CYP11A1

Chr 15

cytochrome P450 family 11 subfamily A member 1

Also known as: CYP11A, CYPXIA1, P450SCC

NCBI Gene: 1583ENSG00000140459UniProt: P05108OMIM: 118485

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismLOEUF 0.881 OMIM phenotype
Clinical Summary— CYP11A1
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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
29 unique Pathogenic / Likely Pathogenic· 52 VUS of 200 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — CYP11A1
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
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 OE0.56 (0.37–0.88)
0≤0.351.4
Missense OE0.88 (0.80–0.97)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 14 / 24.8Missense obs/exp: 277 / 315.4Syn Z: 0.63
DN
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.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic14
VUS52
Likely Benign111
Conflicting2
15
Pathogenic
14
Likely Pathogenic
52
VUS
111
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
0
0
15
Likely Pathogenic
9
4
1
0
14
VUS
0
50
2
0
52
Likely Benign
0
0
41
70
111
Benign
0
0
0
0
0
Conflicting
—2
Total23554470194

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

View in ClinVar →

Protein Context — Lollipop Plot

CYP11A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
NPC1L1, stabilized by PABPC1/IGF2BP1, accelerates atherosclerosis by enhancing CYP11A1-mediated mitophagy and ferroptosis.
Zhang G et al.·Inflamm Res
2026
L-carnitine improves polycystic ovary syndrome by increasing CYP11A1, estrogen receptor, and decreasing XNIP and VEGF expression.
Lotfishokouh M et al.·Naunyn Schmiedebergs Arch Pharmacol
2026
Spatiotemporal Expression Inversion of CYP11A1 in the HPO Axis and Its Regulation of Granulosa Cell Proliferation via the PI3K/AKT/mTOR Pathway in Wuding Chickens.
Wan E et al.·Animals (Basel)
2026
Design, synthesis, and biological evaluation of cytochrome P450 CYP11A1 inhibitors.
Wang D et al.·Bioorg Med Chem Lett
2026
Protective Effects of Olea europaea L. Leaves and Equisetum arvense L. Extracts Against Testicular Toxicity Induced by Metronidazole Through Reducing Oxidative Stress and Regulating NBN, INSL-3, STAR, HSD-3β, and CYP11A1 Signaling Pathways.
Azouz AA et al.·Toxics
2025Open Access
Top 5 resultsSearch Europe PMC ↗

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