NR5A1

Summary

NR5A1 (nuclear receptor subfamily 5 group A member 1, HGNC:7983) is a protein-coding gene on chromosome 9q33.3, encoding Steroidogenic factor 1 (Q13285). Transcriptional activator. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a transcriptional activator involved in sex determination. The encoded protein binds DNA as a monomer. Defects in this gene are a cause of XY sex reversal with or without adrenal failure as well as adrenocortical insufficiency without ovarian defect.

Source: NCBI Gene 2516 — RefSeq curated summary.

At a glance

• Gene–disease (curated): premature ovarian failure 7 (Strong, GenCC) — +11 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 364 total — 75 pathogenic, 48 likely-pathogenic
• Phenotypes (HPO): 88
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 116 downstream targets (CollecTRI)
• MANE Select transcript: NM_004959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7983
Approved symbol	NR5A1
Name	nuclear receptor subfamily 5 group A member 1
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	FTZ1, SF-1, ELP, AD4BP, hSF-1, SF1
Ensembl gene	ENSG00000136931
Ensembl biotype	protein_coding
OMIM	184757
Entrez	2516

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000373587, ENST00000373588, ENST00000455734, ENST00000620110, ENST00000911688, ENST00000950383, ENST00000950384, ENST00000950385, ENST00000950386, ENST00000950387, ENST00000950388, ENST00000950389, ENST00000950390, ENST00000950391, ENST00000950392

RefSeq mRNA: 1 — MANE Select: NM_004959 NM_004959

CCDS: CCDS6856

Canonical transcript exons

ENST00000373588 — 7 exons

Exon	Start	End
ENSE00000726934	124491081	124491228
ENSE00000726936	124493030	124493149
ENSE00000726937	124500090	124500715
ENSE00000726938	124503079	124503220
ENSE00001460969	124503294	124503410
ENSE00001460970	124507249	124507399
ENSE00003742853	124481236	124483005

Expression profiles

Bgee: expression breadth broad, 77 present calls, max score 98.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2517 / max 134.5937, expressed in 25 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102432	0.2217	25
102430	0.0216	3
102431	0.0039	2
102429	0.0023	2
102427	0.0022	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	98.48	gold quality
right adrenal gland	UBERON:0001233	98.28	gold quality
left adrenal gland	UBERON:0001234	98.01	gold quality
left adrenal gland cortex	UBERON:0035825	97.96	gold quality
adrenal tissue	UBERON:0018303	97.29	gold quality
adrenal cortex	UBERON:0001235	95.49	gold quality
adrenal gland	UBERON:0002369	94.93	gold quality
spleen	UBERON:0002106	94.67	gold quality
left ovary	UBERON:0002119	89.34	gold quality
right ovary	UBERON:0002118	86.85	gold quality
adenohypophysis	UBERON:0002196	81.28	gold quality
pituitary gland	UBERON:0000007	80.69	gold quality
ovary	UBERON:0000992	80.52	gold quality
right testis	UBERON:0004534	78.94	gold quality
left testis	UBERON:0004533	78.67	gold quality
testis	UBERON:0000473	75.67	gold quality
tongue squamous epithelium	UBERON:0006919	67.93	gold quality
olfactory bulb	UBERON:0002264	67.51	gold quality
type B pancreatic cell	CL:0000169	62.59	gold quality
cervix squamous epithelium	UBERON:0006922	62.02	gold quality
pancreatic ductal cell	CL:0002079	60.79	silver quality
buccal mucosa cell	CL:0002336	60.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.59	gold quality
cerebellar vermis	UBERON:0004720	59.41	gold quality
secondary oocyte	CL:0000655	58.93	gold quality
male germ cell	CL:0000015	58.46	gold quality
quadriceps femoris	UBERON:0001377	58.08	gold quality
vastus lateralis	UBERON:0001379	57.86	gold quality
sperm	CL:0000019	57.69	gold quality
triceps brachii	UBERON:0001509	56.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.53

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

116 targets.

Target	Regulation
A2M
ADAM2
ADCY4	Activation
ADCYAP1
AFP
AKR1B1
AKR1B10	Activation
AKR1B15
ALAS1
AMH	Activation
AMHR2	Activation
ANGPT2
APRT
BTK
CAMK1
CAT
CCN3	Repression
CCND2
CD44
CD74
CD86
CEL
CGA	Unknown
CITED2	Activation
CNR1	Activation
CREBBP
CTLA4
CYB5A	Activation
CYP11A1	Unknown
CYP11B1	Unknown

JASPAR motifs

Motif	Name	Family
MA1540.1	NR5A1	FTZF1-related (NR5A)

JASPAR matrix evidence (PMIDs): PMID:10913126

Upstream regulators (CollecTRI, top): AR, CEBPA, DMRT1, NR0B1, NR5A1, PBX1, PKNOX1, SOX9, SP1, TCF21, TCF3, USF1, USF2, WT1

miRNA regulators (miRDB)

