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NM_000176.3(NR3C1):c.2209T>C (p.Phe737Leu) AND Glucocorticoid resistance

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 1, 2006
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000017541.27

Allele description [Variation Report for NM_000176.3(NR3C1):c.2209T>C (p.Phe737Leu)]

NM_000176.3(NR3C1):c.2209T>C (p.Phe737Leu)

Gene:
NR3C1:nuclear receptor subfamily 3 group C member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q31.3
Genomic location:
Preferred name:
NM_000176.3(NR3C1):c.2209T>C (p.Phe737Leu)
HGVS:
  • NC_000005.10:g.143282014A>G
  • NG_009062.1:g.158499T>C
  • NM_000176.3:c.2209T>CMANE SELECT
  • NM_001018074.1:c.2209T>C
  • NM_001018075.1:c.2209T>C
  • NM_001018076.2:c.2209T>C
  • NM_001018077.1:c.2209T>C
  • NM_001020825.2:c.2181+554T>C
  • NM_001024094.2:c.2212T>C
  • NM_001204258.2:c.2131T>C
  • NM_001204259.2:c.1954T>C
  • NM_001204260.2:c.1942T>C
  • NM_001204261.2:c.1918T>C
  • NM_001204262.2:c.1264T>C
  • NM_001204263.2:c.1219T>C
  • NM_001204264.2:c.1204T>C
  • NM_001364180.2:c.2209T>C
  • NM_001364181.2:c.2209T>C
  • NM_001364182.1:c.2209T>C
  • NM_001364183.2:c.2212T>C
  • NM_001364184.2:c.2212T>C
  • NM_001364185.1:c.2212T>C
  • NP_000167.1:p.Phe737Leu
  • NP_001018084.1:p.Phe737Leu
  • NP_001018085.1:p.Phe737Leu
  • NP_001018086.1:p.Phe737Leu
  • NP_001018087.1:p.Phe737Leu
  • NP_001019265.1:p.Phe738Leu
  • NP_001191187.1:p.Phe711Leu
  • NP_001191188.1:p.Phe652Leu
  • NP_001191189.1:p.Phe648Leu
  • NP_001191190.1:p.Phe640Leu
  • NP_001191191.1:p.Phe422Leu
  • NP_001191192.1:p.Phe407Leu
  • NP_001191193.1:p.Phe402Leu
  • NP_001351109.1:p.Phe737Leu
  • NP_001351110.1:p.Phe737Leu
  • NP_001351111.1:p.Phe737Leu
  • NP_001351112.1:p.Phe738Leu
  • NP_001351113.1:p.Phe738Leu
  • NP_001351114.1:p.Phe738Leu
  • NC_000005.9:g.142661579A>G
  • NR_157096.2:n.1132T>C
  • P04150:p.Phe737Leu
Protein change:
F402L; PHE737LEU
Links:
UniProtKB: P04150#VAR_071935; OMIM: 138040.0015; dbSNP: rs121909727
NCBI 1000 Genomes Browser:
rs121909727
Molecular consequence:
  • NM_001020825.2:c.2181+554T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000176.3:c.2209T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018074.1:c.2209T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018075.1:c.2209T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018076.2:c.2209T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018077.1:c.2209T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024094.2:c.2212T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204258.2:c.2131T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204259.2:c.1954T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204260.2:c.1942T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204261.2:c.1918T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204262.2:c.1264T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204263.2:c.1219T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204264.2:c.1204T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364180.2:c.2209T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364181.2:c.2209T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364182.1:c.2209T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364183.2:c.2212T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364184.2:c.2212T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364185.1:c.2212T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_157096.2:n.1132T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Glucocorticoid resistance
Synonyms:
Glucocorticoid resistance, generalized; Gccr deficiency; Glucocorticoid receptor deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0014421; MedGen: C1841972; Orphanet: 786; OMIM: 615962

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000037813OMIM
no assertion criteria provided
Pathogenic
(Apr 1, 2006) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Functional characterization of the natural human glucocorticoid receptor (hGR) mutants hGRalphaR477H and hGRalphaG679S associated with generalized glucocorticoid resistance.

Charmandari E, Kino T, Ichijo T, Zachman K, Alatsatianos A, Chrousos GP.

J Clin Endocrinol Metab. 2006 Apr;91(4):1535-43. Epub 2006 Jan 31.

PubMed [citation]
PMID:
16449337

Details of each submission

From OMIM, SCV000037813.5

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

Description

In a boy with generalized glucocorticoid resistance (GCCR; 615962), Charmandari et al. (2007) identified a 2209T-C transition in exon 9 of the GR-alpha gene, resulting in a phe737-to-leu (F737L) substitution within helix 11 of the ligand-binding domain of the protein. Compared to wildtype, the mutant receptor demonstrated decreased affinity for the ligand, marked delay in nuclear translocation, and/or abnormal interaction with the GR-interacting protein-1 coactivator (NCOA2; 601993). Charmandari et al. (2007) concluded that these findings confirm the importance of the C terminus of the ligand-binding domain of the receptor in conferring transactivational activity.

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

Last Updated: Apr 23, 2022