CYP11A1

Summary

CYP11A1 (cytochrome P450 family 11 subfamily A member 1, HGNC:2590) is a protein-coding gene on chromosome 15q24.1, encoding Cholesterol side-chain cleavage enzyme, mitochondrial (P05108). A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones.

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.

Source: NCBI Gene 1583 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 440 total — 28 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 55
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000781

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2590
Approved symbol	CYP11A1
Name	cytochrome P450 family 11 subfamily A member 1
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	P450SCC
Ensembl gene	ENSG00000140459
Ensembl biotype	protein_coding
OMIM	118485
Entrez	1583

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000268053, ENST00000358632, ENST00000416978, ENST00000435365, ENST00000450547, ENST00000466978, ENST00000467407, ENST00000498141, ENST00000566674, ENST00000569662, ENST00000950903, ENST00000950904, ENST00000950905

RefSeq mRNA: 2 — MANE Select: NM_000781 NM_000781, NM_001099773

CCDS: CCDS32291, CCDS45303

Canonical transcript exons

ENST00000268053 — 9 exons

Exon	Start	End
ENSE00003524286	74347900	74348055
ENSE00003576531	74343789	74343992
ENSE00003585060	74345044	74345243
ENSE00003598172	74342977	74343137
ENSE00003606922	74367317	74367646
ENSE00003626746	74338571	74338768
ENSE00003638728	74339237	74339315
ENSE00003784293	74339587	74339753
ENSE00003848560	74337762	74338103

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 99.82.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2327 / max 1964.3410, expressed in 238 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150903	2.7497	59
150900	0.3755	151
150899	0.0440	9
150901	0.0364	12
150904	0.0192	8
150902	0.0079	5

Top tissues by expression

140 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.82	gold quality
right adrenal gland	UBERON:0001233	99.77	gold quality
right adrenal gland cortex	UBERON:0035827	99.75	gold quality
left adrenal gland	UBERON:0001234	99.71	gold quality
left adrenal gland cortex	UBERON:0035825	99.66	gold quality
adrenal gland	UBERON:0002369	98.30	gold quality
placenta	UBERON:0001987	96.05	gold quality
right uterine tube	UBERON:0001302	94.33	gold quality
left ovary	UBERON:0002119	91.08	gold quality
medulla oblongata	UBERON:0001896	90.00	gold quality
ovary	UBERON:0000992	89.93	gold quality
right testis	UBERON:0004534	89.51	gold quality
testis	UBERON:0000473	88.78	gold quality
left testis	UBERON:0004533	88.62	gold quality
right ovary	UBERON:0002118	86.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.24	gold quality
lower esophagus mucosa	UBERON:0035834	81.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.18	gold quality
esophagus mucosa	UBERON:0002469	76.06	gold quality
fallopian tube	UBERON:0003889	75.88	gold quality
mucosa of stomach	UBERON:0001199	73.48	gold quality
spleen	UBERON:0002106	72.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.36	gold quality
caudate nucleus	UBERON:0001873	71.80	gold quality
adenohypophysis	UBERON:0002196	70.83	gold quality
putamen	UBERON:0001874	70.72	gold quality
esophagus	UBERON:0001043	70.22	gold quality
right lobe of liver	UBERON:0001114	70.12	gold quality
gastrocnemius	UBERON:0001388	69.90	gold quality
muscle of leg	UBERON:0001383	69.48	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ANND-5	yes	554.10
E-MTAB-6678	yes	16.68
E-MTAB-9388	yes	7.14
E-MTAB-9801	yes	4.80
E-GEOD-109979	no	45.00
E-ANND-3	no	3.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CREB1, DGKQ, DNMT1, ESR1, FOXL2, GATA6, GRHL1, JUN, KLF13, KLF4, KLF9, NCOA1, NR0B1, NR4A1, NR5A1, NR5A2, PHF20, RUNX2, SALL3, SF1, SFPQ, SP1, SP3, SPI1, TCF21, TCF3, TFAP2A, TFCP2L1, TRERF1, UBP1, ZGPAT

miRNA regulators (miRDB)

10 targeting CYP11A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-1302	97.92	67.27	844
HSA-MIR-4298	97.26	66.59	765

Literature-anchored findings (GeneRIF, showing 40)