71 targeting NR5A1, 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-4283	100.00	66.42	2097
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• describe phenotypic spectrum of disorders associated with mutations and reveal how the discovery of naturally occurring mutations is helping to unravel the role in development and disease [review] (PMID:11738790)
• important regulators of steroidogeneisis are present in human skin and its appendages. (PMID:11886523)
• Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1. (PMID:11932209)
• SF-1 mutation (R92Q) in a highly conserved residue of the A-box, a region that functions as a secondary DNA-binding domain. partial loss of DNA binding and transcriptional activity, its phenotypic expression only when transmitted as a homozygous trait. (PMID:11932325)
• steroidogenic factor 1 mutations in primary adrenal failure and 46,XY sex-reversal (PMID:12083805)
• adrenal hypoplasia congenita and multiple pituitary hormone deficiency without mutations in the DAX1 or SF1 genes (PMID:12083815)
• SF1 plays a role in regulating p450scc expression with TReP-132 and CBP/p300 (PMID:12101186)
• Spatially heterogeneous expression of aromatase P450 through promoter II is closely correlated with the level of steroidogenic factor-1 transcript in endometrioma tissues. (PMID:12161505)
• modulation of DAX-1 and steroidogenic factor-1 intracellular levels in granulosa cells suggests that these transcription factors could be involved in mitogen-activated protein kinase suppression of steroidogenic acute regulatory protein expression (PMID:12727988)
• Wild-type SF1 but not SF1 G35E is a potent transactvator in GAGA4-expressing cells. Results strengthen the importance of a GATA-4/SF-1 cooperation for MIS transcription; disruption of this synergism might lead to abnormal sex differentiation. (PMID:12907682)
• Protein kinse A signal pathway may modify the interaction between Ad4BP/SF-1 and its activators and repressors. (PMID:14555713)
• We report the first functional characterization of a new variation found in the hinge region of human Ad4BP/SF-1, G146A (PMID:14623279)
• DAX-1alpha can bind to steroidogenic factor 1 and to DNA but is unable to repress steroidogenic factor 1-mediated transcriptional activation of the reporter gene and acts as an antagonist of DAX-1 under certain conditions (PMID:15044589)
• It is revealed with an in vitro sumoylated Ad4BP/SF-1 that DNA binding activity and interaction with Sox9 are unaffected. (PMID:15192080)
• SF1 has a role in basal expression of ACTH receptor and its induction by potassium and cAMP (PMID:15261303)
• It remains probable that this unusual patient has either a DAX1 or SF1 mutation defect. A Wnt-4 defect was not evaluated. (PMID:15379426)
• Both SF1 and GATA-6 were positive regulators of Steroid sulfotransferase 2A1 promoter constructs (PMID:15388788)
• 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)
• Increased copy number of the SF-1 gene in adrenocortical tumorigenesis. (PMID:15546904)
• Mutations in SF-1 cause spectrum of phenotypes associated with loss of SF-1 function. Mutations in SF-1 should be considered in XY gonadal dysgenesis, whether or not there is evidence of adrenal insufficinecy. Review. (PMID:15579738)
• SF1 contained a fortuitous ligand in the binding pocket. This ligand may account for the relatively high basal activity observed for SF1 in cofactor recruitment and cell-based assays. (PMID:15666825)
• Human SF-1 receptor binds phosphatidyl inositol second messengers;ligand binding is required for maximal activity. (PMID:15707893)
• cytochrome b5 gene transcription is regulated by Sp3, GATA-6, and steroidogenic factor 1 in human adrenal NCI-H295A cells (PMID:15831526)
• Mutation of the SF-1-binding sites within the hACTH-R promoter resulted in reduced or abolished DAX-1 inhibition, arguing for a mechanism that involves SF-1 for DAX-1 inhibition (PMID:15879363)
• the SF-1 Gly146Ala polymorphism may constitute a susceptibility factor for the development of severe micropenis, and that mild micropenis can be regarded as a normal variation in terms of the polymorphism effec (PMID:16127213)
• the SULT2A1 gene is mediated by SF1 and indirectly regulated by T(3) (PMID:16469813)
• Ala allele, the Ala/Gly genotype, and the Ala/Ala plus Ala/Gly genotype frequencies were significantly higher in cryptorchidism. Gly146Ala polymorphism may be susceptibility factor for cryptorchidism. (PMID:16500365)
• The SF-1 Gly146Ala variation may constitute a susceptible factor for development of type 2 diabetes and impairment of insulin actions. (PMID:16564598)
• steroidogenic factor 1 mutations causing adrenal failure in humans are rare and are more likely to be associated with significant underandrogenization and gonadal dysfunction in 46,XY individuals (PMID:16684822)
• expressed widely throughout the adrenal and reproductive axes during development and plays a central role in the function of these endocrine systems in post-natal and adult life (PMID:16816804)
• Ad4bp/SF-1 is important for the maintenance of steroidogenesis in the human testis (PMID:16834661)
• Sphingosine is a bonafide endogenous ligand for SF1 and a negative regulator of CYP17 gene expression. (PMID:16887917)
• These data indicate that SF-1 plays a crucial role in the regulation of hOct4 transcription through direct binding to the 1st SF-1 in Conserved Regions 1 of the hOct4 proximal promoter. (PMID:17226773)
• atrazine binds to and activates SF-1 to induce aromatase gene expression via promoter II (PMID:17331471)
• study reporta a SF-1 mutation that caused ambiguous genitalia associated with strikingly different hormonal phenotypes in two affected 46,XY children from the same family (PMID:17488792)
• this is the first demonstration of methylation-dependent regulation of SF-1 in any mammalian tissue (PMID:17519303)
• Atrazine-induced aromatase expression is SF-1 dependent: implications for endocrine disruption in wildlife and reproductive cancers in humans. (PMID:17520059)
• Data show that cyclic AMP-stimulated interaction between steroidogenic factor 1 and diacylglycerol kinase theta facilitates induction of CYP17. (PMID:17664281)
• SF1 mutations are a relatively frequent cause of 46,XY disorders of sex development in humans. (PMID:17694559)
• reveal a critical role for SF-1 dosage in adrenocortical tumorigenesis (PMID:17761949)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr5a1b	ENSDARG00000023362
danio_rerio	nr5a1a	ENSDARG00000103176
mus_musculus	Nr5a1	ENSMUSG00000026751
rattus_norvegicus	Nr5a1	ENSRNOG00000012682
drosophila_melanogaster	ftz-f1	FBGN0001078
drosophila_melanogaster	Hr39	FBGN0261239
caenorhabditis_elegans		WBGENE00003604
caenorhabditis_elegans		WBGENE00003607
caenorhabditis_elegans		WBGENE00003623
caenorhabditis_elegans		WBGENE00003625
caenorhabditis_elegans	nhr-74	WBGENE00003664
caenorhabditis_elegans	nhr-89	WBGENE00003679
caenorhabditis_elegans		WBGENE00003687
caenorhabditis_elegans	nhr-113	WBGENE00003703
caenorhabditis_elegans		WBGENE00003709
caenorhabditis_elegans	nhr-259	WBGENE00007770
caenorhabditis_elegans	nhr-244	WBGENE00014186
caenorhabditis_elegans		WBGENE00015869
caenorhabditis_elegans		WBGENE00016777
caenorhabditis_elegans		WBGENE00022062
caenorhabditis_elegans		WBGENE00022374

Paralogs (1): NR5A2 (ENSG00000116833)

Protein

Protein identifiers

Steroidogenic factor 1 — Q13285 (reviewed: Q13285)

Alternative names: Adrenal 4-binding protein, Fushi tarazu factor homolog 1, Nuclear receptor subfamily 5 group A member 1, Steroid hormone receptor Ad4BP

All UniProt accessions (5): Q13285, F1D8R8, F1DAM0, Q5T6F6, Q5T6F7

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator. Essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5’-YCAAGGYC-3’ and 5’-RRAGGTCA-3’ are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. Binds phosphatidylcholine. Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.

Subunit / interactions. Binds DNA as a monomer. Interacts with NR0B2 and PPARGC1A. Part of a complex consisting of SFPQ, NONO and NR5A1. Interacts with NCOA2. Interacts with DGKQ and CDK7. Binds to and activated by HIPK3.

Subcellular location. Nucleus.

Tissue specificity. High expressed in the adrenal cortex, the ovary, the testis, and the spleen.

Post-translational modifications. Acetylation stimulates the transcriptional activity. Sumoylation reduces CDK7-mediated phosphorylation on Ser-203. Phosphorylated on Ser-203 by CDK7. This phosphorylation promotes transcriptional activity.

