Corticosterone methyloxidase type 1 deficiency

Summary

Corticosterone methyloxidase type 1 deficiency (MONDO:0008751) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 253

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	corticosterone methyloxidase type 1 deficiency
Mondo ID	MONDO:0008751
OMIM	203400
DOID	DOID:0080626
SNOMED CT	47757001
UMLS	C0268293
MedGen	82784
GARD	0005660
Is cancer (heuristic)	no

Also known as: 18 alpha hydroxylase deficiency · 18 Hydroxylase deficiency · aldosterone deficiency 1 · aldosterone deficiency due to defect in 18 hydroxylase · CMO 1 deficiency · corticosterone 18-monooxygenase deficiency · corticosterone methyloxidase type 1 deficiency · hypoaldosteronism, congenital, due to cmo i deficiency

Data availability: 253 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › corticosterone methyloxidase type 1 deficiency

Related subtypes (28): cortisone reductase deficiency, familial hyperlipidemia, hypolipoproteinemia, steroid inherited metabolic disorder, lipoid proteinosis, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, vitamin D hydroxylation-deficient rickets, type 1B, mitochondrial trifunctional protein deficiency, pancreatic triacylglycerol lipase deficiency, glucocorticoid resistance, syndromic dyslipidemia, inborn disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation, disorder of plasmalogens biosynthesis, disorder of phospholipids, sphingolipids and fatty acids biosynthesis, inborn disorder of ketolysis, lysosomal lipid storage disorder, sterol metabolism disorder, disorder of sphingolipid biosynthesis, glycosylphosphatidylinositol biosynthesis defect 18, neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 55, inherited fatty acid metabolism disorder, glycosylphosphatidylinositol biosynthesis defect 16, glycosylphosphatidylinositol biosynthesis defect 15, glycosylphosphatidylinositol biosynthesis defect 17, CYP7B1-related disorder of oxysterol accumulation

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

253 retrieved; paginated sample, class counts are floors:

109 uncertain significance, 38 conflicting classifications of pathogenicity, 35 benign, 22 likely benign, 13 benign/likely benign, 12 pathogenic/likely pathogenic, 12 likely pathogenic, 11 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
16877	NM_000498.3(CYP11B2):c.[594A>C;1157T>C]		Pathogenic	no assertion criteria provided
3897878	NM_000498.3:c.[554C>T];[541C>T]		Pathogenic	criteria provided, single submitter
1179210	GRCh37/hg19 8q24.3(chr8:143958418-143996344)	CYP11B1	Pathogenic	no assertion criteria provided
1494402	NM_000498.3(CYP11B2):c.517AAG[2] (p.Lys175del)	CYP11B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16878	NM_000498.3(CYP11B2):c.104_109delinsG (p.Val35fs)	CYP11B2	Pathogenic	no assertion criteria provided
16881	NM_000498.3(CYP11B2):c.554C>T (p.Thr185Ile)	CYP11B2	Pathogenic	criteria provided, multiple submitters, no conflicts
1697321	NM_000498.3(CYP11B2):c.922T>C (p.Ser308Pro)	CYP11B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136711	NM_000498.3(CYP11B2):c.788T>A (p.Ile263Asn)	CYP11B2	Pathogenic	criteria provided, multiple submitters, no conflicts
2136713	NM_000498.3(CYP11B2):c.508C>T (p.Gln170Ter)	CYP11B2	Pathogenic	criteria provided, multiple submitters, no conflicts
242702	NM_000498.3(CYP11B2):c.594A>C (p.Glu198Asp)	CYP11B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3595424	NM_000498.3(CYP11B2):c.64del (p.Arg22fs)	CYP11B2	Pathogenic	criteria provided, single submitter
834390	NM_000498.3(CYP11B2):c.1398+1G>A	CYP11B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
847988	NM_000498.3(CYP11B2):c.139_148del (p.Gly46_Asn47insTer)	CYP11B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
853826	NM_000498.3(CYP11B2):c.953C>T (p.Thr318Met)	CYP11B2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1382371	NM_000498.3(CYP11B2):c.682G>T (p.Glu228Ter)	LOC106799834	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454609	NM_000498.3(CYP11B2):c.240-2A>G	LOC106799834	Pathogenic	criteria provided, multiple submitters, no conflicts
16880	NM_000498.3(CYP11B2):c.763G>T (p.Glu255Ter)	LOC106799834	Pathogenic	criteria provided, multiple submitters, no conflicts
1951257	NM_000498.3(CYP11B2):c.446_449dup (p.Pro151fs)	LOC106799834	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2674685	NM_000498.3(CYP11B2):c.780G>A (p.Trp260Ter)	LOC106799834	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2987719	NM_000498.3(CYP11B2):c.1210C>T (p.Gln404Ter)	LOC106799834	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2999450	NM_000498.3(CYP11B2):c.1002del (p.Asp335fs)	LOC106799834	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3595401	NM_000498.3(CYP11B2):c.520A>T (p.Lys174Ter)	LOC106799834	Pathogenic	criteria provided, single submitter
655196	NM_000498.3(CYP11B2):c.1200+1G>A	LOC106799834	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3595377	NM_000498.3(CYP11B2):c.1128C>A (p.Tyr376Ter)	CYP11B2	Likely pathogenic	criteria provided, single submitter
3595408	NM_000498.3(CYP11B2):c.396-2A>G	CYP11B2	Likely pathogenic	criteria provided, single submitter
3595426	NM_000498.3(CYP11B2):c.10_11del (p.Arg4fs)	CYP11B2	Likely pathogenic	criteria provided, single submitter
3595428	NM_000498.3(CYP11B2):c.2T>C (p.Met1Thr)	CYP11B2	Likely pathogenic	criteria provided, single submitter
4849347	NM_000498.3(CYP11B2):c.55C>T (p.Gln19Ter)	CYP11B2	Likely pathogenic	criteria provided, single submitter
971333	NM_000498.3(CYP11B2):c.395+1G>A	CYP11B2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
16879	NM_000498.3(CYP11B2):c.1382T>C (p.Leu461Pro)	LOC106799834	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CYP11B2	Strong	Autosomal recessive	corticosterone methyloxidase type 2 deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP11B2	Orphanet:403	Familial hyperaldosteronism type I
CYP11B2	Orphanet:556030	Early-onset familial hypoaldosteronism
CYP11B1	Orphanet:403	Familial hyperaldosteronism type I
CYP11B1	Orphanet:90795	Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CYP11B2	HGNC:2592	ENSG00000179142	P19099	Cytochrome P450 11B2, mitochondrial	gencc,clinvar
CYP11B1	HGNC:2591	ENSG00000160882	P15538	Cytochrome P450 11B1, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP11B2	Cytochrome P450 11B2, mitochondrial	A cytochrome P450 monooxygenase that catalyzes the biosynthesis of aldosterone, the main mineralocorticoid in the human body responsible for salt and water homeostasis, thus involved in blood pressure regulation, arterial hypertension, and…
CYP11B1	Cytochrome P450 11B1, mitochondrial	A cytochrome P450 monooxygenase involved in the biosynthesis of adrenal corticoids.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	2	12.0×	0.007

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CYP11B2	Enzyme (other)	yes	1.14.15.4	Cyt_P450, Cyt_P450_mitochondrial, Cyt_P450_CS
CYP11B1	Enzyme (other)	yes	1.14.15.4	Cyt_P450, Cyt_P450_mitochondrial, Cyt_P450_CS

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	2
right adrenal gland	2
right adrenal gland cortex	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP11B2	30		yes	right adrenal gland cortex, right adrenal gland, left adrenal gland
CYP11B1	137		yes	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP11B2	1,718
CYP11B1	1,596