• Salt-inducible kinase represses cAMP-dependent protein kinase-mediated activation of cyp11a promoter through the CREB basic leucine zipper domain (PMID:11864972)
• p450scc expression is regulated by TReP-132, steroidogenic factor-1 and CBP/p300 (PMID:12101186)
• cholesterol is near-saturating for cytochrome P450scc activity in placental mitochondria due to the P450scc displaying a low K(m) for cholesterol resulting from the low and rate-limiting concentration of adrenodoxin reductase present (PMID:12137805)
• Transcription of cholesterol side-chain cleavage cytochrome P450 in the placenta: activating protein-2 assumes the role of steroidogenic factor-1 by binding to an overlapping promoter element. (PMID:12145340)
• Results support the hypothesis that NO inhibits the rate-limiting enzyme CYP11A1 in steroidogenesis independent of guanylyl cyclase activation. (PMID:12242026)
• cytochrome P450 side chain cleavage mRNA was increased threefold in the ovarian stroma of postmenopausal women with endometrial cancer and endometrial hyperplasia (PMID:12517592)
• TReP-132 interacts with steroidogenic factor-1 (SF-1) through specific domains; and along with the interaction with CBP/p300 these factors are postulated to form a complex to regulate expression of the P450scc gene. (PMID:12530663)
• CYP11A and CYP17 expressed centrally within fetal zone at 50 days post-conception and later during first trimester. Weaker CYP11A immunoreactivity also was visible in outer region of adrenal cortex consistent with definitive zone expresion. (PMID:12530676)
• CYP11A mRNAs were more abundant in polycystic ovary syndrome theca cells than in normal theca cells. (PMID:14644808)
• Associations between CYP11A promoter variation and androgen-related phenotypes has been substantially overestimated in previous studies. (PMID:15126571)
• CYP11A1 polymorphism near the promoter region may be an important susceptibility factor for breast cancer risk. (PMID:15159300)
• Findings suggest that the syncytiotrophoblast cells are the major site expressing P450scc in early placenta, and that increasing P450scc in placental villi lay a foundation for site-shift of progesterone biosynthesis from the corpus luteum to placenta. (PMID:15323426)
• LBP-1b is an important SF1-independent transcriptional activator stimulating P450scc expression in human placental JEG-3 cells, whereas LBP-9 modulates the action of LBP-1b, exerting both positive and negative effects (PMID:15471945)
• CYP11A1 expression in human granulosa cells is regulated by LRH-1. (PMID:15613430)
• CYP11A1 induces apoptosis by the generation of reactive oxygen species in mitochondria (PMID:15927889)
• An association between the (TTTTA)(n) microsatellite polymorphism in the promoter of the CYP11A gene and the pathogenesis of ovarian hyperstimulation syndrome could not be confirmed. (PMID:16391898)
• Although granulosa cells in arrested follicles in PCOS fail to express significant amounts of aromatase, there is an overexpression of 5alpha-reductase activity and premature expression of cholesterol side-chain cleavage cytochrome P450. (PMID:16798289)
• Leydig cells (LCs) of GR1 and GR2 showed strong immunostaining of aromatase and cP450scc but weak staining of ERbeta and AR. Interstitial cells (ICs) and Sertoli cells (SCs) expressed ERbeta, particularly in GR1 and GR2 (PMID:17065579)
• CYP11A should be considered as a candidate breast cancer susceptibility gene in men and women. (PMID:17178901)
• study found that among genes controlling endogenous estrogen metabolism, CYP11A1 harbors common variants that may influence expression to significantly modify risk of breast cancer (PMID:17575134)
• A review of trans-acting factors and cis-acting elements that regulate CYP11A1 gene expression. (PMID:17594537)
• An interaction exists among LBP transcriptional factors at the transcriptional level of P450scc regulation. (PMID:18004979)
• Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc. (PMID:18182448)
• No difference in StAR and P450scc protein levels in granulosa cells obtained from older low-responder in vitro fertilization patients with that of young good-responder patients. (PMID:18191841)
• data imply that the previously unreported pathway of vitamin D3 metabolism by P450scc may have wider biological implications depending, for example, on the extent of adrenal gland or cutaneous metabolism. (PMID:18368131)
• For CYP11A1 (cytochrome P450 family 11 subfamily A polypeptide 1), there was no association between the number of TTTTA repeats (D15S520) and risk of endometrial cancer (PMID:18437511)
• CYP11A1 pentanucleotide repeat polymorphism is associated with the risk of breast cancer but not fibrocystic breast disease in CHinese women. (PMID:18483327)
• Cholesterol sulfate has an inhibitory effect on progesterone production by regulating the expression of StAR and P450scc gene expression. (PMID:18490834)
• Data show that CYP11A1 were expressed mainly in the zona fasciculata (ZF), followed by the zona reticularis in adrenal cortex attached to adrenocortical adenomas. (PMID:18505908)
• Differential expression of steroidogenic factors 1 and 2, cytochrome p450scc, and steroidogenic acute regulatory protein in the pancreas. (PMID:18665078)
• Our study carried out in a defined group of Indian women with PCOS suggests for the first time an individual, as well as combined, association of polymorphisms in CYP11A1 and CYP17 promoters with T levels. (PMID:18725155)
• A microsatellite polymorphism (TTTTA)n in the promoter region of the CYP11A1 gene is associated with an increased risk of metastatic and high-grade prostate cancer. with microsatellite instability as a potential markrs for early detection. (PMID:18992638)
• A novel homozygous mutation in CYP11A1 gene is associated with late-onset adrenal insufficiency and hypospadias in a 46,XY patient. (PMID:19116240)
• Among patients with essential hypertension, cholesterol side-chain cleavage & MDR1 loci are related to circulating endogenous ouabain & diastolic blood pressure, most likely by influencing EO synthesis and transmembrane transport, respectively. (PMID:19197249)
• Promoter pentanucleotide variant may confer risk susceptibility in abnormal metabolism of patients with PCOS in Han Chinese women. (PMID:19300392)
• Runx2 regulates enzymes involved in sterol/steroid-related metabolic pathways and that activation of Cyp11a1 by Runx2 may contribute to attenuation of osteoblast growth. (PMID:19342447)
• 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes (PMID:19543524)
• No significant difference in P450(scc) mRNA was found among normal adrenal gland, APA or idiopathic hyperplastic nodules (P > 0.05). These results suggest that P450(scc) contributes little to the overproduction of aldosterone in APA and IHA. (PMID:20066577)
• Genetic variants in CYP11A1 may influence endometrial cancer risk or may be markers for causal variants elsewhere. (PMID:20199803)
• Polymorphism of CYP11A1 was associated with polycystic ovarian syndrome in Chinese patients. (PMID:20450755)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp11a1.1	ENSDARG00000002347
danio_rerio	cyp11a1.2	ENSDARG00000092696
mus_musculus	Cyp11a1	ENSMUSG00000032323
rattus_norvegicus	Cyp11a1	ENSRNOG00000008074

