Affinage

CYP11B1

Cytochrome P450 11B1, mitochondrial · UniProt P15538

Round 2 corrected
Length
503 aa
Mass
57.6 kDa
Annotated
2026-04-28
130 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYP11B1 is a mitochondrial cytochrome P450 (steroid 11β-hydroxylase) that catalyzes the final step of cortisol biosynthesis by converting 11-deoxycortisol to cortisol, receiving electrons from NADPH via the adrenodoxin reductase–adrenodoxin chain, with which it forms multiple productive complexes (PMID:18215163, PMID:2401360). Substrate regioselectivity—distinguishing CYP11B1 (11β-hydroxylase) from the paralog CYP11B2 (aldosterone synthase)—is determined by a small cluster of residues in the I-helix region (positions 301–335), where single substitutions can confer 18-oxidase activity on CYP11B1 (PMID:9546661, PMID:8969896). Zona fasciculata–specific transcription is driven by cooperative action of a CRE/Ad1 element bound by CREB/ATF factors, an Ad4 element bound by SF-1, an Ad5 element occupied by ERRα, and an AP-1 complex whose composition shifts upon ACTH stimulation, while post-transcriptional regulation occurs through mRNA stabilization and miR-10b–mediated repression, and promoter DNA methylation modulates expression in cortisol-producing adenomas (PMID:11196473, PMID:8247022, PMID:22079243, PMID:9746364, PMID:24768260, PMID:28894201). Loss-of-function mutations cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency, with residual enzymatic activity directly correlating with clinical severity, and Cyp11b1-knockout mice recapitulate glucocorticoid deficiency, mineralocorticoid excess, and hypertension (PMID:20089618, PMID:19029289).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1987 High

    Establishing that CYP11B1 encodes a mitochondrial cytochrome P450 with steroid 11β-hydroxylase activity resolved the molecular identity of the enzyme responsible for cortisol's final biosynthetic step.

    Evidence cDNA cloning, sequencing, and chromosomal mapping to 8q from bovine/human adrenal libraries

    PMID:3499608

    Open questions at the time
    • Enzymatic activity not yet demonstrated from the cloned cDNA
    • Paralogous gene (CYP11B2) not yet distinguished
  2. 1990 High

    Functional expression in heterologous cells demonstrated that CYP11B1 has exclusively 11β-hydroxylase activity (cortisol synthesis) and cannot synthesize aldosterone, definitively distinguishing it from CYP11B2 despite 93% sequence identity.

    Evidence COS-7 transient transfection with steroid conversion assays for CYP11B1 vs CYP11B2; genomic structure comparison

    PMID:2401360 PMID:2592361

    Open questions at the time
    • Structural determinants of substrate selectivity unknown
    • Electron-transfer partner requirements not quantified
  3. 1993 High

    Systematic expression of disease-causing mutations revealed that residues in exons 6–8—including the heme-ligand-proximal Arg-448—are essential for catalysis, mapping functionally critical domains before any crystal structure was available.

    Evidence In vitro COS cell expression of five missense and one nonsense mutation with steroid conversion assays; family segregation studies

    PMID:2022736 PMID:7903314 PMID:8506298

    Open questions at the time
    • Three-dimensional structure not determined
    • Mechanism by which individual residues contribute to catalysis unresolved
  4. 1993 High

    Identification of Ad4BP (SF-1) as the steroidogenic cell–specific transcription factor driving CYP11B1 promoter activity via the Ad4 element explained why this gene is expressed only in adrenocortical cells.

    Evidence Cotransfection of Ad4BP expression vector restores CYP11B1 reporter activity in non-steroidogenic cells; immunoblot confirmation

    PMID:1336011 PMID:8247022

    Open questions at the time
    • Additional cis-elements (CRE/Ad1, AP-1) not yet integrated into a unified regulatory model
    • In vivo chromatin context not assessed
  5. 1996 High

    Reciprocal mutagenesis at I-helix positions (296, 301, 302, 320, 335) between CYP11B1 and CYP11B2 showed that a handful of residues in this region determine whether the enzyme performs 11β-hydroxylation or aldosterone synthesis, resolving the structural basis of paralog divergence.

