CYP21A2

Protein identityUniProt · HPA

UniProt accession

P08686

Gene

CYP21A2

Ensembl

ENSG00000231852

Chromosome

6

Canonical length

495 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

OverviewNCBI Gene

This gene 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. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

495 residues, UniProt reviewed canonical sequence.

>P08686|CYP21A2
     1  MLLLGLLLLL PLLAGARLLW NWWKLRSLHL PPLAPGFLHL LQPDLPIYLL GLTQKFGPIY
    61  RLHLGLQDVV VLNSKRTIEE AMVKKWADFA GRPEPLTYKL VSRNYPDLSL GDYSLLWKAH
   121  KKLTRSALLL GIRDSMEPVV EQLTQEFCER MRAQPGTPVA IEEEFSLLTC SIICYLTFGD
   181  KIKDDNLMPA YYKCIQEVLK TWSHWSIQIV DVIPFLRFFP NPGLRRLKQA IEKRDHIVEM
   241  QLRQHKESLV AGQWRDMMDY MLQGVAQPSM EEGSGQLLEG HVHMAAVDLL IGGTETTANT
   301  LSWAVVFLLH HPEIQQRLQE ELDHELGPGA SSSRVPYKDR ARLPLLNATI AEVLRLRPVV
   361  PLALPHRTTR PSSISGYDIP EGTVIIPNLQ GAHLDETVWE RPHEFWPDRF LEPGKNSRAL
   421  AFGCGARVCL GEPLARLELF VVLTRLLQAF TLLPSGDALP SLQPLPHCSV ILKMQPFQVR
   481  LQPRGMGAHS PGQSQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CYP21A2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

2,047 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CYP21A2.

Disease | AllUniProt

Conditions CYP21A2 is implicated in, by any mechanism.

• Adrenal hyperplasia 3 (AH3) MIM:201910

Disease | GeneticClinVar

118 pathogenic / likely-pathogenic of 365 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia
• CYP21A2-related disorder
• Congenital adrenal hyperplasia
• Inborn genetic diseases
• Carcinoma, adrenocortical, androgen-secreting

Disease | ImmuneIEDB

Conditions an epitope on CYP21A2 was assayed in.

• Addison's disease T cell
• autoimmune disease of endocrine system T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against CYP21A2 are reported. Each links to that disease's full target list.

• Addison Disease 12
• Polyendocrinopathies, Autoimmune 5

Showing 2 of 3 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for CYP21A2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.82

gnomAD pLI

0

gnomAD missense Z

1.15

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cortisol biosynthetic process
• glucocorticoid biosynthetic process
• mineralocorticoid biosynthetic process
• steroid biosynthetic process
• steroid metabolic process
• sterol metabolic process

Molecular functions

• heme binding
• iron ion binding
• steroid binding
• steroid hydroxylase activity
• 17-hydroxyprogesterone 21-hydroxylase activity
• progesterone 21-hydroxylase activity
• steroid 21-monooxygenase activity

Cellular components

• endoplasmic reticulum membrane

Protein domainsUniProt · Pfam · InterPro

• Cytochrome P450
• Cytochrome P450, E-class, group I
• Cytochrome P450, conserved site
• Cytochrome P450 superfamily
• Cytochrome P450

KeywordsUniProt

• Congenital adrenal hyperplasia
• Endoplasmic reticulum
• Heme
• Iron
• Lipid metabolism
• Lipid-binding
• Membrane
• Metal-binding
• Microsome
• Monooxygenase
• Oxidoreductase
• Steroid-binding
• Steroidogenesis