UniProtKB/SwissProt variant VAR

Variant information

Variant position:

281

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 Tyrosine (Y) to Cysteine (C) at position 281 (Y281C, p.Tyr281Cys).

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 aromatic (Y) to medium size and polar (C)

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

Variant description:

In CS.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1057519038 [ dbSNP | Ensembl ]

Sequence information

Variant position:

281

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

Protein sequence length:

821

The length of the canonical sequence.

Location on the sequence:

GLPANASTVVGGDVEFVCKV Y SDAQPHIQWIKHVEKNGSKY

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                         GLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKY

Mouse                         GLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKN

Chicken                       GLPANASAVVGGDVEFVCKVYSDAQPHIQWIKHVERNGSKY

Xenopus laevis                GLPANTTAVVGGDAEFVCKVYSDAQPHIRWVRYIEKNGSRF

Zebrafish                     GLPANVTVQVGQDAKFVCKVYSDAQPHIQWLQHYTKNGSCC

Drosophila                    -VPQNQTVKVNGSLVMKCTVYSDLHPTVSWKRVVLKNAS--

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	22 – 821	Fibroblast growth factor receptor 2
Topological domain	22 – 377	Extracellular
Domain	256 – 358	Ig-like C2-type 3
Glycosylation	265 – 265	N-linked (GlcNAc...) asparagine
Glycosylation	297 – 297	N-linked (GlcNAc...) asparagine
Disulfide bond	278 – 342
Alternative sequence	250 – 361	Missing. In isoform 17.
Alternative sequence	255 – 821	Missing. In isoform 8.
Mutagenesis	265 – 265	N -> Q. Reduced N-glycosylation. Reduced expression at the cell surface.

Literature citations

Mutation analysis of Crouzon syndrome and identification of one novel mutation in Taiwanese patients.
Tsai F.-J.; Yang C.-F.; Wu J.-Y.; Tsai C.-H.; Lee C.-C.;
Pediatr. Int. 43:263-266(2001)
Cited for: VARIANTS CS CYS-281; PRO-289; ARG-342 AND TYR-342;

Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis.
Kan S.-H.; Elanko N.; Johnson D.; Cornejo-Roldan L.R.; Cook J.; Reich E.W.; Tomkins S.; Verloes A.; Twigg S.R.F.; Rannan-Eliya S.; McDonald-McGinn D.M.; Zackai E.H.; Wall S.A.; Muenke M.; Wilkie A.O.M.;
Am. J. Hum. Genet. 70:472-486(2002)
Cited for: VARIANTS CS CYS-105; PRO-267; VAL-276; CYS-281; PRO-289; ARG-338; HIS-340; PHE-342; TRP-342; CYS-347; CYS-354; HIS-549 AND GLY-678; VARIANTS PS PHE-172; 252-PHE-SER-253; CYS-290; CYS-340; PRO-341; ARG-342; SER-342; CYS-375; GLY-565; ARG-641 AND GLU-663; VARIANTS APRS TRP-252 AND ARG-253; VARIANTS CS/PS PHE-278 AND TYR-342; VARIANT CRANIOSYNOSTOSIS ASN-659; VARIANTS THR-186 AND SER-315;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P21802: Variant p.Tyr281Cys