Home  |  Contact

UniProtKB/Swiss-Prot P22607: Variant p.Pro250Arg

Fibroblast growth factor receptor 3
Gene: FGFR3
Variant information

Variant position:  250
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Proline (P) to Arginine (R) at position 250 (P250R, p.Pro250Arg).
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 hydrophobic (P) to large size and basic (R)
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

Involvement in disease:  Muenke syndrome (MNKS) [MIM:602849]: A condition characterized by premature closure of coronal suture of skull during development (coronal craniosynostosis), which affects the shape of the head and face. It may be uni- or bilateral. When bilateral, it is characterized by a skull with a small antero-posterior diameter (brachycephaly), often with a decrease in the depth of the orbits and hypoplasia of the maxillae. Unilateral closure of the coronal sutures leads to flattening of the orbit on the involved side (plagiocephaly). The intellect is normal. In addition to coronal craniosynostosis some affected individuals show skeletal abnormalities of hands and feet, sensorineural hearing loss, mental retardation and respiratory insufficiency. {ECO:0000269|PubMed:11746040, ECO:0000269|PubMed:9042914, ECO:0000269|PubMed:9950359}. 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 MNKS; also some individuals with autosomal dominant congenital sensorineural deafness without craniosynostosis.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  250
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  806
The length of the canonical sequence.

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.






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.

Chain 23 – 806 Fibroblast growth factor receptor 3
Topological domain 23 – 375 Extracellular
Glycosylation 262 – 262 N-linked (GlcNAc...) asparagine

Literature citations

A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.
Muenke M.; Gripp K.W.; McDonald-Mcginn D.M.; Gaudenz K.; Whitaker L.A.; Bartlett S.P.; Markowitz R.I.; Robin N.H.; Nwokoro N.; Mulvihill J.J.; Losken H.W.; Mulliken J.B.; Guttmacher A.E.; Wilroy R.S.; Clarke L.A.; Hollway G.; Ades L.C.; Haan E.A.; Mulley J.C.; Cohen M.M. Jr.; Bellus G.A.; Francomano C.A.; Moloney D.M.; Wall S.A.; Wilkie A.O.M.; Zackai E.H.;
Am. J. Hum. Genet. 60:555-564(1997)
Cited for: VARIANT MNKS ARG-250;

Deafness due to Pro250Arg mutation of FGFR3.
Hollway G.E.; Suthers G.K.; Battese K.M.; Turner A.M.; David D.J.; Mulley J.C.;
Lancet 351:877-878(1998)
Cited for: VARIANT ARG-250;

Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.
Lajeunie E.; El Ghouzzi V.; Le Merrer M.; Munnich A.; Bonaventure J.; Renier D.;
J. Med. Genet. 36:9-13(1999)
Cited for: VARIANT MNKS ARG-250;

Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel shoulder with and without Pro250Arg mutation in the FGFR3 gene.
Lowry R.B.; Jabs E.W.; Graham G.E.; Gerritsen J.; Fleming J.;
Am. J. Med. Genet. 104:112-119(2001)
Cited for: VARIANT MNKS ARG-250;

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.