UniProtKB/Swiss-Prot P04150: Variant p.Val571Ala

Glucocorticoid receptor
Gene: NR3C1
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Variant information Variant position:

571 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 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.

Variant rs104893911 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
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.