UniProtKB/Swiss-Prot P30968: Variant p.Arg262Gln

Gonadotropin-releasing hormone receptor
Gene: GNRHR
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Variant information Variant position:

262 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 262 (R262Q, p.Arg262Gln). 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 HH7; uncertain significance; some patients also carry mutations in FGFR1; minimal effects upon receptor affinity but expression decreased; altered activation of phospholipase C. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs104893837 [ dbSNP | Ensembl ]

Sequence information Variant position:

262 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

328 The length of the canonical sequence.
Location on the sequence:

LHQDPHELQLNQSKNNIPRA R LKTLKMTVAFATSFTVCWTP 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                         LHQDPHELQLNQSKNNIPRARLKTLKMTVAFATSFTVCWTP

                              LHQDPHELQLNQSKNNIPRARLRTLKMTVAFATSFTVCWTP

Mouse                         LHQDPRKLQLNQSKNNIPRARLRTLKMTVAFATSFVVCWTP

Rat                           LHQDPRKLQLNQSKNNIPRARLRTLKMTVAFGTSFVICWTP

Pig                           LQQDPHNLQLNQSKNNIPRARLRTLKMTVAFAASFIVCWTP

Bovine                        LHQDPHKLQLNQSKNNIPRARLRTLKMTVAFATSFTVCWTP

Sheep                         LHQDPHKLQLNQSKNNIPQARLRTLKMTVAFATSFTVCWTP

Horse                         LHQDPHKLQLNQSKNNIPRARLRTLKMTVAFATSFTVCWTP

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	1 – 328	Gonadotropin-releasing hormone receptor
Topological domain	233 – 281	Cytoplasmic
Alternative sequence	176 – 328	YIFRMIHLADSSGQTKVFSQCVTHCSFSQWWHQAFYNFFTFSCLFIIPLFIMLICNAKIIFTLTRVLHQDPHELQLNQSKNNIPRARLKTLKMTVAFATSFTVCWTPYYVLGIWYWFDPEMLNRLSDPVNHFFFLFAFLNPCFDPLIYGYFSL -> PLHHPSFHHADLQCKNHLHPDTGPSSGPPRTTTESVQEQYTKSTAEDSKNDGCICHFIYCLLDSLLCPRNLVLV. In isoform 2.
Helix	260 – 292

Literature citations
A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor.
de Roux N.; Young J.; Misrahi M.; Genet R.; Chanson P.; Schaison G.; Milgrom E.;
N. Engl. J. Med. 337:1597-1602(1997)
Cited for: VARIANTS HH7 ARG-106 AND GLN-262; CHARACTERIZATION OF VARIANTS HH7 ARG-106 AND GLN-262; Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism.
Layman L.C.; Cohen D.P.; Jin M.; Xie J.; Li Z.; Reindollar R.H.; Bolbolan S.; Bick D.P.; Sherins R.R.; Duck L.W.; Musgrove L.C.; Sellers J.C.; Neill J.D.;
Nat. Genet. 18:14-15(1998)
Cited for: VARIANTS HH7 GLN-262 AND CYS-284; CHARACTERIZATION OF VARIANTS HH7 GLN-262 AND CYS-284; The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.
de Roux N.; Young J.; Brailly-Tabard S.; Misrahi M.; Milgrom E.; Schaison G.;
J. Clin. Endocrinol. Metab. 84:567-572(1999)
Cited for: VARIANTS HH7 ARG-106; ARG-217 AND GLN-262; CHARACTERIZATION OF VARIANTS HH7 ARG-106; ARG-217 AND GLN-262; Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration.
Caron P.; Chauvin S.; Christin-Maitre S.; Bennet A.; Lahlou N.; Counis R.; Bouchard P.; Kottler M.-L.;
J. Clin. Endocrinol. Metab. 84:990-996(1999)
Cited for: VARIANTS HH7 ASP-129 AND GLN-262; CHARACTERIZATION OF VARIANT HH7 ASP-129; 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 HH7 VAL-83; ARG-106 AND GLN-262; 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 HH7 SER-18; SER-37; ASP-90; ARG-106; ASP-129; HIS-139; SER-146; GLN-262 AND ARG-266;

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.