Paralogs (2): CYP11B1 (ENSG00000160882), CYP11B2 (ENSG00000179142)

Protein

Protein identifiers

Cholesterol side-chain cleavage enzyme, mitochondrial — P05108 (reviewed: P05108)

Alternative names: CYPXIA1, Cholesterol desmolase, Cytochrome P450 11A1, Cytochrome P450(scc)

All UniProt accessions (7): P05108, A0A0S2Z3R3, C9JPU9, C9JXV4, E7EPP8, H3BS93, H3BSZ1

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones. Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin).

Subunit / interactions. Interacts with FDX1/adrenodoxin.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Adrenal insufficiency, congenital, with 46,XY sex reversal (AICSR) [MIM:613743] A rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure. Patients with congenital adrenal insufficiency do not manifest the massive adrenal enlargement typical of congenital lipoid adrenal hyperplasia. The disease is caused by variants affecting the gene represented in this entry.

Induction. By 8-bromo cyclic AMP.

Pathway. Lipid metabolism; C21-steroid hormone metabolism. Steroid metabolism; cholesterol metabolism.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P05108-1	1	yes
P05108-2	2

RefSeq proteins (2): NP_000772, NP_001093243 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050479	CYP11_CYP27_families	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.15.6 — cholesterol monooxygenase (side-chain-cleaving) (BRENDA: 20 organisms, 66 substrates, 34 inhibitors, 23 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CHOLESTEROL	0.0005–1.18	10
REDUCED ADRENODOXIN	0.0004–0.0012	3
CHOLESTEROL SULFATE	0.0003–0.0232	2
VITAMIN D3	0.0296–3.67	2
17,20-DIHYDROXYVITAMIN D2	0.0181	1
20-HYDROXYVITAMIN D2	0.012	1
20-HYDROXYVITAMIN D3	0.067	1
20ALPHA-HYDROXYCHOLESTEROL	0.012	1
VITAMIN D2	0.0175	1

Catalyzed reactions (Rhea), 4 shown:

• 2 reduced [adrenodoxin] + cholesterol + O2 + 2 H(+) = (22R)-hydroxycholesterol + 2 oxidized [adrenodoxin] + H2O (RHEA:34335)
• (22R)-hydroxycholesterol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (20R,22R)-20,22-dihydroxycholesterol + 2 oxidized [adrenodoxin] + H2O (RHEA:34339)
• (20R,22R)-20,22-dihydroxycholesterol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 4-methylpentanal + pregnenolone + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:34343)
• 6 reduced [adrenodoxin] + cholesterol + 3 O2 + 6 H(+) = 4-methylpentanal + pregnenolone + 6 oxidized [adrenodoxin] + 4 H2O (RHEA:35739)

