CYP11A1

Chr 15

cytochrome P450 family 11 subfamily A member 1

Also known as: CYP11A, CYPXIA1, P450SCC

NCBI Gene: 1583 ENSG00000140459 UniProt: P05108

This cytochrome P450 enzyme catalyzes the conversion of cholesterol to pregnenolone in the mitochondrial inner membrane, representing the first and rate-limiting step in steroid hormone synthesis. Mutations cause congenital adrenal insufficiency with partial or complete 46XY sex reversal, inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants (LOEUF 0.881), and affected individuals present with severe adrenal insufficiency and disorders of sex development.

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 catalyzes the conversion of cholesterol to pregnenolone, the first and rate-limiting step in the synthesis of the steroid hormones. Two transcript variants encoding different isoforms have been found for this gene. The cellular location of the smaller isoform is unclear since it lacks the mitochondrial-targeting transit peptide. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.88

Clinical Summary— CYP11A1

⚡

Population Constraint (gnomAD)

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

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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?

0.88LOEUF

pLI 0.000

Z-score 2.01

OE 0.56 (0.37–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.77Z-score

OE missense 0.88 (0.80–0.97)

277 obs / 315.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.37–0.88)

0≤0.351.4

Missense OE?0.88 (0.80–0.97)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 14 / 24.8Missense obs/exp: 277 / 315.4Syn Z: 0.63

This gene — mechanism propensity

0.74top 25%

GOF

0.73top 25%

LOF

0.2386th %ile

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

DNprediction above median

GOFprediction 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.