    Evidence Site-directed mutagenesis with COS cell expression and steroid product profiling

    PMID:8969896 PMID:9546661

    Open questions at the time
    • Crystal structure needed to explain how these residues position substrate
    • Residues 301–335 necessary but possibly not sufficient for full selectivity switch
  6. 1998 High

    ACTH-stimulated CYP11B1 transcription was shown to operate through an AP-1 site whose factor composition shifts from constitutive JunD/Fra-2 to induced c-Jun/c-Fos via cAMP, integrating hormonal signaling with zona fasciculata–specific expression.

    Evidence Promoter mutant transfection, AP-1 supershift EMSA, and in vivo ACTH treatment in rat adrenal

    PMID:7565753 PMID:9746364

    Open questions at the time
    • Chromatin remodeling events at the endogenous locus not examined
    • Relative contribution of AP-1 vs CRE/Ad1 to ACTH response not quantified in human cells
  7. 2001 High

    Stopped-flow kinetics with adrenodoxin mutants revealed that CYP11B1 and CYP11A1 have distinct electron-transfer requirements, and Biacore data later showed CYP11B1 possesses more than one adrenodoxin-binding site, explaining how multiple productive complexes form.

    Evidence Stopped-flow CO-complex kinetics with adrenodoxin variants; SPR (Biacore) binding of purified CYP11B1

    PMID:11459837 PMID:18215163

    Open questions at the time
    • Stoichiometry and structural arrangement of the multi-adrenodoxin complex not resolved
    • In vivo relevance of multiple binding sites not tested
  8. 2008 High

    A Cyp11b1-knockout mouse confirmed the enzyme's non-redundant in vivo role: loss of 11β-hydroxylase causes glucocorticoid deficiency, DOC-driven mineralocorticoid excess with hypertension, adrenal hyperplasia, and female infertility, phenocopying human 11β-hydroxylase deficiency.

    Evidence Targeted exon 3–7 replacement; urinary steroid profiling, blood pressure, reproductive phenotyping

    PMID:19029289

    Open questions at the time
    • Rescue experiments not performed
    • Sex-specific phenotypic mechanisms (anovulation) not dissected molecularly
  9. 2010 High

    Quantitative in vitro activity measurement of classic and non-classic disease mutations established that residual enzyme activity directly predicts clinical severity, providing a mechanistic framework for genotype–phenotype correlation.

    Evidence COS7 expression of seven mutations; steroid conversion assay correlated with clinical phenotype

    PMID:20089618 PMID:9302260

    Open questions at the time
    • Protein stability versus catalytic impairment not distinguished for all mutations
    • Effects of compound heterozygosity on net activity not modeled
  10. 2017 High

    Epigenetic regulation was added to the CYP11B1 regulatory model when promoter DNA hypomethylation was shown to increase CYP11B1 expression in cortisol-producing adenomas, linking somatic PRKACA/GNAS mutations to epigenetic de-repression.

    Evidence Bisulfite sequencing of adenoma vs. normal adrenal; methylated reporter assay; somatic mutation genotyping

    PMID:28894201

    Open questions at the time
    • Causal direction (does mutation cause demethylation or vice versa?) not established by intervention
    • Methylation dynamics during normal adrenal zonation unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • No experimentally determined crystal or cryo-EM structure of human CYP11B1 has been reported; structural understanding still relies on homology models, leaving the precise geometry of the substrate-binding pocket and the multi-adrenodoxin interaction surface unresolved.
  • Experimental 3D structure not available
  • Molecular dynamics of substrate access channel and product release not characterized
  • In vivo regulation by adrenal zonation-specific chromatin architecture not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 9 GO:0140096 catalytic activity, acting on a protein 5
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 8 R-HSA-1643685 Disease 7
Partners
ATF2CREB1ESRRAFDX1FDXRJUNNR5A1