UniProt features (57 total): helix 25, strand 12, sequence variant 8, sequence conflict 5, turn 3, transit peptide 1, chain 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3N9Y	X-RAY DIFFRACTION	2.1
3N9Z	X-RAY DIFFRACTION	2.17
3NA1	X-RAY DIFFRACTION	2.25
3NA0	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05108-F1	92.37	0.90

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 462 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-196108	Pregnenolone biosynthesis
R-HSA-211976	Endogenous sterols
R-HSA-5579026	Defective CYP11A1 causes AICSR

MSigDB gene sets: 331 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, MORF_RAGE, RNGTGGGC_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_BIOLOGICAL_OXIDATIONS, MORF_FLT1, MORF_MSH3, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_GLUCOCORTICOID_METABOLIC_PROCESS, MODULE_45, MORF_BRCA1, MORF_ATRX, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (13): C21-steroid hormone biosynthetic process (GO:0006700), glucocorticoid biosynthetic process (GO:0006704), cholesterol metabolic process (GO:0008203), sterol metabolic process (GO:0016125), cortisol metabolic process (GO:0034650), vitamin D metabolic process (GO:0042359), cellular response to peptide hormone stimulus (GO:0071375), steroid hormone biosynthetic process (GO:0120178), alcohol metabolic process (GO:0006066), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), steroid metabolic process (GO:0008202), C21-steroid hormone metabolic process (GO:0008207)

GO Molecular Function (10): iron ion binding (GO:0005506), cholesterol monooxygenase (side-chain-cleaving) activity (GO:0008386), heme binding (GO:0020037), monooxygenase activity (GO:0004497), protein binding (GO:0005515), steroid hydroxylase activity (GO:0008395), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen (GO:0016713), metal ion binding (GO:0046872)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of steroid hormones	1
Cytochrome P450 - arranged by substrate type	1
Metabolic disorders of biological oxidation enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	4
steroid hormone biosynthetic process	2
glucocorticoid metabolic process	2
oxidoreductase activity	2
monooxygenase activity	2
C21-steroid hormone metabolic process	1
hormone biosynthetic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
primary alcohol metabolic process	1
ketone metabolic process	1
olefinic compound metabolic process	1
tertiary alcohol metabolic process	1
cellular response to hormone stimulus	1
response to peptide hormone	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
steroid biosynthetic process	1
small molecule metabolic process	1
primary metabolic process	1
lipid biosynthetic process	1
lipid metabolic process	1
hormone metabolic process	1
transition metal ion binding	1
steroid hydroxylase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen	1
tetrapyrrole binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP11A1	FDX1	P10109	995
CYP11A1	FDXR	P22570	988
CYP11A1	HSD3B1	P14060	972
CYP11A1	STAR	P49675	954
CYP11A1	HSD3B2	P26439	925
CYP11A1	MC2R	Q01718	893
CYP11A1	NR5A1	Q13285	876
CYP11A1	LHCGR	P22888	853
CYP11A1	HSD11B2	P80365	851
CYP11A1	NR0B1	P51843	840
CYP11A1	POMC	P01189	833
CYP11A1	HSD17B3	P37058	816
CYP11A1	SULT2A1	Q06520	809
CYP11A1	FSHR	P23945	809
CYP11A1	HSD17B1	P14061	801

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CYP11A1	NLGN3	psi-mi:“MI:0915”(physical association)	0.460
NLGN3	CYP11A1	psi-mi:“MI:0403”(colocalization)	0.460
CYP11A1	SMAD2	psi-mi:“MI:0915”(physical association)	0.370
CYP11A1	SMAD3	psi-mi:“MI:0915”(physical association)	0.370
CYP11A1	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
A2M	TPP1	psi-mi:“MI:0403”(colocalization)	0.350

BioGRID (7): CYP11A1 (Two-hybrid), CYP11A1 (Affinity Capture-Western), FDX1 (Reconstituted Complex), C19orf26 (Cross-Linking-MS (XL-MS)), CYP11A1 (Two-hybrid), CYP11A1 (Two-hybrid), CYP11A1 (Two-hybrid)

ESM2 similar proteins: B2RXA7, E1BHJ4, F1RE08, G3V7X8, O02766, O35074, O35084, O43174, O46491, O46515, O75881, O88962, O93323, P00189, P05108, P0DOX0, P10612, P14137, P15393, P17177, P17178, P18125, P22680, P46634, P51542, P79153, P79202, P97720, Q08D50, Q16647, Q28827, Q29626, Q2XV99, Q4G0S4, Q60991, Q62969, Q63688, Q64408, Q64505, Q6EIG3

