Affinage

CYP11B2

Cytochrome P450 11B2, mitochondrial · UniProt P19099

Length
503 aa
Mass
57.6 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYP11B2 (aldosterone synthase) is the mitochondrial cytochrome P450 enzyme that catalyzes the terminal steps of aldosterone biosynthesis in adrenal zona glomerulosa cells, converting 11-deoxycorticosterone to aldosterone through sequential 11β-hydroxylation, 18-hydroxylation, and 18-oxidation reactions (PMID:1775135, PMID:2256920). Heterologous reconstitution established that only CYP11B2 — not the closely related CYP11B1 — completes the full conversion to aldosterone, while it can also 18-hydroxylate other steroid substrates (PMID:1775135, PMID:7779756). Catalysis depends on the adrenodoxin/adrenodoxin reductase electron-transfer system (PMID:19622340), and the enzyme localizes to mitochondria via its endogenous targeting sequence, where a ferredoxin-domain donor can functionally substitute for adrenodoxin (PMID:11841224). Loss-of-function mutations partition the biosynthetic defect by step: a frameshift abolishing the protein causes CMO-I deficiency (loss of corticosterone methyl oxidase I activity) (PMID:8439335), whereas active-site missense mutations such as R181W, T318M, and S308P selectively impair 18-hydroxylase/18-oxidase steps to produce CMO-II deficiency (PMID:1594605, PMID:7485152, PMID:19116236). CYP11B2 transcription is driven by angiotensin II (acting through the AT1 receptor) and potassium via a calcium/CaMK signaling pathway that converges on a proximal CRE/Ad1 element and an SF-1/COUP-TF (Ad5) element in the 5'-flanking region (PMID:9139807, PMID:8969900, PMID:9430819, PMID:11196473). This promoter is modulated by COUP-TFI together with Ubc9/PIAS1 coactivators (PMID:15611122), by ERRα at the Ad5 site (PMID:22079243), and is suppressed by high SF-1, PPARγ, and Klotho (PMID:18974272, PMID:21106862, PMID:26471128), with post-transcriptional repression by miR-193a-3p and miR-10b targeting the 3'-UTR (PMID:29665181, PMID:24768260). Its enzymatic specificity underlies the development of selective aldosterone synthase inhibitors as antihypertensive agents (PMID:27872236, PMID:35127376).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1991 High

    Established the core catalytic identity of CYP11B2 — that a single enzyme performs all three oxidative steps of aldosterone synthesis, distinguishing it from CYP11B1 which cannot.

    Evidence Heterologous cDNA expression in COS-1/COS-7 cells with steroid product analysis comparing CYP11B2 and CYP11B1

    PMID:1775135 PMID:2256920

    Open questions at the time
    • Did not resolve the structural basis for the bifunctional 18-oxidase activity
    • Did not address electron-donor requirements in vivo
  2. 1995 Medium

    Mapped the substrate panel and intermediate flux of the enzyme, showing corticosterone is converted more efficiently than DOC and that 18-OH-DOC is not a productive intermediate for aldosterone.

    Evidence Stable transfection in MA-10 Leydig cells with radiolabeled substrate panel and Northern blot

    PMID:7779756

    Open questions at the time
    • Single lab; in vitro reconstitution may not reflect zona glomerulosa kinetics
    • No structural model for substrate channeling
  3. 1995 Medium

    Localized CYP11B2 specifically to the zona glomerulosa and linked angiotensin II to expansion of aldosterone-producing cells, connecting enzyme expression to adrenal zonation and cell proliferation.

    Evidence Immunohistochemistry, double immunostaining, and BrdU pulse-chase in rat adrenal sections

    PMID:7588405

    Open questions at the time
    • Rat model; human zonation dynamics not directly tested
    • Stem cell migration mechanism not molecularly defined
  4. 1993 Medium

    Defined the genotype-phenotype basis for inherited aldosterone deficiency, showing protein-null mutations cause CMO-I deficiency and step-selective active-site mutations cause CMO-II deficiency.

    Evidence Patient gene analysis (frameshift) plus site-directed mutagenesis of R181W/V386A/T318M/S308P with in vitro activity assays

    PMID:1594605 PMID:19116236 PMID:7485152 PMID:8439335

    Open questions at the time
    • CMO-II vs CMO-I phenotypic distinction not fully explained by in vitro activity
    • S308P case suggested an alternative in vivo mineralocorticoid pathway not yet identified
  5. 1997 High

    Identified the cis-regulatory architecture by which angiotensin II and potassium control CYP11B2 transcription, defining the CRE/Ad1 and SF-1/COUP-TF (Ad5) elements where calcium and cAMP pathways converge.

