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NM_000500.9(CYP21A2):c.361A>C (p.Lys121Gln) AND Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 1, 2008
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:
RCV000012966.4

Allele description [Variation Report for NM_000500.9(CYP21A2):c.361A>C (p.Lys121Gln)]

NM_000500.9(CYP21A2):c.361A>C (p.Lys121Gln)

Genes:
LOC106780800:CYP21A2 recombination region [Gene]
CYP21A2:cytochrome P450 family 21 subfamily A member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.33
Genomic location:
Preferred name:
NM_000500.9(CYP21A2):c.361A>C (p.Lys121Gln)
HGVS:
  • NC_000006.12:g.32039162A>C
  • NG_007941.3:g.5858A>C
  • NG_008337.2:g.75213T>G
  • NG_045215.1:g.1391A>C
  • NM_000500.9:c.361A>CMANE SELECT
  • NM_001128590.4:c.271A>C
  • NM_001368143.2:c.-45A>C
  • NM_001368144.2:c.-45A>C
  • NP_000491.4:p.Lys121Gln
  • NP_001122062.3:p.Lys91Gln
  • LRG_829t1:c.361A>C
  • LRG_829:g.5858A>C
  • LRG_829p1:p.Lys121Gln
  • NC_000006.11:g.32006939A>C
Protein change:
K121Q; LYS121GLN
Links:
OMIM: 613815.0035; dbSNP: rs267606757
NCBI 1000 Genomes Browser:
rs267606757
Molecular consequence:
  • NM_001368143.2:c.-45A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001368144.2:c.-45A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000500.9:c.361A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128590.4:c.271A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Synonyms:
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency; CYP21 deficiency; 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia
Identifiers:
MONDO: MONDO:0008728; MedGen: C2936858; Orphanet: 90794; OMIM: 201910

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000033210OMIM
no assertion criteria provided
Pathogenic
(Jul 1, 2008) 		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 and structural consequences of a novel point mutation in the CYP21A2 gene causing congenital adrenal hyperplasia: potential relevance of helix C for P450 oxidoreductase-21-hydroxylase interaction.

Riepe FG, Hiort O, Grötzinger J, Sippell WG, Krone N, Holterhus PM.

J Clin Endocrinol Metab. 2008 Jul;93(7):2891-5. doi: 10.1210/jc.2007-2646. Epub 2008 Apr 29.

PubMed [citation]
PMID:
18445671

Details of each submission

From OMIM, SCV000033210.2

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

Description

In a female patient with nonclassic 21-hydroxylase deficiency (201910), Riepe et al. (2008) detected heterozygosity for a novel mutation in the CYP21A2 gene, a 364A-C transversion in exon 3 resulting in a lys121-to-gln substitution (K121Q). This mutation was present on the maternal allele; the paternal allele carried a P453S mutation (613815.0010). In vitro expression analysis of the mutant K121Q enzyme in transiently transfected COS-7 cells revealed reduced CYP21 activity of approximately 14.0% for the conversion of 17-hydroxyprogesterone and 19.5% for the conversion of progesterone. K121 is located on helix C in the CYP21 protein, which is part of the heme coordinating system. In addition, helix C is involved in the interaction with the electron-providing enzyme P450 oxidoreductase (124015). Riepe et al. (2008) hypothesized that the K121Q mutation impairs electron flux between P450 oxidoreductase and CYP21 and alters substrate affinity by displacing the heme coordination site.

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

Last Updated: Apr 23, 2022