Diamond homologs: A0A067DT54, A0A067E1K2, A0A0E3D8P0, A0A140JWM8, A0A1B4XBH8, A0A3Q7HBJ5, A0A517FNB9, A0A517FNC5, A0A5B8ND22, A0A9Y1LLN2, A2QTE8, A2RRT9, A2Z212, A9QNE7, B5BSX1, B8AV52, B8BJ22, D4AY62, I1IUJ6, I7ZK32, K4CI52, L0N063, O13820, O23051, O46515, O81077, P05108, P0DXH4, P12394, P14137, P29981, P30612, P36423, P37121, P51870, P51871, P70085, P78329, P79690, P93147

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
FOXL2	“down-regulates quantity by repression”	CYP11A1	“transcriptional regulation”
GATA6	“up-regulates quantity by expression”	CYP11A1	“transcriptional regulation”
CYP11A1	“up-regulates quantity”	pregnenolone	“chemical modification”
CYP11A1	“down-regulates quantity”	cholesterol	“chemical modification”
SIRT3	“up-regulates quantity by stabilization”	CYP11A1	deacetylation
Corticotropin	“up-regulates quantity”	CYP11A1

Disease & clinical

Clinical variants and AI predictions

ClinVar

440 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	21
Uncertain significance	120
Likely benign	224
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1179133	NM_000781.3(CYP11A1):c.358del (p.Arg120fs)	Pathogenic
1322181	NM_000781.3(CYP11A1):c.694C>T (p.Arg232Ter)	Pathogenic
17516	NM_000781.3(CYP11A1):c.809_814dup (p.Asp271_Val272insGlyAsp)	Pathogenic
17522	NM_000781.3(CYP11A1):c.422T>G (p.Leu141Trp)	Pathogenic
17523	NM_000781.3(CYP11A1):c.1244T>A (p.Val415Glu)	Pathogenic
1804587	NM_000781.3(CYP11A1):c.1270C>T (p.Arg424Ter)	Pathogenic
265094	NM_000781.3(CYP11A1):c.835del (p.Ile279fs)	Pathogenic
2791426	NM_000781.3(CYP11A1):c.622G>T (p.Glu208Ter)	Pathogenic
280582	NM_000781.3(CYP11A1):c.425+1G>A	Pathogenic
2820948	NM_000781.3(CYP11A1):c.809G>A (p.Trp270Ter)	Pathogenic
2837364	NM_000781.3(CYP11A1):c.788G>A (p.Trp263Ter)	Pathogenic
2839944	NM_000781.3(CYP11A1):c.976G>T (p.Gly326Ter)	Pathogenic
2864775	NM_000781.3(CYP11A1):c.1126del (p.Leu376fs)	Pathogenic
2888346	NM_000781.3(CYP11A1):c.1393C>T (p.Arg465Trp)	Pathogenic
29625	NM_000781.3(CYP11A1):c.665T>C (p.Leu222Pro)	Pathogenic
3068398	NM_000781.3(CYP11A1):c.740_744dup (p.Asn249fs)	Pathogenic
3609110	NM_000781.3(CYP11A1):c.73G>T (p.Glu25Ter)	Pathogenic
3617139	NM_000781.3(CYP11A1):c.515dup (p.Asp172fs)	Pathogenic
3631434	NM_000781.3(CYP11A1):c.590del (p.Asp197fs)	Pathogenic
3669223	NM_000781.3(CYP11A1):c.306del (p.Ile102fs)	Pathogenic
3672122	NM_000781.3(CYP11A1):c.31del (p.Val11fs)	Pathogenic
3672595	NM_000781.3(CYP11A1):c.174del (p.Trp59fs)	Pathogenic
3672842	NM_000781.3(CYP11A1):c.868C>T (p.Gln290Ter)	Pathogenic
3706399	NM_000781.3(CYP11A1):c.1315C>T (p.Arg439Ter)	Pathogenic
3721829	NM_000781.3(CYP11A1):c.857G>A (p.Trp286Ter)	Pathogenic
379354	NM_000781.3(CYP11A1):c.358C>T (p.Arg120Ter)	Pathogenic
631742	NM_000781.3(CYP11A1):c.508_509del (p.Leu170fs)	Pathogenic
988386	NM_000781.3(CYP11A1):c.440G>A (p.Trp147Ter)	Pathogenic
1481573	NM_000781.3(CYP11A1):c.806C>T (p.Ala269Val)	Likely pathogenic
17517	NM_000781.3(CYP11A1):c.1057C>T (p.Arg353Trp)	Likely pathogenic

SpliceAI

1912 predictions. Top by Δscore:

