Gene Symbol: Cyp21a1
Description: cytochrome P450, family 21, subfamily a, polypeptide 1
Alias: 21-OH, 21OH, 21OHA, 21OHB, CYP21OH-A, Cyp21, Cyp21-ps1, Cyp21B, Cyp21a2-ps, Cyp21a2ps, Oh21-1, Oh21-2, steroid 21-hydroxylase, 21-OHase, 21-hydroxylase, cytochrome P-450, cytochrome P-450c21, cytochrome P450 21, cytochrome P450 XXI, cytochrome P450 hydroxylase A, cytochrome P450, 21, pseudogene, cytochrome P450, 21, steroid 21 hydroxylase, cytochrome P450, family 21, subfamily a, polypeptide 2, pseudogene, cytochrome P450-C21
Species: mouse
Products:     Cyp21a1

Top Publications

  1. Val P, Jeays Ward K, Swain A. Identification of a novel population of adrenal-like cells in the mammalian testis. Dev Biol. 2006;299:250-6 pubmed
    ..They express the adrenal markers Cyp11b1 and Cyp21 and respond to ACTH...
  2. Val P, Martinez Barbera J, Swain A. Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage. Development. 2007;134:2349-58 pubmed
    ..These results highlight the importance of transcription factor dosage in organogenesis and the role of transcription co-factors such as Cited2 in determining the levels of these factors. ..
  3. Cole T, Blendy J, Monaghan A, Krieglstein K, Schmid W, Aguzzi A, et al. Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 1995;9:1608-21 pubmed
  4. Huang C, Miyagawa S, Matsumaru D, Parker K, Yao H. Progenitor cell expansion and organ size of mouse adrenal is regulated by sonic hedgehog. Endocrinology. 2010;151:1119-28 pubmed publisher
    ..Our results not only provide the genetic evidence to support that the adrenal capsule contributes to the growth of adrenocortex in both fetal and adult life but also identify a novel role of Shh in this process...
  5. Kim A, Reuter A, Zubair M, Else T, Serecky K, Bingham N, et al. Targeted disruption of beta-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex. Development. 2008;135:2593-602 pubmed publisher
    ..These results define crucial roles for beta-catenin--presumably as part of the Wnt canonical signaling pathway--in both embryonic development of the adrenal cortex and in maintenance of the adult organ. ..
  6. Liu C, Bingham N, Parker K, Yao H. Sex-specific roles of beta-catenin in mouse gonadal development. Hum Mol Genet. 2009;18:405-17 pubmed publisher
    ..Our results demonstrate that beta-catenin is responsible for transducing sex-specific signals in the SF1-positive somatic cell population during mouse gonadal development. ..
  7. Lavery R, Chassot A, Pauper E, Gregoire E, Klopfenstein M, de Rooij D, et al. Testicular differentiation occurs in absence of R-spondin1 and Sox9 in mouse sex reversals. PLoS Genet. 2012;8:e1003170 pubmed publisher
    ..The dogma that considers female differentiation as a default pathway therefore needs to be definitively revised. ..
  8. Gotoh H, Kusakabe M, Shiroishi T, Moriwaki K. Survival of steroid 21-hydroxylase-deficient mice without endogenous corticosteroids after neonatal treatment and genetic rescue by transgenesis as a model system for treatment of congenital adrenal hyperplasia in humans. Endocrinology. 1994;135:1470-6 pubmed
    ..This observation indicates that corticosteroids down-stream of 21-OHase in the pathway for adrenal steroidogenesis are not essential for the survival of mice, except during the period immediately after birth. ..
  9. Taylor C, Everest M, Smith C. Restriction fragment length polymorphism in amplification products of the bovine butyrophilin gene: assignment of bovine butyrophilin to bovine chromosome 23. Anim Genet. 1996;27:183-5 pubmed
    ..Screening of a half-sib family established for the heterozygous sire allowed the localization of BTN to bovine chromosome 23 (BTA23). ..