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 CYP11B1 (P450c11) encodes a 479-amino-acid mature protein (plus a 24-residue mitochondrial signal sequence) that catalyzes steroid 11β-hydroxylation; cDNA cloning established the primary structure and chromosomal localization to 8q. cDNA cloning and sequencing; in vitro translation; chromosomal hybridization Proceedings of the National Academy of Sciences of the United States of America High 3499608
1989 CYP11B1 and the paralog CYP11B2 each contain nine exons (introns in identical positions to CYP11A); the encoded proteins are 93% identical to each other, yet their 5'-flanking regions have diverged considerably, consistent with distinct transcriptional regulation. CYP11B2 transcripts were not detected in normal adrenal mRNA. Genomic library cloning, sequencing, and Northern blot The Journal of biological chemistry High 2592361
1990 CYP11B1 (P-45011β) expressed in COS-7 cells exhibits exclusively 11β-hydroxylase activity, converting 11-deoxycortisol to cortisol, but fails to catalyze aldosterone or 18-oxocortisol synthesis, distinguishing it functionally from CYP11B2. Transient transfection of full-length cDNA in COS-7 cells; steroid conversion assay FEBS letters High 2401360
1991 A single base substitution in CYP11B1 exon 8 (Arg-448→His, within the heme-binding peptide containing the cysteine heme-ligand) abolishes 11β-hydroxylase activity, demonstrating that Arg-448 is essential for enzymatic function. PCR-selective amplification of CYP11B1, DNA sequencing; family linkage The Journal of clinical investigation High 2022736
1992 CYP11B1 encodes a protein with only 11β-hydroxylase activity; the hybrid gene in glucocorticoid-suppressible hyperaldosteronism (GSH) has CYP11B1 5'-regulatory and coding sequences fused to 3'-CYP11B2 coding sequences. Transfection experiments showed that hybrids retaining ≤3 CYP11B1 exons could synthesize aldosterone near wild-type CYP11B2 levels, while hybrids containing ≥5 CYP11B1 exons could not, mapping aldosterone synthase determinants to exons 4–9 of CYP11B2. Transfection of hybrid cDNAs into COS-1 cells; aldosterone synthesis assay Proceedings of the National Academy of Sciences of the United States of America High 1518866
1992 Hereditary hypertension (glucocorticoid-remediable aldosteronism) is caused by chimeric gene duplications that fuse CYP11B1 regulatory sequences to CYP11B2 coding sequences, resulting in ectopic aldosterone synthase activity regulated by ACTH; crossing-over occurs between introns 2 and 4. Southern blot, genomic PCR, chimeric gene characterization in 12 kindreds Nature genetics High 1303253
1992 CYP11B1 exon 7 frameshift (2-bp insertion at codon 394) destroys the heme-binding domain and completely abolishes 11β-hydroxylase activity. Gene cloning and sequencing; inference from protein structure The Journal of clinical endocrinology and metabolism Medium 1430088
1992 CYP11B1 promoter activity requires a CRE-like Ad1 element and upstream elements Ad3/Ad4 for full cAMP-dependent transcription; both elements must cooperate for maximal cAMP response in steroidogenic cells. Transient transfection reporter assay with deletion/mutation constructs; in vitro transcription; CREB/nuclear factor binding assays Journal of biochemistry High 1336011
1993 All five known missense mutations causing 11β-hydroxylase deficiency (including Arg-448→His, Arg-384→Gly, and three others) abolish enzymatic activity when expressed in vitro; mutations cluster in exons 6–8, suggesting these regions harbor functionally critical residues. In vitro transfection assay (COS cell expression) of mutant cDNAs; steroid conversion measurement Proceedings of the National Academy of Sciences of the United States of America High 8506298
