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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04150: Variant p.Arg23Lys

Glucocorticoid receptor
Gene: NR3C1
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Variant information Variant position: help 23
Type of variant: help LB/B
Residue change: help From Arginine (R) to Lysine (K) at position 23 (R23K, p.Arg23Lys).
Physico-chemical properties: help Similar physico-chemical property. Both residues are large size and basic.
BLOSUM score: help 2
Polymorphism: help 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.
Variant description: help Reduces transactivation activity; does not affect transrepression activity.
Other resources: help


Sequence information Variant position: help 23
Protein sequence length: help 777
Location on the sequence: help SKESLTPGREENPSSVLAQE R GDVMDFYKTLRGGATVKVSA
Residue conservation: help
Human                         SKESLTP--GREENPSSVL-AQERGDVMDFYKTLRGGATVKVSA

Mouse                         SKESLAP-PGRDEVPSSLL-GRGRGSVMDLYKTLRGGATVK

Rat                           SKESLAP-PGRDEVPGSLL-GQGRGSVMDFYKSLRGGATVK

Pig                           PKESLTP-PSREEIPSSVL-GRERAHVMDFYKSLRGGTPVK

Rabbit                        SKESLSP-PGREEVPSSVLRPAERGNVMDLYKTLRGGAPVR

Xenopus laevis                PKDLLKPSSGSPAVRGSPHYNDKPGNVIEFFGNYRGGVSVS

Sequence annotation in neighborhood: help
TypePositionsDescription
Chain 1 – 777 Glucocorticoid receptor
Region 1 – 420 Modulating
Region 1 – 23 Disordered
Modified residue 8 – 8 Phosphothreonine
Modified residue 23 – 23 Omega-N-methylarginine
Alternative sequence 1 – 335 Missing. In isoform Alpha-D3.
Alternative sequence 1 – 330 Missing. In isoform Alpha-D2.
Alternative sequence 1 – 315 Missing. In isoform Alpha-D1.
Alternative sequence 1 – 97 Missing. In isoform Alpha-C3.
Alternative sequence 1 – 89 Missing. In isoform Alpha-C2.
Alternative sequence 1 – 85 Missing. In isoform Alpha-C1.
Alternative sequence 1 – 26 Missing. In isoform Alpha-B and isoform Beta-B.
Mutagenesis 27 – 27 M -> T. Abolishes expression of B-type isoforms.



Literature citations
Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LYS-23 AND VAL-65; 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; A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels.
van Rossum E.F.C.; Koper J.W.; Huizenga N.A.T.M.; Uitterlinden A.G.; Janssen J.A.M.J.L.; Brinkmann A.O.; Grobbee D.E.; de Jong F.H.; van Duyn C.M.; Pols H.A.P.; Lamberts S.W.J.;
Diabetes 51:3128-3134(2002)
Cited for: VARIANT LYS-23; Association of the ER22/23EK polymorphism in the glucocorticoid receptor gene with survival and C-reactive protein levels in elderly men.
van Rossum E.F.C.; Feelders R.A.; van den Beld A.W.; Uitterlinden A.G.; Janssen J.A.M.J.L.; Ester W.; Brinkmann A.O.; Grobbee D.E.; de Jong F.H.; Pols H.A.P.; Koper J.W.; Lamberts S.W.J.;
Am. J. Med. 117:158-162(2004)
Cited for: VARIANT LYS-23; The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults.
van Rossum E.F.C.; Voorhoeve P.G.; te Velde S.J.; Koper J.W.; Delemarre-van de Waal H.A.; Kemper H.C.G.; Lamberts S.W.J.;
J. Clin. Endocrinol. Metab. 89:4004-4009(2004)
Cited for: VARIANT LYS-23; 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.