CYP11B1
cytochrome P450 family 11 subfamily B member 1, the group of Cytochrome P450 family 11
Basic information
Region (hg38): 8:142872355-142879846
Previous symbols: [ "CYP11B" ]
Links
Phenotypes
GenCC
Source:
- congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency (Definitive), mode of inheritance: AR
- congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency (Definitive), mode of inheritance: AR
- congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency (Supportive), mode of inheritance: AR
- congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency (Strong), mode of inheritance: AR
- glucocorticoid-remediable aldosteronism (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency; Hyperaldosteronism, familial, type I | AD/AR | Endocrine; Oncologic; Genitourinary | 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 | Endocrine; Oncologic; Genitourinary | 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; 24022297 |
| Glucocorticoid-remediable aldosteronism involves a fusion gene (with CYP11B2) |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (512 variants)
- Deficiency of steroid 11-beta-monooxygenase (230 variants)
- Glucocorticoid-remediable aldosteronism (124 variants)
- Deficiency of steroid 11-beta-monooxygenase;Glucocorticoid-remediable aldosteronism (39 variants)
- Congenital adrenal hyperplasia (33 variants)
- not specified (31 variants)
- Inborn genetic diseases (19 variants)
- Glucocorticoid-remediable aldosteronism;Deficiency of steroid 11-beta-monooxygenase (17 variants)
- CYP11B1-related condition (5 variants)
- - (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP11B1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 210 | 219 | ||||
| missense | 10 | 32 | 78 | 10 | 131 | |
| nonsense | 20 | 16 | 36 | |||
| start loss | 0 | |||||
| frameshift | 21 | 22 | 44 | |||
| inframe indel | 4 | |||||
| splice donor/acceptor (+/-2bp) | 19 | 23 | ||||
| splice region ? | 3 | 5 | 41 | 1 | 50 | |
| non coding ? | 39 | 54 | 35 | 129 | ||
| Total | 54 | 91 | 124 | 274 | 43 |
Highest pathogenic variant AF is 0.000303
Variants in CYP11B1
This is a list of pathogenic ClinVar variants found in the CYP11B1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-142872394-C-T | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 13, 2018) | ||
| 8-142872429-C-T | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Apr 27, 2017) | ||
| 8-142872444-T-G | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 13, 2018) | ||
| 8-142872502-A-T | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Benign/Likely benign (Jan 13, 2018) | ||
| 8-142872521-A-C | Deficiency of steroid 11-beta-monooxygenase • Glucocorticoid-remediable aldosteronism | Benign (Jan 13, 2018) | ||
| 8-142872603-T-A | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 12, 2018) | ||
| 8-142872750-C-G | Deficiency of steroid 11-beta-monooxygenase • Glucocorticoid-remediable aldosteronism | Uncertain significance (Jan 13, 2018) | ||
| 8-142872751-G-A | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 12, 2018) | ||
| 8-142872783-C-G | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 12, 2018) | ||
| 8-142872807-C-A | Deficiency of steroid 11-beta-monooxygenase • Glucocorticoid-remediable aldosteronism | Benign (Jan 13, 2018) | ||
| 8-142872817-AG-A | Congenital adrenal hyperplasia • Glucocorticoid-remediable aldosteronism | Likely benign (Jun 14, 2016) | ||
| 8-142872823-G-A | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 12, 2018) | ||
| 8-142872861-C-T | Deficiency of steroid 11-beta-monooxygenase • Glucocorticoid-remediable aldosteronism | Benign/Likely benign (Jan 13, 2018) | ||
| 8-142872862-G-A | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 13, 2018) | ||
| 8-142872874-G-A | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Benign (Jan 12, 2018) | ||
| 8-142872897-C-G | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 13, 2018) | ||
| 8-142872938-A-G | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 13, 2018) | ||
| 8-142872956-C-T | Deficiency of steroid 11-beta-monooxygenase • Glucocorticoid-remediable aldosteronism | Benign (Jan 13, 2018) | ||
| 8-142873015-A-G | Deficiency of steroid 11-beta-monooxygenase • Glucocorticoid-remediable aldosteronism | Uncertain significance (Jan 13, 2018) | ||
| 8-142873060-G-A | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 13, 2018) | ||
| 8-142873077-T-C | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 12, 2018) | ||
| 8-142873085-T-C | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Benign (Jan 12, 2018) | ||
| 8-142873109-T-G | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Mar 30, 2018) | ||
| 8-142873115-C-T | Deficiency of steroid 11-beta-monooxygenase • Glucocorticoid-remediable aldosteronism | Benign/Likely benign (Jan 13, 2018) | ||
| 8-142873120-C-A | Glucocorticoid-remediable aldosteronism • Deficiency of steroid 11-beta-monooxygenase | Uncertain significance (Jan 12, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CYP11B1 | protein_coding | protein_coding | ENST00000292427 | 9 | 7491 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 8.25e-7 | 0.919 | 125695 | 0 | 53 | 125748 | 0.000211 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -1.56 | 367 | 292 | 1.26 | 0.0000201 | 3280 |
| Missense in Polyphen | 131 | 110.01 | 1.1908 | 1260 | ||
| Synonymous | -4.03 | 174 | 118 | 1.47 | 0.00000780 | 1011 |
| Loss of Function | 1.72 | 13 | 21.6 | 0.601 | 0.00000113 | 230 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00119 | 0.00118 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000177 | 0.000176 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000164 | 0.000163 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- 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.;
- Pathway
- Cortisol synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Steroidogenesis;Apparent mineralocorticoid excess syndrome;3-Beta-Hydroxysteroid Dehydrogenase Deficiency;21-hydroxylase deficiency (CYP21);Corticosterone methyl oxidase I deficiency (CMO I);Corticosterone methyl oxidase II deficiency - CMO II;Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia due to 17 Alpha-hydroxylase Deficiency;Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency;Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAH;17-alpha-hydroxylase deficiency (CYP17);11-beta-hydroxylase deficiency (CYP11B1);Corticotropin-releasing hormone signaling pathway;Oxidation by Cytochrome P450;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Endogenous sterols;Androgen and estrogen biosynthesis and metabolism;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Metabolism of steroid hormones;Metabolism of steroids;C21-steroid hormone biosynthesis and metabolism;Glucocorticoid biosynthesis;glucocorticoid biosynthesis;mineralocorticoid biosynthesis;superpathway of steroid hormone biosynthesis;Steroid hormones
(Consensus)
Recessive Scores
- pRec
- 0.248
Intolerance Scores
- loftool
- 0.508
- rvis_EVS
- -1.19
- rvis_percentile_EVS
- 5.85
Haploinsufficiency Scores
- pHI
- 0.284
- hipred
- N
- hipred_score
- 0.132
- ghis
- 0.445
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.158
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cyp11b2
- Phenotype
- renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype;
Gene ontology
- Biological process
- C21-steroid hormone biosynthetic process;glucocorticoid biosynthetic process;immune response;cholesterol metabolic process;regulation of blood pressure;sterol metabolic process;aldosterone biosynthetic process;cellular response to hormone stimulus;cortisol metabolic process;cortisol biosynthetic process;cellular response to potassium ion;glucose homeostasis;oxidation-reduction process;cellular response to peptide hormone stimulus
- Cellular component
- mitochondrion;mitochondrial inner membrane
- Molecular function
- steroid 11-beta-monooxygenase activity;iron ion binding;heme binding;corticosterone 18-monooxygenase activity