1993 Ad4BP (steroidogenic cell-specific transcription factor, now SF-1/NR5A1) binds the Ad4 cis-element in the CYP11B promoter and is required for cAMP-dependent, steroidogenic cell-specific transcription; its absence in non-steroidogenic cells accounts for lack of CYP11B expression there. Transient transfection reporter assay; immunoblot; cotransfection of Ad4BP expression vector Molecular endocrinology High 8247022
1993 A nonsense mutation (Trp116→Stop) in CYP11B1 exon 2 results in complete absence of 11β-hydroxylase activity in mitochondria of transfected COS-7 cells, demonstrating that intact protein is required for activity. PCR, sequencing, RFLP, COS-7 cell transfection and enzyme activity assay The Journal of clinical endocrinology and metabolism High 7903314
1994 Two Ad4 sites in the distal promoter of bovine CYP11B (−1.5 to −1.1 kb) confer steroidogenic cell-specific and cAMP-stimulated transcriptional activation through Ad4BP; distal and proximal promoters interact in a gene-specific manner. Transient transfection of CAT reporter constructs with distal promoter fragments in steroidogenic and non-steroidogenic cells Journal of biochemistry Medium 7798178
1995 CYP11B1 expressed in COS-1 cells and stably in V79 Chinese hamster cells retains 11β-hydroxylase activity without requiring exogenous electron-transfer proteins, indicating that hamster cells provide sufficient endogenous adrenodoxin/adrenodoxin reductase-like activity. cDNA cloning; COS-7 transient transfection; V79 stable transfection; Northern blot; steroid hydroxylase activity assay Endocrine research Medium 7588408
1995 CYP11B1 (P450c11β) metabolizes and bioactivates the adrenotoxic xenobiotic MeSO2-DDE, establishing that this mitochondrial steroidogenic P450 can also perform xenobiotic metabolism; activity demonstrated by correlation with DOC metabolism induction by forskolin, inhibition of P450c11-dependent activities by MeSO2-DDE, and COS cell transfection experiments. Correlation of enzyme induction; inhibition assays in Y1 and Kin-8 cells; COS cell transfection with CYP11B1 cDNA followed by MeSO2-DDE metabolism assay The Journal of biological chemistry High 7673111
1995 An AP-1 transcription factor complex (containing JunD and a Fos-related protein) binds adjacent to the Ad4BP site in the rat CYP11B1 promoter; AP-1 binding suppresses Ad4BP binding, and the AP-1 site (not the Ad4 site) drives transcriptional activation in zona fasciculata cells. AP-1 factor is present in nuclei of CYP11B1-expressing zona fasciculata cells but not in other zones. Transient transfection with promoter mutants in Y1 cells; EMSA with nuclear extracts; immunohistochemistry Molecular and cellular biology High 7565753
1996 Point mutations in the putative I-helix of CYP11B1 (e.g., Val-320→Ala, the CYP11B2-specific residue) confer aldosterone synthesis (18-oxidase activity) on CYP11B1, while the reciprocal CYP11B2 mutations at positions 296, 301, 302, and 320 elevate its 11β-hydroxylase activity and diminish aldosterone synthase activity, identifying this region as determining regioselectivity. Site-directed mutagenesis; COS cell expression; steroid product profiling Endocrine research High 8969896