More Information


  1. Lee F, Faivre E, Suzawa M, Lontok E, Ebert D, Cai F, et al. Eliminating SF-1 (NR5A1) sumoylation in vivo results in ectopic hedgehog signaling and disruption of endocrine development. Dev Cell. 2011;21:315-27 pubmed publisher
    ..We conclude that the sumoylation cycle greatly expands the functional capacity of transcription factors such as SF-1 and is leveraged during development to achieve cell-type-specific gene expression in multicellular organisms. ..
  2. Mathew P, Kumar V, Bennett M, Flaherty L. Identification of a recombinational breakpoint at the BAT5 locus in three intra-H-2 recombinant inbred mouse strains. Exp Clin Immunogenet. 1995;12:261-7 pubmed
    ..Our present data identify a recombinational hot spot at the Bat-5 locus. The expression of Bat-5 or a nearby gene may influence the immunogenicity of BMCs. ..
  3. White P, New M, Dupont B. Adrenal 21-hydroxylase cytochrome P-450 genes within the MHC class III region. Immunol Rev. 1985;87:123-50 pubmed
    ..Thus the 21-OH B gene is normally active in man, but the 21-OH A gene is not. ..
  4. Ikuta T, Sogawa N, Ariga H, Ikemura T, Matsumoto K. Structural analysis of mouse tenascin-X: evolutionary aspects of reduplication of FNIII repeats in the tenascin gene family. Gene. 1998;217:1-13 pubmed
    ..nucleotide sequence of the entire mouse tenascin-X (Tnx) gene, which also includes the last exon of Creb-rp and Cyp21. We compared it with the orthologous human locus...
  5. Zubair M, Oka S, Parker K, Morohashi K. Transgenic expression of Ad4BP/SF-1 in fetal adrenal progenitor cells leads to ectopic adrenal formation. Mol Endocrinol. 2009;23:1657-67 pubmed publisher
    ..The effects of FAdE-controlled Ad4BP/SF-1 overexpression in mice provide a novel model of ectopic adrenal formation that further supports the critical role of Ad4BP/SF-1 in the determination of steroidogenic cell fate in vivo. ..
  6. Yang Z, Yu C. Organizations and gene duplications of the human and mouse MHC complement gene clusters. Exp Clin Immunogenet. 2000;17:1-17 pubmed
    ..The modular duplications of human and mouse RP-C4-CYP21-TNX (RCCX) are sharply different as SKI2W2 is absent in the human MCGC, and TNXA and RP2 are smaller in size but ..
  7. White P, Chaplin D, Weis J, Dupont B, New M, Seidman J. Two steroid 21-hydroxylase genes are located in the murine S region. Nature. 1984;312:465-7 pubmed
    ..We found that there are two 21-OH genes in this region, located immediately 3' to the C4 and Slp genes. ..
  8. Moore A, McInnes L, Kreidberg J, Hastie N, Schedl A. YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis. Development. 1999;126:1845-57 pubmed
    ..These data demonstrate a variety of new functions for WT1 and suggest a general requirement for this protein in the formation of organs derived from the intermediate mesoderm. ..
  9. Chaplin D, Galbraith L, Seidman J, White P, Parker K. Nucleotide sequence analysis of murine 21-hydroxylase genes: mutations affecting gene expression. Proc Natl Acad Sci U S A. 1986;83:9601-5 pubmed
    ..These findings demonstrate that the 21-OHase B gene promoter is functional and suggest that mutations within the 21-OHase B structural gene are responsible for its lack of expression. ..
  10. Zhang Y, Wu S, Gu S, Lv F. Changes of renal vitamin D metabolic enzyme expression and calcium transporter abundance in obstructive nephropathy. Nephrology (Carlton). 2011;16:710-4 pubmed publisher
  11. Tajima T, Ma X, Bornstein S, Aguilera G. Prenatal dexamethasone treatment does not prevent alterations of the hypothalamic pituitary adrenal axis in steroid 21-hydroxylase deficient mice. Endocrinology. 1999;140:3354-62 pubmed
    ..These studies in 21-hydroxylase deficient mice may provide new insights on the mechanism, clinical manifestations and management of some types of human CAH. ..
