Familial hypoaldosteronism

Summary

Familial hypoaldosteronism (MONDO:0018541) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 19

Clinical features

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0000127	Renal salt wasting	Obligate (100%)
HP:0000848	Increased circulating renin level	Obligate (100%)
HP:0000846	Adrenal insufficiency	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0002153	Hyperkalemia	Very frequent (80-99%)
HP:0002615	Hypotension	Very frequent (80-99%)
HP:0002902	Hyponatremia	Very frequent (80-99%)
HP:0004319	Decreased circulating aldosterone level	Very frequent (80-99%)
HP:0011106	Hypovolemia	Very frequent (80-99%)
HP:0001254	Lethargy	Frequent (30-79%)
HP:0001278	Orthostatic hypotension	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001942	Metabolic acidosis	Frequent (30-79%)
HP:0001954	Recurrent fever	Frequent (30-79%)
HP:0002014	Diarrhea	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002049	Proximal renal tubular acidosis	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0012364	Decreased urinary potassium	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	familial hypoaldosteronism
Mondo ID	MONDO:0018541
Orphanet	427
ICD-11	712299654
SNOMED CT	715343000
UMLS	C4275180
MedGen	899592
GARD	0016532
Is cancer (heuristic)	no

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

Disease family

An umbrella term covering 5 Mondo subtypes.

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

Subtypes (5): corticosterone methyloxidase type 1 deficiency, familial hyperreninemic hypoaldosteronism type 2, 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 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2581484	NM_000498.3(CYP11B2):c.945C>G (p.Ser315Arg)	CYP11B2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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	Supportive	Autosomal recessive	familial hypoaldosteronism	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

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	gencc,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.