UniProtKB/Swiss-Prot P11362: Variant p.Pro772Ser

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 772 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Proline (P) to Serine (S) at position 772 (P772S, p.Pro772Ser). 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 small size and polar (S) 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
Other resources: Links to websites of interest for the variant.

• Variant rs56234888 [ dbSNP | Ensembl ]

Sequence information

Variant position: 772 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 822 The length of the canonical sequence.
Location on the sequence: EDLDRIVALTSNQEYLDLSM P LDQYSPSFPDTRSSTCSSGE 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.
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 – 822	Fibroblast growth factor receptor 1
Topological domain	398 – 822	Cytoplasmic
Site	766 – 766	Mediates interaction with PLCG1 and SHB
Modified residue	766 – 766	Phosphotyrosine; by autocatalysis
Alternative sequence	62 – 822	Missing. In isoform 3.
Alternative sequence	151 – 822	Missing. In isoform 16.
Alternative sequence	392 – 822	Missing. In isoform 17 and isoform 18.
Alternative sequence	663 – 822	Missing. In isoform 2, isoform 5, isoform 7, isoform 9, isoform 11 and isoform 13.
Mutagenesis	755 – 755	D -> V. Abolishes interaction with PLCG1.
Mutagenesis	766 – 766	Y -> F. Abolishes interaction with PLCG1 and SHB. Decreases phosphorylation of FRS2, activation of RAS and MAP kinase signaling and stimulation of cell proliferation.

Literature citations

Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.
Dode C.; Levilliers J.; Dupont J.-M.; De Paepe A.; Le Du N.; Soussi-Yanicostas N.; Coimbra R.S.; Delmaghani S.; Compain-Nouaille S.; Baverel F.; Pecheux C.; Le Tessier D.; Cruaud C.; Delpech M.; Speleman F.; Vermeulen S.; Amalfitano A.; Bachelot Y.; Bouchard P.; Cabrol S.; Carel J.-C.; Delemarre-van de Waal H.; Goulet-Salmon B.; Kottler M.-L.; Richard O.; Sanchez-Franco F.; Saura R.; Young J.; Petit C.; Hardelin J.-P.;
Nat. Genet. 33:463-465(2003)
Cited for: VARIANTS HH2 ASP-97; CYS-99; SER-167; TYR-277; MET-607; 622-ARG--ARG-822 DEL; ARG-666 AND ARG-719; VARIANT SER-772; Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis.
Dode C.; Fouveaut C.; Mortier G.; Janssens S.; Bertherat J.; Mahoudeau J.; Kottler M.-L.; Chabrolle C.; Gancel A.; Francois I.; Devriendt K.; Wolczynski S.; Pugeat M.; Pineiro-Garcia A.; Murat A.; Bouchard P.; Young J.; Delpech M.; Hardelin J.-P.;
Hum. Mutat. 28:97-98(2007)
Cited for: VARIANTS HH2 PHE-101; TRP-250; ASP-270; ARG-283; 324-GLU--ARG-822 DEL; CYS-332; ARG-621; 661-ARG--ARG-822 DEL; PHE-685 AND PHE-693; VARIANTS LYS-77; SER-772 AND CYS-822;