UniProtKB/Swiss-Prot P07911: Variant p.Cys248Trp

Uromodulin
Gene: UMOD
Chromosomal location: 16p13.11
Variant information

Variant position:  248
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 Tryptophan (W) at position 248 (C248W, p.Cys248Trp).
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 large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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

Variant description:  In MCKD2 and HNFJ1; causes a delay in protein export to the plasma membrane due to a longer retention time in the ER.
Any additional useful information about the variant.



Sequence information

Variant position:  248
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  640
The length of the canonical sequence.

Location on the sequence:   PMWLNGTHPSSDEGIVSRKA  C AHWSGHCCLWDASVQVKACA
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                         PMWLNGTHPSSDEGIVSRKACAHWSGHCCLWDASVQVKACA

Mouse                         PMWLNGSHPSSSEGIVSRTACAHWSDQCCRWSTEIQVKACP

Rat                           PMWLNGSHPSSREGIVSRTACAHWSDHCCLWSTEIQVKACP

Bovine                        PMWLNGTHPSSDEGIVNRVACAHWSGDCCLWDAPIQVKACA

Dog                           PMWLNGTHPTRDQGIVNRTACAHWRGHCCLWDASIQVKACA

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 25 – 614 Uromodulin
Chain 25 – 587 Uromodulin, secreted form
Glycosylation 232 – 232 N-linked (GlcNAc...) (complex)


Literature citations

Mutations of the Uromodulin gene in MCKD type 2 patients cluster in exon 4, which encodes three EGF-like domains.
Wolf M.T.F.; Mucha B.E.; Attanasio M.; Zalewski I.; Karle S.M.; Neumann H.P.H.; Rahman N.; Bader B.; Baldamus C.A.; Otto E.; Witzgall R.; Fuchshuber A.; Hildebrandt F.;
Kidney Int. 64:1580-1587(2003)
Cited for: VARIANTS MCKD2 93-VAL--GLY-97 DELINS ALA-ALA-SER-CYS; LYS-225 AND TRP-248;

Novel UMOD mutations in familial juvenile hyperuricemic nephropathy lead to abnormal uromodulin intracellular trafficking.
Liu M.; Chen Y.; Liang Y.; Liu Y.; Wang S.; Hou P.; Zhang H.; Zhao M.;
Gene 531:363-369(2013)
Cited for: VARIANTS HNFJ1 GLU-109; GLN-236 AND TRP-248; CHARACTERIZATION OF VARIANTS HNFJ1 GLU-109; GLN-236 AND TRP-248; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;

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.