CYP11B2

Chr 8

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.

GeneReviews 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 ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCorticosterone methyloxidase 1 deficiency

UniProtCorticosterone methyloxidase 2 deficiency

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · familial hyperreninemic hypoaldosteronism type 2 · AR · ClinGen 2023

Active trials

166

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.57

LOEUF

Mechanism· predicted

📖

GeneReview available — CYP11B2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in CYP11B2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

713 rare PASS variants

Rare truncating (LoF)

1 in 740

81 rare PASS variants

Rare synonymous (reference)

1 in 65

307 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CYP11B2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 79	1 in 1,500
South Asian	~43k	1 in 41	1 in 1,300
Remaining (unassigned)	~30k	1 in 51	1 in 290
European (Finnish)	~27k	1 in 370	1 in 2,200
Admixed American	~22k	1 in 63	1 in 3,700
African / African American	~21k	1 in 87	1 in 1,100
East Asian	~20k	1 in 53	1 in 4,000
Ashkenazi Jewish	~13k	1 in 130	1 in 1,700
Middle Eastern	~2,884	1 in 60	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