NM_000901.4(NR3C2):c.2453C>T (p.Ser818Leu) AND Pseudohypoaldosteronism type 1 autosomal dominant

Clinical significance:Pathogenic (Last evaluated: Nov 1, 2006)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000009102.3

Allele description [Variation Report for NM_000901.4(NR3C2):c.2453C>T (p.Ser818Leu)]

NM_000901.4(NR3C2):c.2453C>T (p.Ser818Leu)

Gene:
NR3C2:nuclear receptor subfamily 3 group C member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q31.23
Genomic location:
Preferred name:
NM_000901.4(NR3C2):c.2453C>T (p.Ser818Leu)
HGVS:
  • NC_000004.12:g.148152526G>A
  • NG_013350.1:g.294996C>T
  • NM_000901.4:c.2453C>T
  • NM_001166104.1:c.2102C>T
  • NP_000892.2:p.Ser818Leu
  • NP_001159576.1:p.Ser701Leu
  • NC_000004.11:g.149073677G>A
Protein change:
S181L; SER181LEU
Links:
OMIM: 600983.0019; dbSNP: rs121912573
NCBI 1000 Genomes Browser:
rs121912573
Molecular consequence:
  • NM_000901.4:c.2453C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Pseudohypoaldosteronism type 1 autosomal dominant (PHA1A)
Synonyms:
Pseudohypoaldosteronism, Type I, Autosomal Dominant; PHA I, AUTOSOMAL DOMINANT; Pseudohypoaldosteronism, Type I, Dominant
Identifiers:
MedGen: C1449842; Orphanet: 171871; Orphanet: 756; OMIM: 177735

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000029319OMIMno assertion criteria providedPathogenic
(Nov 1, 2006)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1.

Riepe FG, Finkeldei J, de Sanctis L, Einaudi S, Testa A, Karges B, Peter M, Viemann M, Grötzinger J, Sippell WG, Fejes-Toth G, Krone N.

J Clin Endocrinol Metab. 2006 Nov;91(11):4552-61. Epub 2006 Sep 5.

PubMed [citation]
PMID:
16954160

Autosomal dominant pseudohypoaldosteronism type 1: mechanisms, evidence for neonatal lethality, and phenotypic expression in adults.

Geller DS, Zhang J, Zennaro MC, Vallo-Boado A, Rodriguez-Soriano J, Furu L, Haws R, Metzger D, Botelho B, Karaviti L, Haqq AM, Corey H, Janssens S, Corvol P, Lifton RP.

J Am Soc Nephrol. 2006 May;17(5):1429-36. Epub 2006 Apr 12.

PubMed [citation]
PMID:
16611713

Details of each submission

From OMIM, SCV000029319.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In 2 sibs with PHA1 (177735) and their father, Riepe et al. (2006) detected a C-to-T transition at nucleotide 2453 in exon 6 of the NR3C1 gene, resulting in substitution of leu for ser at codon 181 (S181L). This mutation had been reported by Geller et al. (2006). The S181L mutant showed no aldosterone binding, transcription activation, or translocation to the nucleus. Based on in vitro studies Riepe et al. (2006) hypothesized that substitution of the bulky apolar leucine for serine-818 displaces beta-sheet-1, which severely disturbs the interaction of the receptor with its ligand.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 24, 2018