UniProtKB/Swiss-Prot P21802: Variant p.Cys278Phe

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

278 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 Cysteine (C) to Phenylalanine (F) at position 278 (C278F, p.Cys278Phe). 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 medium size and polar (C) to large size and aromatic (F) 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, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs776587763 [ dbSNP | Ensembl ]

Sequence information Variant position:

278 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:

LQAGLPANASTVVGGDVEFV C KVYSDAQPHIQWIKHVEKNG 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                         LQAGLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNG

Mouse                         LQAGLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNG

Chicken                       LQAGLPANASAVVGGDVEFVCKVYSDAQPHIQWIKHVERNG

Xenopus laevis                LQAGLPANTTAVVGGDAEFVCKVYSDAQPHIRWVRYIEKNG

Zebrafish                     LQAGLPANVTVQVGQDAKFVCKVYSDAQPHIQWLQHYTKNG

Drosophila                    IV--VPQNQTVKVNGSLVMKCTVYSDLHPTVSWKRVVLKNA

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
Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F.
Hatch N.E.; Hudson M.; Seto M.L.; Cunningham M.L.; Bothwell M.;
J. Biol. Chem. 281:27292-27305(2006)
Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG1 (ISOFORM 1); CATALYTIC ACTIVITY; AUTOPHOSPHORYLATION; GLYCOSYLATION; INTERACTION WITH PLCG1; SUBCELLULAR LOCATION; MUTAGENESIS OF ASN-265 AND 656-TYR-TYR-657; UBIQUITINATION; CHARACTERIZATION OF VARIANT PS PHE-278; Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome.
Oldridge M.; Wilkie A.O.M.; Slaney S.F.; Poole M.D.; Pulleyn L.J.; Rutland P.; Hockley A.D.; Wake M.J.C.; Goldin J.H.; Winter R.M.; Reardon W.; Malcolm S.;
Hum. Mol. Genet. 4:1077-1082(1995)
Cited for: VARIANTS CS PRO-267; PHE-278 AND ARG-290; FGFR2 exon IIIa and IIIc mutations in Crouzon, Jackson-Weiss, and Pfeiffer syndromes: evidence for missense changes, insertions, and a deletion due to alternative RNA splicing.
Meyers G.A.; Day D.; Goldberg R.; Daentl D.L.; Przylepa K.A.; Abrams L.J.; Graham J.M. Jr.; Feingold M.; Moeschler J.B.; Rawnsley E.; Scott A.F.; Jabs E.W.;
Am. J. Hum. Genet. 58:491-498(1996)
Cited for: VARIANTS CS GLY-268 INS; PHE-342 AND TYR-342; VARIANTS PS PHE-278; ARG-342; SER-342; PRO-344 AND PHE-359; VARIANT JWS PRO-289; 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; Clustering of FGFR2 gene mutations in patients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses).
Kress W.; Collmann H.; Buesse M.; Halliger-Keller B.; Mueller C.R.;
Cytogenet. Cell Genet. 91:134-137(2000)
Cited for: VARIANTS CS/PS ARG-342 AND TYR-342; VARIANTS CS LEU-263; VAL-276; PHE-278; TYR-278; SER-288; PRO-289; PRO-341; TRP-342; CYS-354; TYR-354 AND PHE-359; VARIANT PS SER-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-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.