1997 Non-classic 11β-hydroxylase deficiency is caused by partial-loss-of-function missense mutations in CYP11B1 (e.g., N133H, T319M, P42S) that reduce but do not abolish enzymatic activity when expressed in vitro, establishing a genotype–phenotype correlation. In vitro expression in COS cells; steroid conversion assay Human molecular genetics High 9302260
1998 Replacement of CYP11B1 residues at positions 320 (Val→Ala) and 335 with CYP11B2-specific residues confers 18-oxidase activity (~20% of CYP11B2 WT), converting CYP11B1 into a partial aldosterone synthase; combining substitutions at positions 296, 301, 302, 320, 335, and 339 did not further enhance activity. The region spanning residues 301–335 constitutes part of the substrate-binding site. Site-directed mutagenesis; chimeric protein construction; COS cell transfection; steroid product analysis European journal of biochemistry High 9546661
1998 CYP11B1 hybrid enzymes with CYP11B2 residues at Ser-288 and Val-320 can catalyze conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol; additional substitutions from CYP11B2 exons 4–6 further enhance 18-hydroxylcortisol and 18-oxocortisol production. Recombinant hybrid cDNA construction; cell transfection; steroid product measurement The Journal of clinical endocrinology and metabolism High 9814482
1998 CYP11B1 expressed in E. coli retains 11β-hydroxylase activity; Dahl salt-resistant rat CYP11B1 (DR-CYP11B1) has decreased 18-hydroxylase and 19-hydroxylase activities compared to WT; the double mutation V381L/I384L accounts for decreased 18-OHase activity, and V443M accounts for decreased 19-OHase activity. Bacterial expression; site-directed mutagenesis; steroid conversion assays European journal of biochemistry High 9874258
1998 ACTH-stimulated transcription of rat CYP11B1 requires an AP-1 binding site in the 5'-flanking region; corticotropin induces compositional changes in AP-1 factors (increasing c-Jun/c-Fos over constitutive JunD/Fra-2) via a cAMP-dependent pathway, and c-Jun/c-Fos overexpression transactivates CYP11B1 more strongly than other combinations. Transient transfection with promoter mutants; AP-1 supershift EMSA; cAMP treatment; in vivo corticotropin treatment + mRNA analysis European journal of biochemistry High 9746364
1999 CYP11B1 and CYP11A1 co-expressed in COS-1 cells compete for reducing equivalents from the endogenous electron-transfer system; excess adrenodoxin resolves this competition. Bovine CYP11B1 co-expressed with CYP11A1 and adrenodoxin shows stimulated 11β-hydroxylation but reduced 18-hydroxycorticosterone and aldosterone formation, indicating functional interaction between the mitochondrial P450 enzymes. Co-transfection of COS-1 cells; steroid product analysis with and without exogenous adrenodoxin European journal of biochemistry Medium 10411633
2000 The CRE/Ad1 element in the hCYP11B1 promoter is required for both basal expression and agonist (angiotensin II, potassium, cAMP, forskolin) responsiveness; mutation of this element reduces basal activity and agonist response. CREB, ATF-1, and ATF-2 bind this element in vitro, with ATF-2 complexes seen in adrenocortical nuclear extracts. Transient transfection reporter assays in H295R cells; EMSA with in vitro prepared and nuclear extract proteins Endocrine research High 11196473
2001 Adrenodoxin mutants with C-terminal truncation and introduction of Trp at position 112 (e.g., S112W) show markedly faster reduction kinetics with CYP11A1 but not CYP11B1, demonstrating that CYP11A1 and CYP11B1 have distinct requirements for adrenodoxin-mediated electron transfer. CYP11B1 reduction rate constants were similar across adrenodoxin mutants, unlike CYP11A1. Stopped-flow kinetics of CO-complex formation; substrate conversion assays; site-directed mutagenesis of adrenodoxin The Journal of biological chemistry High 11459837
