UniProtKB/Swiss-Prot P04150: Variant p.Arg714Gln

Glucocorticoid receptor
Gene: NR3C1
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Variant information Variant position:

714 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 Arginine (R) to Glutamine (Q) at position 714 (R714Q, p.Arg714Gln). 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 large size and basic (R) to medium size and polar (Q) 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
Variant description:

In GCCR; uncertain significance; reduces transactivation; reduces affinity for ligand; exerts a dominant negative effect; does not impair DNA binding. Any additional useful information about the variant.

Sequence information Variant position:

714 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:

IKELGKAIVKREGNSSQNWQ R FYQLTKLLDSMHEVVENLLN 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                         IKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVVENLLN

Mouse                         IKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHDVVENLLS

Rat                           IKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVVENLLT

Pig                           IKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHDVVENLLN

Rabbit                        IKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVVENLLH

Xenopus laevis                IKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVAENLLA

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
Cross	703 – 703	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Mutagenesis	703 – 703	K -> R. Slightly reduces sumoylation. Inhibits the stimulatory effect of RWDD3 on its transcriptional activity.
Helix	708 – 741

Literature citations
A novel point mutation in helix 10 of the human glucocorticoid receptor causes generalized glucocorticoid resistance by disrupting the structure of the ligand-binding domain.
Nader N.; Bachrach B.E.; Hurt D.E.; Gajula S.; Pittman A.; Lescher R.; Kino T.;
J. Clin. Endocrinol. Metab. 95:2281-2285(2010)
Cited for: VARIANT GCCR GLN-714; CHARACTERIZATION OF VARIANT GCCR GLN-714;

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.