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
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2D Sequence (FASTA)
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3D Structure (PDB)
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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 REF
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) 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.