Disease relevance. 46,XY sex reversal 3 (SRXY3) [MIM:612965] A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. The disease is caused by variants affecting the gene represented in this entry. 46,XX sex reversal 4 (SRXX4) [MIM:617480] A condition in which male gonads develop in a genetic female (female to male sex reversal). The disease is caused by variants affecting the gene represented in this entry. Adrenal insufficiency, NR5A1-related (AINR) [MIM:612964] A disorder characterized by adrenal insufficiency, muscular hypotonia, decreased sodium and increased potassium levels, elevated ACTH, salt-wasting crisis, prolonged jaundice, hypoglycemia, and vomiting. The disease is caused by variants affecting the gene represented in this entry. Premature ovarian failure 7 (POF7) [MIM:612964] An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. The disease is caused by variants affecting the gene represented in this entry. Spermatogenic failure 8 (SPGF8) [MIM:613957] An infertility disorder characterized by spermatogenesis failure and severe oligozoospermia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the nuclear hormone receptor family. NR5 subfamily.

RefSeq proteins (1): NP_004950* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR016355	NR5-like	Family
IPR035500	NHR-like_dom_sf	Homologous_superfamily

Pfam: PF00104, PF00105

UniProt features (67 total): sequence variant 22, helix 12, mutagenesis site 8, binding site 6, modified residue 4, strand 4, cross-link 2, zinc finger region 2, region of interest 2, chain 1, domain 1, DNA-binding region 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1ZDT	X-RAY DIFFRACTION	2.1
4QJR	X-RAY DIFFRACTION	2.4
7KHT	X-RAY DIFFRACTION	2.5
8DAF	X-RAY DIFFRACTION	2.59
4QK4	X-RAY DIFFRACTION	2.81
1YOW	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13285-F1	78.83	0.53

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 (6): 436; 436; 440; 440; 341; 341

Post-translational modifications (6): 34, 38, 72, 203, 119, 194

Mutagenesis-validated functional residues (8):

Position	Phenotype
119	loss of sumoylation; when associated with r-194.
194	loss of sumoylation.
269	strongly reduced transactivation.
341	reduced transactivation. strongly reduced transactivation; when associated with f-344.
344	reduced transactivation. strongly reduced transactivation; when associated with e-341.
433	strongly reduced transactivation.
436	loss of transactivation; when associated with a-440.
440	loss of transactivation; when associated with f-436.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-4090294	SUMOylation of intracellular receptors
R-HSA-452723	Transcriptional regulation of pluripotent stem cells
R-HSA-9690406	Transcriptional regulation of testis differentiation
R-HSA-1266738	Developmental Biology
R-HSA-212436	Generic Transcription Pathway
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 548 (showing top): GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, WALLACE_PROSTATE_CANCER_RACE_UP, TGCGCANK_UNKNOWN, GCM_MSN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_MALE_SEX_DETERMINATION, GOBP_REGULATION_OF_HORMONE_LEVELS, HSIAO_HOUSEKEEPING_GENES, GOBP_SEX_DETERMINATION, TATTATA_MIR374, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, AP2_Q3, BROWNE_HCMV_INFECTION_12HR_UP

GO Biological Process (25): luteinization (GO:0001553), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), sex determination (GO:0007530), primary sex determination (GO:0007538), male gonad development (GO:0008584), female gonad development (GO:0008585), hormone-mediated signaling pathway (GO:0009755), tissue development (GO:0009888), positive regulation of gene expression (GO:0010628), male sex determination (GO:0030238), adrenal gland development (GO:0030325), Leydig cell differentiation (GO:0033327), hormone metabolic process (GO:0042445), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of steroid biosynthetic process (GO:0050810), maintenance of protein location in nucleus (GO:0051457), Sertoli cell differentiation (GO:0060008), response to gonadotropin-releasing hormone (GO:0097210), calcineurin-mediated signaling (GO:0097720), positive regulation of male gonad development (GO:2000020), negative regulation of female gonad development (GO:2000195), regulation of DNA-templated transcription (GO:0006355), intracellular receptor signaling pathway (GO:0030522), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (17): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coregulator binding (GO:0001221), DNA binding (GO:0003677), chromatin binding (GO:0003682), nuclear receptor activity (GO:0004879), phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), lipid binding (GO:0008289), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Developmental Biology	2
Generic Transcription Pathway	1
SUMO E3 ligases SUMOylate target proteins	1
RNA Polymerase II Transcription	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	3
binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
multicellular organism development	2
sex determination	2
gonad development	2
male gonad development	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA binding	2
female gonad development	1
ovulation cycle process	1
DNA-templated transcription	1
development of primary male sexual characteristics	1
development of primary female sexual characteristics	1
signal transduction	1
cellular response to hormone stimulus	1
anatomical structure development	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
endocrine system development	1
gland development	1
cell differentiation	1
metabolic process	1
regulation of hormone levels	1
positive regulation of DNA-templated transcription	1
steroid biosynthetic process	1
regulation of steroid metabolic process	1
regulation of lipid biosynthetic process	1
nucleus	1
protein localization to nucleus	1
maintenance of protein localization in organelle	1
epithelial cell differentiation	1
response to peptide hormone	1
calcium-mediated signaling	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

1996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR5A1	NR0B1	P51843	986
NR5A1	FOXL2	P58012	926
NR5A1	STAR	P49675	920
NR5A1	AMH	P03971	898
NR5A1	CYP11A1	P05108	876
NR5A1	SRY	Q05066	858
NR5A1	CYP17A1	P05093	849
NR5A1	WT1	P19544	845
NR5A1	SOX9	P48436	835
NR5A1	CYP19A1	P11511	834
NR5A1	CYP11B2	P19099	829
NR5A1	LHX9	Q9NQ69	798
NR5A1	CYP11B1	P15538	787
NR5A1	INSL3	P51460	775
NR5A1	DDX20	Q9UHI6	745

IntAct

89 interactions, top by confidence:

A	B	Type	Score
NR0B1	NR5A1	psi-mi:“MI:0915”(physical association)	0.810
NR5A1	NCK1	psi-mi:“MI:0915”(physical association)	0.610
NCK1	NR5A1	psi-mi:“MI:0407”(direct interaction)	0.610
NR5A1	NCK2	psi-mi:“MI:0915”(physical association)	0.560
NCK2	NR5A1	psi-mi:“MI:0915”(physical association)	0.560
RFC5	NR5A1	psi-mi:“MI:0915”(physical association)	0.560
NR5A1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
NR5A1	C2CD6	psi-mi:“MI:0915”(physical association)	0.560
NR5A1	TEKT4	psi-mi:“MI:0915”(physical association)	0.560
CKS1B	NR5A1	psi-mi:“MI:0915”(physical association)	0.560
ASAH1	NR5A1	psi-mi:“MI:0914”(association)	0.550
NR5A1	ASAH1	psi-mi:“MI:0914”(association)	0.550
NR5A1	ASAH1	psi-mi:“MI:0915”(physical association)	0.550
	NR5A1	psi-mi:“MI:0914”(association)	0.530
NR5A1		psi-mi:“MI:0914”(association)	0.530
NR5A1	ASAH1	psi-mi:“MI:0915”(physical association)	0.520
ASAH1	NR5A1	psi-mi:“MI:0915”(physical association)	0.520
NR5A1	PNRC2	psi-mi:“MI:0915”(physical association)	0.490
PNRC2	NR5A1	psi-mi:“MI:0915”(physical association)	0.490
CYP17A1	NR5A1	psi-mi:“MI:0914”(association)	0.460
	NR5A1	psi-mi:“MI:0914”(association)	0.460

