CYP11B2

cytochrome P450 family 11 subfamily B member 2, the group of Cytochrome P450 family 11

Basic information

Region (hg38): 8:142910559-142917843

Previous symbols: [ "CYP11B" ]

Links

ENSG00000179142 ∙ NCBI:1585 ∙ OMIM:124080 ∙ HGNC:2592 ∙ Uniprot:P19099 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• corticosterone methyloxidase type 1 deficiency (Moderate), mode of inheritance: AR
• familial hypoaldosteronism (Supportive), mode of inheritance: AR
• corticosterone methyloxidase type 2 deficiency (Strong), mode of inheritance: AR
• familial hyperreninemic hypoaldosteronism type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Corticosterone methyloxidase type I deficiency; Corticosterone methyloxidase type II deficiency; Glucocorticoid-remediable aldosteronism	AD/AR	Endocrine; Genitourinary; Oncologic	In Corticosterone methyloxidase deficiency, treatment of salt wasting (eg, with salt/mineralocorticoid supplementation) has shown success; In Glucocorticoid-remediable aldosteronism, medical treatment (eg, with glucocorticoids) can be beneficial; Surgical interventions may decrease the risk of gonadal tumors	Endocrine; Genitourinary; Oncologic	14212087; 14250395; 295679; 4121586; 838841; 6268979; 2044581; 1731223; 1472060; 1601005; 1594605; 8439335; 7550315; 8825044; 9360501; 9814506; 10566645; 10999827; 10852446; 11238478; 12107222; 18178501; 19116236; 20494601; 22465514
Glucocorticoid-remediable aldosteronism involves a fusion gene (with CYP11B1)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP11B2 gene.

• not_provided (530 variants)
• Corticosterone_18-monooxygenase_deficiency (197 variants)
• Corticosterone_methyloxidase_type_2_deficiency (190 variants)
• Corticosterone_methyl_oxidase_type_II_deficiency (112 variants)
• Inborn_genetic_diseases (57 variants)
• Glucocorticoid-remediable_aldosteronism (51 variants)
• CYP11B2-related_disorder (22 variants)
• not_specified (14 variants)
• Hypoaldosteronism,_congenital (2 variants)
• Aldosterone_Synthase_Deficiency (1 variants)
• Early-onset_familial_hypoaldosteronism (1 variants)
• Familial_hypoaldosteronism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP11B2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000498.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	1	6	257	7	272
missense	6	15	156	32	5	214
nonsense	20	5				25
start loss		1				1
frameshift	29	7				36
splice donor/acceptor (+/-2bp)	6	19	2			27
Total	62	48	164	289	12

Highest pathogenic variant AF is 0.000121775

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP11B2	protein_coding	protein_coding	ENST00000323110	9	7285

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.13e-19	0.00101	125690	0	58	125748	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.849	330	289	1.14	0.0000197	3258
Missense in Polyphen		109	106.8	1.0206		1270
Synonymous	-1.18	138	121	1.14	0.00000807	1016
Loss of Function	-0.598	26	22.9	1.13	0.00000128	236

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000660	0.000637
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000257	0.000255
Middle Eastern	0.000435	0.000435
South Asian	0.000197	0.000196
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Preferentially catalyzes the conversion of 11- deoxycorticosterone to aldosterone via corticosterone and 18- hydroxycorticosterone. {ECO:0000269|PubMed:23322723}.
• Disease: DISEASE: Corticosterone methyloxidase 1 deficiency (CMO-1 deficiency) [MIM:203400]: Autosomal recessive disorder of aldosterone biosynthesis. There are two biochemically different forms of selective aldosterone deficiency be termed corticosterone methyloxidase (CMO) deficiency type 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18-hydroxycorticosterone, is low or normal. {ECO:0000269|PubMed:11238478, ECO:0000269|PubMed:9177280}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corticosterone methyloxidase 2 deficiency (CMO-2 deficiency) [MIM:610600]: Autosomal recessive disorder of aldosterone biosynthesis. In CMO-2 deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18- hydroxycorticosterone. Consequently, patients have a greatly increased ratio of 18-hydroxycorticosterone to aldosterone and a low ratio of corticosterone to 18-hydroxycorticosterone in serum. {ECO:0000269|PubMed:12788848, ECO:0000269|PubMed:1346492, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:9625333, ECO:0000269|PubMed:9814506}. 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: Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics;Aldosterone synthesis and secretion - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);ACE Inhibitor Pathway, Pharmacodynamics;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);Glucocorticoid and Mineralcorticoid Metabolism;Oxidation by Cytochrome P450;ACE Inhibitor Pathway;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;Mineralocorticoid biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;C21-steroid hormone biosynthesis and metabolism;Glucocorticoid biosynthesis;mineralocorticoid biosynthesis;superpathway of steroid hormone biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.172

Intolerance Scores

• loftool: 0.917
• rvis_EVS: 0.56
• rvis_percentile_EVS: 81.67

Haploinsufficiency Scores

• pHI: 0.450
• hipred: N
• hipred_score: 0.112
• ghis: 0.416

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.878

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: regulation of blood volume by renal aldosterone;renal water homeostasis;C21-steroid hormone biosynthetic process;glucocorticoid biosynthetic process;mineralocorticoid biosynthetic process;cholesterol metabolic process;sterol metabolic process;aldosterone biosynthetic process;cellular response to hormone stimulus;cortisol metabolic process;cortisol biosynthetic process;cellular response to potassium ion;potassium ion homeostasis;sodium ion 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;steroid hydroxylase activity;heme binding;corticosterone 18-monooxygenase activity