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UniProtKB/Swiss-Prot P15289: Variant p.Pro425Thr

Arylsulfatase A
Gene: ARSA
Chromosomal location: 22q13.31-qter
Variant information

Variant position:  425
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 Proline (P) to Threonine (T) at position 425 (P425T, p.Pro425Thr).
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 hydrophobic (P) to medium size and polar (T)
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:  Leukodystrophy metachromatic (MLD) [MIM:250100]: A leukodystrophy due to a lysosomal storage defect. Characterized by intralysosomal storage of cerebroside-3-sulfate in neural and non-neural tissues, with a diffuse loss of myelin in the central nervous system. Progressive demyelination causes a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Three forms of the disease can be distinguished according to the age at onset: late-infantile, juvenile and adult. {ECO:0000269|PubMed:10220151, ECO:0000269|PubMed:10381328, ECO:0000269|PubMed:10477432, ECO:0000269|PubMed:10533072, ECO:0000269|PubMed:10751093, ECO:0000269|PubMed:11020646, ECO:0000269|PubMed:11061266, ECO:0000269|PubMed:11456299, ECO:0000269|PubMed:11941485, ECO:0000269|PubMed:12503099, ECO:0000269|PubMed:12788103, ECO:0000269|PubMed:1353340, ECO:0000269|PubMed:14517960, ECO:0000269|PubMed:14680985, ECO:0000269|PubMed:15026521, ECO:0000269|PubMed:15326627, ECO:0000269|PubMed:15710861, ECO:0000269|PubMed:1670590, ECO:0000269|PubMed:1673291, ECO:0000269|PubMed:1678251, ECO:0000269|PubMed:18693274, ECO:0000269|PubMed:19606494, ECO:0000269|PubMed:20339381, ECO:0000269|PubMed:21265945, ECO:0000269|PubMed:7581401, ECO:0000269|PubMed:7825603, ECO:0000269|PubMed:7860068, ECO:0000269|PubMed:7902317, ECO:0000269|PubMed:7906588, ECO:0000269|PubMed:7909527, ECO:0000269|PubMed:8095918, ECO:0000269|PubMed:8101038, ECO:0000269|PubMed:8101083, ECO:0000269|PubMed:8104633, ECO:0000269|PubMed:8891236, ECO:0000269|PubMed:9090526, ECO:0000269|PubMed:9272717, ECO:0000269|PubMed:9452102, ECO:0000269|PubMed:9490297, ECO:0000269|PubMed:9600244, ECO:0000269|PubMed:9819708}. 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 MLD; juvenile-onset; retains about 12% of specific enzyme activity; the mutant protein is unstable; results in more rapid enzyme degradation in lysosomes; addition of the cysteine protease inhibitor leupeptin increases the amount of the enzyme activity; displays a modest reduction in the octamerization process of the enzyme at low pH.
Any additional useful information about the variant.

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



Sequence information

Variant position:  425
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  507
The length of the canonical sequence.

Location on the sequence:   HSDTTADPACHASSSLTAHE  P PLLYDLSKDPGENYNLLGGV
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.

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 19 – 507 Arylsulfatase A
Chain 19 – 444 Arylsulfatase A component B
Beta strand 421 – 430


Literature citations

Metachromatic leucodystrophy in Portugal-finding of four new molecular lesions: C300F, P425T, g.1190-1191insC, and g.2408delC.
Marcao A.; Amaral O.; Pinto E.; Pinto R.; Sa Miranda M.C.;
Hum. Mutat. 13:337-338(1999)
Cited for: VARIANTS MLD PHE-300 AND THR-425;

Biochemical characterization of two (C300F, P425T) arylsulfatase A missense mutations.
Marcao A.; Simonis H.; Schestag F.; Sa Miranda M.C.; Gieselmann V.;
Am. J. Med. Genet. A 116:238-242(2003)
Cited for: CHARACTERIZATION OF VARIANTS MLD PHE-300 AND THR-425;

Oligomerization capacity of two arylsulfatase A mutants: C300F and P425T.
Marcao A.; Azevedo J.E.; Gieselmann V.; Sa Miranda M.C.;
Biochem. Biophys. Res. Commun. 306:293-297(2003)
Cited for: CHARACTERIZATION OF VARIANTS MLD PHE-300 AND THR-425;

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.