Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2PJYHX)

• DOT Name: Calsyntenin-2 (CLSTN2)
• Synonyms: Alcadein-gamma; Alc-gamma
• Gene Name: CLSTN2
• Related Disease:
  Classic Hodgkin lymphoma
  Autism
  Dementia
  Liver cancer
  Multiple sclerosis
  Rheumatoid arthritis
  Acute myelogenous leukaemia
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: CSTN2_HUMAN
• Pfam ID: PF00028 ; PF19699
• Sequence:
  MLPGRLCWVPLLLALGVGSGSGGGGDSRQRRLLAAKVNKHKPWIETSYHGVITENNDTVI
  LDPPLVALDKDAPVPFAGEICAFKIHGQELPFEAVVLNKTSGEGRLRAKSPIDCELQKEY
  TFIIQAYDCGAGPHETAWKKSHKAVVHIQVKDVNEFAPTFKEPAYKAVVTEGKIYDSILQ
  VEAIDEDCSPQYSQICNYEIVTTDVPFAIDRNGNIRNTEKLSYDKQHQYEILVTAYDCGQ
  KPAAQDTLVQVDVKPVCKPGWQDWTKRIEYQPGSGSMPLFPSIHLETCDGAVSSLQIVTE
  LQTNYIGKGCDRETYSEKSLQKLCGASSGIIDLLPSPSAATNWTAGLLVDSSEMIFKFDG
  RQGAKVPDGIVPKNLTDQFTITMWMKHGPSPGVRAEKETILCNSDKTEMNRHHYALYVHN
  CRLVFLLRKDFDQADTFRPAEFHWKLDQICDKEWHYYVINVEFPVVTLYMDGATYEPYLV
  TNDWPIHPSHIAMQLTVGACWQGGEVTKPQFAQFFHGSLASLTIRPGKMESQKVISCLQA
  CKEGLDINSLESLGQGIKYHFNPSQSILVMEGDDIGNINRALQKVSYINSRQFPTAGVRR
  LKVSSKVQCFGEDVCISIPEVDAYVMVLQAIEPRITLRGTDHFWRPAAQFESARGVTLFP
  DIKIVSTFAKTEAPGDVKTTDPKSEVLEEMLHNLDFCDILVIGGDLDPRQECLELNHSEL
  HQRHLDATNSTAGYSIYGVGSMSRYEQVLHHIRYRNWRPASLEARRFRIKCSELNGRYTS
  NEFNLEVSILHEDQVSDKEHVNHLIVQPPFLQSVHHPESRSSIQHSSVVPSIATVVIIIS
  VCMLVFVVAMGVYRVRIAHQHFIQETEAAKESEMDWDDSALTITVNPMEKHEGPGHGEDE
  TEGEEEEEAEEEMSSSSGSDDSEEEEEEEGMGRGRHGQNGARQAQLEWDDSTLPY
• Function: Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate synapse formation, and which is involved in learning and memory. Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with neurexin-alpha at the presynaptic membrane.
• Tissue Specificity: Restricted to the brain.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Genetic Variation	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Dementia	DISXL1WY	Strong	Genetic Variation	[3]
Liver cancer	DISDE4BI	Strong	Biomarker	[4]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[5]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[6]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[7]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[8]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Calsyntenin-2 (CLSTN2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calsyntenin-2 (CLSTN2).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Calsyntenin-2 (CLSTN2).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Calsyntenin-2 (CLSTN2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Calsyntenin-2 (CLSTN2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Calsyntenin-2 (CLSTN2).	[14]

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 Calsyntenin-2 (CLSTN2).	[13]

References

• [1] A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.Nat Commun. 2014 Jun 12;5:3856. doi: 10.1038/ncomms4856.
• [2] Features of emotional and social behavioral phenotypes of calsyntenin2 knockout mice.Behav Brain Res. 2017 Aug 14;332:343-354. doi: 10.1016/j.bbr.2017.06.029. Epub 2017 Jun 21.
• [3] Interactive effects of KIBRA and CLSTN2 polymorphisms on episodic memory in old-age unipolar depression.Neuropsychologia. 2014 Sep;62:137-42. doi: 10.1016/j.neuropsychologia.2014.07.020. Epub 2014 Jul 29.
• [4] Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
• [5] Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles.PLoS One. 2013;8(3):e58352. doi: 10.1371/journal.pone.0058352. Epub 2013 Mar 5.
• [6] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [7] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [8] Deep RNA sequencing reveals the dynamic regulation of miRNA, lncRNAs, and mRNAs in osteosarcoma tumorigenesis and pulmonary metastasis.Cell Death Dis. 2018 Jul 10;9(7):772. doi: 10.1038/s41419-018-0813-5.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] 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.
• [14] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.