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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P22607: Variant p.Arg248Cys

Fibroblast growth factor receptor 3
Gene: FGFR3
Variant information Variant position: help 248 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help From Arginine (R) to Cysteine (C) at position 248 (R248C, p.Arg248Cys). 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: help Change from large size and basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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

Variant description: help In KERSEB, BLC, keratinocytic non-epidermolytic nevus and TD1; severe and lethal; also found as somatic mutation in one patient with multiple myeloma; constitutive dimerization and kinase activation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.

Sequence information Variant position: help 248 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 806 The length of the canonical sequence.
Location on the sequence: help CVVENKFGSIRQTYTLDVLE R SPHRPILQAGLPANQTAVLG 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.





Sequence annotation in neighborhood: help 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.
Chain 23 – 806 Fibroblast growth factor receptor 3
Topological domain 23 – 375 Extracellular
Glycosylation 262 – 262 N-linked (GlcNAc...) asparagine

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; ACTIVITY REGULATION; CHARACTERIZATION OF VARIANTS CYS-248; CYS-373 AND MET-650; Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.
Tavormina P.L.; Shiang R.; Thompson L.M.; Zhu Y.-Z.; Wilkin D.J.; Lachman R.S.; Wilcox W.R.; Rimoin D.L.; Cohn D.H.; Wasmuth J.J.;
Nat. Genet. 9:321-328(1995)
Cited for: VARIANTS TD1 CYS-248 AND CYS-371; VARIANT TD2 GLU-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; 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; Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas.
Cappellen D.; De Oliveira C.; Ricol D.; Gil Diez de Medina S.; Bourdin J.; Sastre-Garau X.; Chopin D.; Thiery J.P.; Radvanyi F.;
Nat. Genet. 23:18-20(1999)
Cited for: VARIANTS BLC CYS-248; CYS-249; CYS-370 AND GLU-650; VARIANTS CERCA CYS-248; CYS-249; CYS-370 AND GLU-650; Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14).
Intini D.; Baldini L.; Fabris S.; Lombardi L.; Ciceri G.; Maiolo A.T.; Neri A.;
Br. J. Haematol. 114:362-364(2001)
Cited for: INVOLVEMENT IN MULTIPLE MYELOMA; VARIANT CYS-248; 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; Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.
Hafner C.; van Oers J.M.M.; Vogt T.; Landthaler M.; Stoehr R.; Blaszyk H.; Hofstaedter F.; Zwarthoff E.C.; Hartmann A.;
J. Clin. Invest. 116:2201-2207(2006)
Cited for: VARIANTS KNEN CYS-248; CYS-370 AND ARG-380;
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.