Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3Z51KH)

• DOT Name: Transmembrane anterior posterior transformation protein 1 homolog (TAPT1)
• Synonyms: Cytomegalovirus partial fusion receptor
• Gene Name: TAPT1
• Related Disease:
  Ciliopathy
  Complex lethal osteochondrodysplasia
  Morquio syndrome
  Osteochondrodysplasia
  Osteogenesis imperfecta
  Obesity
• UniProt ID: TAPT1_HUMAN
• Pfam ID: PF05346
• Sequence:
  MAGVGDAAAPGEGGGGGVDGPQRDGRGEAEQPGGSGGQGPPPAPQLTETLGFYESDRRRE
  RRRGRTELSLLRFLSAELTRGYFLEHNEAKYTERRERVYTCLRIPRELEKLMVFGIFLCL
  DAFLYVFTLLPLRVFLALFRLLTLPCYGLRDRRLLQPAQVCDILKGVILVICYFMMHYVD
  YSMMYHLIRGQSVIKLYIIYNMLEVADRLFSSFGQDILDALYWTATEPKERKRAHIGVIP
  HFFMAVLYVFLHAILIMVQATTLNVAFNSHNKSLLTIMMSNNFVEIKGSVFKKFEKNNLF
  QMSNSDIKERFTNYVLLLIVCLRNMEQFSWNPDHLWVLFPDVCMVIASEIAVDIVKHAFI
  TKFNDITADVYSEYRASLAFDLVSSRQKNAYTDYSDSVARRMGFIPLPLAVLLIRVVTSS
  IKVQGILSYACVILFYFGLISLKVLNSIVLLGKSCQYVKEAKMEEKLSNPPATCTPGKPS
  SKSQNKCKPSQGLSTEENLSASITKQPIHQKENIIPLLVTSNSDQFLTTPDGDEKDITQD
  NSELKHRSSKKDLLEIDRFTICGNRID
• Function: Plays a role in primary cilia formation. May act as a downstream effector of HOXC8 possibly by transducing or transmitting extracellular information required for axial skeletal patterning during development. May be involved in cartilage and bone development. May play a role in the differentiation of cranial neural crest cells; (Microbial infection) In case of infection, may act as a fusion receptor for cytomegalovirus (HCMV) strain AD169.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[1]
Complex lethal osteochondrodysplasia	DISD9O8G	Strong	Autosomal recessive	[2]
Morquio syndrome	DIS2Y2P2	Strong	Genetic Variation	[1]
Osteochondrodysplasia	DIS9SPWW	Strong	Genetic Variation	[1]
Osteogenesis imperfecta	DIS7XQSD	Strong	Biomarker	[1]
Obesity	DIS47Y1K	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transmembrane anterior posterior transformation protein 1 homolog (TAPT1).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transmembrane anterior posterior transformation protein 1 homolog (TAPT1).	[8]

3 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 Transmembrane anterior posterior transformation protein 1 homolog (TAPT1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transmembrane anterior posterior transformation protein 1 homolog (TAPT1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane anterior posterior transformation protein 1 homolog (TAPT1).	[7]

References

• [1] Genetic Defects in TAPT1 Disrupt Ciliogenesis and Cause a Complex Lethal Osteochondrodysplasia. Am J Hum Genet. 2015 Oct 1;97(4):521-34. doi: 10.1016/j.ajhg.2015.08.009. Epub 2015 Sep 10.
• [2] Mutation of a ubiquitously expressed mouse transmembrane protein (Tapt1) causes specific skeletal homeotic transformations. Genetics. 2007 Feb;175(2):699-707. doi: 10.1534/genetics.106.065177. Epub 2006 Dec 6.
• [3] About the existence of common determinants of gene expression in the porcine liver and skeletal muscle.BMC Genomics. 2019 Jun 24;20(1):518. doi: 10.1186/s12864-019-5889-5.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.