  12. Nelson D, Kamataki T, Waxman D, Guengerich F, Estabrook R, Feyereisen R, et al. The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol. 1993;12:1-51 pubmed
    ..Finally, we describe P450 genes that have been detected by expressed sequence tags (ESTs), as well as the relationship between the P450 and the nitric oxide synthase gene superfamilies, as a likely example of convergent evolution. ..
  13. Coeli F, Soardi F, Bernardi R, de Araujo M, Paulino L, Lau I, et al. Novel deletion alleles carrying CYP21A1P/A2 chimeric genes in Brazilian patients with 21-hydroxylase deficiency. BMC Med Genet. 2010;11:104 pubmed publisher
    ..within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module...
  14. Tachibana M, Adachi W, Kinoshita S, Kobayashi Y, Honma Y, Hiai H, et al. Androgen-dependent hereditary mouse keratoconus: linkage to an MHC region. Invest Ophthalmol Vis Sci. 2002;43:51-7 pubmed
    ..Alternatively, SKC mouse keratoconus could be a model for other human or mouse-specific keratopathies. ..
  15. Poole T, Drinkwater N. Two genes abrogate the inhibition of murine hepatocarcinogenesis by ovarian hormones. Proc Natl Acad Sci U S A. 1996;93:5848-53 pubmed
    ..2 +/- 3.9). In backcross male mice, the double heterozygotes (35 +/- 22) and Hcf1 heterozygotes (28 +/- 12) were 5.4- and 4.3-fold more sensitive than mice homozygous for B6 alleles at both loci (6.5 +/- 5.4). ..
  16. Yoshino M, Sagai T, Lindahl K, Toyoda Y, Shiroishi T, Moriwaki K. No dosage effect of recombinational hotspots in the mouse major histocompatibility complex. Immunogenetics. 1994;39:381-9 pubmed
    ..Twenty-three breakpoints were confined within 5.4 kb in the Lmp-2 hotspot, and six breakpoints from the cas4 cross were located in the Pb hotspot, which we have now confined to a 15 kb segment. ..
  17. Ogata R, Rosa P, Zepf N. Sequence of the gene for murine complement component C4. J Biol Chem. 1989;264:16565-72 pubmed
    ..The length of the murine C4 gene relative to the isotypic C4A and C4B genes in man suggests the independent loss of a 6-kilobase intron from both murine and human C4 genes. ..
  18. Gardner S, Mock B, Hilgers J, Huppi K, Roeder W. Mouse lymphotoxin and tumor necrosis factor: structural analysis of the cloned genes, physical linkage, and chromosomal position. J Immunol. 1987;139:476-83 pubmed
    ..Comparison of the 5' flanking sequence of LT to a number of genes that are specifically expressed in activated T cells reveals a number of conserved sequences that may play a role in control of these genes. ..
  19. Crawford P, Sadovsky Y, Woodson K, Lee S, Milbrandt J. Adrenocortical function and regulation of the steroid 21-hydroxylase gene in NGFI-B-deficient mice. Mol Cell Biol. 1995;15:4331-16 pubmed
  20. Parker K, Chaplin D, Wong M, Seidman J, Smith J, Schimmer B. Expression of murine 21-hydroxylase in mouse adrenal glands and in transfected Y1 adrenocortical tumor cells. Proc Natl Acad Sci U S A. 1985;82:7860-4 pubmed
    ..The regulated expression of the 21-OHase A gene in transfected Y1 cells should provide a useful system for the investigation of factors controlling the adrenal-specific regulation of 21-OHase activity. ..
  21. Yoshino M, Sagai T, Lindahl K, Toyoda Y, Shirayoshi Y, Matsumoto K, et al. Recombination in the class III region of the mouse major histocompatibility complex. Immunogenetics. 1994;40:280-6 pubmed
    ..The results gave the gene order of Eb-61.1-Int3-Tnx-Cyp21/C4-Bf-Hsp68c-D17Mit13+ ++-Tnfa/Tnfb-D...
