UniProtKB/Swiss-Prot O76024: Variant p.Pro504Leu

Wolframin
Gene: WFS1
Chromosomal location: 4p16.1
Variant information

Variant position:  504
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 Proline (P) to Leucine (L) at position 504 (P504L, p.Pro504Leu).
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:  Wolfram syndrome 1 (WFS1) [MIM:222300]: A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. 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 WFS1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  504
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  890
The length of the canonical sequence.

Location on the sequence:   LGQTFITVPVGHLVVLNVSV  P CLLYVYLLYLFFRMAQLRNF
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                         LGQTFITVPVGHLVVLNVSVPCLLYVYLLYLFFRMAQLRNF

Mouse                         LGQTFFTVPVGHFIILNVSLPCLLYVYLFYLFFRMAQLRNF

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 1 – 890 Wolframin
Transmembrane 496 – 516 Helical;


Literature citations

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram Syndrome).
Inoue H.; Tanizawa Y.; Wasson J.; Behn P.; Kalidas K.; Bernal-Mizrachi E.; Mueckler M.; Marshall H.; Donis-Keller H.; Crock P.; Rogers D.; Mikuni M.; Kumashiro H.; Higashi K.; Sobue G.; Oka Y.; Permutt M.A.;
Nat. Genet. 20:143-148(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS WFS1 LEU-504; 508-TYR--LEU-512 DEL; VAL-695 AND LEU-724; VARIANTS ILE-333; HIS-456 AND HIS-611;

Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees.
Gomez-Zaera M.; Strom T.M.; Rodriguez B.; Estivill X.; Meitinger T.; Nunes V.;
Mol. Genet. Metab. 72:72-81(2001)
Cited for: VARIANTS WFS1 VAL-58; THR-126; PHE-350 DEL; PHE-354 DEL; LEU-504; ARG-780 AND CYS-818; VARIANTS ARG-674 AND LYS-737;

Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene.
Giuliano F.; Bannwarth S.; Monnot S.; Cano A.; Chabrol B.; Vialettes B.; Delobel B.; Paquis-Flucklinger V.;
Hum. Mutat. 25:99-100(2005)
Cited for: VARIANTS WFS1 ASN-110; THR-133; PHE-414 DEL; VAL-415 DEL; SER-457; LEU-468 DEL; LEU-504; TRP-540 DEL; TRP-629 AND SER-736; VARIANTS VAL-326; ILE-333; HIS-456; HIS-611; VAL-802 AND MET-871;

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.