CYP11B1 (cytochrome P450 family 11 subfamily B member 1)

Gene

• Entrez ID: 1584
• Gene name: Cytochrome P450 family 11 subfamily B member 1
• Gene symbol: CYP11B1
• Synonyms: CPN1, CYP11B, FHI, P450C11
• Chromosome: 8
• Chromosome location: 8q24.3
• Summary: This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of progesterone to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28934586	C>T	Likely-pathogenic, pathogenic	Intron variant, coding sequence variant, missense variant
rs61751149	G>A,C,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, missense variant
rs61752766	T>C	Benign, uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs61752786	G>A,C,T	Benign, likely-pathogenic, likely-benign, benign-likely-benign	Coding sequence variant, synonymous variant, missense variant
rs104894061	G>A,C,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs104894062	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs104894066	C>T	Pathogenic	Coding sequence variant, stop gained
rs104894067	T>C,G	Pathogenic	Coding sequence variant, missense variant
rs104894068	G>A	Pathogenic	Coding sequence variant, missense variant
rs104894069	G>A	Not-provided, pathogenic	Coding sequence variant, missense variant
rs104894070	G>A,T	Not-provided, pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs104894071	G>T	Pathogenic	Coding sequence variant, missense variant
rs140336749	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs146124466	G>A	Pathogenic	Coding sequence variant, stop gained
rs193922538	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs193922539	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs193922540	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs193922541	A>G	Likely-pathogenic	Splice donor variant
rs267606755	A>C	Pathogenic-likely-pathogenic	Stop gained, intron variant, coding sequence variant
rs367634557	C>T	Likely-pathogenic	Missense variant, intron variant, coding sequence variant
rs387907572	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs387907573	A>G,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs577022490	A>G,T	Likely-pathogenic	Splice donor variant, intron variant
rs748867146	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs753774484	C>A,G,T	Likely-pathogenic	Coding sequence variant, synonymous variant
rs760880418	G>A,T	Likely-pathogenic	Synonymous variant, coding sequence variant, stop gained
rs763195324	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant, stop gained
rs764418169	CCAGGCTCATCCTGTGGGGATGCAGGCT>-	Pathogenic	Frameshift variant, coding sequence variant
rs764598023	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs768007725	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs775128501	->GTGTACTGTTG	Pathogenic, likely-pathogenic	Frameshift variant, coding sequence variant
rs779103938	C>T	Pathogenic-likely-pathogenic, likely-pathogenic	Missense variant, intron variant, coding sequence variant
rs866430018	C>T	Pathogenic	Stop gained, coding sequence variant
rs1131691992	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1249087390	G>-	Pathogenic	Frameshift variant, intron variant, coding sequence variant
rs1256580853	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs1264073726	C>T	Pathogenic, likely-pathogenic	Splice donor variant
rs1326688256	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs1365173817	C>A,T	Pathogenic	Intron variant
rs1379392398	->T	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1383321200	C>G,T	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs1456715954	C>T	Likely-pathogenic	Splice acceptor variant
rs1554652650	A>-	Likely-pathogenic	Coding sequence variant, frameshift variant, intron variant
rs1554652990	C>G	Likely-pathogenic	Splice donor variant
rs1554652998	C>T	Pathogenic	Coding sequence variant, stop gained
rs1554652999	C>T	Pathogenic	Coding sequence variant, stop gained
rs1554653514	C>G	Likely-pathogenic	Splice donor variant
rs1554653520	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1554653551	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1554653675	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1554653714	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1563867899	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant
rs1586557065	T>C	Pathogenic	Intron variant

Transcription factors

Transcription factor	Regulation	Reference
ATF1	Unknown	11014212;11196473
ATF2	Unknown	11014212;11196473
CREB1	Unknown	11196473
NR5A1	Unknown	11014212
NR5A2	Activation	11564608

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004507	Function	Steroid 11-beta-monooxygenase activity	IBA	21873635
GO:0004507	Function	Steroid 11-beta-monooxygenase activity	IDA	2256920, 8506298
GO:0004507	Function	Steroid 11-beta-monooxygenase activity	IMP	2022736
GO:0005506	Function	Iron ion binding	IEA
GO:0005739	Component	Mitochondrion	IDA	2256920
GO:0005743	Component	Mitochondrial inner membrane	IBA	21873635
GO:0005743	Component	Mitochondrial inner membrane	IC	8506298
GO:0005743	Component	Mitochondrial inner membrane	TAS	15026188
GO:0006700	Process	C21-steroid hormone biosynthetic process	IBA	21873635
GO:0006700	Process	C21-steroid hormone biosynthetic process	IDA	2256920
GO:0006704	Process	Glucocorticoid biosynthetic process	IBA	21873635
GO:0006704	Process	Glucocorticoid biosynthetic process	TAS
GO:0006955	Process	Immune response	TAS	12452430
GO:0008203	Process	Cholesterol metabolic process	IBA	21873635
GO:0008217	Process	Regulation of blood pressure	IMP	2022736
GO:0016125	Process	Sterol metabolic process	TAS
GO:0020037	Function	Heme binding	IC	2256920
GO:0032342	Process	Aldosterone biosynthetic process	IBA	21873635
GO:0032342	Process	Aldosterone biosynthetic process	IDA	2256920
GO:0032342	Process	Aldosterone biosynthetic process	IMP	19342457
GO:0032870	Process	Cellular response to hormone stimulus	IEP	19342457
GO:0034650	Process	Cortisol metabolic process	IBA	21873635
GO:0034651	Process	Cortisol biosynthetic process	IDA	8506298
GO:0034651	Process	Cortisol biosynthetic process	IMP	2022736, 19342457
GO:0035865	Process	Cellular response to potassium ion	IEP	19342457
GO:0042593	Process	Glucose homeostasis	TAS	16114325
GO:0047783	Function	Corticosterone 18-monooxygenase activity	IBA	21873635
GO:0071375	Process	Cellular response to peptide hormone stimulus	IBA	21873635