  22. Nebert D, Nelson D, Adesnik M, Coon M, Estabrook R, Gonzalez F, et al. The P450 superfamily: updated listing of all genes and recommended nomenclature for the chromosomal loci. DNA. 1989;8:1-13 pubmed
    ..Numbers of the individual genes usually will be assigned in the order the genes are identified. This system is consistent with our earlier proposed nomenclature for P450 families and gene products from all eukaryotes and prokaryotes. ..
  23. Tajima T, Okada T, Ma X, Ramsey W, Bornstein S, Aguilera G. Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochromeP450 21-hydroxylase into the adrenal gland of21-hydroxylase-deficient mice. Gene Ther. 1999;6:1898-903 pubmed
    21-Hydroxylase deficiency, a potentially fatal disease due to deletions or mutations of the cytochrome P450 21-hydroxylase gene (CYP21), causes congenital adrenal hyperplasia (CAH) with low or absent glucocorticoid and mineralocorticoid ..
  24. Pazirandeh A, Xue Y, Rafter I, Sjovall J, Jondal M, Okret S. Paracrine glucocorticoid activity produced by mouse thymic epithelial cells. FASEB J. 1999;13:893-901 pubmed
    ..we demonstrate that the mouse thymic epithelial cells (TEC) express the cytochrome P450 hydroxylases Cyp11A1, Cyp21, and Cyp11B1...
  25. Levi Strauss M, Tosi M, Steinmetz M, Klein J, Meo T. Multiple duplications of complement C4 gene correlate with H-2-controlled testosterone-independent expression of its sex-limited isoform, C4-Slp. Proc Natl Acad Sci U S A. 1985;82:1746-50 pubmed
    ..Multiple C4-related gene copies characterize those exceptional wild-derived H-2 haplotypes, H-2w7, H-2w16, and H-2w19, that determine the expression of the C4-Slp protein in female animals. ..
  26. Amor M, Tosi M, Duponchel C, Steinmetz M, Meo T. Liver mRNA probes disclose two cytochrome P-450 genes duplicated in tandem with the complement C4 loci of the mouse H-2S region. Proc Natl Acad Sci U S A. 1985;82:4453-7 pubmed
    ..The detection of a liver transcript of P-450(C21) raises the issue of the specific metabolic role of this enzyme in this organ and may have implications for the interpretation of human congenital adrenal hyperplasia. ..
  27. Chaplin D, Woods D, Whitehead A, Goldberger G, Colten H, Seidman J. Molecular map of the murine S region. Proc Natl Acad Sci U S A. 1983;80:6947-51 pubmed
    ..Regulation of circulating C4 levels in high C4 and low C4 strains is at least partly at the level of mRNA transcription, processing, or degradation. ..
  28. Boucher E, Provost P, Tremblay Y. Ontogeny of adrenal-like glucocorticoid synthesis pathway and of 20?-hydroxysteroid dehydrogenase in the mouse lung. BMC Res Notes. 2014;7:119 pubmed publisher
    ..Glucocorticoids from lung 21-hydroxylase appear to modulate lung ontogenesis through paracrine/intracrine actions. ..
  29. Matsumoto K, Saga Y, Ikemura T, Sakakura T, Chiquet Ehrismann R. The distribution of tenascin-X is distinct and often reciprocal to that of tenascin-C. J Cell Biol. 1994;125:483-93 pubmed
    ..In skin and tissues of the digestive tract often a reciprocal distribution of TN-X and TN-C was observed. ..
  30. Morley S, Viard I, Chung B, Ikeda Y, Parker K, Mullins J. Variegated expression of a mouse steroid 21-hydroxylase/beta- galactosidase transgene suggests centripetal migration of adrenocortical cells. Mol Endocrinol. 1996;10:585-98 pubmed
  31. Turner S, Miller C, Wettstein P, Hasenkrug K, Stimpfling J, Carlson G. Meiotic recombination within the H-2K-H-2D interval: characterization of a panel of congenic mice, including 12 new strains, using DNA markers. Immunogenetics. 1993;38:332-40 pubmed
    ..We have extended the analysis of the crossover sites in these mice using DNA markers for Ab, Aa, Eb, Ea, Cyp21-ps, D17Tu3, Bat7, and Bat5...
