UniProtKB/Swiss-Prot P04150: Variant p.Val423Ala

Glucocorticoid receptor
Gene: NR3C1
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Variant information Variant position:

423 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 Valine (V) to Alanine (A) at position 423 (V423A, p.Val423Ala). 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
Variant description:

In GCCR; uncertain significance; reduces transactivation activity; delays nuclear translocation; does not exert a dominant negative effect; impairs DNA binding. Any additional useful information about the variant.

Sequence information Variant position:

423 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:

SSPPSSSSTATTGPPPKLCL V CSDEASGCHYGVLTCGSCKV 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                         SSPPSSSSTATTGPPPKLCLVCSDEASGCHYGVLTCGSCKV

Mouse                         SSPPSSSSTA-TGPPPKLCLVCSDEASGCHYGVLTCGSCKV

Rat                           SSPPSSSSAA-TGPPPKLCLVCSDEASGCHYGVLTCGSCKV

Pig                           SSPPSSSSAA-TGPPPKLCLVCSDEASGCHYGVLTCGSCKV

Rabbit                        SSPPSNSTTA-AGPPPKLCLVCSDEASGCHYGVLTCGSCKV

Xenopus laevis                SPSPSTSSTS-TGPPPKLCLVCSDEASGCHYGVLTCGSCKV

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
DNA binding	418 – 493	Nuclear receptor
Zinc finger	421 – 441	NR C4-type
Modified residue	404 – 404	Phosphoserine; by GSK3-beta
Cross	419 – 419	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	404 – 404	S -> A. Abolishes phosphorylation. Does not affect translocation to the nucleus following ligand stimulation. Increases protein half-life and transcriptional repressor activity. Alters repertoire of regulated genes. Increases cell death.
Mutagenesis	404 – 404	S -> D. Does not affect translocation to the nucleus following ligand stimulation.
Turn	422 – 424

Literature citations
A novel point mutation in the DNA-binding domain (DBD) of the human glucocorticoid receptor causes primary generalized glucocorticoid resistance by disrupting the hydrophobic structure of its DBD.
Roberts M.L.; Kino T.; Nicolaides N.C.; Hurt D.E.; Katsantoni E.; Sertedaki A.; Komianou F.; Kassiou K.; Chrousos G.P.; Charmandari E.;
J. Clin. Endocrinol. Metab. 98:E790-E795(2013)
Cited for: CHARACTERIZATION OF VARIANT GCCR ALA-423;

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.