BioGRID (61): NR5A1 (Two-hybrid), NCK2 (Two-hybrid), NR5A1 (Biochemical Activity), NR5A1 (Affinity Capture-Western), TRAPPC2 (Two-hybrid), NR5A1 (Synthetic Lethality), NR5A1 (Two-hybrid), NRIP1 (Two-hybrid), NRIP1 (Two-hybrid), NR5A1 (Two-hybrid), NR5A1 (Proximity Label-MS), STMN1 (Negative Genetic), P2RY6 (Negative Genetic), PRKCZ (Negative Genetic), NR5A1 (Positive Genetic)

ESM2 similar proteins: O08580, O09017, O09018, O75064, O95718, P10588, P10589, P11474, P11475, P12813, P22736, P22829, P24468, P28702, P28704, P33242, P43135, P43136, P49743, P49870, P50569, P51666, P54779, P55055, P79387, Q03181, Q04752, Q06725, Q0V8F0, Q0ZAQ8, Q13285, Q3U1Y4, Q5BIS6, Q5QJV7, Q5TJF7, Q60632, Q60644, Q61539, Q62755, Q6QMY5

Diamond homologs: A0JNE3, A2T928, A4IIG7, G5ECR9, G5EDJ0, O02151, O45666, O76202, O97716, P10276, P10588, P10826, P10827, P10828, P11416, P12813, P13056, P13631, P16376, P18117, P18514, P18515, P18516, P18911, P20153, P22448, P22449, P22605, P22736, P22829, P28699, P31396, P33242, P33244, P41828, P41830, P43354, P45447, P49116, P49117

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
AR	up-regulates	NR5A1	binding
CDK7	up-regulates	NR5A1	phosphorylation
NR5A1	“down-regulates quantity by repression”	CYP11B2	“transcriptional regulation”
NR5A1	“up-regulates quantity by expression”	HSD3B2	“transcriptional regulation”
NR5A1	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
NR5A1	“up-regulates quantity by expression”	CYP19A1	“transcriptional regulation”
TFIIH	up-regulates	NR5A1	phosphorylation
NR0B1	“down-regulates activity”	NR5A1	binding
CLK4	“up-regulates activity”	NR5A1	phosphorylation
PTEN	“down-regulates activity”	NR5A1	dephosphorylation
MAPK1	“up-regulates activity”	NR5A1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	6	47.6×	1e-06
RHOU GTPase cycle	5	29.0×	7e-05
FCGR3A-mediated phagocytosis	6	23.4×	2e-05
VEGFA-VEGFR2 Pathway	6	17.4×	8e-05
mRNA Polyadenylation	7	12.8×	8e-05
mRNA Splicing	5	11.4×	2e-03
mRNA Splicing - Major Pathway	10	11.4×	3e-06
Processing of Capped Intron-Containing Pre-mRNA	6	10.3×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	35.0×	6e-06
mRNA splicing, via spliceosome	9	14.0×	6e-06
mRNA processing	7	9.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	48
Uncertain significance	120
Likely benign	62
Benign	29

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1031482	NM_004959.5(NR5A1):c.637_640dup (p.Pro214fs)	Pathogenic
1068954	NM_004959.5(NR5A1):c.232_244del (p.Met78fs)	Pathogenic
1075535	NM_004959.5(NR5A1):c.75C>G (p.Tyr25Ter)	Pathogenic
1075935	NM_004959.5(NR5A1):c.572del (p.Arg191fs)	Pathogenic
1202586	NM_004959.5(NR5A1):c.244+1G>T	Pathogenic
1202587	NM_004959.5(NR5A1):c.218G>A (p.Cys73Tyr)	Pathogenic
1202588	NM_004959.5(NR5A1):c.104G>A (p.Gly35Asp)	Pathogenic
1202604	NM_004959.5(NR5A1):c.1223A>C (p.His408Pro)	Pathogenic
1256020	NM_004959.5(NR5A1):c.559del (p.Ala187fs)	Pathogenic
12794	NM_004959.5(NR5A1):c.104_105delinsAA (p.Gly35Glu)	Pathogenic
12796	NM_004959.5(NR5A1):c.275G>A (p.Arg92Gln)	Pathogenic
12797	NM_004959.5(NR5A1):c.1058_1065del (p.Glu353fs)	Pathogenic
12798	NM_004959.5(NR5A1):c.48C>A (p.Cys16Ter)	Pathogenic
12799	NM_004959.5(NR5A1):c.18del (p.Asp6fs)	Pathogenic
12800	NM_004959.5(NR5A1):c.43G>A (p.Val15Met)	Pathogenic
12801	NM_004959.5(NR5A1):c.234G>A (p.Met78Ile)	Pathogenic
12803	NM_004959.5(NR5A1):c.1310T>A (p.Leu437Gln)	Pathogenic
12804	NM_004959.5(NR5A1):c.666del (p.Asn222fs)	Pathogenic
12805	NM_004959.5(NR5A1):c.877G>A (p.Asp293Asn)	Pathogenic
12806	NM_004959.5(NR5A1):c.3G>A (p.Met1Ile)	Pathogenic
12807	NM_004959.5(NR5A1):c.390del (p.Pro131fs)	Pathogenic
12808	NM_004959.5(NR5A1):c.682CTGCAGCTG[1] (p.228LQL[1])	Pathogenic
1338234	NM_004959.5(NR5A1):c.958G>T (p.Glu320Ter)	Pathogenic
1341694	NM_004959.5(NR5A1):c.19G>T (p.Glu7Ter)	Pathogenic
1342834	NM_004959.5(NR5A1):c.1048C>T (p.Arg350Trp)	Pathogenic
1354651	NM_004959.5(NR5A1):c.231del (p.Met78fs)	Pathogenic
1412226	NM_004959.5(NR5A1):c.895C>T (p.Gln299Ter)	Pathogenic
1454827	NM_004959.5(NR5A1):c.984del (p.Gln329fs)	Pathogenic
1687524	NM_004959.5(NR5A1):c.11C>A (p.Ser4Ter)	Pathogenic
1687572	NM_004959.5(NR5A1):c.259C>T (p.Arg87Cys)	Pathogenic

SpliceAI

1669 predictions. Top by Δscore:

