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UniProtKB/Swiss-Prot P22607: Variant p.Lys650Gln

Fibroblast growth factor receptor 3
Gene: FGFR3
Variant information Variant position: help 650 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 Lysine (K) to Glutamine (Q) at position 650 (K650Q, p.Lys650Gln). 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 (K) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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 hypochondroplasia and BLC; in hypochondroplasia the form is milder than that seen in individuals with the K-540 or M-650 mutations; constitutively activated kinase. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.

Sequence information Variant position: help 650 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 VMKIADFGLARDVHNLDYYK K TTNGRLPVKWMAPEALFDRV 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 397 – 806 Cytoplasmic
Domain 472 – 761 Protein kinase
Modified residue 647 – 647 Phosphotyrosine; by autocatalysis
Modified residue 648 – 648 Phosphotyrosine; by autocatalysis
Mutagenesis 650 – 650 K -> D. Constitutively activated kinase.
Mutagenesis 650 – 650 K -> L. Constitutively activated kinase.

Literature citations
Profound ligand-independent kinase activation of fibroblast growth factor receptor 3 by the activation loop mutation responsible for a lethal skeletal dysplasia, thanatophoric dysplasia type II.
Webster M.K.; D'Avis P.Y.; Robertson S.C.; Donoghue D.J.;
Mol. Cell. Biol. 16:4081-4087(1996)
Cited for: CHARACTERIZATION OF VARIANT TD2 GLU-650; CHARACTERIZATION OF VARIANT GLN-650; PHOSPHORYLATION AT TYR-647 AND TYR-648; Distinct missense mutations of the FGFR3 Lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.
Bellus G.A.; Spector E.B.; Speiser P.W.; Weaver C.A.; Garber A.T.; Bryke C.R.; Israel J.; Rosengren S.S.; Webster M.K.; Donoghue D.J.; Francomano C.A.;
Am. J. Hum. Genet. 67:1411-1421(2000)
Cited for: VARIANT HYPOCHONDROPLASIA GLN-650; Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma.
Sibley K.; Cuthbert-Heavens D.; Knowles M.A.;
Oncogene 20:686-691(2001)
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.