    Evidence Reporter assays, deletion/mutation analysis, DNase I footprinting, and EMSA in H295R cells; AT1-receptor-specific pharmacology in rat adrenal

    PMID:11196473 PMID:8969900 PMID:9139807 PMID:9430819

    Open questions at the time
    • CRE/Ad1 alone insufficient for Ang II induction — additional inducible elements not fully mapped
    • Relative contribution of ATF-2 vs CREB at the element unresolved
  6. 2002 High

    Confirmed mitochondrial targeting and the electron-transfer requirement, showing a ferredoxin-domain protein can functionally replace adrenodoxin to support catalysis.

    Evidence S. pombe heterologous expression with imaging-based localization and reconstituted hydroxylation assay using bacterially expressed etp1

    PMID:11841224

    Open questions at the time
    • Whether endogenous human adrenodoxin coupling is rate-limiting in vivo not addressed
    • No structural detail of the CYP11B2-redox partner interface
  7. 2008 Medium

    Expanded the transcription-factor network, identifying COUP-TFI/Ubc9/PIAS1 as activators at Ad5 and SF-1 and PPARγ/Klotho as suppressors, revealing reciprocal regulation of CYP11B2 versus CYP11B1.

    Evidence EMSA, Y2H, Co-IP, ChIP, siRNA, inducible overexpression and reporter assays in H295R cells; Klotho studies in human cells and KL+/- mice

    PMID:15611122 PMID:18974272 PMID:21106862 PMID:26471128

    Open questions at the time
    • Integration of multiple opposing regulators into a single quantitative model not established
    • Most evidence from H295R cell line; in vivo relevance of each factor varies
  8. 2014 Medium

    Established post-transcriptional control of CYP11B2 by miRNAs targeting its 3'-UTR, linking miR-193a-3p and miR-10b to aldosterone output and adrenocortical cell behavior.

    Evidence 3'-UTR luciferase reporter validation, miR mimic/knockdown, rescue experiments, and functional assays in H295R cells

    PMID:24768260 PMID:29665181

    Open questions at the time
    • Physiological contexts driving these miRNAs in vivo not established
    • Single-lab reporter validations
  9. 2016 High

    Demonstrated CYP11B2 as a tractable pharmacological target by characterizing selective competitive inhibitors and a covalent inactivator that spare CYP11B1/cortisol.

    Evidence In vitro Ki determination, structural/docking rationale (Ala320, Cys450), and in vivo pharmacology in monkeys and humans; CYP11B2 also metabolizes spironolactone/canrenone

    PMID:27125452 PMID:27872236 PMID:35127376

    Open questions at the time
    • Long-term in vivo selectivity and resistance not addressed
    • Structural basis of B2/B1 selectivity inferred rather than crystallographically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full integration of upstream GnCa signaling, the complete cis/trans regulatory network, and a high-resolution structural model of substrate/inhibitor selectivity into a unified mechanistic picture remains open.
  • No experimental atomic structure of human CYP11B2 in the timeline
  • Alternative in vivo mineralocorticoid pathway implied by S308P case unidentified
  • Quantitative hierarchy among the many activators/repressors not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0016787 hydrolase activity 3
Localization
GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 3
Partners
COUP-TFIFDX1PIAS1UBC9

