CYP21A2
cytochrome P450 family 21 subfamily A member 2
Theoretical — per Powers
Gene summary
A protein-coding gene on chromosome 6 (steroid hormone synthesis). Encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.
Source: NCBI Gene, accessed 2026-10-07.
Protein reference (UniProt)
- Protein
Steroid 21-hydroxylase
- Function
A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).
- Subcellular location
Endoplasmic reticulum membrane; Microsome membrane.
- Associated conditions
Adrenal hyperplasia 3 (AH3).
Source: UniProtKB/Swiss-Prot P08686, release 2026_03, licensed CC BY 4.0. This is the protein’s normal biology, not evidence about post-drug syndromes; associated conditions are inherited disorders of the gene, not PFS, PSSD or PRSD.
Why its pathway is in the library
Steroid-synthesis enzymes sit directly on the pathways perturbed by 5-alpha-reductase inhibitors and SSRIs; inherited variation here is a candidate susceptibility factor for persistent post-drug phenotypes.
Written for the whole steroid synthesis family, not for CYP21A2 specifically.
Powers’ note (his unpublished theorizing)
Named by Powers in adjacent (non-PFS) work (unpublished): hypothesized reduced functional CYP21A2 copies causing a subclinical adrenal-insufficiency picture with stress-induced androgen byproducts.
Narrative library record
Function
Adrenal endoplasmic-reticulum P450 (steroid 21-hydroxylase) required for cortisol and aldosterone synthesis, converting progesterone and 17-hydroxyprogesterone toward their 21-hydroxylated products; mutations are the cause of congenital adrenal hyperplasia.
Corpus relevance
Adjacent gene (not PFS-specific): from Powers' MTF subtype post (r/DrWillPowers/comments/1ctrlyu, circa 2016, direct retrieval), where he hypothesized that patients carrying fewer than two fully functional CYP21A2 copies (one normal plus one weak, two weak, or a single weak copy) develop a subclinical adrenal-insufficiency picture - poor stress tolerance with paradoxical stress-induced androgen byproducts, including elevated 11-oxo-androgens on Labcorp panels. Low-dose hydrocortisone reportedly helped selected patients. Included as adjacent methodology context for Powers' gene-hunting approach; flagged as not a PFS claim. Attribution: theoretical-per-Powers (adjacent, trans-HRT context).
Powers’ claims naming CYP21A2
- Powers gene claim
CYP21A2; CYP21A2P — hypothesized reduced functional copies (one normal + one weak, two weak, single weak) or extra transcribed pseudogene copies
Confidence: direct (adjacent)
Some patients may carry fewer than two fully functional CYP21A2 copies, producing a subclinical adrenal-insufficiency picture: poor stress tolerance with paradoxical androgen byproduct synthesis (elevated 11-oxo-androgens on Labcorp panel) during stress…
CYP21A2CYP21A2PPGL-CYP21A2-CYP21A2P2016PFS
Mentioned in 2 corpus records
- Gene recordPowers’ theory
CYP21A2P — cytochrome P450 family 21 subfamily A member 2, pseudogene (HGNC: CYP21A1P)
6p21.3 (approx. 30 kb from CYP21A2)
Nonfunctional pseudogene sharing about 98 percent exon sequence identity with CYP21A2, carrying deteriorating mutations (frameshifts, premature stop codons); it acts as the reservoir for gene-conversion events that create most pathogenic CYP21A2 alleles.
CYP11A1CYP21A2CYP21A2PGENE-CYP21A2PPFSCore corpus - Gene recordPowers’ theory
Mitochondrial P450 (P450scc, cholesterol side-chain cleavage enzyme) catalyzing the first, rate-limiting step of steroidogenesis - three sequential reactions converting cholesterol to pregnenolone; severe loss disrupts all adrenal and gonadal steroid…
CYP11A1CYP17A1CYP21A2HSD3B2GENE-CYP11A1PFSCore corpus
Also in steroid hormone synthesis
All 38 genes- SRD5A2
steroid 5 alpha-reductase 2
chr 2· Steroid synthesis· 19 records - SRD5A1Powers
steroid 5 alpha-reductase 1
chr 5· Steroid synthesis· 17 records - AKR1C2Powers
aldo-keto reductase family 1 member C2
chr 10· Steroid synthesis· 12 records - AKR1C3Powers
aldo-keto reductase family 1 member C3
chr 10· Steroid synthesis· 9 records - CYP17A1
cytochrome P450 family 17 subfamily A member 1
chr 10· Steroid synthesis· 9 records - AKR1C4Powers
aldo-keto reductase family 1 member C4
chr 10· Steroid synthesis· 8 records - AKR1C1Powers
aldo-keto reductase family 1 member C1
chr 10· Steroid synthesis· 7 records - HSD3B2
hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2
chr 1· Steroid synthesis· 7 records
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