CYP11B1

Chr 8ARAD

cytochrome P450 family 11 subfamily B member 1

Also known as: CPN1, CYP11B, FHI, P450C11

NCBI Gene: 1584 ENSG00000160882 UniProt: P15538 OMIM: 610613

This mitochondrial cytochrome P450 enzyme catalyzes the 11β-hydroxylation of steroid precursors to produce cortisol and corticosterone in the adrenal cortex. Mutations cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency (autosomal recessive) presenting in infancy with virilization and hypertension, or glucocorticoid-remediable aldosteronism (autosomal dominant) with early-onset hypertension. The gene shows low constraint to loss-of-function variation (pLI near zero), consistent with the recessive inheritance pattern of the classic form.

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 and is involved in the conversion of progesterone to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismAR/ADLOEUF 0.952 OMIM phenotypes

Clinical Summary— CYP11B1

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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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Clinical Trials

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

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GeneReview available — CYP11B1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.72

OE 0.60 (0.39–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.56Z-score

OE missense 1.26 (1.15–1.37)

367 obs / 291.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.60 (0.39–0.95)

0≤0.351.4

Missense OE?1.26 (1.15–1.37)

0≤0.61.4

Synonymous OE?1.47

0≤1.21.6

LoF obs/exp: 13 / 21.6Missense obs/exp: 367 / 291.9Syn Z: -4.03

This gene — mechanism propensity

0.75top 25%

GOF

0.76top 25%

LOF

0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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.