CYP11B2

Chr 8AR

cytochrome P450 family 11 subfamily B member 2

Also known as: ALDOS, CPN2, CYP11B, CYP11BL, CYPXIB2, P-450C18, P450C18, P450aldo

NCBI Gene: 1585 ENSG00000179142 UniProt: P19099

This enzyme catalyzes the biosynthesis of aldosterone, the primary mineralocorticoid responsible for salt and water homeostasis and blood pressure regulation. Mutations cause autosomal recessive congenital hypoaldosteronism (corticosterone methyl oxidase deficiency types I and II), presenting with salt wasting, dehydration, and failure to thrive in infancy. The gene shows tolerance to loss-of-function variants (LOEUF 1.572), consistent with the recessive inheritance pattern where both alleles must be affected to cause disease.

Summary from RefSeq, OMIM, UniProt

Research Assistant →

Primary Disease Associations & Inheritance

{Low renin hypertension, susceptibility to}

Aldosterone to renin ratio raised

Hypoaldosteronism, congenital, due to CMO I deficiencyMIM #203400

Hypoaldosteronism, congenital, due to CMO II deficiencyMIM #610600

UniProtCorticosterone methyloxidase 1 deficiency

UniProtCorticosterone methyloxidase 2 deficiency

Active trials

109

Pubs (1 yr)

116

P/LP submissions

14%

P/LP missense

1.57

LOEUF

Mechanism· predicted

Clinical Summary— CYP11B2

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Gene-Disease Validity (ClinGen)

familial hyperreninemic hypoaldosteronism type 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

96 unique Pathogenic / Likely Pathogenic· 162 VUS of 600 total submissions

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Clinical Trials

9 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CYP11B2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.57LOEUF

pLI 0.000

Z-score -0.60

OE 1.13 (0.83–1.57)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-0.85Z-score

OE missense 1.14 (1.04–1.25)

330 obs / 289.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE1.13 (0.83–1.57)

0≤0.351.4

Missense OE1.14 (1.04–1.25)

0≤0.61.4

Synonymous OE1.14

0≤1.21.6

LoF obs/exp: 26 / 22.9Missense obs/exp: 330 / 289.4Syn Z: -1.18

0.6549th %ile

GOF

0.6346th %ile

LOF

0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

600 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60

Likely Pathogenic36

VUS162

Likely Benign307

Benign24

Conflicting9

Pathogenic

Likely Pathogenic

162

VUS

307

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	31	3	25	1	60
Likely Pathogenic	17	10	9	0	36
VUS	1	135	21	5	162
Likely Benign	0	7	102	198	307
Benign	0	0	20	4	24
Conflicting	—				9
Total	49	155	177	208	598

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CYP11B2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

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GeneReview available — CYP11B2

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Primary Aldosteronism Due to Adrenal Hyperplasia (Bilateral)

Non Invasive Imaging Methods for Detecting PA：a Clinical PET Study of 18F-Pentixather

RECRUITING

NCT06581744Phase NAFangfang SunStarted 2024-06-12

[18F]AlF-NOTA-Pentixather

Hyperaldosteronism Primary

Is the Evolution of the Aldosterone-renin Ratio Pre- Versus Post-operative on Day 1 Following Unilateral Adrenalectomy for Primary Hyperaldosteronism Predictive of Blood Pressure Outcomes

NOT YET RECRUITING

NCT07110155Central Hospital, Nancy, FranceStarted 2025-08-15

Primary Aldosteronism

Subtyping Primary Aldosteronism With Para-chloro-2-[18F]Fluoroethyl-etomidate

RECRUITING

NCT06616142Phase PHASE1, PHASE2University Medical Center GroningenStarted 2024-11-06

[18F]CETO tracerDexamethasone oralAdrenal vein sampling

HyperaldosteronismHypertensionAldosterone-producing Adenoma

Water and Electrolytes Content in HYpertension (WHYSKI) in the SKIn

RECRUITING

NCT06090617University Hospital PadovaStarted 2021-01-01

Skin BiopsyVideo-laparoscopic adrenalectomy