2002 The steroidogenic factor SF-1 (Ad4BP/NR5A1) positively regulates CYP11B1 transcription (increasing reporter activity) via the Ad4 element in the promoter; mutation of the Ad4 element blocks agonist stimulation of CYP11B1 but not CYP11B2. EMSA shows SF-1 binds the CYP11B1 Ad4 element. Conversely, SF-1 overexpression inhibits CYP11B2 expression. Transient transfection reporter assays; EMSA; SF-1 siRNA knockdown; doxycycline-inducible SF-1 overexpression in H295R cells Journal of molecular endocrinology High 11932209
2005 CYP11B1 missense mutations W116C and L299P reduce enzymatic activity to ~3% and ~1% of WT respectively, and ΔF438 abolishes activity entirely; 3D modeling suggests W116C disrupts conformational change for substrate access/product release, L299P alters I-helix positioning relative to heme, and ΔF438 causes steric disarrangement of the heme group. COS-7 cell in vitro expression; steroid conversion assay; 3D computational modeling The Journal of clinical endocrinology and metabolism High 15755848
2006 PCB126 up-regulates CYP11B1 and CYP11B2 mRNA not through AhR-mediated transcriptional activation but by stabilizing mRNA post-transcriptionally; an internal region of CYP11B1 mRNA (nucleotides 881–1285) is important for PCB126-mediated transcript stabilization. RNA degradation assays; promoter analysis; AhR antagonist treatment; mRNA stability assays with defined CYP11B1 mRNA fragments in H295R cells Endocrinology High 16396990
2007 Co-expression of adrenodoxin and adrenodoxin reductase with CYP11B1 in fission yeast (S. pombe) increases 11β-hydroxylation activity 3.4-fold; site-directed mutagenesis at position 78 (isoleucine) of CYP11B1 confers highest hydroxylation activity, demonstrating that the redox partner system and specific amino acid identity at position 78 are rate-limiting for cortisol production. S. pombe expression system; site-directed mutagenesis; cortisol production measurement Journal of biotechnology High 17935813
2008 Purified recombinant human CYP11B1 (co-expressed with GroES/GroEL chaperones in E. coli) retains 11β-hydroxylase activity with ~75% NADPH coupling efficiency for both 11-deoxycortisol and 11-deoxycorticosterone substrates. Biacore and stopped-flow measurements indicate CYP11B1 possesses more than one binding site for adrenodoxin, suggesting formation of multiple productive complexes. E. coli expression with chaperone co-expression; purification to homogeneity; mass spectrometry; substrate conversion assays; Biacore (SPR); stopped-flow spectroscopy; CD spectroscopy The FEBS journal High 18215163
2008 Cyp11b1 knockout mice (exons 3–7 replaced by ECFP cDNA) lack 11β-hydroxylase activity (confirmed by urinary steroid profiles and absent immunostaining), exhibit glucocorticoid deficiency, mineralocorticoid excess (DOC accumulation), adrenal hyperplasia, mild hypertension, hypokalemia, glucose intolerance, and female infertility due to anovulation. Targeted gene knockout (exon replacement); urinary steroid profiling; immunocytochemistry; blood pressure measurement; reproductive phenotyping The Journal of biological chemistry High 19029289