Variant	Effect	Δscore
9:124491076:CTCA:C	donor_loss	1.0000
9:124491079:A:AC	donor_gain	1.0000
9:124491079:AC:A	donor_gain	1.0000
9:124491079:ACC:A	donor_gain	1.0000
9:124491080:C:CC	donor_gain	1.0000
9:124491080:CC:C	donor_gain	1.0000
9:124491080:CCC:C	donor_gain	1.0000
9:124491236:C:CT	acceptor_gain	1.0000
9:124500086:TCA:T	donor_loss	1.0000
9:124500087:CAC:C	donor_loss	1.0000
9:124503288:GCTCA:G	donor_loss	1.0000
9:124503290:TCAC:T	donor_loss	1.0000
9:124503291:CA:C	donor_loss	1.0000
9:124503292:A:T	donor_loss	1.0000
9:124503293:C:G	donor_loss	1.0000
9:124503407:CCGC:C	acceptor_gain	1.0000
9:124503408:CGC:C	acceptor_gain	1.0000
9:124503408:CGCC:C	acceptor_gain	1.0000
9:124503411:C:CC	acceptor_gain	1.0000
9:124503412:T:A	acceptor_loss	1.0000
9:124482775:G:A	donor_gain	0.9900
9:124483005:TC:T	acceptor_loss	0.9900
9:124483006:C:CA	acceptor_loss	0.9900
9:124483007:T:G	acceptor_loss	0.9900
9:124491080:CCCA:C	donor_gain	0.9900
9:124491080:CCCAG:C	donor_gain	0.9900
9:124491224:TCCAC:T	acceptor_gain	0.9900
9:124491225:CCAC:C	acceptor_gain	0.9900
9:124491225:CCACC:C	acceptor_gain	0.9900
9:124491226:CAC:C	acceptor_gain	0.9900

AlphaMissense

2999 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:124500660:C:A	K100N	1.000
9:124500660:C:G	K100N	1.000
9:124500665:A:G	Y99H	1.000
9:124500673:C:T	G96E	1.000
9:124500674:C:G	G96R	1.000
9:124500674:C:T	G96R	1.000
9:124500675:A:C	F95L	1.000
9:124500675:A:T	F95L	1.000
9:124500676:A:G	F95S	1.000
9:124500677:A:G	F95L	1.000
9:124500681:G:C	N93K	1.000
9:124500681:G:T	N93K	1.000
9:124500688:C:T	G91D	1.000
9:124500689:C:A	G91C	1.000
9:124500689:C:G	G91R	1.000
9:124500691:C:T	G90D	1.000
9:124500692:C:A	G90C	1.000
9:124500692:C:G	G90R	1.000
9:124500693:C:A	R89S	1.000
9:124500693:C:G	R89S	1.000
9:124500694:C:A	R89M	1.000
9:124500694:C:G	R89T	1.000
9:124500701:G:T	R87S	1.000
9:124500710:G:A	R84C	1.000
9:124500710:G:T	R84S	1.000
9:124500712:A:T	V83E	1.000
9:124503089:C:A	M78I	1.000
9:124503089:C:G	M78I	1.000
9:124503089:C:T	M78I	1.000
9:124503090:A:C	M78R	1.000

dbSNP variants (sampled 300 via entrez): RS1000081942 (9:124483681 C>G,T), RS1000228894 (9:124481077 C>A,G,T), RS1000268927 (9:124507216 C>T), RS1000305511 (9:124489172 T>A), RS1000457574 (9:124500919 C>T), RS1000569654 (9:124490079 C>T), RS1000628748 (9:124495435 C>T), RS1000696267 (9:124484901 C>G), RS1000893549 (9:124507935 A>T), RS1000919547 (9:124490404 G>A), RS1000924440 (9:124509040 T>C), RS1000931551 (9:124504624 C>A,T), RS1001058691 (9:124494009 G>A), RS1001186530 (9:124492465 G>T), RS1001301515 (9:124497941 C>G,T)

Disease associations

OMIM: gene MIM:184757 | disease phenotypes: MIM:258150, MIM:617480, MIM:612965, MIM:613957, MIM:612964

GenCC curated gene-disease

Disease	Classification	Inheritance
premature ovarian failure 7	Strong	Autosomal dominant
46,XY sex reversal 3	Strong	Autosomal dominant
46,XX sex reversal 4	Strong	Autosomal dominant
inherited primary ovarian failure	Strong	Autosomal dominant
46,XX disorder of sex development	Moderate	Autosomal recessive
46,XX ovotesticular disorder of sex development	Supportive	Autosomal dominant
46,XY complete gonadal dysgenesis	Supportive	Autosomal dominant
46 XX gonadal dysgenesis	Supportive	Autosomal dominant
46,XY partial gonadal dysgenesis	Supportive	Autosomal dominant
46,XX sex reversal 1	Supportive	Autosomal dominant
male infertility with azoospermia or oligozoospermia due to single gene mutation	Supportive	Autosomal dominant
spermatogenic failure 8	Limited	Autosomal dominant

Mondo (16): spermatogenic failure 1 (MONDO:0009776), 46 XY differences of sex development (MONDO:0020040), 46,XX sex reversal 4 (MONDO:0060489), male infertility (MONDO:0005372), disorder of sexual differentiation (MONDO:0002145), 46,XY sex reversal 3 (MONDO:0013066), spermatogenic failure 8 (MONDO:0013504), premature ovarian failure 7 (MONDO:0013065), 46,XY partial gonadal dysgenesis (MONDO:0016674), 46,XX ovotesticular disorder of sex development (MONDO:0016281), 46,XY complete gonadal dysgenesis (MONDO:0010765), 46 XX gonadal dysgenesis (MONDO:0009299), (MONDO:0010766), (MONDO:0018393), 46,XX disorder of sex development (MONDO:0017576)

Orphanet (5): 46,XY difference of sex development (Orphanet:98085), Difference of sex development (Orphanet:90771), Rare genetic premature ovarian failure (Orphanet:485382), 46,XY partial gonadal dysgenesis (Orphanet:251510), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805)

