UniProtKB/Swiss-Prot P22607: Variant p.Tyr373Cys

Fibroblast growth factor receptor 3
Gene: FGFR3
Chromosomal location: 4p16.3
Variant information

Variant position:  373
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 Tyrosine (Y) to Cysteine (C) at position 373 (Y373C, p.Tyr373Cys).
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 large size and aromatic (Y) to medium size and polar (C)
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 KERSEB and TD1; disulfide-linked dimer with constitutive kinase activation.
Any additional useful information about the variant.



Sequence information

Variant position:  373
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  806
The length of the canonical sequence.

Location on the sequence:   WLVVLPAEEELVEADEAGSV  Y AGILSYGVGFFLFILVVAAV
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                         WLVVL-PAEEELVEAD-EAGSVYAGILSYGVGFFLFILVVAAV

Mouse                         WLVVL-PAEEELMETD-EAGSVYAGVLSYGVVFFLFILVVA

Chicken                       WLTVL-PAEE-LMEMD-DSGSVYAGILSYGTGLVLFILVLV

Xenopus laevis                WLHIYKPAPAEPVEKALTTSSSSITVLIVVTSTIVFILLVI

Zebrafish                     WLTVL-PAVE--MERE-DD---YADILIYVTSCVLFILTMV

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 23 – 806 Fibroblast growth factor receptor 3
Topological domain 23 – 375 Extracellular
Alternative sequence 311 – 422 Missing. In isoform 3.


Literature citations

The localization of FGFR3 mutations causing thanatophoric dysplasia type I differentially affects phosphorylation, processing and ubiquitylation of the receptor.
Bonaventure J.; Horne W.C.; Baron R.;
FEBS J. 274:3078-3093(2007)
Cited for: FUNCTION IN PHOSPHORYLATION OF CBL; UBIQUITINATION; GLYCOSYLATION; SUBCELLULAR LOCATION; ENZYME REGULATION; CHARACTERIZATION OF VARIANTS CYS-248; CYS-373 AND MET-650;

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).
Rousseau F.; el Ghouzzi V.; Delezoide A.-L.; Legeai-Mallet L.; le Merrer M.; Munnich A.; Bonaventure J.;
Hum. Mol. Genet. 5:509-512(1996)
Cited for: VARIANTS TD1 CYS-248; CYS-249; CYS-370 AND CYS-373;

Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.
Chesi M.; Nardini E.; Brents L.A.; Schroeck E.; Ried T.; Kuehl W.M.; Bergsagel P.L.;
Nat. Genet. 16:260-264(1997)
Cited for: INVOLVEMENT IN MULTIPLE MYELOMA; VARIANTS CYS-373; GLU-650 AND MET-650;

Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations.
Brodie S.G.; Kitoh H.; Lachman R.S.; Nolasco L.M.; Mekikian P.B.; Wilcox W.R.;
Am. J. Med. Genet. 84:476-480(1999)
Cited for: VARIANTS TD1 CYS-248; CYS-249 AND CYS-373;

Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.
Logie A.; Dunois-Larde C.; Rosty C.; Levrel O.; Blanche M.; Ribeiro A.; Gasc J.-M.; Jorcano J.; Werner S.; Sastre-Garau X.; Thiery J.P.; Radvanyi F.;
Hum. Mol. Genet. 14:1153-1160(2005)
Cited for: VARIANTS KERSEB CYS-248; CYS-249; CYS-370; CYS-371; CYS-373; GLU-650 AND MET-650;

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.