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CYP11B2 protein (P450aldo) catalyzes all three steps required for aldosterone biosynthesis from deoxycorticosterone: 11β-hydroxylation, 18-hydroxylation, and 18-oxidation. Expression of CYP11B2 cDNA in COS-1 cells demonstrated that only CYP11B2 (not CYP11B1) could synthesize aldosterone from deoxycorticosterone, and CYP11B2 could also 18-hydroxylate cortisol/corticosterone. Heterologous cDNA expression in COS-1 cells with steroid product analysis Molecular endocrinology High 1775135
1990 CYP11B2 (P-450aldo) expressed in COS-7 cells preferentially catalyzes the complete conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone, whereas CYP11B1 (P-450(11)β) substantially fails to produce aldosterone from the same substrate. Heterologous cDNA expression in COS-7 cells with steroid product analysis Biochemical and biophysical research communications High 2256920
1992 Mutations R181W and V386A in CYP11B2 cause CMO-II deficiency: R181W reduces 18-hydroxylase and abolishes 18-oxidase activities while leaving 11β-hydroxylase activity intact; V386A causes a small reduction in 18-hydroxycorticosterone production. Both mutations together compound to eliminate aldosterone synthesis. Site-directed mutagenesis of CYP11B2 cDNA with expression in cultured cells and steroid product analysis Proceedings of the National Academy of Sciences of the United States of America High 1594605
1993 A 5-nucleotide deletion in exon 1 of CYP11B2 causes a frameshift and premature stop codon, resulting in complete absence of P-450C18 protein and total lack of aldosterone biosynthesis (CMO-I deficiency), demonstrating CYP11B2 is the sole enzyme for corticosterone methyl oxidase I activity. Molecular genetic analysis (PCR, sequencing, RFLP) of patient CYP11B2 gene Biochemical and biophysical research communications Medium 8439335
1995 The T318M mutation in CYP11B2 causes CMO-II deficiency. When expressed singly and in parental allele pairs in cDNA expression vectors, neither the T318M/V386A allele nor the R181W/ΔC372 allele showed measurable enzymatic activity, yet the clinical phenotype is CMO-II rather than CMO-I, suggesting other factors modulate phenotypic expression. Site-directed mutagenesis and cDNA expression with in vitro steroid activity assay American journal of human genetics Medium 7485152
2002 Human CYP11B2 expressed in fission yeast (Schizosaccharomyces pombe) localizes to mitochondria via its endogenous signal sequence, and converts 11-deoxycorticosterone to corticosterone, 18-hydroxycorticosterone, and aldosterone in vivo. A fission yeast ferredoxin-domain protein (etp1) was identified that can functionally replace adrenodoxin as an electron donor to CYP11B2 in a reconstituted steroid hydroxylation assay. Heterologous expression in S. pombe, Western blot/fluorescence/electron microscopy for localization, in vitro reconstituted steroid hydroxylation assay with bacterially expressed etp1 Biochemistry High 11841224
1997 Angiotensin II and potassium regulate CYP11B2 transcription through two cis-elements in the 5'-flanking region: a CRE-like element at -71/-64 (binding CREB proteins) and an SF-1/COUP-TF binding element at -129/-114 (Ad5). Both calcium and cAMP signaling pathways converge on these same elements to drive CYP11B2 expression. Transient transfection with luciferase reporter constructs, deletion/mutation analysis, DNase I footprinting, electrophoretic mobility shift assay (EMSA) in H295R cells Molecular endocrinology High 9139807
1996 Calcium signaling pathways (activated by Ang II, K+, BAYK8644, ionomycin) regulate human CYP11B2 transcription in H295R adrenocortical cells. Protein kinase C activation did not alter CYP11B2 reporter gene expression. Transient transfection of luciferase reporter construct with CYP11B2 5'-flanking DNA in H295R and Y-1 adrenocortical cell lines Endocrine research Medium 8969900
2004 COUP-TFI binds the Ad5 element (-129/-114) of the CYP11B2 promoter and activates transcription. Ubc9 (SUMO E2 conjugase) and PIAS1 (SUMO E3 ligase) interact with COUP-TFI and act as transcriptional coactivators of CYP11B2; sumoylation activity is separable from coactivator function. All three proteins are recruited to the endogenous CYP11B2 promoter in ChIP assays. EMSA, transient transfection, yeast two-hybrid, coimmunoprecipitation, chromatin immunoprecipitation (ChIP), siRNA knockdown in H295R cells The Journal of biological chemistry High 15611122
