Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIU393R)

• DOT Name: NKAP-like protein (NKAPL)
• Gene Name: NKAPL
• Related Disease:
  Rheumatoid arthritis
  Schizophrenia
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: NKAPL_HUMAN
• Pfam ID: PF15692 ; PF06047
• Sequence:
  MPPVSRSSYSEDIVGSRRRRRSSSGSPPSPQSRCSSWDGCSRSHSRGREGLRPPWSELDV
  GALYPFSRSGSRGRLPRFRNYAFASSWSTSYSGYRYHRHCYAEERQSAEDYEKEESHRQR
  RLKERERIGELGAPEVWGPSPKFPQLDSDEHTPVEDEEEVTHQKSSSSDSNSEEHRKKKT
  SRSRNKKKRKNKSSKRKHRKYSDSDSNSESDTNSDSDDDKKRVKAKKKKKKKKHKTKKKK
  NKKTKKESSDSSCKDSEEDLSEATWMEQPNVADTMDLIGPEAPIIHTSQDEKPLKYGHAL
  LPGEGAAMAEYVKAGKRIPRRGEIGLTSEEIGSFECSGYVMSGSRHRRMEAVRLRKENQI
  YSADEKRALASFNQEERRKRESKILASFREMVHKKTKEKDDK
• Function: Transcriptional repressor of Notch-mediated signaling. Required for spermatogenesis.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Limited	Posttranslational Modification	[3]
Neoplasm	DISZKGEW	Limited	Posttranslational Modification	[3]

3 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 NKAP-like protein (NKAPL).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of NKAP-like protein (NKAPL).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of NKAP-like protein (NKAPL).	[6]

References

• [1] 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.
• [2] Further evidence supporting the association of NKAPL with schizophrenia.Neurosci Lett. 2015 Sep 25;605:49-52. doi: 10.1016/j.neulet.2015.08.023. Epub 2015 Aug 18.
• [3] Hypermethylation of NF-B-Activating Protein-Like (NKAPL) Promoter in Hepatocellular Carcinoma Suppresses Its Expression and Predicts a Poor Prognosis.Dig Dis Sci. 2018 Mar;63(3):676-686. doi: 10.1007/s10620-018-4929-3. Epub 2018 Jan 20.
• [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] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.