HPO phenotypes

88 total (30 of 88 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000013	Hypoplasia of the uterus
HP:0000022	Abnormal male internal genitalia morphology
HP:0000026	Male hypogonadism
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000030	Testicular gonadoblastoma
HP:0000037	Male pseudohermaphroditism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000045	Abnormal scrotum morphology
HP:0000046	Small scrotum
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000054	Micropenis
HP:0000058	Abnormal labia morphology
HP:0000062	Ambiguous genitalia
HP:0000100	Nephrotic syndrome
HP:0000118	Phenotypic abnormality
HP:0000130	Abnormality of the uterus
HP:0000133	Gonadal dysgenesis
HP:0000142	Abnormal vagina morphology
HP:0000144	Decreased fertility
HP:0000147	Polycystic ovaries
HP:0000149	Ovarian gonadoblastoma
HP:0000150	Gonadoblastoma
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007576_434	Chronotype	7.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D058489	46, XX Disorders of Sex Development	C12.050.351.875.253.064; C12.200.706.316.064; C12.800.316.064; C16.131.939.316.064; C19.391.119.064
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
D023961	Gonadal Dysgenesis, 46,XX	C12.050.351.875.253.064.249; C12.050.351.875.253.309.193; C12.200.706.316.064.249; C12.200.706.316.309.193; C12.800.316.064.249; C12.800.316.309.193; C16.131.939.316.064.249; C16.131.939.316.309.193; C19.391.119.064.249; C19.391.119.309.193
D006061	Gonadal Dysgenesis, 46,XY	C12.050.351.875.253.096.687; C12.050.351.875.253.309.388; C12.200.706.316.096.687; C12.200.706.316.309.388; C12.800.316.096.687; C12.800.316.309.388; C16.131.939.316.096.687; C16.131.939.316.309.388; C19.391.119.096.687; C19.391.119.309.388
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D050090	Ovotesticular Disorders of Sex Development	C12.050.351.875.253.343; C12.200.706.316.343; C12.800.316.343; C16.131.939.316.343; C19.391.119.343
C562902	Oligosynaptic Infertility (supp.)
C567838	Premature Ovarian Failure 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4666 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 5A. Fushi tarazu F1-like receptors

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
RJW100	Agonist	7.5	pEC50

Binding affinities (BindingDB)

545 measured of 851 human assays (876 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-methylpropyl 6-(furan-2-yl)-3-methyl-4-oxidanylidene-1,5,6,7-tetrahydroindole-2-carboxylate	EC50	0.00157 nM
MLS000056567	EC50	0.0113 nM
2-[[5-cyano-2-keto-4-(5-methyl-2-furyl)-3,4-dihydro-1H-pyridin-6-yl]thio]acetic acid ethyl ester	EC50	0.0249 nM
(3aS,6aR)-4-cyclohexyl-5-[(4E)-oct-4-en-4-yl]-N-phenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	12 nM
(3aS,6aR)-4-butyl-5-[(4E)-oct-4-en-4-yl]-N-phenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	22 nM
(3aS,6aR)-N-(2,3-dimethylphenyl)-5-hexyl-4-phenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	30 nM
(3aS,6aR)-5-hexyl-N,4-diphenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	34 nM
BMCL181297 Compound 5A	IC50	40 nM
3-[3-(4-tert-butylphenyl)-1,2,4-oxadiazol-5-yl]-N-ethyl-propanamide	IC50	45.8 nM
3-[3-(4-tert-butylphenyl)-1,2,4-oxadiazol-5-yl]propanamide	IC50	47.9 nM
3-[3-(4-tert-butylphenyl)-1,2,4-oxadiazol-5-yl]-N-methyl-propanamide	IC50	52 nM
(3aS,6aR)-4-(naphthalen-2-yl)-5-[(4E)-oct-4-en-4-yl]-N-phenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	60 nM
(3aS,6aR)-5-(hexan-2-yl)-N,4-diphenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	70 nM
1-Ethyl-6-methyl-3-thiophen-2-yl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	IC50	72.2 nM
PODOFILOX	IC50	81 nM
(3aS,6aR)-4-methyl-5-[(4E)-oct-4-en-4-yl]-N-phenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	90 nM
(Z)-1-(1,3-benzodioxol-5-yl)-3-(2-bromoanilino)-2-propen-1-one	EC50	96 nM
(3aS,6aR)-4-(3-methoxyphenyl)-5-[(4E)-oct-4-en-4-yl]-N-phenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	100 nM
MLS000056239	IC50	106 nM
ethyl 2-[(2-{[(4-ethylphenyl)carbamoyl]methyl}-1-oxo-1,2-dihydroisoquinolin-5-yl)oxy]propanoate	EC50	110 nM
2-methyl-6-phenyl-3-(1-pyrrolyl)-4-thieno[2,3-d]pyrimidinone	EC50	112 nM
MLS000064750	IC50	113 nM
MLS001074108	IC50	134 nM
2-({[2-(4-ethoxyphenyl)-5-methyl-1,3-oxazol-4-yl]methyl}thio)-N-(2-furylmethyl)acetamide	IC50	140 nM
(3aS,6aR)-N,4,5-triphenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	150 nM
(3aS,6aR)-4-(4-bromophenyl)-5-[(4E)-oct-4-en-4-yl]-N-phenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	160 nM
5-bromanyl-N-(pyridin-4-ylmethyl)thiophene-2-sulfonamide	IC50	185 nM
ethyl 2-[(2-{[(4-ethoxyphenyl)carbamoyl]methyl}-1-oxo-1,2-dihydroisoquinolin-5-yl)oxy]propanoate	EC50	190 nM
ethyl 2-[(2-{[(4-methoxyphenyl)carbamoyl]methyl}-1-oxo-1,2-dihydroisoquinolin-5-yl)oxy]propanoate	EC50	200 nM
ethyl 2-{[1-oxo-2-({[4-(trifluoromethoxy)phenyl]carbamoyl}methyl)-1,2-dihydroisoquinolin-5-yl]oxy}propanoate	EC50	200 nM
cid_426728	IC50	212 nM
(2-phenyl-1,3-thiazol-4-yl)methyl 1-methylpyrrole-2-carboxylate	EC50	221 nM
3-[(4-ethoxyphenoxy)methyl]benzoic acid	IC50	225 nM
(3aS,6aR)-5-cyclohexyl-N,4-diphenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	230 nM
[7-(2-ethoxyethanoylamino)-1,2-dimethoxy-10-methylsulfanyl-9-oxidanylidene-6,7-dihydro-5H-benzo[a]heptalen-3-yl] 2-ethoxyethanoate	IC50	244 nM
1-azepanyl-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl]methanone	EC50	282 nM
3-[(2-chloro-4-methylol-phenoxy)methyl]benzoic acid	IC50	288 nM
2-(1-propyl-4-pyridinylidene)indene-1,3-dione	IC50	296 nM
MLS000077996	EC50	317 nM
(3aS,6aR)-5-(decan-2-yl)-N,4-diphenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	320 nM
(3aS,6aR)-N-(3-fluorophenyl)-5-hexyl-4-phenyl-1,2,3,3a,6,6a-hexahydropentalen-3a-amine	EC50	330 nM
ethyl 2-[(2-{[(4-methylphenyl)carbamoyl]methyl}-1-oxo-1,2-dihydroisoquinolin-5-yl)oxy]propanoate	EC50	340 nM
2-[(1-bicyclo[2.2.1]hept-2-yl-1H-tetrazol-5-yl)thio]-N-4-quinolinylacetamide	IC50	353 nM
7-amino-3-phenyl-6-pyrazolo[1,5-a]pyrimidinecarboxylic acid ethyl ester	EC50	356 nM
ethyl 2-[(1-oxo-2-{[(2-phenylethyl)carbamoyl]methyl}-1,2-dihydroisoquinolin-5-yl)oxy]propanoate	EC50	360 nM
ethyl 2-[(2-{[(4-butylphenyl)carbamoyl]methyl}-1-oxo-1,2-dihydroisoquinolin-5-yl)oxy]propanoate	EC50	360 nM
3-[(4-methoxyphenoxy)methyl]benzoic acid	IC50	370 nM
4-acetyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-3,5-dimethyl-1H-pyrrole-2-carboxamide	EC50	400 nM
5-(4-butylcyclohexyl)-3-(2-pyridinyl)-1,2,4-oxadiazole	EC50	403 nM
MLS000100813	IC50	409 nM

