Scarpa M.; Parenti G.; Antuzzi D.; Dalmau J.; Di Rocco M.; Vici C.D.; Okur I.; Rosell J.; Rovelli A.; Furlan F.; Rigoldi M.; Biondi A.; Cooper D.N.; Parini R.;
Hum. Mutat. 32:E2189-E2210(2011)
Cited for: VARIANTS MPS1H/S ARG-84; LYS-178; LEU-188; ARG-265; LYS-276; PRO-396; ARG-423; PRO-436; ARG-496; ARG-533 AND PHE-535; VARIANTS MPS1H ASP-51; PRO-103; PRO-327 AND ARG-385; VARIANTS MPS1S CYS-76; TRP-89; GLU-219; LYS-276; LEU-306; LYS-348; PRO-490 AND PRO-492; VARIANTS GLN-33; GLN-105; THR-361; ASN-449; ILE-454 AND THR-591;

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.