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYP11B2	P19099	7
CYP11B1	P15538	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glucocorticoid biosynthesis	2	878.5×	9e-06	CYP11B2, CYP11B1
Metabolic disorders of biological oxidation enzymes	2	878.5×	9e-06	CYP11B2, CYP11B1
Cytochrome P450 - arranged by substrate type	2	713.8×	9e-06	CYP11B2, CYP11B1
Metabolism of steroid hormones	2	519.1×	1e-05	CYP11B2, CYP11B1
Endogenous sterols	2	393.8×	2e-05	CYP11B2, CYP11B1
Phase I - Functionalization of compounds	2	219.6×	5e-05	CYP11B2, CYP11B1
Metabolism of steroids	2	137.6×	1e-04	CYP11B2, CYP11B1
Biological oxidations	2	129.8×	1e-04	CYP11B2, CYP11B1
Diseases of metabolism	2	80.4×	3e-04	CYP11B2, CYP11B1
Defective CYP11B2 causes CMO-1 deficiency	1	2855.0×	5e-04	CYP11B2
Defective CYP11B1 causes AH4	1	2855.0×	5e-04	CYP11B1
Metabolism of lipids	2	31.6×	0.001	CYP11B2, CYP11B1
Mineralocorticoid biosynthesis	1	713.8×	0.002	CYP11B2
Disease	2	13.1×	0.006	CYP11B2, CYP11B1
Metabolism	2	11.6×	0.007	CYP11B2, CYP11B1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
aldosterone biosynthetic process	2	3370.4×	1e-06	CYP11B2, CYP11B1
cortisol metabolic process	2	2808.7×	1e-06	CYP11B2, CYP11B1
cortisol biosynthetic process	2	2106.5×	1e-06	CYP11B2, CYP11B1
C21-steroid hormone biosynthetic process	2	1872.4×	1e-06	CYP11B2, CYP11B1
glucocorticoid biosynthetic process	2	1532.0×	1e-06	CYP11B2, CYP11B1
cellular response to potassium ion	2	1053.2×	3e-06	CYP11B2, CYP11B1
sterol metabolic process	2	842.6×	3e-06	CYP11B2, CYP11B1
cellular response to peptide hormone stimulus	2	842.6×	3e-06	CYP11B2, CYP11B1
cellular response to hormone stimulus	2	383.0×	1e-05	CYP11B2, CYP11B1
cholesterol metabolic process	2	195.9×	5e-05	CYP11B2, CYP11B1
regulation of blood volume by renal aldosterone	1	2808.7×	6e-04	CYP11B2
mineralocorticoid biosynthetic process	1	2106.5×	7e-04	CYP11B2
sodium ion homeostasis	1	468.1×	0.003	CYP11B2
potassium ion homeostasis	1	383.0×	0.003	CYP11B2
renal water homeostasis	1	255.3×	0.005	CYP11B2
regulation of blood pressure	1	110.9×	0.010	CYP11B1
glucose homeostasis	1	65.3×	0.016	CYP11B1
immune response	1	23.5×	0.042	CYP11B1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CYP11B2	FLUCONAZOLE
CYP11B1	FLUCONAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP11B1	13	4
CYP11B2	12	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLUCONAZOLE	4	CYP11B1, CYP11B2
POSACONAZOLE	4	CYP11B1, CYP11B2
LETROZOLE	4	CYP11B1, CYP11B2
KETOCONAZOLE	4	CYP11B1, CYP11B2
ABIRATERONE	4	CYP11B1, CYP11B2
OSILODROSTAT	4	CYP11B1, CYP11B2
ETOMIDATE	4	CYP11B1, CYP11B2
METYRAPONE	4	CYP11B1, CYP11B2
BAXDROSTAT	3	CYP11B1, CYP11B2
LORUNDROSTAT	3	CYP11B2
DEXFADROSTAT	2	CYP11B1, CYP11B2
FADROZOLE	2	CYP11B1, CYP11B2
VOROZOLE	2	CYP11B1
AZALANSTAT	2	CYP11B1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CYP11B2	147	Binding:135, ADMET:12
CYP11B1	113	Binding:95, ADMET:16, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYP11B2	1.14.15.4, 1.14.15.5	steroid 11beta-monooxygenase, corticosterone 18-monooxygenase
CYP11B1	1.14.15.4	steroid 11beta-monooxygenase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CYP11B2	147
CYP11B1	113

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

14 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FLUCONAZOLE	4	CYP11B1, CYP11B2
POSACONAZOLE	4	CYP11B1, CYP11B2
LETROZOLE	4	CYP11B1, CYP11B2
KETOCONAZOLE	4	CYP11B1, CYP11B2
ABIRATERONE	4	CYP11B1, CYP11B2
OSILODROSTAT	4	CYP11B1, CYP11B2
ETOMIDATE	4	CYP11B1, CYP11B2
METYRAPONE	4	CYP11B1, CYP11B2
BAXDROSTAT	3	CYP11B1, CYP11B2
LORUNDROSTAT	3	CYP11B2
DEXFADROSTAT	2	CYP11B1, CYP11B2
FADROZOLE	2	CYP11B1, CYP11B2
VOROZOLE	2	CYP11B1
AZALANSTAT	2	CYP11B1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CYP11B2, CYP11B1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.