Details of Drug Off-Target (DOT)

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

• DOT Name: Kinesin-like protein KIF12 (KIF12)
• Gene Name: KIF12
• Related Disease:
  Cholestasis
  Breast cancer
  Cholestasis, progressive familial intrahepatic, 8
  Primary sclerosing cholangitis
  Sclerosing cholangitis
• UniProt ID: KIF12_HUMAN
• Pfam ID: PF00225
• Sequence:
  MEERGSPDGDLARSLEQGPEGPETPIQVVLRVRPMSAAELRRGQQSVLHCSGTRTLQGGP
  EVAFRFGAVLDAARTQEDVFRACGVRRLGELALRGFSCTVFTFGQTGSGKTYTLTGPPPQ
  GEGVPVPPSLAGIMQRTFAWLLDRVQHLGAPVTLRASYLEIYNEQVRDLLSLGSPRPLPV
  RWNKTRGFYVEQLRVVEFGSLEALMELLQTGLSRRRNSAHTLNQASSRSHALLTLYISRQ
  TAQQMPSVDPGEPPVGGKLCFVDLAGSEKVAATGSRGELMLEANSINRSLLALGHCISLL
  LDPQRKQSHIPFRDSKLTKLLADSLGGRGVTLMVACVSPSAQCLPETLSTLRYASRAQRV
  TTRPQAPKSPVAKQPQRLETEMLQLQEENRRLQFQLDQMDCKASGLSGARVAWAQRNLYG
  MLQEFMLENERLRKEKSQLQNSRDLAQNEQRILAQQVHALERRLLSACYHHQQGPGLTPP
  CPCLMAPAPPCHALPPLYSCPCCHICPLCRVPLAHWACLPGEHHLPQVLDPEASGGRPPS
  ARPPPWAPPCSPGSAKCPRERSHSDWTQTRVLAEMLTEEEVVPSAPPLPVRPPKTSPGLR
  GGAGVPNLAQRLEALRDQIGSSLRRGRSQPPCSEGARSPGQVLPPH
• Tissue Specificity: Expressed in fetal liver, adult brain and pancreatic islet as well as in kidney tumors, uterus cancer and pancreatic cancer.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  Kinesins (R-HSA-983189)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholestasis	DISDJJWE	Definitive	Autosomal recessive	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Cholestasis, progressive familial intrahepatic, 8	DIS252DT	Strong	Autosomal recessive	[1]
Primary sclerosing cholangitis	DISTH5WJ	Strong	Genetic Variation	[1]
Sclerosing cholangitis	DIS7GZNB	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Docetaxel	DMDI269	Approved	Kinesin-like protein KIF12 (KIF12) decreases the response to substance of Docetaxel.	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Kinesin-like protein KIF12 (KIF12).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Kinesin-like protein KIF12 (KIF12).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kinesin-like protein KIF12 (KIF12).	[6]

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 Kinesin-like protein KIF12 (KIF12).	[5]

References

• [1] Identification of novel loci for pediatric cholestatic liver disease defined by KIF12, PPM1F, USP53, LSR, and WDR83OS pathogenic variants. Genet Med. 2019 May;21(5):1164-1172. doi: 10.1038/s41436-018-0288-x. Epub 2018 Sep 25.
• [2] Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer. Breast Cancer Res Treat. 2012 Feb;131(3):849-58. doi: 10.1007/s10549-011-1500-8. Epub 2011 Apr 9.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer. Breast Cancer Res Treat. 2012 Feb;131(3):849-58. doi: 10.1007/s10549-011-1500-8. Epub 2011 Apr 9.