2010 Novel CYP11B1 missense mutations causing classic 11β-OHD (W116G, A165D, K254_A259del) show absent or near-absent 11β-hydroxylase activity; mutations causing non-classic 11β-OHD (P159L, M88I) show partial activity (~25% and ~40% of WT respectively), demonstrating a direct correlation between residual enzyme activity level and disease severity. COS7 cell in vitro expression system; steroid conversion assay; 3D computational modeling The Journal of clinical endocrinology and metabolism High 20089618
2011 The Ad5/SF-1 binding element in the CYP11B1 core promoter is required for basal expression; ERRα is the transcription factor that interacts with the Ad5 site during basal expression. Insertion of an L1 transposable element (CYP11B1-L1.2) between the Alu elements and the proximal core promoter suppresses Alu enhancer activity on CYP11B1; deletion of CYP11B1-L1.2 greatly increases promoter activity. Promoter deletion/mutation reporter assays; transcription factor identification by EMSA; Alu and L1 element functional analysis; luciferase assays in H295R cells Steroids Medium 22079243
2011 Nonhydroxylated flavones (3',4'-dimethoxyflavone, α- and β-naphthoflavone) up-regulate CYP11B1 expression and cortisol production in H295R cells; this induction requires the Ad5 element (−121/−106) in the CYP11B1 promoter and is partially dependent on PKA signaling (sensitive to H-89) but independent of AhR and ERK1/2 signaling. H295R cell model; qRT-PCR; promoter reporter assays with Ad5 mutations; pharmacological inhibitors; western blot Toxicology and applied pharmacology Medium 22172629
2014 miR-10b is a hypoxia-inducible microRNA that negatively regulates CYP11B1 and CYP11B2 at the post-transcriptional level by targeting their 3'-UTRs; luciferase reporter assays with 3'-UTR constructs and miRNA overexpression/knockdown confirmed this interaction in H295R cells. miRNA array; in silico target prediction; luciferase 3'-UTR reporter assays; miR-10b overexpression and knockdown in H295R cells Marine pollution bulletin Medium 24768260
2015 An E. coli whole-cell system co-expressing CYP11B1, adrenodoxin, and adrenodoxin reductase selectively converts 11-deoxycortisol to cortisol; CYP11B1 expression was enhanced 3.3-fold by mutagenesis of Gly-23→Arg, improving cortisol yield 2.6-fold. Additional Adx copies further accelerated conversion, demonstrating that electron-transfer chain stoichiometry is rate-limiting. E. coli whole-cell biocatalysis; site-directed mutagenesis; copy-number variation of Adx; LC-MS cortisol quantification; directed evolution screening Microbial cell factories High 25880059
2017 DNA hypomethylation of the CYP11B1 promoter is associated with increased CYP11B1 expression and cortisol overproduction in cortisol-producing adenomas (CPA); reporter assays confirmed that DNA methylation directly reduces CYP11B1 promoter activity. Somatic mutations in PRKACA or GNAS in CPA are associated with significant CYP11B1 promoter hypomethylation. Bisulfite sequencing of CYP11B1 promoter; methylated reporter assay; comparison between CPA, adjacent adrenal, and white blood cells; somatic mutation genotyping Scientific reports High 28894201
2017 Computational 3D modeling of 25 CYP11B1 missense mutations reveals that modifications in the heme-binding site (R374W, R448C), substrate-binding site (W116C), or protein stability (L299P, G267S) predict severe 11β-hydroxylase deficiency, providing a structural basis for genotype-severity correlation in the largest cohort (108 patients) studied to date. Homology-based computational structural modeling; clinical/hormonal correlation with genotype in 108 patients Proceedings of the National Academy of Sciences of the United States of America Medium 28228528

