Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOULYR4)

• DOT Name: Steroidogenic factor 1 (NR5A1)
• Synonyms: SF-1; STF-1; hSF-1; Adrenal 4-binding protein; Fushi tarazu factor homolog 1; Nuclear receptor subfamily 5 group A member 1; Steroid hormone receptor Ad4BP
• Gene Name: NR5A1
• Related Disease:
  Turner syndrome
  46,XX sex reversal 4
  46,XX testicular disorder of sex development
  46,XY disorder of sex development
  46,XY sex reversal 2
  46,XY sex reversal 3
  Addison disease
  Adenoma
  Adrenocortical carcinoma
  Azoospermia
  Childhood kidney Wilms tumor
  Colon carcinoma
  Disorder of sexual differentiation
  Endometriosis
  Epithelial ovarian cancer
  Female hypogonadism
  Gonadal dysgenesis
  Huntington disease
  Hyperaldosteronism
  Hypogonadotropic hypogonadism
  Klinefelter syndrome
  Lung carcinoma
  Neoplasm
  Ovarian cancer
  Ovarian dysgenesis 1
  Ovarian neoplasm
  Premature ovarian failure 1
  Premature ovarian failure 7
  Primary adrenal insufficiency
  Primary aldosteronism
  Wilms tumor
  X-linked adrenal hypoplasia congenita
  46,XX sex reversal 1
  Advanced cancer
  46 XX gonadal dysgenesis
  46,XX ovotesticular disorder of sex development
  46,XY complete gonadal dysgenesis
  46,XY partial gonadal dysgenesis
  Obsolete 46,XX sex reversal 1
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
  Aplasia cutis congenita
  Corpus callosum, agenesis of
  Cryptorchidism
  Germ cell tumor
  Obesity
  Oligospermia
  Spermatogenic failure 8
• UniProt ID: STF1_HUMAN
• PDB ID: 1YOW; 1ZDT; 4QJR; 4QK4; 7KHT; 8DAF
• Pfam ID: PF00104 ; PF00105
• Sequence:
  MDYSYDEDLDELCPVCGDKVSGYHYGLLTCESCKGFFKRTVQNNKHYTCTESQSCKIDKT
  QRKRCPFCRFQKCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQIRANGFKL
  ETGPPMGVPPPPPPAPDYVLPPSLHGPEPKGLAAGPPAGPLGDFGAPALPMAVPGAHGPL
  AGYLYPAFPGRAIKSEYPEPYASPPQPGLPYGYPEPFSGGPNVPELILQLLQLEPDEDQV
  RARILGCLQEPTKSRPDQPAAFGLLCRMADQTFISIVDWARRCMVFKELEVADQMTLLQN
  CWSELLVFDHIYRQVQHGKEGSILLVTGQEVELTTVATQAGSLLHSLVLRAQELVLQLLA
  LQLDRQEFVCLKFIILFSLDLKFLNNHILVKDAQEKANAALLDYTLCHYPHCGDKFQQLL
  LCLVEVRALSMQAKEYLYHKHLGNEMPRNNLLIEMLQAKQT
• 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.
• Tissue Specificity: High expressed in the adrenal cortex, the ovary, the testis, and the spleen .
• KEGG Pathway:
  Cortisol synthesis and secretion (hsa04927)
  Cushing syndrome (hsa04934)
• Reactome Pathway:
  SUMOylation of intracellular receptors (R-HSA-4090294)
  Transcriptional regulation of pluripotent stem cells (R-HSA-452723)
  Transcriptional regulation of testis differentiation (R-HSA-9690406)
  Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Turner syndrome	DIS2035C	Definitive	Genetic Variation	[1]
46,XX sex reversal 4	DISMUNZZ	Strong	Autosomal dominant	[2]
46,XX testicular disorder of sex development	DISTZBTV	Strong	Genetic Variation	[3]
46,XY disorder of sex development	DIS78CGG	Strong	Genetic Variation	[1]
46,XY sex reversal 2	DIS0USUN	Strong	Biomarker	[4]
46,XY sex reversal 3	DISJ0VQH	Strong	Autosomal dominant	[5]
Addison disease	DIS7HNOH	Strong	Genetic Variation	[6]
Adenoma	DIS78ZEV	Strong	Altered Expression	[7]
Adrenocortical carcinoma	DISZF4HX	Strong	Altered Expression	[8]
Azoospermia	DIS94181	Strong	Genetic Variation	[9]
Childhood kidney Wilms tumor	DIS0NMK3	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Disorder of sexual differentiation	DISRMAEZ	Strong	Genetic Variation	[12]
