UniProtKB/SwissProt variant VAR

Variant information

Variant position:

650

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

Type of variant:

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:

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:

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:

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:

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:

Links to websites of interest for the variant.

Variant rs78311289 [ dbSNP | Ensembl ]

Sequence information

Variant position:

650

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:

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:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         VMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRV

Mouse                         VMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRV

Chicken                       VMKIADFGLARDVHNIDYYKKTTNGRLPVKWMAPEALFDRV

Xenopus laevis                VMKIADFGLARDIHNIDYYKKTTNGRLPVKWMAPEALFDRI

Zebrafish                     VMKIADFGLARDVHNIDYYKKTTNGRLPVKWMAPEALFDRV

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.

Type	Positions	Description
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)
Cited for: VARIANT BLC CANCER GLN-650;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P22607: Variant p.Lys650Gln