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1999 Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature genetics 1381 10391209
2004 Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocrine reviews 1274 15583024
2009 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 843 19490893
1999 Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nature genetics 769 10391210
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2004 Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics 729 15128046
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1989 Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta). The Journal of biological chemistry 436 2592361
1992 Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase. Nature genetics 273 1303253
2013 Development of monoclonal antibodies against human CYP11B1 and CYP11B2. Molecular and cellular endocrinology 245 24325867
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
2009 Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. Autism research : official journal of the International Society for Autism Research 223 19598235
1992 Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans. Proceedings of the National Academy of Sciences of the United States of America 213 1741400
1993 Activation of CYP11A and CYP11B gene promoters by the steroidogenic cell-specific transcription factor, Ad4BP. Molecular endocrinology (Baltimore, Md.) 211 8247022
1992 Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2. Proceedings of the National Academy of Sciences of the United States of America 207 1518866
1987 Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11). Proceedings of the National Academy of Sciences of the United States of America 207 3499608
1991 A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin. The Journal of clinical investigation 200 2022736
1993 Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8. Proceedings of the National Academy of Sciences of the United States of America 165 8506298
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
1990 Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism. Biochemical and biophysical research communications 150 2256920
2002 Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1. Journal of molecular endocrinology 126 11932209
1990 Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta. FEBS letters 104 2401360
2008 Steroid 11beta- hydroxylase deficiency congenital adrenal hyperplasia. Trends in endocrinology and metabolism: TEM 99 18294861
2017 Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Proceedings of the National Academy of Sciences of the United States of America 93 28228528
1997 CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Human molecular genetics 92 9302260
2014 Adrenal CYP11B1/2 expression in primary aldosteronism: immunohistochemical analysis using novel monoclonal antibodies. Molecular and cellular endocrinology 89 24837548
1998 Recombinant CYP11B genes encode enzymes that can catalyze conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol. The Journal of clinical endocrinology and metabolism 86 9814482
2010 Functional consequences of seven novel mutations in the CYP11B1 gene: four mutations associated with nonclassic and three mutations causing classic 11{beta}-hydroxylase deficiency. The Journal of clinical endocrinology and metabolism 75 20089618
2019 The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis. Nature communications 74 31586073
2008 Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma. PloS one 70 18636124
1991 Zone-specific regulation of two messenger RNAs for P450c11 in the adrenals of pregnant and nonpregnant rats. Proceedings of the National Academy of Sciences of the United States of America 70 2052554
2008 [123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes. The Journal of clinical endocrinology and metabolism 69 18397978
2002 The human steroid hydroxylases CYP1B1 and CYP11B2. Biological chemistry 68 12452430
1995 Cloning of CYP11B1 and CYP11B2 from normal human adrenal and their functional expression in COS-7 and V79 Chinese hamster cells. Endocrine research 67 7588408
2004 Modulation of aldosterone and cortisol synthesis on the molecular level. Molecular and cellular endocrinology 66 15026188
2002 Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosterone-producing adenomas. European journal of endocrinology 59 12457455
2010 First Selective CYP11B1 Inhibitors for the Treatment of Cortisol-Dependent Diseases. ACS medicinal chemistry letters 58 24900247
2014 The CYP11B subfamily. The Journal of steroid biochemistry and molecular biology 57 25465475
1993 Isolation and characterization of rat CYP11B genes involved in late steps of mineralo- and glucocorticoid syntheses. The Journal of biological chemistry 56 8473352
1994 Contribution of Ad4BP, a steroidogenic cell-specific transcription factor, to regulation of the human CYP11A and bovine CYP11B genes through their distal promoters. Journal of biochemistry 55 7798178
1992 Frame shift by insertion of 2 basepairs in codon 394 of CYP11B1 causes congenital adrenal hyperplasia due to steroid 11 beta-hydroxylase deficiency. The Journal of clinical endocrinology and metabolism 53 1430088
2009 High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 52 19453261
2001 Unequal crossing-over between aldosterone synthase and 11beta-hydroxylase genes causes congenital adrenal hyperplasia. The Journal of clinical endocrinology and metabolism 52 11549691
1995 P450c11B3 mRNA, transcribed from a third P450c11 gene, is expressed in a tissue-specific, developmentally, and hormonally regulated fashion in the rodent adrenal and encodes a protein with both 11-hydroxylase and 18-hydroxylase activities. The Journal of biological chemistry 51 7829497
2008 Differential effects of high and low steroidogenic factor-1 expression on CYP11B2 expression and aldosterone production in adrenocortical cells. Endocrinology 50 18974272
2003 Defining the blood pressure QTL on chromosome 7 in Dahl rats by a 177-kb congenic segment containing Cyp11b1. Mammalian genome : official journal of the International Mammalian Genome Society 49 12682779
1993 Three forms of rat CYP11B genes: 11 beta-hydroxylase gene, aldosterone synthase gene, and a novel gene. Journal of biochemistry 49 8468320
2009 Determination of genetic predisposition to patent ductus arteriosus in preterm infants. Pediatrics 48 19336370
1998 Conferring aldosterone synthesis to human CYP11B1 by replacing key amino acid residues with CYP11B2-specific ones. European journal of biochemistry 48 9546661
2007 Joint analysis of the influence of CYP11B1 and DGAT1 genetic variation on milk production, somatic cell score, conformation, reproduction, and productive lifespan in German Holstein cattle. Journal of animal science 46 17179535
2005 Congenital adrenal hyperplasia due to 11-hydroxylase deficiency: functional characterization of two novel point mutations and a three-base pair deletion in the CYP11B1 gene. The Journal of clinical endocrinology and metabolism 45 15755848
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