Endometriosis	DISX1AG8	Strong	Altered Expression	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[14]
Female hypogonadism	DISWASB4	Strong	Biomarker	[15]
Gonadal dysgenesis	DISIL2ZI	Strong	Genetic Variation	[1]
Huntington disease	DISQPLA4	Strong	Genetic Variation	[16]
Hyperaldosteronism	DIS3WGAL	Strong	Altered Expression	[17]
Hypogonadotropic hypogonadism	DIS8JSKR	Strong	Altered Expression	[18]
Klinefelter syndrome	DISOUI7W	Strong	Altered Expression	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[14]
Ovarian dysgenesis 1	DISXIXHW	Strong	Genetic Variation	[21]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[14]
Premature ovarian failure 1	DISYHHEN	Strong	Biomarker	[22]
Premature ovarian failure 7	DISR5L24	Strong	Autosomal dominant	[22]
Primary adrenal insufficiency	DISNMBYU	Strong	Genetic Variation	[6]
Primary aldosteronism	DISOEFNH	Strong	Biomarker	[23]
Wilms tumor	DISB6T16	Strong	Biomarker	[10]
X-linked adrenal hypoplasia congenita	DISNMXY8	Strong	Biomarker	[24]
46,XX sex reversal 1	DISRDCZR	moderate	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[25]
46 XX gonadal dysgenesis	DISBB9HA	Supportive	Autosomal dominant	[26]
46,XX ovotesticular disorder of sex development	DISQO3XF	Supportive	Autosomal dominant	[2]
46,XY complete gonadal dysgenesis	DISLF3LT	Supportive	Autosomal dominant	[27]
46,XY partial gonadal dysgenesis	DISMNH0C	Supportive	Autosomal dominant	[28]
Obsolete 46,XX sex reversal 1	DIS79VJ6	Supportive	Autosomal dominant	[2]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Supportive	Autosomal dominant	[29]
Aplasia cutis congenita	DISMDAYM	Limited	Biomarker	[30]
Corpus callosum, agenesis of	DISO9P40	Limited	Biomarker	[30]
Cryptorchidism	DISYUD2P	Limited	Genetic Variation	[31]
Germ cell tumor	DIS62070	Limited	Altered Expression	[32]
Obesity	DIS47Y1K	Limited	Genetic Variation	[33]
Oligospermia	DIS6YJF3	Limited	Altered Expression	[32]
Spermatogenic failure 8	DISTFDQP	Limited	Autosomal dominant	[29]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Steroidogenic factor 1 (NR5A1) increases the abundance of Progesterone.	[45]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Steroidogenic factor 1 (NR5A1).	[34]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Steroidogenic factor 1 (NR5A1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Steroidogenic factor 1 (NR5A1).	[40]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the activity of Steroidogenic factor 1 (NR5A1).	[35]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Steroidogenic factor 1 (NR5A1).	[37]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Steroidogenic factor 1 (NR5A1).	[38]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Steroidogenic factor 1 (NR5A1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Steroidogenic factor 1 (NR5A1).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Steroidogenic factor 1 (NR5A1).	[39]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Steroidogenic factor 1 (NR5A1).	[42]
Forskolin	DM6ITNG	Investigative	Forskolin affects the expression of Steroidogenic factor 1 (NR5A1).	[43]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the activity of Steroidogenic factor 1 (NR5A1).	[44]
Bafilomycin A1	DMUNK59	Investigative	Bafilomycin A1 decreases the expression of Steroidogenic factor 1 (NR5A1).	[38]
25-hydroxycholesterol	DMCHAQ7	Investigative	25-hydroxycholesterol increases the activity of Steroidogenic factor 1 (NR5A1).	[44]

References

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