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UniProtKB/Swiss-Prot P22607: Variant p.Ala391Glu

Fibroblast growth factor receptor 3
Gene: FGFR3
Variant information

Variant position:  391
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 Alanine (A) to Glutamate (E) at position 391 (A391E, p.Ala391Glu).
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 hydrophobic (A) to medium size and acidic (E)
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 with acanthosis nigricans (CAN) [MIM:612247]: Classic Crouzon disease which is caused by mutations in the FGFR2 gene is characterized by craniosynostosis (premature fusion of the skull sutures), and facial hypoplasia. Crouzon syndrome with acanthosis nigricans (a skin disorder characterized by pigmentation anomalies), CAN, is considered to be an independent disorder from classic Crouzon syndrome. CAN is characterized by additional more severe physical manifestation, such as Chiari malformation, hydrocephalus, and atresia or stenosis of the choanas, and is caused by a specific mutation (Ala-391 to Glu) in the transmembrane domain of FGFR3. It is proposed to have an autosomal dominant mode of inheritance. {ECO:0000269|PubMed:17935505, ECO:0000269|PubMed:7493034}. 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 CAN.
Any additional useful information about the variant.

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



Sequence information

Variant position:  391
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

Location on the sequence:   SVYAGILSYGVGFFLFILVV  A AVTLCRLRSPPKKGLGSPTV
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                         SVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTV

Mouse                         SVYAGVLSYGVVFFLFILVVAAVILCRLRSPPKKGLGSPTV

Chicken                       SVYAGILSYGTGLVLFILVLVIVIICRMKMPNKKAMNTTTV

Xenopus laevis                SSSITVLIVVTSTIVFILLVIIVITHLMKVPSKKSMTAPPV

Zebrafish                     --YADILIYVTSCVLFILTMVIIILCRMWINTQKTLPAPPV

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 23 – 806 Fibroblast growth factor receptor 3
Transmembrane 376 – 396 Helical
Alternative sequence 311 – 422 Missing. In isoform 3.
Helix 374 – 398


Literature citations

Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.
Meyers G.A.; Orlow S.J.; Munro I.R.; Przylepa K.A.; Jabs E.W.;
Nat. Genet. 11:462-464(1995)
Cited for: VARIANT CAN GLU-391;

Crouzon with acanthosis nigricans. Further delineation of the syndrome.
Arnaud-Lopez L.; Fragoso R.; Mantilla-Capacho J.; Barros-Nunez P.;
Clin. Genet. 72:405-410(2007)
Cited for: VARIANT CAN GLU-391;

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.