  32. Ogata R, Zepf N. The murine Slp gene. Additional evidence that sex-limited protein has no biologic function. J Immunol. 1991;147:2756-63 pubmed
    ..The gene for Slp lies in the S region of the murine H-2 complex adjacent to the gene Cyp21 that encodes the Cytochrome P-450 enzyme steroid 21-hydroxylase...
  33. Pihlajoki M, Gretzinger E, Cochran R, Kyrönlahti A, Schrade A, Hiller T, et al. Conditional mutagenesis of Gata6 in SF1-positive cells causes gonadal-like differentiation in the adrenal cortex of mice. Endocrinology. 2013;154:1754-67 pubmed publisher
    ..Our findings offer genetic proof that GATA6 regulates the differentiation of steroidogenic progenitors into adrenocortical cells. ..
  34. Gaskins H, Prochazka M, Nadeau J, Henson V, Leiter E. Localization of a mouse heat shock Hsp70 gene within the H-2 complex. Immunogenetics. 1990;32:286-9 pubmed
  35. Naiki Y, Miyado M, Horikawa R, Katsumata N, Onodera M, Pang S, et al. Extra-adrenal induction of Cyp21a1 ameliorates systemic steroid metabolism in a mouse model of congenital adrenal hyperplasia. Endocr J. 2016;63:897-904 pubmed
    ..In this study, we examined whether transduction of murine Cyp21a1 in extra-adrenal tissues could rescue steroid metabolism in 21-OHD mice...
  36. Heikkilä M, Peltoketo H, Leppäluoto J, Ilves M, Vuolteenaho O, Vainio S. Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology. 2002;143:4358-65 pubmed
    ..Finally, some cells that are positive for Cyp21, which is normally expressed only in the adrenal gland, are found in the gonads of Wnt-4-deficient embryos, ..
  37. Cortese Hassett A, Radojcic A, Watters J, Locker J, Kunz H, Gill T. Mapping and sequencing analysis of the rat MHC. Transplant Proc. 1989;21:3244-6 pubmed
  38. Jareborg N, Birney E, Durbin R. Comparative analysis of noncoding regions of 77 orthologous mouse and human gene pairs. Genome Res. 1999;9:815-24 pubmed
    ..This data set complements earlier sets on the basis of cDNA sequences and will be useful for further comparative studies. [This paper contains supplementary data that can be found at [corrected]]. ..
  39. Makałowski W, Zhang J, Boguski M. Comparative analysis of 1196 orthologous mouse and human full-length mRNA and protein sequences. Genome Res. 1996;6:846-57 pubmed
    ..Also, they should prove useful in estimating the additional sampling diversity provided by mouse EST sequencing projects designed to complement the existing human cDNA collection. ..
  40. Tevosian S, Jiménez E, Hatch H, Jiang T, Morse D, Fox S, et al. Adrenal Development in Mice Requires GATA4 and GATA6 Transcription Factors. Endocrinology. 2015;156:2503-17 pubmed publisher
    ..Our results reveal a requirement for GATA factors in adrenal development and provide a novel tool to characterize the transcriptional network controlling adrenocortical cell fates. ..
  41. Yoshino M, Sagai T, Moriwaki K, Shiroishi T. Meiotic recombination at the Lmp2 hotspot tolerates minor sequence divergence between homologous chromosomes. Immunogenetics. 1996;43:80-2 pubmed
  42. Keeney D, Jenkins C, Waterman M. Developmentally regulated expression of adrenal 17 alpha-hydroxylase cytochrome P450 in the mouse embryo. Endocrinology. 1995;136:4872-9 pubmed
  43. Gillet D, Mornet E, Rocca A, Degos L, Cohen D, Pla M. Extensive genomic polymorphism in mouse 21-hydroxylase region. Immunogenetics. 1988;27:133-6 pubmed
  44. Muller U, Stephan D, Philippsen P, Steinmetz M. Orientation and molecular map position of the complement genes in the mouse MHC. EMBO J. 1987;6:369-73 pubmed
    ..The distances between the E alpha and 21-OHB genes is 430 kb and between the C2 and TNF-alpha genes at least 420 kb. ..
