UniProtKB/Swiss-Prot P21802: Variant p.Ser252Trp

Fibroblast growth factor receptor 2
Gene: FGFR2
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Variant information Variant position:

252 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 Serine (S) to Tryptophan (W) at position 252 (S252W, p.Ser252Trp). 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 small size and polar (S) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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 APRS and PS; common mutation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs79184941 [ dbSNP | Ensembl ]

Sequence information Variant position:

252 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:

VVENEYGSINHTYHLDVVER S PHRPILQAGLPANASTVVGG 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                         VVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGG

Mouse                         LVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGG

Chicken                       IVENQYGSINHTYHLDVVERSPHRPILQAGLPANASAVVGG

Xenopus laevis                IVENEHGSINHTYHLDVIERSSHRPILQAGLPANTTAVVGG

Zebrafish                     LVENQYGSIDHTYTLDVVERSPHRPILQAGLPANVTVQVGQ

Drosophila                    KVCNAWGCIQFDFSVQINDRTRSAPIIV--VPQNQTVKVNG

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
Glycosylation	241 – 241	N-linked (GlcNAc...) asparagine
Glycosylation	265 – 265	N-linked (GlcNAc...) asparagine
Alternative sequence	250 – 361	Missing. In isoform 17.
Alternative sequence	250 – 254	ERSPH -> GSQGL. In isoform 8.
Mutagenesis	265 – 265	N -> Q. Reduced N-glycosylation. Reduced expression at the cell surface.

Literature citations
Analysis of phenotypic features and FGFR2 mutations in Apert syndrome.
Park W.-J.; Theda C.; Maestri N.E.; Meyers G.A.; Fryburg J.S.; Dufresne C.; Cohen M.M. Jr.; Jabs E.W.;
Am. J. Hum. Genet. 57:321-328(1995)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 249-313; VARIANTS APRS TRP-252 AND ARG-253; Cbl-mediated degradation of Lyn and Fyn induced by constitutive fibroblast growth factor receptor-2 activation supports osteoblast differentiation.
Kaabeche K.; Lemonnier J.; Le Mee S.; Caverzasio J.; Marie P.J.;
J. Biol. Chem. 279:36259-36267(2004)
Cited for: FUNCTION IN OSTEOBLAST DIFFERENTIATION AND IN PHOSPHORYLATION OF CBL; INTERACTION WITH CBL; UBIQUITINATION; CHARACTERIZATION OF VARIANT APRS TRP-252; Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome.
Ibrahimi O.A.; Eliseenkova A.V.; Plotnikov A.N.; Yu K.; Ornitz D.M.; Mohammadi M.;
Proc. Natl. Acad. Sci. U.S.A. 98:7182-7187(2001)
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 147-366 OF VARIANTS APRS TRP-252 AND ARG-253 IN COMPLEX WITH FGF2; Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome.
Wilkie A.O.M.; Slaney S.F.; Oldridge M.; Poole M.D.; Ashworth G.J.; Hockley A.D.; Hayward R.D.; David D.J.; Pulleyn L.J.; Rutland P.; Malcolm S.; Winter R.M.; Reardon W.;
Nat. Genet. 9:165-172(1995)
Cited for: VARIANTS APRS TRP-252 AND ARG-253; Description of a new mutation and characterization of FGFR1, FGFR2, and FGFR3 mutations among Brazilian patients with syndromic craniosynostoses.
Passos-Bueno M.R.; Sertie A.L.; Richieri-Costa A.; Alonso L.G.; Zatz M.; Alonso N.; Brunoni D.; Ribeiro S.F.M.;
Am. J. Med. Genet. 78:237-241(1998)
Cited for: VARIANTS CS PHE-278; PRO-337; ARG-338; ARG-342; PHE-342 AND TYR-342; VARIANTS APRS TRP-252 AND ARG-253; VARIANT JWS PHE-278; Two common mutations 934C to G and 937C to G of fibroblast growth factor receptor 2 (FGFR2) gene in Chinese patients with Apert syndrome.
Tsai F.-J.; Hwu W.-L.; Lin S.-P.; Chang J.-G.; Wang T.-R.; Tsai C.-H.;
Hum. Mutat. Suppl. 1:S18-S19(1998)
Cited for: VARIANTS APRS TRP-252 AND ARG-253; Presence of the Apert canonical S252W FGFR2 mutation in a patient without severe syndactyly.
Passos-Bueno M.R.; Richieri-Costa A.; Sertie A.L.; Kneppers A.;
J. Med. Genet. 35:677-679(1998)
Cited for: VARIANT PS TRP-252; 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-SER-PRO-253 DELINS PHE-SER; 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;

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.