Variant	Effect	Δscore
15:74338565:ACTC:A	donor_loss	1.0000
15:74338567:T:TA	donor_loss	1.0000
15:74338568:CA:C	donor_loss	1.0000
15:74338569:A:AC	donor_gain	1.0000
15:74338569:ACATT:A	donor_loss	1.0000
15:74338570:C:CG	donor_gain	1.0000
15:74338570:C:G	donor_loss	1.0000
15:74338570:CA:C	donor_gain	1.0000
15:74338570:CAT:C	donor_gain	1.0000
15:74338570:CATTG:C	donor_gain	1.0000
15:74338764:AGTGT:A	acceptor_gain	1.0000
15:74338765:GTGT:G	acceptor_gain	1.0000
15:74338766:TGT:T	acceptor_gain	1.0000
15:74338767:GT:G	acceptor_gain	1.0000
15:74338768:TCT:T	acceptor_loss	1.0000
15:74338769:C:CC	acceptor_gain	1.0000
15:74338769:CTG:C	acceptor_loss	1.0000
15:74338775:C:CT	acceptor_gain	1.0000
15:74339596:T:TA	donor_gain	1.0000
15:74342971:CCTCA:C	donor_loss	1.0000
15:74342972:CTCA:C	donor_loss	1.0000
15:74342973:TCA:T	donor_loss	1.0000
15:74342974:CA:C	donor_loss	1.0000
15:74342975:A:AC	donor_gain	1.0000
15:74342975:A:C	donor_loss	1.0000
15:74342976:C:CC	donor_gain	1.0000
15:74342989:T:TA	donor_gain	1.0000
15:74342993:G:A	donor_gain	1.0000
15:74343133:GTCAG:G	acceptor_gain	1.0000
15:74343134:TCAG:T	acceptor_gain	1.0000

AlphaMissense

3441 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:74338640:A:C	F455L	0.998
15:74338640:A:T	F455L	0.998
15:74338642:A:G	F455L	0.998
15:74343886:G:C	S244R	0.998
15:74343886:G:T	S244R	0.998
15:74343888:T:G	S244R	0.998
15:74339587:C:G	R386T	0.997
15:74339604:G:C	S380R	0.997
15:74339604:G:T	S380R	0.997
15:74339606:T:G	S380R	0.997
15:74345217:C:G	R151P	0.997
15:74347949:A:G	W126R	0.997
15:74347949:A:T	W126R	0.997
15:74339315:T:A	R386S	0.996
15:74339315:T:G	R386S	0.996
15:74348029:A:T	V99D	0.996
15:74339285:T:A	R396S	0.995
15:74339285:T:G	R396S	0.995
15:74339735:A:G	W337R	0.995
15:74339735:A:T	W337R	0.995
15:74345230:A:G	W147R	0.995
15:74345230:A:T	W147R	0.995
15:74343810:A:G	W270R	0.994
15:74343810:A:T	W270R	0.994
15:74347947:C:A	W126C	0.994
15:74347947:C:G	W126C	0.994
15:74338638:C:T	G456D	0.993
15:74343912:C:G	A236P	0.993
15:74338602:G:T	A468D	0.992
15:74338611:C:G	R465P	0.992

dbSNP variants (sampled 300 via entrez): RS1000008386 (15:74354023 T>A), RS1000039052 (15:74346239 G>A), RS1000039330 (15:74361146 C>T), RS1000086776 (15:74349799 G>T), RS1000363600 (15:74340957 C>G,T), RS1000471363 (15:74356858 T>G), RS1000515269 (15:74360722 G>A,C,T), RS1000649806 (15:74344615 A>G), RS1000707463 (15:74338014 G>A), RS1000818707 (15:74338359 A>G,T), RS1000936868 (15:74344257 C>T), RS1001106866 (15:74359035 C>T), RS1001110434 (15:74363565 G>T), RS1001293993 (15:74339576 T>A), RS1001299803 (15:74362875 T>G)

Disease associations

OMIM: gene MIM:118485 | disease phenotypes: MIM:613743, MIM:277900

GenCC curated gene-disease

Disease	Classification	Inheritance
Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency	Strong	Autosomal recessive
inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency	Supportive	Autosomal recessive

Mondo (5): Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency (MONDO:0013400), pulmonary disease, chronic obstructive, susceptibility to (MONDO:0100167), congenital adrenal hyperplasia (MONDO:0018479), Wilson disease (MONDO:0010200), inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency (MONDO:0017337)

