UniProtKB/Swiss-Prot P07602: Variant p.Cys241Ser

Prosaposin
Gene: PSAP
Chromosomal location: 10q21-q22
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Cysteine (C) to Serine (S) at position 241 (C241S, p.Cys241Ser).
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 (C) to small size and polar (S)
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 due to saposin-B deficiency (MLD-SAPB) [MIM:249900]: An atypical form of metachromatic leukodystrophy. It is characterized by tissue accumulation of cerebroside-3-sulfate, demyelination, periventricular white matter abnormalities, peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotor regression, seizures, cognitive decline and spastic quadriparesis. 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-SAPB; severe.
Any additional useful information about the variant.

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



Sequence information

Variant position:  241
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  524
The length of the canonical sequence.

Location on the sequence:   ALVEHVKEECDRLGPGMADI  C KNYISQYSEIAIQMMMHMQP
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                         ALVEHVKEECDRLGPGMADICKNYISQYSEIAIQMMMHMQ---P

Mouse                         GFVDHVKEDCDRLGPGVSDICKNYVDQYSEVCVQMLMHMQD

Rat                           GLVDHVKEDCDRLGPGVSDICKNYVDQYSEVAVQMMMHMQ-

Pig                           ALVNHAKEECDRLGPGMADMCKNYISQYSEIAIQMMMHMQ-

Bovine                        ALVDHAKEECDRLGPGMSDMCKNYINQYSEVAIQMVMHMQ-

Chicken                       SLVAHAKEECDRLGPGMSDMCKSYISEYSDLAIQMMMHMKD

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 17 – 524 Prosaposin
Chain 195 – 274 Saposin-B-Val
Chain 195 – 273 Saposin-B
Domain 194 – 275 Saposin B-type 2
Disulfide bond 198 – 271
Disulfide bond 201 – 265
Disulfide bond 230 – 241
Alternative sequence 259 – 259 M -> MDQ. In isoform Sap-mu-6.
Alternative sequence 260 – 260 Q -> QDQQ. In isoform Sap-mu-9.
Mutagenesis 240 – 240 I -> C. Strongly decreases stimulation of cerebroside sulfate hydrolysis.
Helix 237 – 256


Literature citations

Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease.
Holtschmidt H.; Sandhoff K.; Kwon H.Y.; Harzer K.; Nakano T.; Suzuki K.;
J. Biol. Chem. 266:7556-7560(1991)
Cited for: VARIANT MLD-SAPB SER-241; NUCLEOTIDE SEQUENCE [MRNA]; ALTERNATIVE SPLICING;

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.