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Literature summary for 1.14.14.16 extracted from

  • Gaffney, D.; Howie, A.; Bakkush, A.; Hoffmann, T.; Mason, J.; Wallace, A.; Donaldson, M.
    Functional characterisation of the H365Y mutation of the 21-hydroxylase gene in congenital adrenal hyperplasia (2011), J. Steroid Biochem. Mol. Biol., 123, 109-114.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
gene CYP21A2, DNA and amino acid sequence determination and analysis, genotyping. Recombinant expression of mutant H365Y/R356W in HEK-293T cells Homo sapiens
gene CYP21A2, genotyping, expression of wild-type and mutant enzymes in HEK-293T and hepatoblastoma C3A cells, the H365Y enzyme is produced in more variable amounts than wild-type CYP21A2 Homo sapiens

Protein Variants

Protein Variants Comment Organism
H365W the naturally occuring CYP21A2 mutant exhibits minimal 21-hydroxylase activity to convert 17-hydroxyprogesterone to 11-deoxycortisol or progesterone to 11-deoxycorticosterone compared to the wild-type Homo sapiens
H365Y the naturally occuring CYP21A2 mutant exhibits minimal 21-hydroxylase activity to convert 17-hydroxyprogesterone to 11-deoxycortisol or progesterone to 11-deoxycorticosterone compared to the wild-type Homo sapiens
H365Y/R356W a naturally occuring 21-hydroxylase mutation in the CYP21A2 gene, that is involved in congenital adrenal hyperplasia, an autosomal recessive disorder, phenotype, overview. The H365Y enzyme is produced in more variable amounts than wild type Homo sapiens
H365Y/R356W heterozygote H365Y/R356W individuum for two CYP21A2 gene mutations each inherited from a different parent Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
17-hydroxyprogesterone + NADPH + H+ + O2 Homo sapiens
-
11-deoxycortisol + NADP+ + H2O
-
?
17alpha-hydroxyprogesterone + [reduced NADPH-P450 reductase] + O2 Homo sapiens
-
11-deoxycortisol + [oxidized NADPH-P450 reductase] + H2O
-
?
progesterone + NADPH + H+ + O2 Homo sapiens
-
11-deoxycorticosterone + NADP+ + H2O
-
?
progesterone + [reduced NADPH-P450 reductase] + O2 Homo sapiens
-
11-deoxycorticosterone + [oxidized NADPH-P450 reductase] + H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Homo sapiens
-
gene CYP21A2
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
17-hydroxyprogesterone + NADPH + H+ + O2
-
Homo sapiens 11-deoxycortisol + NADP+ + H2O
-
?
17alpha-hydroxyprogesterone + [reduced NADPH-P450 reductase] + O2
-
Homo sapiens 11-deoxycortisol + [oxidized NADPH-P450 reductase] + H2O
-
?
progesterone + NADPH + H+ + O2
-
Homo sapiens 11-deoxycorticosterone + NADP+ + H2O
-
?
progesterone + [reduced NADPH-P450 reductase] + O2
-
Homo sapiens 11-deoxycorticosterone + [oxidized NADPH-P450 reductase] + H2O
-
?

Synonyms

Synonyms Comment Organism
21-hydroxylase
-
Homo sapiens
CYP21A2
-
Homo sapiens

General Information

General Information Comment Organism
malfunction the naturally occuring 21-hydroxylase mutation H365Y/R356W is involved in congenital adrenal hyperplasia, an autosomal recessive The CYP21A2 H365Y mutant exhibits minimal 21-hydroxylase activity to convert 17-hydroxyprogesterone to 11-deoxycortisol or progesterone to 11-deoxycorticosterone. The H365Y mutant protein may be unstable and/or subject to a more rapid degradation by the human proteosome as well as catalytically inefficient. The double mutant genotype with a severe mutation on each allele is compatible with the clinical presentation Homo sapiens
malfunction mutations in the 21-hydroxylase CYP21A2 gene, e.g. H365Y, cause the autosomal recessive disorder congenital adrenal hyperplasia, phenotype, overview Homo sapiens