Home  |  Contact

UniProtKB/Swiss-Prot P04150: Variant p.Val571Ala

Glucocorticoid receptor
Gene: NR3C1
Variant information

Variant position:  571
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Valine (V) to Alanine (A) at position 571 (V571A, p.Val571Ala).
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 hydrophobic (V) to small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  In pseudohermaphroditism; female with hypokalemia due to glucocorticoid resistance; 6-fold reduction in binding affinity compared with the wild-type receptor.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  571
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:   SVPDSTWRIMTTLNMLGGRQ  V IAAVKWAKAIPGFRNLHLDD
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                         SVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDD

Mouse                         SVPDSAWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDD

Rat                           SVPDSAWRIMTTLNMLGGRQVIAAVKWAKAILGLRNLHLDD

Pig                           SIPDSTWRIMTALNMLGGRQVIAAVKWAKAIPGFRNLHLDD

Rabbit                        SVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDD

Xenopus laevis                SIPDTTRRLMSSLNMLGGRQVVSAVRWAKAIPGFRNLHLDD

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.

TypePositionsDescription
Chain 1 – 777 Glucocorticoid receptor
Domain 524 – 758 NR LBD
Region 485 – 777 Interaction with CLOCK
Region 532 – 697 Interaction with CRY1
Alternative sequence 491 – 674 Missing. In isoform GR-A alpha and isoform GR-A beta.
Mutagenesis 585 – 585 R -> A. Reduces activation mediated by ligand binding domain; when associated with A-590.
Mutagenesis 590 – 590 D -> A. Reduces activation mediated by ligand binding domain; when associated with A-585.
Helix 556 – 579


Literature citations

Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene.
Mendonca B.B.; Leite M.V.; de Castro M.; Kino T.; Elias L.L.K.; Bachega T.A.S.; Arnhold I.J.P.; Chrousos G.P.; Latronico A.C.;
J. Clin. Endocrinol. Metab. 87:1805-1809(2002)
Cited for: VARIANT PSEUDOHERMAPHRODITISM ALA-571;

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.