UniProtKB/Swiss-Prot P11362: Variant p.Leu245Pro

Fibroblast growth factor receptor 1
Gene: FGFR1
Chromosomal location: 8p11.1-p11.2
Variant information

Variant position:  245
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 Leucine (L) to Proline (P) at position 245 (L245P, p.Leu245Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:147950]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:12627230, ECO:0000269|PubMed:15001591, ECO:0000269|PubMed:15605412, ECO:0000269|PubMed:15845591, ECO:0000269|PubMed:16606836, ECO:0000269|PubMed:16757108, ECO:0000269|PubMed:16764984, ECO:0000269|PubMed:16882753, ECO:0000269|PubMed:17154279, ECO:0000269|PubMed:19820032, ECO:0000269|PubMed:21700882, ECO:0000269|PubMed:22927827, ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900, ECO:0000269|PubMed:26277103}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FGFR1 also have a mutation other HH-associated genes including DUSP6, FGF8, FGF17, FLRT3, GNRH1, GNRHR, HS6ST1, IL17RD, ANOS1, KISS1R, NSMF, PROKR2, SPRY4 and TACR3 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.
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 HH2.
Any additional useful information about the variant.

Sequence information

Variant position:  245
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  822
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.

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 22 – 822 Fibroblast growth factor receptor 1
Topological domain 22 – 376 Extracellular
Domain 158 – 246 Ig-like C2-type 2
Glycosylation 227 – 227 N-linked (GlcNAc...) asparagine
Glycosylation 240 – 240 N-linked (GlcNAc...) asparagine
Glycosylation 264 – 264 N-linked (GlcNAc...) asparagine
Alternative sequence 62 – 822 Missing. In isoform 3.
Alternative sequence 151 – 822 Missing. In isoform 16.
Beta strand 237 – 248

Literature citations

Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia.
Trarbach E.B.; Costa E.M.F.; Versiani B.; de Castro M.; Baptista M.T.M.; Garmes H.M.; de Mendonca B.B.; Latronico A.C.;
J. Clin. Endocrinol. Metab. 91:4006-4012(2006)
Cited for: VARIANTS HH2 SER-48; PRO-245; TRP-250; VAL-343; LEU-366; SER-722 AND ILE-795;

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.