Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNXU9QW)

• DOT Name: Transmembrane 4 L6 family member 20 (TM4SF20)
• Gene Name: TM4SF20
• Related Disease: Specific language impairment 5
• UniProt ID: T4S20_HUMAN
• Pfam ID: PF05805
• Sequence:
  MTCCEGWTSCNGFSLLVLLLLGVVLNAIPLIVSLVEEDQFSQNPISCFEWWFPGIIGAGL
  MAIPATTMSLTARKRACCNNRTGMFLSSLFSVITVIGALYCMLISIQALLKGPLMCNSPS
  NSNANCEFSLKNISDIHPESFNLQWFFNDSCAPPTGFNKPTSNDTMASGWRASSFHFDSE
  ENKHRLIHFSVFLGLLLVGILEVLFGLSQIVIGFLGCLCGVSKRRSQIV
• Function: Polytopic transmembrane protein that inhibits regulated intramembrane proteolysis (RIP) of CREB3L1, inhibiting its activation and the induction of collagen synthesis. In response to ceramide, which alters TM4SF20 membrane topology, stimulates RIP activation of CREB3L1. Ceramide reverses the direction through which transmembrane helices are translocated into the endoplasmic reticulum membrane during translation of TM4SF20, this mechanism is called 'regulated alternative translocation' (RAT) and regulates the function of the transmembrane protein.
• Tissue Specificity: Expressed in the brain, with high levels in the parietal lobe, hippocampus, pons, white matter and cerebellum.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Specific language impairment 5	DIS4PPKA	Limited	Autosomal dominant	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	Transmembrane 4 L6 family member 20 (TM4SF20) affects the response to substance of Daunorubicin.	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transmembrane 4 L6 family member 20 (TM4SF20).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane 4 L6 family member 20 (TM4SF20).	[3]

References

• [1] TM4SF20 ancestral deletion and susceptibility to a pediatric disorder of early language delay and cerebral white matter hyperintensities. Am J Hum Genet. 2013 Aug 8;93(2):197-210. doi: 10.1016/j.ajhg.2013.05.027. Epub 2013 Jun 27.
• [2] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [3] Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
• [4] Mapping genes that contribute to daunorubicin-induced cytotoxicity. Cancer Res. 2007 Jun 1;67(11):5425-33. doi: 10.1158/0008-5472.CAN-06-4431.