Other IDs

• MIM: 610613
• HGNC: 2591
• e!Ensembl: ENSG00000160882

Protein

• UniProt ID: P15538
• Protein name: Cytochrome P450 11B1, mitochondrial (CYPXIB1) (Cytochrome P-450c11) (Cytochrome P450C11) (Steroid 11-beta-hydroxylase, CYP11B1) (EC 1.14.15.4)
• Protein function: A cytochrome P450 monooxygenase involved in the biosynthesis of adrenal corticoids (PubMed:18215163). Catalyzes the hydroxylation of carbon hydrogen bond at 11-beta position of 11-deoxycortisol and 11-deoxycorticosterone/21-hydroxyprogesterone yielding cortisol or corticosterone, respectively (PubMed:18215163). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:18215163).
• PDB: 6M7X
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00067	p450	42 → 498	Cytochrome P450	Domain

• Sequence:

  MALRAKAEVCMAVPWLSLQRAQALGTRAARVPRTVLPFEAMPRRPGNRWLRLLQIWREQG
  YEDLHLEVHQTFQELGPIFRYDLGGAGMVCVMLPEDVEKLQQVDSLHPHRMSLEPWVAYR
  QHRGHKCGVFLLNGPEWRFNRLRLNPEVLSPNAVQRFLPMVDAVARDFSQALKKKVLQNA
  RGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFM
  PRSLSRWTSPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFSRPQQYTSIVAELLLNAELS
  PDAIKANSMELTAGSVDTTVFPLLMTLFELARNPNVQQALRQESLAAAASISEHPQKATT
  ELPLLRAALKETLRLYPVGLFLERVASSDLVLQNYHIPAGTLVRVFLYSLGRNPALFPRP
  ERYNPQRWLDIRGSGRNFYHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHLQVETLTQED
  IKMVYSFILRPSMFPLLTFRAIN

• Sequence length: 503

Pathways

KEGG:

Steroid hormone biosynthesis
Metabolic pathways
Cortisol synthesis and secretion
Cushing syndrome

Reactome:

Glucocorticoid biosynthesis
Endogenous sterols
Defective CYP11B1 causes Adrenal hyperplasia 4 (AH4)

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Hyperaldosteronism	Hyperaldosteronism, Glucocorticoid-remediable aldosteronism, Familial hyperaldosteronism type I	rs28934586, rs104894068, rs387906778, rs386352319, rs587777437, rs587777438, rs587777439, rs786205050, rs771507094, rs1085307938, rs1553853557, rs1553856214, rs1293789661, rs1553857113, rs758379595	11085685, 24817817, 20634641, 11549691
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia, Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency, Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency	rs104894069, rs1365173817, rs104894070, rs556794126, rs104894138, rs104894139, rs104894149, rs104894142, rs104894153, rs6471, rs7769409, rs9378251, rs201552310, rs397509367, rs6445, rs387906510, rs1474566961, rs7755898, rs72552754, rs151344503, rs151344504, rs1582299448, rs1582302625, rs72552757, rs80358217, rs80358220, rs80358221, rs121912974, rs28931607, rs72552772, rs72552771, rs28931608, rs786205875, rs121912976, rs1554299737, rs193922538, rs193922539, rs193922541, rs387907572, rs267606756, rs786204728, rs886038207, rs753774484, rs1554304513, rs1554305880, rs1429901248, rs767128094, rs367634557, rs936203749, rs1563435458, rs754609778, rs1563867837, rs776989258, rs1582298980, rs1582309414, rs1582300748, rs781805159, rs782336856, rs373613946, rs770199817, rs1582304457, rs1582304536, rs1582305275, rs182942340, rs1582307951, rs1367112998, rs1582312633, rs779791105, rs72552758, rs1447069098	9302260, 8506298, 20331679, 23940125, 15751602, 28228528, 2022736, 16046588, 16670167, 24022297, 26265915, 18663314, 8964882, 24987415, 26053152, 15755848, 24334966, 26476331, 26066897, 8768848, 22964742, 20947076, 17371482, 11549691, 26280318, 24536089, 15807871, 25911436, 17726333, 26956189, 20089618, 9435454, 10487675
Cryptorchidism	Bilateral Cryptorchidism	rs121912555, rs104894697, rs104894698, rs398122886
Hypertension	Hypertensive disease	rs13306026
Osteoporosis	Osteoporosis	rs72658152, rs72667023, rs587776916, rs72656370, rs768615287

Unknown
Disease name	Disease term	dbSNP ID	References
Ambiguous genitalia	Ambiguous genitalia, female	rs782562963
11-beta-hydroxylase deficiency	11-Beta-hydroxylase deficiency
Adrenal hyperplasia	Adrenal hyperplasia
Adrenogenital syndrome	Adrenogenital Syndrome
Conn syndrome	Conn Syndrome		11085685
Dwarfism	Dwarfism
Ectopic adrenal gland	Ectopic adrenal gland
Enlarged polycystic ovaries	Enlarged polycystic ovaries
Female sexual dysfunction	Female sexual dysfunction
Gynecomastia	Gynecomastia
Hypernatriuria	Hypernatriuria
Hypertrophy of clitoris	Hypertrophy of clitoris
Hypoplasia of vagina	Hypoplasia of vagina
Premature adrenarche	Premature adrenarche
Secretory adrenocortical adenoma	Secretory adrenocortical adenoma
Stroke	Cerebrovascular accident