Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSVIJ6I)

• DOT Name: Lutropin-choriogonadotropic hormone receptor (LHCGR)
• Synonyms: LH/CG-R; Luteinizing hormone receptor; LHR; LSH-R
• Gene Name: LHCGR
• Related Disease:
  Familial male-limited precocious puberty
  Leydig cell hypoplasia, type 1
• UniProt ID: LSHR_HUMAN
• PDB ID: 7FIG; 7FIH; 7FII; 7FIJ
• Pfam ID: PF00001 ; PF13306
• Sequence:
  MKQRFSALQLLKLLLLLQPPLPRALREALCPEPCNCVPDGALRCPGPTAGLTRLSLAYLP
  VKVIPSQAFRGLNEVIKIEISQIDSLERIEANAFDNLLNLSEILIQNTKNLRYIEPGAFI
  NLPRLKYLSICNTGIRKFPDVTKVFSSESNFILEICDNLHITTIPGNAFQGMNNESVTLK
  LYGNGFEEVQSHAFNGTTLTSLELKENVHLEKMHNGAFRGATGPKTLDISSTKLQALPSY
  GLESIQRLIATSSYSLKKLPSRETFVNLLEATLTYPSHCCAFRNLPTKEQNFSHSISENF
  SKQCESTVRKVNNKTLYSSMLAESELSGWDYEYGFCLPKTPRCAPEPDAFNPCEDIMGYD
  FLRVLIWLINILAIMGNMTVLFVLLTSRYKLTVPRFLMCNLSFADFCMGLYLLLIASVDS
  QTKGQYYNHAIDWQTGSGCSTAGFFTVFASELSVYTLTVITLERWHTITYAIHLDQKLRL
  RHAILIMLGGWLFSSLIAMLPLVGVSNYMKVSICFPMDVETTLSQVYILTILILNVVAFF
  IICACYIKIYFAVRNPELMATNKDTKIAKKMAILIFTDFTCMAPISFFAISAAFKVPLIT
  VTNSKVLLVLFYPINSCANPFLYAIFTKTFQRDFFLLLSKFGCCKRRAELYRRKDFSAYT
  SNCKNGFTGSNKPSQSTLKLSTLHCQGTALLDKTRYTEC
• Function: Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
• Tissue Specificity: Gonadal and thyroid cells.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Ovarian steroidogenesis (hsa04913)
  Prolactin sig.ling pathway (hsa04917)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Hormone ligand-binding receptors (R-HSA-375281)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial male-limited precocious puberty	DISNNKVB	Strong	Autosomal dominant	[1]
Leydig cell hypoplasia, type 1	DISIX1DZ	Strong	Autosomal recessive	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Lutropin-choriogonadotropic hormone receptor (LHCGR) increases the Blood luteinising hormone increased ADR of Estradiol.	[6]
Progesterone	DMUY35B	Approved	Lutropin-choriogonadotropic hormone receptor (LHCGR) increases the Blood luteinising hormone increased ADR of Progesterone.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Lutropin-choriogonadotropic hormone receptor (LHCGR).	[3]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Lutropin-choriogonadotropic hormone receptor (LHCGR).	[5]

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 increases the methylation of Lutropin-choriogonadotropic hormone receptor (LHCGR).	[4]

References

• [1] Substitution of M398T in the second transmembrane helix of the LH receptor in a patient with familial male-limited precocious puberty. Endocr J. 2000 Oct;47(5):595-9. doi: 10.1507/endocrj.47.595.
• [2] Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice. Mol Endocrinol. 2001 Jan;15(1):172-83. doi: 10.1210/mend.15.1.0582.
• [3] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [4] 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.
• [5] 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.
• [6] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.