2008 SF-1 (steroidogenic factor-1) overexpression dramatically inhibits CYP11B2 mRNA expression and aldosterone production in adrenocortical H295R cells, while SF-1 knockdown by siRNA reverses this inhibition. Conversely, SF-1 overexpression increases CYP11B1 expression, demonstrating opposing regulatory roles. A minimal level of SF-1 is required for basal expression of both genes. Doxycycline-inducible SF-1 overexpression, siRNA knockdown, real-time RT-PCR, immunoassay in H295R/TR/SF-1 cells Endocrinology High 18974272
2011 PPARγ suppresses CYP11B2 expression and aldosterone secretion via the Ad1/CRE element in the CYP11B2 5'-flanking region. PPARγ activation by pioglitazone inhibits CaMKI-mediated CYP11B2 transcriptional activation. The PPARγ L466A/E469A mutant abolishes this suppression, indicating ligand-binding domain requirement. Transient transfection with promoter-reporter constructs, PPARγ overexpression/mutation, CaMKI transfection, pharmacological inhibition in H295R cells Journal of molecular endocrinology Medium 21106862
2015 Klotho (KL) regulates CYP11B2 expression in adrenal zona glomerulosa cells: KL silencing upregulates and KL overexpression downregulates CYP11B2 in human adrenocortical cells. KL deficiency decreases SF-1 expression (a negative regulator of CYP11B2) and increases ATF2 phosphorylation (a positive regulator), providing a mechanistic link. KL and CYP11B2 proteins co-localize in adrenal zona glomerulosa cells. siRNA knockdown, overexpression, Western blot, immunofluorescence co-localization, immunoassay in human adrenocortical cells and KL+/- mice Journal of the American Society of Nephrology Medium 26471128
2000 The CRE/Ad1 cis-element in the CYP11B2 promoter is required for basal expression but is not sufficient for hormonal regulation by angiotensin II; mutation of this element abolishes basal expression while retaining agonist response, suggesting additional cis-elements mediate Ang II induction. Both ATF-2 and CREB bind this element, but only ATF-2 complexes match those in H295R nuclear extract. Transient transfection with reporter constructs, promoter deletion/mutation, EMSA with recombinant transcription factors and H295R nuclear extracts Endocrine research Medium 11196473
2009 CYP11B2 requires the adrenodoxin/adrenodoxin reductase electron transfer system for catalytic activity. A stable cell line co-expressing CYP11B2 with adrenodoxin and adrenodoxin reductase was established, demonstrating that FAD286 inhibits CYP11B2 competitively with a Ki of 0.8 nM using 11-deoxycorticosterone as substrate. Stable cell transfection, in vitro enzyme activity assay with radiolabeled substrate, competitive kinetics analysis Analytical biochemistry Medium 19622340
1995 CYP11B2 (P450aldo) is localized specifically to zona glomerulosa cells of the rat adrenal cortex, while CYP11B1 (P45011β) is in zona fasciculata. A novel cell layer lacking both enzymes exists between zones and contains adrenal stem cells. Angiotensin II stimulation (via Na-deficiency) increases P450aldo-containing zona glomerulosa cell number and triggers proliferation of cells in this intermediate zone, which then migrate outward. Immunohistochemistry, double immunostaining, BrdU pulse-chase in rat adrenal sections Endocrine research Medium 7588405
1997 CYP11B2 (P450aldo) mRNA and protein expression in rat adrenal zona glomerulosa is upregulated approximately 8.5-fold by dietary sodium restriction (which elevates angiotensin II) and this upregulation is blocked by the selective AT1 receptor antagonist E4177 but not by the AT2 antagonist PD123177, demonstrating that CYP11B2 expression is regulated specifically through the AT1 receptor. RT-PCR with specific primers, immunoblot analysis, pharmacological receptor antagonism in rat adrenal gland Endocrine research Medium 9430819
2014 GnRH acting through ectopically expressed GnRH receptor (GnRHR) increases CYP11B2 reporter activity and aldosterone production in H295R cells in a concentration-dependent manner. These effects are blocked by calcium signaling inhibitors KN93 and calmidazolium, placing GnRHR-mediated CYP11B2 regulation upstream of the calcium/calmodulin kinase pathway. Transient transfection with CYP11B2 reporter, doxycycline-inducible GnRHR cell line, pharmacological inhibition, RT-PCR, immunoassay Molecular and cellular endocrinology Medium 24472523
2016 Atractylenolide-I (AT-I) selectively covalently binds CYP11B2 at Cys450 (via C8/C9 epoxide intermediate) in the catalytic pocket, disrupts heme-CYP11B2 interaction, and inactivates aldosterone synthesis. The selectivity over CYP11B1 is due to Ala320 in CYP11B2 (versus a different residue in CYP11B1). This covalent inhibition suppresses aldosterone but not cortisol production. Chemical biology covalent binding studies, molecular docking, cell-based steroid synthesis assay, in vivo hyperaldosteronism model Acta pharmaceutica Sinica. B Medium 35127376
