Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT8DXKS)

• DOT Name: SH2 domain-containing protein 6 (SH2D6)
• Gene Name: SH2D6
• Related Disease:
  Pervasive developmental disorder
  Deafness
  Autism spectrum disorder
• UniProt ID: SH2D6_HUMAN
• Pfam ID: PF00017
• Sequence:
  MDKLSGSRPRLGPPLPPPRCVDSPGWREDAPSPSFLPAPGTWRHKAQEEDEEENKYELPP
  CEALPLSLAPAHLPGTEEDSLYLDHSGPLGPSKPSPPLPQPTMLKGAVSLPVAGKQGPIF
  GRREQGASSRVVPGPPKKPDEDLYLECEPDPVLALTQTLSFQVLMPSGPLPRTSVVPRPT
  TAPQETRNGTADAASKEGRKSSLPSVAPTGSASAAEDSDLLTQPWYSGNCDRYAVESALL
  HLQKDGAYTVRPSSGPHGSQPFTLAVLLRGRVFNIPIRRLDGGRHYALGREGRNREELFS
  SVAAMVQHFMWHPLPLVDRHSGSRELTCLLFPTKP

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[1]
Deafness	DISKCLH4	moderate	Biomarker	[2]
Autism spectrum disorder	DISXK8NV	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SH2 domain-containing protein 6 (SH2D6).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of SH2 domain-containing protein 6 (SH2D6).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH2 domain-containing protein 6 (SH2D6).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SH2 domain-containing protein 6 (SH2D6).	[5]

References

• [1] ELMOD3-SH2D6 gene fusion as a possible co-star actor in autism spectrum disorder scenario.J Cell Mol Med. 2020 Jan;24(2):2064-2069. doi: 10.1111/jcmm.14733. Epub 2019 Dec 4.
• [2] Homozygous 2p11.2 deletion supports the implication of ELMOD3 in hearing loss and reveals the potential association of CAPG with ASD/ID etiology.J Appl Genet. 2019 Feb;60(1):49-56. doi: 10.1007/s13353-018-0472-3. Epub 2018 Oct 4.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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.