GeneBe

CYP11B1

protein-coding

cytochrome P450 family 11 subfamily B member 1, the group of Cytochrome P450 family 11

Gene 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]

Previous symbols:
  • CYP11B

MANE transcript

NM_000497.4

Inheritance

AR, AD

ClinVar variants

P:227U:222B:298

Top phenotype

Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency; Hyperaldosteronism, familial, type I

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr8:142,872,356-142,879,846

External References & Databases

Ensembl (ENSG00000160882)NCBI Gene (1584)OMIM (610613)HGNC:2591GenCCUniProt (P15538)AlphaFoldClinVar (CYP11B1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~7.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008729

Submitter: Labcorp Genetics (formerly Invitae)

glucocorticoid-remediable aldosteronismSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007080

Submitter: Labcorp Genetics (formerly Invitae)

congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008729

Submitter: Ambry Genetics

congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008729

Submitter: Myriad Women's Health

congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008729

Submitter: Natera

congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008729

Submitter: Orphanet

Clinical Genomic Database (CGD)

Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency; Hyperaldosteronism, familial, type IAD/AR

Manifestation: Endocrine; Oncologic; Genitourinary

Intervention: Endocrine; Oncologic; Genitourinary

Rationale: In Adrenal hyperplasia, treatment of manifestations such as hypertension (fatal vascular accidents have been reported in individuals with relatively mild virilization) and hypokalemia, as well as genitourinary anomalies, can be beneficial; Screening for oncologic complications (eg, testicular adrenal rest tumors) can allow early detection and treatment; In Hyperaldosteronism, familial, type I, medical treatment (eg, with glucocorticoids) can be beneficial

Comments: Glucocorticoid-remediable aldosteronism involves a fusion gene (with CYP11B2)

Refs: 13345203; 7355668; 7026592; 6268979; 7049883; 3875277; 2022736; 1430088; 17172090; 1731223; 1472060; 1554023; 7670248; 7550315; 8825044; 8768848; 10689646; 10566645; 10999827; 10852446; 11549669; 12107222; 16551734; 20980225; 22508345; 22790459; 23057653; 23146819; 23291679; 23345044; 23441661; 23940125; 24022297Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP11B1 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 660
Deficiency of steroid 11-beta-monooxygenaseTotal: 354
Glucocorticoid-remediable aldosteronismTotal: 214
not specifiedTotal: 84
Inborn genetic diseasesTotal: 62
Congenital adrenal hyperplasiaTotal: 44
CYP11B1-related disorderTotal: 34
Differences in sex developmentTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000497.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
6
clinvar
277
clinvar
3
clinvar
 289
missense
15
clinvar
53
clinvar
213
clinvar
18
clinvar
 299
nonsense
25
clinvar
17
clinvar
 42
start loss
0
frameshift
52
clinvar
33
clinvar
2
clinvar
 87
splice donor/acceptor (+/-2bp)
5
clinvar
24
clinvar
1
clinvar
 30
Total971302222953747

Highest pathogenic variant AF is 0.00017547105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 139 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000497.4RefSeqNP_000488.39MANE Select
ENST00000292427.10EnsemblENSP00000292427.59MANE Select
NM_001026213.1RefSeqNP_001021384.18Standard
ENST00000377675.3EnsemblENSP00000366903.311Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Cortisol synthesis and secretion - Homo sapiens (human)
  • Cushing,s syndrome - Homo sapiens (human)
  • Steroid hormone biosynthesis - Homo sapiens (human)
  • Steroidogenesis
  • Apparent mineralocorticoid excess syndrome

Biological Process

  • C21-steroid hormone biosynthetic process
  • glucocorticoid biosynthetic process
  • immune response
  • cholesterol metabolic process
  • regulation of blood pressure

Molecular Function

  • steroid 11-beta-monooxygenase activity
  • iron ion binding
  • heme binding
  • corticosterone 18-monooxygenase activity

Cellular Component

  • mitochondrion
  • mitochondrial inner membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000292427
Coding exons
9
Length
7491
Individuals with no LoFs
125695
Homozygous LoFs
0
Heterozygous LoFs
53
Defined
125748
p
0.000211
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-1.563672921.260.00002013280
Missense (PolyPhen)131110.011.19081260
Synonymous-4.031741181.470.000007801011
Loss of Function1.721321.60.6010.00000113230

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000930.00092rare
Latino/Admixed American0.000260.00026rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish00.0absent
European (Non-Finnish)0.000180.00018rare
South Asian0.000160.00016rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB.;
Disease
DISEASE: Adrenal hyperplasia 4 (AH4) [MIM:202010]: A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late- onset (NC or LOAH) and 'cryptic' (asymptomatic). {ECO:0000269|PubMed:16046588, ECO:0000269|PubMed:20089618, ECO:0000269|PubMed:2022736, ECO:0000269|PubMed:20331679, ECO:0000269|PubMed:20947076, ECO:0000269|PubMed:23940125, ECO:0000269|PubMed:24022297, ECO:0000269|PubMed:24536089, ECO:0000269|PubMed:24987415, ECO:0000269|PubMed:26053152, ECO:0000269|PubMed:26476331, ECO:0000269|PubMed:9302260}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hyperaldosteronism, familial, 1 (HALD1) [MIM:103900]: A disorder characterized by hypertension, variable hyperaldosteronism, and abnormal adrenal steroid production, including 18-oxocortisol and 18-hydroxycortisol. There is significant phenotypic heterogeneity, and some individuals never develop hypertension. Note=The disease is caused by mutations affecting the gene represented in this entry. The molecular defect causing hyperaldosteronism familial 1 is an anti-Lepore-type fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the promoting part of CYP11B1, ACTH-sensitive, and the coding part of CYP11B2.;

Recessive Scores

pRec
0.248

Intolerance Scores

LoFtool
0.508
RVIS EVS
-1.19
RVIS percentile EVS
5.85

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.158

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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