Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7E1S57)

• DOT Name: Neuroligin-4, Y-linked (NLGN4Y)
• Synonyms: Neuroligin Y
• Gene Name: NLGN4Y
• Related Disease:
  Autism
  Prostate cancer
  Prostate carcinoma
  Acute graft versus host disease
  Anxiety
  Anxiety disorder
  Depression
  Intellectual disability
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
• UniProt ID: NLGNY_HUMAN
• Pfam ID: PF00135
• Sequence:
  MLRPQGLLWLPLLFTSVCVMLNSNVLLWITALAIKFTLIDSQAQYPVVNTNYGKIQGLRT
  PLPSEILGPVEQYLGVPYASPPTGERRFQPPESPSSWTGIRNATQFSAVCPQHLDERFLL
  HDMLPIWFTTSLDTLMTYVQDQNEDCLYLNIYVPMEDDIHEQNSKKPVMVYIHGGSYMEG
  TGNMIDGSILASYGNVIVITINYRLGILGFLSTGDQAAKGNYGLLDQIQALRWIEENVGA
  FGGDPKRVTIFGSGAGASCVSLLTLSHYSEGLFQKAIIQSGTALSSWAVNYQPAKYTRIL
  ADKVGCNMLDTTDMVECLKNKNYKELIQQTITPATYHIAFGPVIDGDVIPDDPQILMEQG
  EFLNYDIMLGVNQGEGLKFVDGIVDNEDGVTPNDFDFSVSNFVDNLYGYPEGKDTLRETI
  KFMYTDWADKENPETRRKTLVALFTDHQWVAPAVATADLHAQYGSPTYFYAFYHHCQSEM
  KPSWADSAHGDEVPYVFGIPMIGPTELFSCNFSKNDVMLSAVVMTYWTNFAKTGDPNQPV
  PQDTKFIHTKPNRFEEVAWSKYNPKDQLYLHIGLKPRVRDHYRATKVAFWLELVPHLHNL
  NEIFQYVSTTTKVPPPDMTSFPYGTRRSPAKIWPTTKRPAITPANNPKHSKDPHKTGPED
  TTVLIETKRDYSTELSVTIAVGASLLFLNILAFAALYYKKDKRRHETHRHPSPQRNTTND
  ITHIQNEEIMSLQMKQLEHDHECESLQAHDTLRLTCPPDYTLTLRRSPDDIPFMTPNTIT
  MIPNTLMGMQPLHTFKTFSGGQNSTNLPHGHSTTRV
• Function: Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members.
• Tissue Specificity: Expressed in fetal and adult brain, prostate and testis.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Genetic Variation	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[2]
Acute graft versus host disease	DIS8KLVM	Strong	Biomarker	[3]
Anxiety	DISIJDBA	Strong	Altered Expression	[4]
Anxiety disorder	DISBI2BT	Strong	Altered Expression	[4]
Depression	DIS3XJ69	Strong	Altered Expression	[4]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[5]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Limited	Y-linked inheritance	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Neuroligin-4, Y-linked (NLGN4Y).	[7]

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 decreases the methylation of Neuroligin-4, Y-linked (NLGN4Y).	[8]

References

• [1] Y chromosome gene copy number and lack of autism phenotype in a male with an isodicentric Y chromosome and absent NLGN4Y expression.Am J Med Genet B Neuropsychiatr Genet. 2019 Oct;180(7):471-482. doi: 10.1002/ajmg.b.32745. Epub 2019 Jun 3.
• [2] Constructing Bayesian networks by integrating gene expression and copy number data identifies NLGN4Y as a novel regulator of prostate cancer progression.Oncotarget. 2016 Oct 18;7(42):68688-68707. doi: 10.18632/oncotarget.11925.
• [3] Chromosome Y-encoded antigens associate with acute graft-versus-host disease in sex-mismatched stem cell transplant.Blood Adv. 2018 Oct 9;2(19):2419-2429. doi: 10.1182/bloodadvances.2018019513.
• [4] Behavioral phenotypes in males with XYY and possible role of increased NLGN4Y expression in autism features.Genes Brain Behav. 2015 Feb;14(2):137-44. doi: 10.1111/gbb.12200. Epub 2015 Feb 1.
• [5] Analysis of the neuroligin 4Y gene in patients with autism.Psychiatr Genet. 2008 Aug;18(4):204-7. doi: 10.1097/YPG.0b013e3282fb7fe6.
• [6] A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.