ChEMBL bioactivities

75 potent at pChembl≥5 of 77 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	EC50	10	nM	CHEMBL384424
7.96	EC50	11	nM	CHEMBL216179
7.91	Kd	12.3	nM	CHEMBL4515639
7.85	EC50	14	nM	CHEMBL214414
7.52	EC50	30	nM	CHEMBL425623
7.52	IC50	30	nM	CHEMBL259067
7.50	EC50	31.62	nM	CHEMBL1765959
7.40	EC50	39.81	nM	CHEMBL1765953
7.40	EC50	39.81	nM	CHEMBL384153
7.37	EC50	43	nM	CHEMBL384153
7.27	EC50	54	nM	CHEMBL385911
7.20	EC50	63.1	nM	CHEMBL1765960
7.20	EC50	63.1	nM	CHEMBL1765955
7.20	EC50	63.1	nM	CHEMBL1765934
7.20	EC50	63.1	nM	CHEMBL1765933
7.20	EC50	63.1	nM	CHEMBL1765956
7.10	EC50	79.43	nM	CHEMBL1765962
7.10	EC50	79.43	nM	CHEMBL1765931
6.96	IC50	110	nM	CHEMBL408947
6.92	EC50	120	nM	CHEMBL409954
6.90	EC50	125.9	nM	CHEMBL1765945
6.89	EC50	130	nM	CHEMBL214076
6.89	EC50	130	nM	CHEMBL213816
6.89	EC50	130	nM	CHEMBL216778
6.85	EC50	140	nM	CHEMBL410341
6.80	EC50	158.5	nM	CHEMBL385911
6.80	EC50	158.5	nM	CHEMBL1765954
6.80	EC50	158.5	nM	CHEMBL1765941
6.80	EC50	158.5	nM	CHEMBL1765936
6.77	EC50	170	nM	CHEMBL384937
6.75	EC50	180	nM	CHEMBL217106
6.72	IC50	190	nM	CHEMBL265938
6.70	IC50	200	nM	CHEMBL410467
6.70	IC50	200	nM	CHEMBL262079
6.70	EC50	199.5	nM	CHEMBL1765966
6.70	EC50	199.5	nM	CHEMBL1765950
6.70	EC50	199.5	nM	CHEMBL1765942
6.70	EC50	199.5	nM	CHEMBL1765930
6.70	EC50	199.5	nM	CHEMBL1765927
6.60	EC50	251.2	nM	CHEMBL1765963
6.60	EC50	251.2	nM	CHEMBL1765948
6.60	EC50	251.2	nM	CHEMBL1765929
6.58	IC50	260	nM	CHEMBL408702
6.50	EC50	316.2	nM	CHEMBL1765964
6.50	EC50	316.2	nM	CHEMBL1765957
6.47	IC50	340	nM	CHEMBL412079
6.44	IC50	360	nM	CHEMBL411889
6.44	IC50	360	nM	CHEMBL412080
6.40	EC50	398.1	nM	CHEMBL1765961
6.40	EC50	398.1	nM	CHEMBL1765947