1995 Stable expression of CYP11B2 cDNA in MA-10 Leydig tumor cells demonstrates the enzyme converts DOC to corticosterone, 18-OH-corticosterone, aldosterone, and small amounts of 18-OH-DOC. Corticosterone is more efficiently converted to 18-OH-corticosterone than is DOC. CYP11B2 (but not CYP11B1) can also transform 18-OH-DOC to 18-OH-corticosterone but cannot convert 18-OH-DOC to aldosterone. Stable transfection of MA-10 cells with CYP11B2 cDNA, enzyme activity assay with radiolabeled substrates, Northern blot The Journal of steroid biochemistry and molecular biology Medium 7779756
2016 CYP11B2 metabolizes spironolactone (producing 11β-OH-, 18-OH-, and 19-OH-spironolactone) and canrenone (producing 11β-OH-, 18-OH-canrenone, and the CYP11B2-specific 11β,18-diOH-canrenone) via its hydroxylase activities. Binding constants for these exogenous substrates are comparable to natural substrates. 11β-OH-spironolactone retains mineralocorticoid receptor antagonist activity, while other hydroxylation products lose antagonist properties. In vitro assay with purified CYP11B2, spectroscopic binding assay, preparative-scale whole-cell biotransformation, HPLC purification, NMR structural characterization of metabolites, mineralocorticoid receptor transactivation assay The Journal of steroid biochemistry and molecular biology High 27125452
2008 The S308P mutation in CYP11B2 (located within alpha-helix I near the heme-binding active site per structural modeling) causes complete loss of enzyme activity when expressed in vitro. However, dexamethasone suppressed residual aldosterone/metabolite levels in affected subjects in vivo, suggesting some mineralocorticoid biosynthesis occurs through an alternative pathway in vivo. Sequencing, in vitro functional characterization of mutant CYP11B2, structural homology modeling, in vivo dexamethasone suppression test The Journal of clinical endocrinology and metabolism Medium 19116236
2011 The CYP11B2 and CYP11B1 promoters diverged due to insertion of Alu and L1 transposable elements. Alu elements act as enhancers for both genes regardless of orientation. The Ad5 and SF-1 binding elements in the proximal core promoter are required for basal expression; mutation of Ad5 reduces activity to minimal levels. ERRα is identified as the transcription factor binding the Ad5 site during basal CYP11B2 expression. Promoter deletion/mutation reporter assays, sequence analysis, transcription factor identification by reporter assay in H295R cells Steroids Medium 22079243
2014 miR-193a-3p directly targets the 3'-UTR of CYP11B2 mRNA (validated by luciferase reporter with wild-type vs. mutated binding site) and downregulates CYP11B2 mRNA and protein expression. Overexpression of miR-193a-3p in H295R cells inhibits aldosterone secretion, cell proliferation, induces G1-phase arrest, and promotes apoptosis; these effects are reversed by CYP11B2 overexpression. Luciferase 3'-UTR reporter assay, qRT-PCR, Western blot, miR mimic transfection, flow cytometry, ELISA in H295R cells International journal of experimental pathology Medium 29665181
2014 miR-10b (hypoxia-inducible) negatively regulates CYP11B2 (and CYP11B1) mRNA by targeting their 3'-UTRs, as validated by luciferase reporter assays with CYP11B2 3'-UTR constructs combined with miR-10b overexpression and knockdown in H295R cells. miRNA array profiling, luciferase 3'-UTR reporter assay, miR overexpression/knockdown in H295R cells Marine pollution bulletin Medium 24768260
1995 The CYP11B2 promoter contains a polymorphism at position -344 that influences binding of the transcriptional regulatory protein SF-1. This polymorphism and an intron 2 gene conversion (replacing CYP11B2 sequence with CYP11B1 sequence) are in linkage disequilibrium, defining haplotypes with population frequency differences between Blacks and Whites. PCR-based genotyping, linkage disequilibrium analysis, transcription factor binding inference from sequence analysis Endocrine research Low 7588407
2016 RO6836191 is a competitive inhibitor of CYP11B2 (aldosterone synthase) with Ki of 13 nM and >100-fold selectivity over CYP11B1 in vitro. In cynomolgus monkeys, it inhibits aldosterone synthesis without affecting ACTH-stimulated cortisol. In healthy human subjects, it completely suppresses plasma and urine aldosterone across a dose range without affecting cortisol up to 360 mg. In vitro enzyme inhibition assay (Ki determination), in vivo pharmacology in cynomolgus monkeys, Phase I clinical study in healthy volunteers Hypertension High 27872236