Orphanet (3): 46,XY difference of sex development-adrenal insufficiency due to CYP11A1 deficiency (Orphanet:168558), Congenital adrenal hyperplasia (Orphanet:418), Wilson disease (Orphanet:905)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000033	Ambiguous genitalia, male
HP:0000037	Male pseudohermaphroditism
HP:0000127	Renal salt wasting
HP:0000142	Abnormal vagina morphology
HP:0000144	Decreased fertility
HP:0000151	Aplasia of the uterus
HP:0000771	Gynecomastia
HP:0000823	Delayed puberty
HP:0000835	Adrenal hypoplasia
HP:0000846	Adrenal insufficiency
HP:0000848	Increased circulating renin concentration
HP:0000859	Increased circulating aldosterone concentration
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin
HP:0001197	Abnormality of prenatal development or birth
HP:0001274	Agenesis of corpus callosum
HP:0001508	Failure to thrive
HP:0001622	Premature birth
HP:0001941	Acidosis
HP:0001944	Dehydration
HP:0001998	Neonatal hypoglycemia
HP:0002013	Vomiting
HP:0002153	Hyperkalemia
HP:0002615	Hypotension
HP:0002750	Delayed skeletal maturation
HP:0002902	Hyponatremia
HP:0003107	Abnormal circulating cholesterol concentration
HP:0003154	Increased circulating ACTH level
HP:0004319	Decreased circulating aldosterone concentration

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002875_114	Diisocyanate-induced asthma	1.000000e-06
GCST004412_7	Craniofacial microsomia	1.000000e-23
GCST010108_20	Coffee consumption (cups per day)	8.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0006782	cups of coffee per day measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000312	Adrenal Hyperplasia, Congenital	C12.050.351.875.253.090.500; C12.200.706.316.090.500; C12.800.316.090.500; C16.131.939.316.129.500; C16.320.033; C16.320.565.925.249; C18.452.648.925.249; C19.053.440; C19.391.119.090.500
D006527	Hepatolenticular Degeneration	C06.552.413; C10.228.140.079.493; C10.228.140.163.100.360; C10.228.662.400; C10.574.500.487; C16.320.400.361; C16.320.565.189.360; C16.320.565.618.403; C18.452.132.100.360; C18.452.648.189.360; C18.452.648.618.403
C566130	Adrenal Insufficiency, Congenital (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2033 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 74,271 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL488	AMINOGLUTETHIMIDE	4	74,271

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP11, CYP17, CYP19, CYP20 and CYP21 families

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
opevesostat	Inhibition	6.97	pIC50
(2S,4S)-ketoconazole	Inhibition	5.9	pIC50
aminoglutethimide	Inhibition	4.52	pIC50

CTD chemical–gene interactions

138 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Colforsin	decreases reaction, increases expression, affects expression, affects cotreatment, decreases expression (+1 more)	10
bisphenol A	decreases expression, increases expression, increases methylation, decreases reaction	7
Flame Retardants	affects cotreatment, decreases expression, increases expression	4
Testosterone	affects cotreatment, increases expression, decreases expression	4
Valproic Acid	affects expression, affects reaction, decreases expression, increases expression	4
triphenyl phosphate	affects reaction, affects cotreatment, decreases reaction, increases expression	3
tris(chloroethyl)phosphate	affects cotreatment, increases expression, decreases expression	3
Atrazine	affects reaction, increases expression, increases reaction	3
Diethylhexyl Phthalate	increases expression, affects cotreatment, affects reaction	3
Mitotane	decreases activity, decreases expression, decreases reaction, increases expression	3
Nicotine	decreases expression	3
8-Bromo Cyclic Adenosine Monophosphate	increases expression, decreases reaction	3
IMOL S-140	affects cotreatment, increases expression	2
tris(2-butoxyethyl) phosphate	affects cotreatment, increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression, affects cotreatment	2
tri-(2-chloroisopropyl)phosphate	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	increases expression, decreases expression	2
mono-benzyl phthalate	affects expression, increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Fulvestrant	decreases reaction, increases expression, affects binding, affects cotreatment, increases reaction	2
Ethanol	decreases expression, increases expression	2
Arsenic	decreases expression, affects methylation	2
Cholesterol	affects metabolic processing, increases metabolic processing	2
Dibutyl Phthalate	decreases expression, affects cotreatment, affects reaction, increases expression	2
Hydrocortisone	affects reaction, decreases expression, affects expression, decreases reaction	2
Pregnenolone	increases chemical synthesis	2
Progesterone	affects abundance, affects chemical synthesis	2
Tobacco Smoke Pollution	decreases expression	2
Halogenated Diphenyl Ethers	increases expression	2
fluorene-9-bisphenol	increases expression, decreases expression, decreases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL696209	Functional	In vitro inhibition of progesterone production in hamster ovarian tissue	Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5QA	COS-F2-130	Transformed cell line	Male

Clinical trials (associated diseases)

