UniProtKB/Swiss-Prot P21802: Variant p.Ser354Cys

Fibroblast growth factor receptor 2
Gene: FGFR2
Chromosomal location: 10q26
Variant information

Variant position:  354
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Serine (S) to Cysteine (C) at position 354 (S354C, p.Ser354Cys).
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 medium size and polar (C)
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

Involvement in disease:  Crouzon syndrome (CS) [MIM:123500]: An autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In CS.
Any additional useful information about the variant.



Sequence information

Variant position:  354
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:   FEDAGEYTCLAGNSIGISFH  S AWLTVLPAPGREKEITASPD
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                         FEDAGEYTCLAGNSIGISFHSAWLTVL----PAPGREKEITASPD

Mouse                         FEDAGEYTCLAGNSIGISFHSAWLTVL----PAPVREKEIT

Chicken                       FEDAGEYTCLAGNSIGISFHTAWLTVL----PAPEKEKEFP

Xenopus laevis                FEDAGEYTCIAGNSIGISQHSAWLTVH----PAPVNPLEDN

Zebrafish                     FEDAGEYTCLAGNSIGISYHTAWLTVH----PAETNPIETD

Drosophila                    FDQEGWYTCLASSGLGRSNSSVYLRVVSPLPPLEIYALLHA

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.

TypePositionsDescription
Chain 22 – 821 Fibroblast growth factor receptor 2
Topological domain 22 – 377 Extracellular
Domain 256 – 358 Ig-like C2-type 3
Alternative sequence 250 – 361 Missing. In isoform 23.
Alternative sequence 255 – 821 Missing. In isoform 14.
Alternative sequence 314 – 429 Missing. In isoform 15.
Alternative sequence 361 – 361 P -> PKQQ. In isoform 3, isoform 4, isoform 7, isoform 9, isoform 10, isoform 11, isoform 12, isoform 13, isoform 17, isoform 18, isoform 19 and isoform 22.
Beta strand 350 – 357


Literature citations

Crouzon syndrome: mutations in two spliceoforms of FGFR2 and a common point mutation shared with Jackson-Weiss syndrome.
Gorry M.C.; Preston R.A.; White G.J.; Zhang Y.; Singhal V.K.; Losken H.W.; Parker M.G.; Nwokoro N.A.; Post J.C.; Ehrlich G.D.;
Hum. Mol. Genet. 4:1387-1390(1995)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 263-361; VARIANTS CS PRO-289; ARG-338; SER-342; TYR-342; GLY-344 AND CYS-354;

Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome.
Reardon W.; Winter R.M.; Rutland P.; Pulleyn L.J.; Jones B.M.; Malcolm S.;
Nat. Genet. 8:98-103(1994)
Cited for: VARIANTS CS HIS-340; ARG-342; SER-342; TYR-342 AND CYS-354;

Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability.
Park W.-J.; Meyers G.A.; Li X.; Theda C.; Day D.; Orlow S.J.; Jones M.C.; Jabs E.W.;
Hum. Mol. Genet. 4:1229-1233(1995)
Cited for: VARIANTS CS GLY-290; TRP-342 AND CYS-354; VARIANT JWS ARG-342;

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-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;

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.