• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
NR3C2 (HGNC:7979) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
nuclear receptor subfamily 3 group C member 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
MLR
Alias symbols
MR
%HI
4.63(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.84(Read more about gnomAD pLI score)
LOEUF
0.35(Read more about gnomAD LOEUF score)
Cytoband
4q31
Genomic Coordinates
GRCh37/hg19: chr4:148999915-149365850 NCBI Ensembl UCSC
GRCh38/hg38: chr4:148078764-148445508 NCBI Ensembl UCSC
MANE Select Transcript
NM_000901.5 ENST00000358102.8 (Read more about MANE Select)
Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. {ECO:0000269|PubMed:3037703}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-37111
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
04/06/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • autosomal dominant pseudohypoaldosteronism type 1 Monarch
HI Evidence:
  • PUBMED: 9662404
    Geller et al. (1998): Inactivating mutations in this gene were found to cause a relatively mild form of Pseudohypoaldosteronism type I (PHA1) that is autosomal dominant or sporadic in occurrence. The disease manifestations clear with age. A later study (Pujo et al., 2007, PMID: 16972228) performed a comprehensive genotyping study of 33 patients. A wide range of mutations were found across the gene, half of which were nonsense/frameshift. At least one (p.Arg590*) was proven to be haploinsufficient, although dominant negative effect for some of the mutations remains a possibility.
  • PUBMED: 16954160
    Riepe et al. (2006): The authors evaluated the molecular mechanisms of several frameshift and nonsense mutations using several in vitro experiments. They showed experimentally that destruction or inactivation of the ligand binding domain of the gene was likely the causative mechanism for PHA1 and they ruled out a dominant negative effect. These experiments suggest that haploinsufficiency is the cause of the disorder.
  • PUBMED: 27725360
    Kawashima Sonoyama et al. (2017): The authors reported a case of renal PHA1 due to a c.2889del mutation in the last exon of NR3C2. Although mRNA was produced, the protein product showed decreased function and no dominant negative effect.
HI Evidence Comments:
NR3C2 belongs to the nuclear receptor superfamily. The gene encodes mineralocorticoid receptor (MR), which is a ligand-dependent transcription factor with high affinity to aldosterone and glucocorticoids. Mutations in NR3C2 cause autosomal dominant Pseudohypoaldosteronism type I (PHA1). Missense, nonsense and frameshift mutations in NR3C2 have been found to cause PHA1. Although to date there are no reports of isolated complete gene deletion, in vitro and in silico analyses suggest haploinsufficiency as one of the mechanisms for the disorder.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000004.11) (NC_000004.12)