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Molecular endocrinology (Baltimore, Md.) 316 1775135
2013 Development of monoclonal antibodies against human CYP11B1 and CYP11B2. Molecular and cellular endocrinology 248 24325867
1998 Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation 176 9494027
1995 Haplotype analysis of CYP11B2. Endocrine research 168 7588407
1997 Angiotensin II and potassium regulate human CYP11B2 transcription through common cis-elements. Molecular endocrinology (Baltimore, Md.) 165 9139807
1992 Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency. Proceedings of the National Academy of Sciences of the United States of America 150 1594605
1990 Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism. Biochemical and biophysical research communications 150 2256920
1999 Genetic polymorphism of CYP11B2 gene and hypertension in Japanese. Hypertension (Dallas, Tex. : 1979) 115 9931115
2013 Histopathological diagnosis of primary aldosteronism using CYP11B2 immunohistochemistry. The Journal of clinical endocrinology and metabolism 107 23443813
2016 Preclinical and Early Clinical Profile of a Highly Selective and Potent Oral Inhibitor of Aldosterone Synthase (CYP11B2). Hypertension (Dallas, Tex. : 1979) 91 27872236
2002 Functional expression of human mitochondrial CYP11B2 in fission yeast and identification of a new internal electron transfer protein, etp1. Biochemistry 82 11841224
2000 Lys(173)Arg and -344T/C variants of CYP11B2 in Japanese patients with low-renin hypertension. Hypertension (Dallas, Tex. : 1979) 81 10720581
2006 Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. Journal of medicinal chemistry 71 16570918
1998 Human CYP11B2 (aldosterone synthase) maps to chromosome 8q24.3. The Journal of clinical endocrinology and metabolism 70 9506770
1993 Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients. Biochemical and biophysical research communications 70 8439335
1998 Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. The Journal of clinical endocrinology and metabolism 67 9745430
2002 Aldosterone synthase (CYP11B2) expression and myocardial fibrosis in the failing human heart. Clinical science (London, England : 1979) 64 11914098
2000 CYP11B2 gene polymorphisms in idiopathic hyperaldosteronism. Hypertension (Dallas, Tex. : 1979) 60 10720580
2003 Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension. Journal of hypertension 59 12817181
2002 Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosterone-producing adenomas. European journal of endocrinology 59 12457455
2016 A Novel CYP11B2-Specific Imaging Agent for Detection of Unilateral Subtypes of Primary Aldosteronism. The Journal of clinical endocrinology and metabolism 58 26756116
2005 Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis. Journal of medicinal chemistry 58 16220979
2008 Differential effects of high and low steroidogenic factor-1 expression on CYP11B2 expression and aldosterone production in adrenocortical cells. Endocrinology 50 18974272
2015 Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis. Journal of the American Society of Nephrology : JASN 49 26471128
2001 Aldosterone synthase gene (CYP11B2) C-334T polymorphism, ambulatory blood pressure and nocturnal decline in blood pressure in the general Japanese population: the Ohasama Study. Journal of hypertension 49 11725161
2004 Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension. Journal of the American College of Cardiology 48 14736447
1992 Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients. Biochemical and biophysical research communications 47 1346492
2002 Positive association of CYP11B2 gene polymorphism with genetic predisposition to essential hypertension. Journal of human hypertension 46 12444540
1999 Aldosterone synthase gene (CYP11B2) C-344T polymorphism in Caucasians from the Berlin Salt-Sensitivity Trial (BeSST). Journal of hypertension 46 10608469
1995 Mutation T318M in the CYP11B2 gene encoding P450c11AS (aldosterone synthase) causes corticosterone methyl oxidase II deficiency. American journal of human genetics 46 7485152
2004 Ubc9 and Protein Inhibitor of Activated STAT 1 Activate Chicken Ovalbumin Upstream Promoter-Transcription Factor I-mediated Human CYP11B2 Gene Transcription. The Journal of biological chemistry 45 15611122
2003 A biallelic gene polymorphism of CYP11B2 predicts increased aldosterone to renin ratio in selected hypertensive patients. The Journal of clinical endocrinology and metabolism 45 12788845
2000 Evaluation of the aldosterone synthase (CYP11B2) gene polymorphism in patients with myocardial infarction. Hypertension (Dallas, Tex. : 1979) 44 10720582
2004 Multiple Polymorphisms in the renin- angiotensin-aldosterone system (ACE, CYP11B2, AGTR1) and their contribution to hypertension in African Americans and Latinos in the multiethnic cohort. The American journal of the medical sciences 43 15545843
2011 Peroxisome proliferator-activated receptor-{gamma} suppresses CYP11B2 expression and aldosterone production. Journal of molecular endocrinology 42 21106862
