UniProtKB/Swiss-Prot P04150: Variant p.Asn363Ser

Glucocorticoid receptor
Gene: NR3C1
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Variant information Variant position:

363 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 Asparagine (N) to Serine (S) at position 363 (N363S, p.Asn363Ser). 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 polar (N) 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
Polymorphism:

Carriers of the 22-Glu-Lys-23 allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than non-carriers, resulting in a better metabolic health profile. Carriers have a better survival than non-carriers, as well as lower serum CRP levels. The 22-Glu-Lys-23 polymorphism is associated with a sex-specific, beneficial body composition at young-adult age, as well as greater muscle strength in males. Additional information on the polymorphism described.
Variant description:

Enhances transactivation activity; does not affect transrepression activity; may increase sensitivity to exogenously administered glucocorticoids; may contribute to central obesity in men and show lack of association with other risk factors for coronary heart disease and diabetes mellitus. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs56149945 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

QQQDQKPIFNVIPPIPVGSE N WNRCQGSGDDNLTSLGTLNF 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                         QQQDQKPIFNVIPPIPVGSENWNRCQGSGDDNLTSLGTLNF

Mouse                         QQQDQKPVFNVIPPIPVGSENWNRCQGSGEDNLTSLGAMNF

Rat                           QQQDQKPVFNVIPPIPVGSENWNRCQGSGEDSLTSLGALNF

Pig                           KQQEQKPLFNVIPPIPVGSENWNRCQGSGDDNLTSLGTLNF

Rabbit                        QQQEQKPLFNVIPPIPVGSENWNRCQGSGDDNLTSLGTMNF

Xenopus laevis                -QQDVKPVFNLGSPGTSIAEGWNRCHGSGNDTAASPGNVNF

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 – 777	Glucocorticoid receptor
Region	1 – 420	Modulating

Literature citations
Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene.
Karl M.; Lamberts S.W.J.; Detera-Wadleigh S.D.; Encio I.J.; Stratakis C.A.; Hurley D.M.; Accili D.; Chrousos G.P.;
J. Clin. Endocrinol. Metab. 76:683-689(1993)
Cited for: VARIANT SER-363; Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance.
Koper J.W.; Stolk R.P.; de Lange P.; Huizenga N.A.T.M.; Molijn G.-J.; Pols H.A.P.; Grobbee D.E.; Karl M.; de Jong F.H.; Brinkmann A.O.; Lamberts S.W.J.;
Hum. Genet. 99:663-668(1997)
Cited for: VARIANTS LYS-23 AND SER-363; Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS LYS-23; VAL-65 AND SER-363; Five missense variants in the amino-terminal domain of the glucocorticoid receptor: no association with puerperal psychosis or schizophrenia.
Feng J.; Zheng J.; Bennett W.P.; Heston L.L.; Jones I.R.; Craddock N.; Sommer S.S.;
Am. J. Med. Genet. 96:412-417(2000)
Cited for: VARIANTS LYS-23; LEU-29; PHE-112; ASN-233 AND SER-363; The N363S polymorphism of the glucocorticoid receptor: potential contribution to central obesity in men and lack of association with other risk factors for coronary heart disease and diabetes mellitus.
Dobson M.G.; Redfern C.P.F.; Unwin N.; Weaver J.U.;
J. Clin. Endocrinol. Metab. 86:2270-2274(2001)
Cited for: VARIANT SER-363; Two polymorphisms in the glucocorticoid receptor gene directly affect glucocorticoid-regulated gene expression.
Russcher H.; Smit P.; van den Akker E.L.; van Rossum E.F.; Brinkmann A.O.; de Jong F.H.; Lamberts S.W.; Koper J.W.;
J. Clin. Endocrinol. Metab. 90:5804-5810(2005)
Cited for: VARIANTS LYS-23 AND SER-363; CHARACTERIZATION OF VARIANTS LYS-23 AND SER-363;

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.