148 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03760835	PHASE4	RECRUITING	Congenital Adrenal Hyperplasia Once Daily Hydrocortisone Treatment
NCT04536662	PHASE4	UNKNOWN	Comparisons of Different Forms of Glucocorticoid on the Recovery of Reproductive Function in Patients With 21α-hydroxylase Deficiency
NCT00004338	PHASE4	COMPLETED	Study of Zinc for Wilson Disease
NCT02426905	PHASE4	UNKNOWN	Study to Assess Long-Term Outcomes of Trientine in Wilson Disease Patients Withdrawn From Therapy With d-Penicillamine
NCT05305872	PHASE4	UNKNOWN	Gandouling in the Treatment of Wilson’s Disease
NCT00001521	PHASE3	COMPLETED	Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia
NCT02716818	PHASE3	COMPLETED	Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia
NCT03062280	PHASE3	COMPLETED	A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH
NCT03532022	PHASE3	WITHDRAWN	Open-label Comparison of Chronocort® Versus Standard Glucocorticoid Replacement Therapy
NCT04490915	PHASE3	ACTIVE_NOT_RECRUITING	Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia
NCT04806451	PHASE3	ACTIVE_NOT_RECRUITING	Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Participants With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study)
NCT05063994	PHASE3	COMPLETED	Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia
NCT05299554	PHASE3	COMPLETED	Long-term Safety Study of Chronocort in the Treatment of Participants With Congenital Adrenal Hyperplasia
NCT07144163	PHASE3	RECRUITING	A Study to Evaluate Atumelnant in Adults With Congenital Adrenal Hyperplasia
NCT00004339	PHASE3	COMPLETED	Study of Tetrathiomolybdate in Patients With Wilson Disease
NCT00212355	PHASE3	COMPLETED	Efficacy and Safety, Long-term Study of Zinc Acetate to Treat Wilson’s Disease in Japan.
NCT03403205	PHASE3	TERMINATED	Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
NCT03539952	PHASE3	COMPLETED	Trientine Tetrahydrochloride (TETA 4HCL) for the Treatment of Wilson’s Disease
NCT05047523	PHASE3	TERMINATED	Study of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease
NCT07465718	PHASE3	NOT_YET_RECRUITING	Trientine Tetrahydrochloride Administered Once a Day for the First Line Treatment of Wilson’s Disease Patients.
NCT00621985	PHASE2	COMPLETED	Dexamethasone Treatment of Congenital Adrenal Hyperplasia
NCT01735617	PHASE2	COMPLETED	Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH
NCT01771328	PHASE2	UNKNOWN	Continuous Subcutaneous Hydrocortisone Infusion in Congenital Adrenal Hyperplasia
NCT01859312	PHASE2	COMPLETED	Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia
NCT02804178	PHASE2	COMPLETED	A Study of ATR-101 for the Treatment of Congenital Adrenal Hyperplasia
NCT03257462	PHASE2	COMPLETED	Study of SPR001 in Adults With Classic Congenital Adrenal Hyperplasia
NCT03548246	PHASE2	WITHDRAWN	Androgen Reduction in Congenital Adrenal Hyperplasia
NCT03669549	PHASE2	TERMINATED	Nevanimibe HCl for the Treatment of Classic CAH
NCT03687242	PHASE2	COMPLETED	Study to Evaluate the Safety and Efficacy of SPR001 in Subjects With Classic Congenital Adrenal Hyperplasia
NCT04457336	PHASE2	TERMINATED	A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH
NCT04544410	PHASE2	TERMINATED	A Ph2b to Evaluate Tildacerfont in the Reduction of Glucocorticoid Steroid Doses in Adult CAH
NCT05128942	PHASE2	TERMINATED	A Phase 2 Study to Evaluate the Safety, Efficacy and PK of Tildacerfont in Children Aged 2-17 Years With CAH
NCT05907291	PHASE2	COMPLETED	Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 in Participants With Congenital Adrenal Hyperplasia (TouCAHn)
NCT06712823	PHASE2	RECRUITING	An Extension Study to Evaluate Safety and Efficacy in Participants Treated With CRN04894
NCT07187375	PHASE2	RECRUITING	Pharmacokinetics, Safety and Tolerability of Crinecerfont in Participants With Congenital Adrenal Hyperplasia Who Are Less Than 2 Years Old
NCT07536269	PHASE2	NOT_YET_RECRUITING	Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Crinecerfont in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Who Are Less Than 4 Years Old
NCT02273596	PHASE2	COMPLETED	Efficacy and Safety Study of WTX101 (ALXN1840) in Adult Wilson Disease Patients
NCT04422431	PHASE2	COMPLETED	Copper Concentration & Histopathologic Changes in Liver Biopsy in Participants With Wilson Disease Treated With ALXN1840
NCT04573309	PHASE2	COMPLETED	Copper and Molybdenum Balance in Participants With Wilson Disease Treated With ALXN1840
NCT07010575	PHASE2	COMPLETED	Patient Preference Study: Standard of Care Versus Once-daily Trientine Tetrahydrochloride