  45. Keeney D, Ikeda Y, Waterman M, Parker K. Cholesterol side-chain cleavage cytochrome P450 gene expression in the primitive gut of the mouse embryo does not require steroidogenic factor 1. Mol Endocrinol. 1995;9:1091-8 pubmed
  46. Huang C, Yao H. Inactivation of Dicer1 in Steroidogenic factor 1-positive cells reveals tissue-specific requirement for Dicer1 in adrenal, testis, and ovary. BMC Dev Biol. 2010;10:66 pubmed publisher
    ..Our results reveal a tissue-specific requirement of Dicer1 and microRNAs. Future research is needed to understand how the tissue-specific role of Dicer1 is established. ..
  47. Hu L, Monteiro A, Johnston H, King P, O Shaughnessy P. Expression of Cyp21a1 and Cyp11b1 in the fetal mouse testis. Reproduction. 2007;134:585-91 pubmed
    ..Differences in steroid secretion are largely due to the expression of 21-hydroxylase (CYP21A1) and 11beta-hydroxylase (CYP11B1) activity in the adrenal...
  48. Riepe F, Tatzel S, Sippell W, Pleiss J, Krone N. Congenital adrenal hyperplasia: the molecular basis of 21-hydroxylase deficiency in H-2(aw18) mice. Endocrinology. 2005;146:2563-74 pubmed
    ..A deletion of the active Cyp21a1 gene has been postulated; however, the changes on the nucleotide level are still unknown...
  49. Ren Y, Cowan R, Migone F, Quirk S. Overactivation of hedgehog signaling alters development of the ovarian vasculature in mice. Biol Reprod. 2012;86:174 pubmed publisher
  50. Steinmetz M, Malissen M, Hood L, Orn A, Maki R, Dastoornikoo G, et al. Tracts of high or low sequence divergence in the mouse major histocompatibility complex. EMBO J. 1984;3:2995-3003 pubmed
    ..Variable tracts appear to be the result of mechanisms which mutate certain coding and non-coding sequences to the same extent and selective pressures operating on the genes. ..
  51. Bornstein S, Tajima T, Eisenhofer G, Haidan A, Aguilera G. Adrenomedullary function is severely impaired in 21-hydroxylase-deficient mice. FASEB J. 1999;13:1185-94 pubmed
    ..This hitherto unrecognized mechanism may contribute to the frequent clinical, mental, and therapeutic problems encountered in humans with this genetic disease. ..
  52. Yung Yu C, Yang Z, Blanchong C, Miller W. The human and mouse MHC class III region: a parade of 21 genes at the centromeric segment. Immunol Today. 2000;21:320-8 pubmed
    ..It also provides insights into the relationship between protein function and level of sequence conservation, and on the clustering of genes with related functions. ..
  53. Gilbert C, Provost P, Tremblay Y. Dynamic modulation of Cyp21a1 (21-hydroxylase) expression sites in the mouse developing lung. J Steroid Biochem Mol Biol. 2017;168:102-109 pubmed publisher
    ..We have studied the precise sites of Cyp21a1 expression in the developing mouse lung from the pseudoglandular stage (gestation day (GD) 15...
  54. Buaas F, Gardiner J, Clayton S, Val P, Swain A. In vivo evidence for the crucial role of SF1 in steroid-producing cells of the testis, ovary and adrenal gland. Development. 2012;139:4561-70 pubmed publisher
    ..This study is the first to show the in vivo requirements of SF1 in steroidogenesis and provides novel data on the cellular consequences of the loss of this protein specifically within steroid-producing cells. ..