Familial hyperreninemic hypoaldosteronism type 2

Summary

Familial hyperreninemic hypoaldosteronism type 2 (MONDO:0011754) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial hyperreninemic hypoaldosteronism type 2
Mondo ID	MONDO:0011754
MeSH	C564638
OMIM	606984
Orphanet	99764
UMLS	C1846990
MedGen	335571
GARD	0024822
Is cancer (heuristic)	no

Also known as: aldosterone synthase deficiency unrelated to CYP11B2 · aldosterone synthase deficiency unrelated to the aldosterone synthase gene · FHHA2 · hyperreninemic hypoaldosteronism, familial, type 2

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › adrenal gland disorder › hypoaldosteronism disease › familial hypoaldosteronism › familial hyperreninemic hypoaldosteronism type 2

Related subtypes (4): corticosterone methyloxidase type 1 deficiency, corticosterone methyloxidase type 2 deficiency, early-onset familial hypoaldosteronism, late-onset familial hypoaldosteronism

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4819027	NM_000498.3(CYP11B2):c.476C>G (p.Pro159Arg)	CYP11B2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CYP11B2	HGNC:2592	ENSG00000179142	P19099	Cytochrome P450 11B2, 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…

Protein-family classification

Druggable: 1 · 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)	1	12.0×	0.083

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

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP11B2	1,718

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYP11B2	P19099	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CYP11B2 causes CMO-1 deficiency	1	5710.0×	0.002	CYP11B2
Mineralocorticoid biosynthesis	1	1427.5×	0.004	CYP11B2
Glucocorticoid biosynthesis	1	878.5×	0.004	CYP11B2
Metabolic disorders of biological oxidation enzymes	1	878.5×	0.004	CYP11B2
Cytochrome P450 - arranged by substrate type	1	713.8×	0.004	CYP11B2
Metabolism of steroid hormones	1	519.1×	0.004	CYP11B2
Endogenous sterols	1	393.8×	0.005	CYP11B2
Phase I - Functionalization of compounds	1	219.6×	0.008	CYP11B2
Metabolism of steroids	1	137.6×	0.011	CYP11B2
Biological oxidations	1	129.8×	0.011	CYP11B2
Diseases of metabolism	1	80.4×	0.016	CYP11B2
Metabolism of lipids	1	31.6×	0.037	CYP11B2
Disease	1	13.1×	0.082	CYP11B2
Metabolism	1	11.6×	0.086	CYP11B2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of blood volume by renal aldosterone	1	5617.3×	0.001	CYP11B2
mineralocorticoid biosynthetic process	1	4213.0×	0.001	CYP11B2
aldosterone biosynthetic process	1	3370.4×	0.001	CYP11B2
cortisol metabolic process	1	2808.7×	0.001	CYP11B2
cortisol biosynthetic process	1	2106.5×	0.001	CYP11B2
C21-steroid hormone biosynthetic process	1	1872.4×	0.001	CYP11B2
glucocorticoid biosynthetic process	1	1532.0×	0.001	CYP11B2
cellular response to potassium ion	1	1053.2×	0.002	CYP11B2
sodium ion homeostasis	1	936.2×	0.002	CYP11B2
sterol metabolic process	1	842.6×	0.002	CYP11B2
cellular response to peptide hormone stimulus	1	842.6×	0.002	CYP11B2
potassium ion homeostasis	1	766.0×	0.002	CYP11B2
renal water homeostasis	1	510.7×	0.002	CYP11B2
cellular response to hormone stimulus	1	383.0×	0.003	CYP11B2
cholesterol metabolic process	1	195.9×	0.005	CYP11B2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP11B2	12	4

Drugs targeting cohort genes (top 30)

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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CYP11B2	147	Binding:135, ADMET:12

Cohort enzymes (BRENDA EC)

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

12 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	CYP11B2
POSACONAZOLE	4	CYP11B2
LETROZOLE	4	CYP11B2
KETOCONAZOLE	4	CYP11B2
ABIRATERONE	4	CYP11B2
OSILODROSTAT	4	CYP11B2
ETOMIDATE	4	CYP11B2
METYRAPONE	4	CYP11B2
BAXDROSTAT	3	CYP11B2
LORUNDROSTAT	3	CYP11B2
DEXFADROSTAT	2	CYP11B2
FADROZOLE	2	CYP11B2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CYP11B2
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.