UniProtKB/Swiss-Prot P08235: Variant p.Glu972Gly

Mineralocorticoid receptor
Gene: NR3C2
Chromosomal location: 4q31.1
Variant information

Variant position:  972
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Glutamate (E) to Glycine (G) at position 972 (E972G, p.Glu972Gly).
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 acidic (E) to glycine (G)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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 PHA1A; reduces affinity for aldosterone and transcription transactivation.
Any additional useful information about the variant.



Sequence information

Variant position:  972
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  984
The length of the canonical sequence.

Location on the sequence:   LKVEFPAMLVEIISDQLPKV  E SGNAKPLYFHRK
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                         LKVEFPAMLVEIISDQLPKVESGNAKPLYFHRK

Mouse                         LKVEFPAMLVEIISDQLPKVESGNAKPLYFHRK

Rat                           LKVEFPAMLVEIITDQLPKVESGNAKPLYFHRK

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 – 984 Mineralocorticoid receptor
Region 733 – 984 Steroid-binding
Alternative sequence 707 – 984 Missing. In isoform 2.
Mutagenesis 952 – 952 L -> A. Reduces transcription transactivation.
Mutagenesis 953 – 953 K -> A. Slightly reduces aldosterone binding and abolishes transcription transactivation.
Mutagenesis 954 – 954 V -> A. Reduces aldosterone binding and abolishes transcription transactivation.
Mutagenesis 956 – 956 F -> A. Abolishes aldosterone binding and transcription transactivation.
Mutagenesis 957 – 957 P -> A. Slightly reduces aldosterone binding and transcription transactivation.
Helix 958 – 972


Literature citations

Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1.
Riepe F.G.; Finkeldei J.; de Sanctis L.; Einaudi S.; Testa A.; Karges B.; Peter M.; Viemann M.; Groetzinger J.; Sippell W.G.; Fejes-Toth G.; Krone N.;
J. Clin. Endocrinol. Metab. 91:4552-4561(2006)
Cited for: CHARACTERIZATION OF VARIANTS PHA1A LEU-818 AND GLY-972;

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.