2007 Polymorphism of CYP11B2 determines salt sensitivity in Japanese. Hypertension (Dallas, Tex. : 1979) 41 17296872
2005 The aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are not expressed in the rat heart. Endocrinology 41 16179417
2013 Discovery and in Vivo Evaluation of Potent Dual CYP11B2 (Aldosterone Synthase) and CYP11B1 Inhibitors. ACS medicinal chemistry letters 39 24900631
2010 Association of the -344C/T aldosterone synthase (CYP11B2) gene variant with hypertension and stroke. Journal of the neurological sciences 37 20598712
2000 Regulation of human CYP11B2 and CYP11B1: comparing the role of the common CRE/Ad1 element. Endocrine research 37 11196473
2017 Disordered CYP11B2 Expression in Primary Aldosteronism. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 36 29202495
2014 Computational analysis of functional single nucleotide polymorphisms associated with the CYP11B2 gene. PloS one 36 25102047
2004 CYP11B2 polymorphisms and home blood pressure in a population-based cohort in Japanese: the Ohasama study. Hypertension research : official journal of the Japanese Society of Hypertension 35 15055249
2004 The impact of polymorphisms in the gene encoding aldosterone synthase (CYP11B2) on steroid synthesis and blood pressure regulation. Molecular and cellular endocrinology 35 15134824
1999 Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction. Circulation 35 10577993
2015 Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17. Molecular and cellular endocrinology 34 26597777
2004 Genetic variation in CYP11B2 and AT1R influences heart rate variability conditional on sodium excretion. Hypertension (Dallas, Tex. : 1979) 34 15238568
1996 Calcium regulates human CYP11B2 transcription. Endocrine research 33 8969900
2016 Hypomethylation of CYP11B2 in Aldosterone-Producing Adenoma. Hypertension (Dallas, Tex. : 1979) 30 27754862
2015 Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice. Journal of molecular and cellular cardiology 30 26047574
2009 Coexpression of CYP11B2 or CYP11B1 with adrenodoxin and adrenodoxin reductase for assessing the potency and selectivity of aldosterone synthase inhibitors. Analytical biochemistry 30 19622340
2004 Association of peripheral and central arterial wave reflections with the CYP11B2 -344C allele and sodium excretion. Journal of hypertension 30 15614025
1995 Localization of P450aldo and P45011 beta in normal and regenerating rat adrenal cortex. Endocrine research 30 7588405
2023 Molecular and Epigenetic Control of Aldosterone Synthase, CYP11B2 and 11-Hydroxylase, CYP11B1. International journal of molecular sciences 29 36982850
2021 DNA Methylation of the Angiotensinogen Gene, AGT, and the Aldosterone Synthase Gene, CYP11B2 in Cardiovascular Diseases. International journal of molecular sciences 29 33925539
2014 Regulation of CYP11B1 and CYP11B2 steroidogenic genes by hypoxia-inducible miR-10b in H295R cells. Marine pollution bulletin 28 24768260
2009 High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 27 19151144
2005 CYP11B2 gene polymorphisms and hypertension in highlanders accustomed to high salt intake. Journal of hypertension 27 15643128
2007 Effect of variation in CYP11B1 and CYP11B2 on corticosteroid phenotype and hypothalamic-pituitary-adrenal axis activity in hypertensive and normotensive subjects. Clinical endocrinology 26 17980006
2021 Atractylenolide-I covalently binds to CYP11B2, selectively inhibits aldosterone synthesis, and improves hyperaldosteronism. Acta pharmaceutica Sinica. B 25 35127376
2005 The adrenocortical tumor cell line NCI-H295R as an in vitro screening system for the evaluation of CYP11B2 (aldosterone synthase) and CYP11B1 (steroid-11beta-hydroxylase) inhibitors. The Journal of steroid biochemistry and molecular biology 24 15985365
2005 Association of Lys173Arg polymorphism with CYP11B2 expression in normal adrenal glands and aldosterone-producing adenomas. The Journal of clinical endocrinology and metabolism 23 16118341
2020 Immunohistochemistry of the Human Adrenal CYP11B2 in Normal Individuals and in Patients with Primary Aldosteronism. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 22 32289837
2016 Disordered zonal and cellular CYP11B2 enzyme expression in familial hyperaldosteronism type 3. Molecular and cellular endocrinology 22 27793677
2006 Associations between CYP11B2 gene polymorphisms and the response to angiotensin-converting enzyme inhibitors. Clinical pharmacology and therapeutics 21 16765146
1992 Synthesis of the antibiotic cortalcerone from D-glucose using pyranose 2-oxidase and a novel fungal enzyme, aldos-2-ulose dehydratase. Carbohydrate research 21 1423351
2018 Association of aldosterone synthase CYP11B2 (-344C/T) gene polymorphism with essential hypertension and left ventricular hypertrophy in the Egyptian population. Clinical and experimental hypertension (New York, N.Y. : 1993) 20 30561227
2016 Expression of CYP11B2 in Aldosterone-Producing Adrenocortical Adenoma: Regulatory Mechanisms and Clinical Significance. The Tohoku journal of experimental medicine 20 27853054
