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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P22607: Variant p.Gly380Arg

Fibroblast growth factor receptor 3
Gene: FGFR3
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Variant information Variant position: help 380 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 Glycine (G) to Arginine (R) at position 380 (G380R, p.Gly380Arg). 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 glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In keratinocytic non-epidermolytic nevus and ACH; very common mutation; constitutively activated kinase with impaired internalization and degradation, resulting in prolonged FGFR3 signaling. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 380 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 EEELVEADEAGSVYAGILSY G VGFFLFILVVAAVTLCRLRS 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. 
Human                         EEELVEAD-EAGSVYAGILSYGVGFFLFILVVAAVTLCRLRS

Mouse                         EEELMETD-EAGSVYAGVLSYGVVFFLFILVVAAVILCRLR

Chicken                       EE-LMEMD-DSGSVYAGILSYGTGLVLFILVLVIVIICRMK

Xenopus laevis                PAEPVEKALTTSSSSITVLIVVTSTIVFILLVIIVITHLMK

Zebrafish                     VE--MERE-DD---YADILIYVTSCVLFILTMVIIILCRMW
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.
TypePositionsDescription
Chain 23 – 806 Fibroblast growth factor receptor 3
Transmembrane 376 – 396 Helical
Alternative sequence 311 – 422 Missing. In isoform 3.
Helix 374 – 398



Literature citations
The transmembrane mutation G380R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation.
Monsonego-Ornan E.; Adar R.; Feferman T.; Segev O.; Yayon A.;
Mol. Cell. Biol. 20:516-522(2000)
Cited for: FUNCTION AS FGF9 RECEPTOR IN CHONDROCYTES AND IN ACTIVATION OF SIGNALING PATHWAYS; SUBUNIT; SUBCELLULAR LOCATION; DEGRADATION; AUTOPHOSPHORYLATION; CHARACTERIZATION OF VARIANT ACH ARG-380; FGF receptors ubiquitylation: dependence on tyrosine kinase activity and role in downregulation.
Monsonego-Ornan E.; Adar R.; Rom E.; Yayon A.;
FEBS Lett. 528:83-89(2002)
Cited for: UBIQUITINATION; PHOSPHORYLATION; CATALYTIC ACTIVITY; MUTAGENESIS OF LYS-508; CHARACTERIZATION OF VARIANT ACH ARG-380; CHARACTERIZATION OF VARIANT TD2 GLU-650; Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via PLCgamma-activated STAT1.
Harada D.; Yamanaka Y.; Ueda K.; Nishimura R.; Morishima T.; Seino Y.; Tanaka H.;
Bone 41:273-281(2007)
Cited for: FUNCTION IN REGULATION OF CHONDROCYTE PROLIFERATION AND IN ACTIVATION OF PLCG1 AND STAT1; INTERACTION WITH FHF1 AND HEPARIN; SUBCELLULAR LOCATION; PHOSPHORYLATION; CHARACTERIZATION OF VARIANTS ARG-380; GLU-650 AND MET-650; Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.
Rousseau F.; Bonaventure J.; Legeai-Mallet L.; Pelet A.; Rozet J.-M.; Maroteaux P.; le Merrer M.; Munnich A.;
Nature 371:252-254(1994)
Cited for: VARIANT ACH ARG-380; Achondroplasia is defined by recurrent G380R mutations of FGFR3.
Bellus G.A.; Hefferon T.W.; de Luna R.I.; Hecht J.T.; Horton W.A.; Machado M.; Kaitila I.; McIntosh I.; Francomano C.A.;
Am. J. Hum. Genet. 56:368-373(1995)
Cited for: VARIANT ACH ARG-380; Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia.
Webster M.K.; Donoghue D.J.;
EMBO J. 15:520-527(1996)
Cited for: CHARACTERIZATION OF VARIANT ACH ARG-380; 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.