UniProtKB/Swiss-Prot P11362: Variant p.Arg250Gln

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 250 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Arginine (R) to Glutamine (Q) at position 250 (R250Q, p.Arg250Gln). 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 large size and basic (R) to medium size and polar (Q) 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
Variant description: In HH2; with or without anosmia; results in Kallmann syndrome in the presence of HS6ST1 mutation TRP-306; reduces receptor affinity for fibroblast growth factor. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs121909645 [ dbSNP | Ensembl ]

Sequence information

Variant position: 250 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: CIVENEYGSINHTYQLDVVE R SPHRPILQAGLPANKTVALG 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	22 – 376	Extracellular
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.

Literature citations

Impaired fibroblast growth factor receptor 1 signaling as a cause of normosmic idiopathic hypogonadotropic hypogonadism.
Raivio T.; Sidis Y.; Plummer L.; Chen H.; Ma J.; Mukherjee A.; Jacobson-Dickman E.; Quinton R.; Van Vliet G.; Lavoie H.; Hughes V.A.; Dwyer A.; Hayes F.J.; Xu S.; Sparks S.; Kaiser U.B.; Mohammadi M.; Pitteloud N.;
J. Clin. Endocrinol. Metab. 94:4380-4390(2009)
Cited for: VARIANTS HH2 CYS-99; SER-117; ASP-228; THR-239; GLN-250; LEU-470; ASN-618 AND PRO-671; CHARACTERIZATION OF VARIANTS HH2 CYS-99; SER-117; ASP-228; THR-239; GLN-250; LEU-470; ASN-618 AND PRO-671; Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism.
Tornberg J.; Sykiotis G.P.; Keefe K.; Plummer L.; Hoang X.; Hall J.E.; Quinton R.; Seminara S.B.; Hughes V.; Van Vliet G.; Van Uum S.; Crowley W.F.; Habuchi H.; Kimata K.; Pitteloud N.; Bulow H.E.;
Proc. Natl. Acad. Sci. U.S.A. 108:11524-11529(2011)
Cited for: VARIANT HH2 GLN-250; Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.
Miraoui H.; Dwyer A.A.; Sykiotis G.P.; Plummer L.; Chung W.; Feng B.; Beenken A.; Clarke J.; Pers T.H.; Dworzynski P.; Keefe K.; Niedziela M.; Raivio T.; Crowley W.F. Jr.; Seminara S.B.; Quinton R.; Hughes V.A.; Kumanov P.; Young J.; Yialamas M.A.; Hall J.E.; Van Vliet G.; Chanoine J.P.; Rubenstein J.; Mohammadi M.; Tsai P.S.; Sidis Y.; Lage K.; Pitteloud N.;
Am. J. Hum. Genet. 92:725-743(2013)
Cited for: VARIANTS HH2 SER-117; ASP-228; THR-239; GLN-250; SER-342; ARG-348; LEU-470; THR-483; ASN-618; LYS-670; GLY-692; HIS-722; LYS-724 AND TYR-768; The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients.
Marcos S.; Sarfati J.; Leroy C.; Fouveaut C.; Parent P.; Metz C.; Wolczynski S.; Gerard M.; Bieth E.; Kurtz F.; Verier-Mine O.; Perrin L.; Archambeaud F.; Cabrol S.; Rodien P.; Hove H.; Prescott T.; Lacombe D.; Christin-Maitre S.; Touraine P.; Hieronimus S.; Dewailly D.; Young J.; Pugeat M.; Hardelin J.P.; Dode C.;
J. Clin. Endocrinol. Metab. 99:E2138-2143(2014)
Cited for: VARIANTS HH2 ARG-70; ILE-116; ALA-174; GLN-250 AND ARG-348;