2014 The clinical significance of aldosterone synthase deficiency: report of a novel mutation in the CYP11B2 gene. BMC endocrine disorders 19 24694176
2001 Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene. The Journal of clinical endocrinology and metabolism 19 11701710
1997 Expression of cytochromes P450aldo and P45011 beta in rat adrenal gland during late gestational and neonatal stages. Steroids 19 9029716
2009 Functional polymorphisms in ACE and CYP11B2 genes and atrial fibrillation in patients with hypertensive heart disease. Clinical chemistry and laboratory medicine 18 19117407
2009 Association between aldosterone synthase CYP11B2 polymorphism and essential hypertension in Chinese: a meta-analysis. Kidney & blood pressure research 18 19407459
2021 Long-chain noncoding RNA-GAS5/hsa-miR-138-5p attenuates high glucose-induced cardiomyocyte damage by targeting CYP11B2. Bioscience reports 17 33682891
2018 MiR-193a-3p functions as a tumour suppressor in human aldosterone-producing adrenocortical adenoma by down-regulating CYP11B2. International journal of experimental pathology 17 29665181
2014 Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA). Molecular and cellular endocrinology 17 24472523
2010 Associations of the -344 T>C and the 3097 G>A polymorphisms of CYP11B2 gene with hypertension, type 2 diabetes, and metabolic syndrome in a French population. American journal of hypertension 17 20224556
2006 CYP11B2 -344T/C gene polymorphism and blood pressure in patients with acromegaly. The Journal of clinical endocrinology and metabolism 17 17003099
2019 Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity. The Journal of steroid biochemistry and molecular biology 16 30974191
2018 MiR-4421 regulates the progression of preeclampsia by regulating CYP11B2. European review for medical and pharmacological sciences 16 29630094
2022 Changes of the CYP11B2 Expressing Zona Glomerulosa in Human Adrenals From Birth to 40 Years of Age. Hypertension (Dallas, Tex. : 1979) 15 36036158
2021 Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism. Clinical endocrinology 15 34743356
2019 Analysis of novel heterozygous mutations in the CYP11B2 gene causing congenital aldosterone synthase deficiency and literature review. Steroids 15 31302112
1997 Expression of 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in the human fetal adrenal. Journal of the Society for Gynecologic Investigation 15 9408886
2015 Chimeric CYP11B2/CYP11B1 causing 11β-hydroxylase deficiency in Chinese patients with congenital adrenal hyperplasia. Steroids 14 26066897
2007 Skinfold thickness and blood pressure across C-344T polymorphism of CYP11B2 gene. Journal of hypertension 14 17762647
2000 CYP11B2 expression in rat liver and the effect of spironolactone on hepatic fibrogenesis. Hormone research 14 11146369
2012 Association of CYP11B2 gene polymorphism with ischemic stroke in the north Chinese Han population. Neurology India 13 23135028
2019 miRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma. European journal of endocrinology 12 31096184
2016 Novel mutations in the CYP11B2 gene causing aldosterone synthase deficiency. Molecular medicine reports 12 26936515
2016 Biotransformation of the mineralocorticoid receptor antagonists spironolactone and canrenone by human CYP11B1 and CYP11B2: Characterization of the products and their influence on mineralocorticoid receptor transactivation. The Journal of steroid biochemistry and molecular biology 12 27125452
2015 Analysis of the gene polymorphism of aldosterone synthase (CYP11B2) and atrial natriuretic peptide (ANP) in women with preeclampsia. European journal of obstetrics, gynecology, and reproductive biology 12 26686590
2011 Regulation of human CYP11B1 and CYP11B2 promoters by transposable elements and conserved cis elements. Steroids 12 22079243
2010 Polymorphisms in CYP11B2 and CYP11B1 genes associated with primary hyperaldosteronism. Hypertension research : official journal of the Japanese Society of Hypertension 12 20339375
2008 A novel CYP11B2 gene mutation in an Asian family with aldosterone synthase deficiency. The Journal of clinical endocrinology and metabolism 12 19116236
1995 Stable expression of rat cytochrome P450 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in MA-10 cells. The Journal of steroid biochemistry and molecular biology 12 7779756
2023 Association between Aldosterone Synthase (CYP11B2) Gene Polymorphism and Hypertension in Pashtun Ethnic Population of Khyber Pakhtunkwha, Pakistan. Genes 11 37372364
2012 Control of CYP11B2/CYP11B1 expression ratio and consequences for the zonation of the adrenal cortex. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 11 23235923
2011 Genetic polymorphism of CYP11B2 gene and stroke in the Han Chinese population and a meta-analysis. Pharmacogenetics and genomics 11 21228735
1997 Expression of aldosterone synthase cytochrome P450 (P450aldo) mRNA in rat adrenal glomerulosa cells by angiotensin II type 1 receptor. Endocrine research 11 9430819

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