Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9MVMLI)

DOT Name	Follicle-stimulating hormone receptor (FSHR)
Synonyms	FSH-R; Follitropin receptor
Gene Name	FSHR
Related Disease	Ovarian dysgenesis 1 ( ) Ovarian hyperstimulation syndrome ( ) 46 XX gonadal dysgenesis ( )
UniProt ID	FSHR_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1XWD; 4AY9; 4MQW; 8I2G; 8I2H
Pfam ID	PF00001 ; PF12369 ; PF13306 ; PF01462
Sequence	MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRV IQKGAFSGFGDLEKIEISQNDVLEVIEADVFSNLPKLHEIRIEKANNLLYINPEAFQNLP NLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVILWLNKN GIQEIHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILDISRTRIHSLPSYGLEN LKKLRARSTYNLKKLPTLEKLVALMEASLTYPSHCCAFANWRRQISELHPICNKSILRQE VDYMTQARGQRSSLAEDNESSYSRGFDMTYTEFDYDLCNEVVDVTCSPKPDAFNPCEDIM GYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLCIGIYLLLIAS VDIHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERWHTITHAMQLDCK VQLRHAASVMVMGWIFAFAAALFPIFGISSYMKVSICLPMDIDSPLSQLYVMSLLVLNVL AFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLCMAPISFFAISASLKVP LITVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSKCGCYEMQAQIYRTETSS TVHNTHPRNGHCSSAPRVTNGSTYILVPLSHLAQN
Function	G protein-coupled receptor for follitropin, the follicle-stimulating hormone. Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways.
Tissue Specificity	Sertoli cells and ovarian granulosa cells.
KEGG Pathway	cAMP sig.ling pathway (hsa04024 ) Neuroactive ligand-receptor interaction (hsa04080 ) Ovarian steroidogenesis (hsa04913 )
Reactome Pathway	G alpha (s) signalling events (R-HSA-418555 ) Hormone ligand-binding receptors (R-HSA-375281 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Ovarian dysgenesis 1	DISXIXHW	Strong	Autosomal recessive	[1]
Ovarian hyperstimulation syndrome	DIS4L94Y	Strong	Autosomal dominant	[2]
46 XX gonadal dysgenesis	DISBB9HA	Supportive	Autosomal dominant	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Follicle-stimulating hormone receptor (FSHR) increases the Neutropenia ADR of Etoposide.	[9]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Follicle-stimulating hormone receptor (FSHR).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Follicle-stimulating hormone receptor (FSHR).	[4]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Follicle-stimulating hormone receptor (FSHR).	[4]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Follicle-stimulating hormone receptor (FSHR).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Follicle-stimulating hormone receptor (FSHR).	[7]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Follicle-stimulating hormone receptor (FSHR).	[8]
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⏷ Show the Full List of 6 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Follicle-stimulating hormone receptor (FSHR).	[6]
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References

1	The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction. Endocrinology. 2000 May;141(5):1795-803. doi: 10.1210/endo.141.5.7456.
2	Follicle-stimulating-hormone receptor and twinning. Lancet. 2001 Jan 20;357(9251):230; author reply 231-2. doi: 10.1016/S0140-6736(05)71328-3.
3	Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995 Sep 22;82(6):959-68. doi: 10.1016/0092-8674(95)90275-9.
4	Treatment with anticancer agents induces dysregulation of specific Wnt signaling pathways in human ovarian luteinized granulosa cells in vitro. Toxicol Sci. 2013 Nov;136(1):183-92. doi: 10.1093/toxsci/kft175. Epub 2013 Aug 16.
5	Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
6	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
7	Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
8	Effects of Cyanobacterial Harmful Algal Bloom Toxin Microcystin-LR on Gonadotropin-Dependent Ovarian Follicle Maturation and Ovulation in Mice. Environ Health Perspect. 2023 Jun;131(6):67010. doi: 10.1289/EHP12034. Epub 2023 Jun 21.
9	Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.