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 OMIM: 124080

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity. Mutations in this gene cause corticosterone methyl oxidase deficiency. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.574 OMIM phenotypes

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

138 unique Pathogenic / Likely Pathogenic· 207 VUS of 821 total submissions

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Clinical Trials

8 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 OE?1.13 (0.83–1.57)

0≤0.351.4

Missense OE?1.14 (1.04–1.25)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

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

This gene — mechanism propensity

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

821 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59

Likely Pathogenic79

VUS207

Likely Benign383

Benign49

Conflicting42

Pathogenic

Likely Pathogenic

207

VUS

383

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	49	6	3	1	59
Likely Pathogenic	59	18	2	0	79
VUS	1	160	40	6	207
Likely Benign	0	15	118	250	383
Benign	0	7	30	12	49
Conflicting	—				42
Total	109	206	193	269	819

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

View in ClinVar →

63 pathogenic / likely-pathogenic (of 75) ClinVar copy-number / structural variants overlap CYP11B2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

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 AldosteronismSecondary HypertensionAldosterone-Producing Adenoma

PETAL Trial: Impact of Gallium-68 Pentixafor PET-CT on Surgical Outcomes in Primary Aldosteronism

RECRUITING

NCT07027254Phase NASeoul National University HospitalStarted 2025-06-25

68Ga-pentixafor PET/CT

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

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

Pathological Type，Gene Mutation and Clinical Characteristics of Unilateral Primary Aldosteronism

RECRUITING

NCT06597630Qifu LiStarted 2023-12-01

Tissue specimens were stained by histopathology of hematoxylin-eosin

Breast Cancer and Pregnancy

Registry Study of Pregnancy and Breast Cancer

ACTIVE NOT RECRUITING

NCT04603820Spanish Breast Cancer Research GroupStarted 2019-11-18

Primary AldosteronismAdrenal Cushing SyndromePheochromocytoma