PubChem BioAssay actives

111 with measured affinity, of 207 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3aS,6aR)-4-cyclohexyl-5-[(E)-oct-4-en-4-yl]-N-phenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.0100	uM
(3aS,6aR)-N-(2,3-dimethylphenyl)-5-hexyl-4-phenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.0110	uM
10-[(3aR,6S,6aR)-3-phenyl-3a-(1-phenylethenyl)-6-(sulfamoylamino)-4,5,6,6a-tetrahydro-1H-pentalen-2-yl]-N-(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)decanamide	1547896: Binding affinity to SF1 LBD (218 to 461 residues) (unknown origin) expressed in Escherichia coli BL21 pLysS measured after overnight incubation by fluorescence polarization assay	kd	0.0123	uM
(3aS,6aR)-5-[(E)-dodec-6-en-6-yl]-N,4-diphenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.0140	uM
(3aS,6aR)-4-butyl-5-[(E)-oct-4-en-4-yl]-N-phenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.0300	uM
ethyl 2-[2-[2-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate	1547904: Inhibition of Gal4-fused human SF1 LBD (198 to 462 residues) expressed in CHO-K1 cells	ic50	0.0300	uM
(1R,3aR,6aR)-5-hexyl-4-phenyl-3a-(1-phenylethenyl)-2,3,6,6a-tetrahydro-1H-pentalen-1-ol	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0316	uM
(3aS,6aR)-5-hexyl-N,4-diphenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0398	uM
(3aR,6aR)-5-butyl-6-phenyl-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0398	uM
(3aS,6aR)-5-[(E)-oct-4-en-4-yl]-N,4-diphenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.0540	uM
(3aR,6aR)-5-hexyl-6-phenyl-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0631	uM
(3aR,6aR)-5-hexyl-6a-[1-(3-methoxyphenyl)ethenyl]-6-phenyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0631	uM
[(3aR,6aR)-3-phenyl-3a-(1-phenylethenyl)-4,5,6,6a-tetrahydro-1H-pentalen-2-yl]-dimethyl-phenylsilane	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0631	uM
(1S,3aR,6aR)-5-hexyl-4-phenyl-3a-(1-phenylethenyl)-2,3,6,6a-tetrahydro-1H-pentalen-1-ol	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0631	uM
(3aR,7aR)-2-hexyl-3-phenyl-3a-(1-phenylethenyl)-1,4,5,6,7,7a-hexahydroindene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0631	uM
(3aR,6aS)-6a-cyclohexyloxy-5-hexyl-6-phenyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0794	uM
[(1S,3aR,6aR)-5-hexyl-4-phenyl-3a-(1-phenylethenyl)-2,3,6,6a-tetrahydro-1H-pentalen-1-yl] acetate	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.0794	uM
ethyl 2-[2-[2-(4-ethylanilino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate	1798910: Transactivation Cell-Based Assay from Article 10.1016/j.bmcl.2008.03.027: “Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.”	ec50	0.1100	uM
(3aS,6aR)-N,4,5-triphenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.1200	uM
(3aR,6aR)-5-hexyl-6-(3-methoxyphenyl)-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1259	uM
(3aS,6aR)-4-naphthalen-2-yl-5-[(E)-oct-4-en-4-yl]-N-phenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.1300	uM
(3aS,6aR)-5-hexan-2-yl-N,4-diphenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.1300	uM
(3aS,6aR)-5-decan-2-yl-N,4-diphenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.1300	uM
(3aS,6aR)-4-(3-methoxyphenyl)-5-[(E)-oct-4-en-4-yl]-N-phenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.1400	uM
(3aR,6aR)-5-hexyl-6a-[1-(4-methylphenyl)ethenyl]-6-phenyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1585	uM
(3aR,6aR)-5-hexyl-6a-pent-1-en-2-yl-6-phenyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1585	uM
(3aR,6aR)-5-octyl-6-phenyl-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1585	uM
(3aS,6aR)-4-(4-bromophenyl)-5-[(E)-oct-4-en-4-yl]-N-phenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.1700	uM
(3aS,6aR)-5-cyclohexyl-N,4-diphenyl-2,3,6,6a-tetrahydro-1H-pentalen-3a-amine	1798186: FRET Assay for LRH-1 from Article 10.1021/jm060990k: “Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.”	ec50	0.1800	uM
ethyl 2-[2-[2-(4-ethoxyanilino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate	1798910: Transactivation Cell-Based Assay from Article 10.1016/j.bmcl.2008.03.027: “Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.”	ec50	0.1900	uM
(3aR,6aS)-5-hexyl-6-phenyl-6a-propoxy-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1995	uM
(3aR,6aS)-5-hexyl-6a-(2-methylbutoxy)-6-phenyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1995	uM
(3aR,6aR)-6a-hex-1-en-2-yl-5-hexyl-6-phenyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1995	uM
(3aR,6aR)-6-cyclohexyl-5-hexyl-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1995	uM
[(2R,3aS,6aR)-5-hexyl-6-phenyl-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalen-2-yl] acetate	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.1995	uM
ethyl 2-[2-[2-(4-methoxyanilino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate	1798910: Transactivation Cell-Based Assay from Article 10.1016/j.bmcl.2008.03.027: “Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.”	ec50	0.2000	uM
ethyl 2-[1-oxo-2-[2-oxo-2-[4-(trifluoromethoxy)anilino]ethyl]isoquinolin-5-yl]oxypropanoate	1798910: Transactivation Cell-Based Assay from Article 10.1016/j.bmcl.2008.03.027: “Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.”	ec50	0.2000	uM
(2S,3aS,6aR)-5-hexyl-6-phenyl-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalen-2-ol	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.2512	uM
(3aR,6aS)-6a-butoxy-5-hexyl-6-phenyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.2512	uM
(3aR,6aS)-6-butyl-5-hexyl-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.2512	uM
ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate	1798910: Transactivation Cell-Based Assay from Article 10.1016/j.bmcl.2008.03.027: “Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.”	ec50	0.2600	uM
(3aS,6aR)-5-hexyl-2-methyl-4-phenyl-3a-(1-phenylethenyl)-1,3,6,6a-tetrahydrocyclopenta[c]pyrrole	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.3162	uM
(2R,3aS,6aR)-5-hexyl-6-phenyl-6a-(1-phenylethenyl)-2,3,3a,4-tetrahydro-1H-pentalen-2-ol	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.3162	uM
ethyl 2-[2-[2-(4-methylanilino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate	1798910: Transactivation Cell-Based Assay from Article 10.1016/j.bmcl.2008.03.027: “Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.”	ec50	0.3400	uM
ethyl 2-[1-oxo-2-[2-oxo-2-(2-phenylethylamino)ethyl]isoquinolin-5-yl]oxypropanoate	1798910: Transactivation Cell-Based Assay from Article 10.1016/j.bmcl.2008.03.027: “Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.”	ec50	0.3600	uM
ethyl 2-[2-[2-(4-butylanilino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate	1798910: Transactivation Cell-Based Assay from Article 10.1016/j.bmcl.2008.03.027: “Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.”	ec50	0.3600	uM
[(1R,3aR,6aR)-5-hexyl-4-phenyl-3a-(1-phenylethenyl)-2,3,6,6a-tetrahydro-1H-pentalen-1-yl] acetate	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.3981	uM
(3aR,6aS)-5-hexyl-6-phenyl-6a-propan-2-yloxy-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.3981	uM
(3aR,6aS)-5-hexyl-6a-pentoxy-6-phenyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.3981	uM
(3aR,6aS)-5-hexyl-6a-(1-phenylethenyl)-6-propyl-2,3,3a,4-tetrahydro-1H-pentalene	593529: Agonist activity at human SF-1 assessed as DAX1 1-23 peptide recruitment by TR-FRET assay relative to control	ec50	0.3981	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Atrazine	affects binding, increases activity, increases expression, increases reaction, increases phosphorylation (+1 more)	4
25-hydroxycholesterol	increases expression, increases reaction, increases activity	2
27-hydroxycholesterol	increases expression, increases reaction, increases activity	2
Benzo(a)pyrene	increases expression, increases methylation	2
Bucladesine	affects binding, decreases reaction, increases expression	2
Estradiol	increases activity, decreases response to substance, decreases reaction	2
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	decreases reaction, increases expression, decreases expression	1
22-hydroxycholesterol	increases expression, increases reaction	1
bisphenol A	decreases expression	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	increases expression, decreases expression, decreases reaction	1
benzo(e)pyrene	increases methylation	1
bafilomycin A1	decreases expression	1
tetrachlorodian	decreases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
U 0126	decreases reaction, increases activity	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
quinocetone	affects expression, decreases reaction	1
pyrachlostrobin	decreases expression	1
GSK 8470	affects binding, increases activity	1
2-(4-hydroxyphenyl)-3-phenylpent-2-enoic acid (4-(2-dimethylaminoethoxy)phenyl)amide	increases activity, increases phosphorylation	1
picoxystrobin	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Wortmannin	decreases reaction, increases activity	1
Decitabine	affects methylation	1

ChEMBL screening assays

88 unique, capped per target: 84 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1767443	Functional	Inverse agonist activity at SF-1	Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2). — J Med Chem
CHEMBL1961867	Binding	Effect on SF1(NR5A1) dependent reporter activity in HEK293 cells at 20 uM	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — Nature

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4X4	SEES3-1V human NR5A1, clone1	Embryonic stem cell	Male
CVCL_A4X5	SEES3-1V human NR5A1, clone2	Embryonic stem cell	Male
CVCL_A4X6	SEES3-1V human NR5A1, clone3	Embryonic stem cell	Male
CVCL_A6XP	LCHi002-A	Induced pluripotent stem cell	Male
CVCL_A6XQ	LCHi002-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
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