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UniProtKB/Swiss-Prot P22607: Variant p.Gly380Arg

Fibroblast growth factor receptor 3
Gene: FGFR3
Variant information

Variant position:  380
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  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:  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:  -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

Involvement in disease:  Achondroplasia (ACH) [MIM:100800]: A frequent form of short-limb dwarfism. It is characterized by a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. ACH is an autosomal dominant disease. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:12297284, ECO:0000269|PubMed:7758520, ECO:0000269|PubMed:7847369, ECO:0000269|PubMed:8078586, ECO:0000269|PubMed:8599935}. 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.

Involvement in disease:  Keratinocytic non-epidermolytic nevus (KNEN) [MIM:162900]: Epidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood. {ECO:0000269|PubMed:16841094}. 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 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:  
Links to websites of interest for the variant.



Sequence information

Variant position:  380
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:   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: 
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:  
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.