Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3JVEGV)

• DOT Name: Kinesin-like protein KIF1A (KIF1A)
• Synonyms: Axonal transporter of synaptic vesicles; Microtubule-based motor KIF1A; Unc-104- and KIF1A-related protein; hUnc-104
• Gene Name: KIF1A
• Related Disease:
  Hereditary spastic paraplegia 10
  Intellectual disability, autosomal dominant 9
  Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability
  Molybdenum cofactor deficiency
  Neuroblastoma
  Neuropathy, hereditary sensory, type 2C
  Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
  Syndromic intellectual disability
  Advanced cancer
  Autism
  Autism spectrum disorder
  Autonomic neuropathy
  Charcot-Marie-Tooth disease type 2
  Complex hereditary spastic paraplegia
  Head-neck squamous cell carcinoma
  Hereditary spastic paraplegia
  Hereditary spastic paraplegia 30
  Intellectual disability
  Neoplasm
  Nervous system disease
  Optic nerve disorder
  Peripheral neuropathy
  Pervasive developmental disorder
  Precancerous condition
  Tuberous sclerosis
  Vascular purpura
  Movement disorder
  Nasopharyngeal carcinoma
  Peripheral sensory neuropathies
  Autosomal dominant non-syndromic intellectual disability
  Hereditary sensory and autonomic neuropathy type 2
  PEHO syndrome
  Benign neoplasm
  Breast cancer
  Breast carcinoma
  Paraplegia
  Rett syndrome
  Stroke
  Type-1/2 diabetes
• UniProt ID: KIF1A_HUMAN
• PDB ID: 4EGX; 4EJQ; 4UXO; 4UXP; 4UXR; 4UXS
• Pfam ID: PF12473 ; PF00498 ; PF12423 ; PF00225 ; PF16183 ; PF00169
• Sequence:
  MAGASVKVAVRVRPFNSREMSRDSKCIIQMSGSTTTIVNPKQPKETPKSFSFDYSYWSHT
  SPEDINYASQKQVYRDIGEEMLQHAFEGYNVCIFAYGQTGAGKSYTMMGKQEKDQQGIIP
  QLCEDLFSRINDTTNDNMSYSVEVSYMEIYCERVRDLLNPKNKGNLRVREHPLLGPYVED
  LSKLAVTSYNDIQDLMDSGNKARTVAATNMNETSSRSHAVFNIIFTQKRHDAETNITTEK
  VSKISLVDLAGSERADSTGAKGTRLKEGANINKSLTTLGKVISALAEMDSGPNKNKKKKK
  TDFIPYRDSVLTWLLRENLGGNSRTAMVAALSPADINYDETLSTLRYADRAKQIRCNAVI
  NEDPNNKLIRELKDEVTRLRDLLYAQGLGDITDMTNALVGMSPSSSLSALSSRAASVSSL
  HERILFAPGSEEAIERLKETEKIIAELNETWEEKLRRTEAIRMEREALLAEMGVAMREDG
  GTLGVFSPKKTPHLVNLNEDPLMSECLLYYIKDGITRVGREDGERRQDIVLSGHFIKEEH
  CVFRSDSRGGSEAVVTLEPCEGADTYVNGKKVTEPSILRSGNRIIMGKSHVFRFNHPEQA
  RQERERTPCAETPAEPVDWAFAQRELLEKQGIDMKQEMEQRLQELEDQYRREREEATYLL
  EQQRLDYESKLEALQKQMDSRYYPEVNEEEEEPEDEVQWTERECELALWAFRKWKWYQFT
  SLRDLLWGNAIFLKEANAISVELKKKVQFQFVLLTDTLYSPLPPDLLPPEAAKDRETRPF
  PRTIVAVEVQDQKNGATHYWTLEKLRQRLDLMREMYDRAAEVPSSVIEDCDNVVTGGDPF
  YDRFPWFRLVGRAFVYLSNLLYPVPLVHRVAIVSEKGEVKGFLRVAVQAISADEEAPDYG
  SGVRQSGTAKISFDDQHFEKFQSESCPVVGMSRSGTSQEELRIVEGQGQGADVGPSADEV
  NNNTCSAVPPEGLLLDSSEKAALDGPLDAALDHLRLGNTFTFRVTVLQASSISAEYADIF
  CQFNFIHRHDEAFSTEPLKNTGRGPPLGFYHVQNIAVEVTKSFIEYIKSQPIVFEVFGHY
  QQHPFPPLCKDVLSPLRPSRRHFPRVMPLSKPVPATKLSTLTRPCPGPCHCKYDLLVYFE
  ICELEANGDYIPAVVDHRGGMPCMGTFLLHQGIQRRITVTLLHETGSHIRWKEVRELVVG
  RIRNTPETDESLIDPNILSLNILSSGYIHPAQDDRTFYQFEAAWDSSMHNSLLLNRVTPY
  REKIYMTLSAYIEMENCTQPAVVTKDFCMVFYSRDAKLPASRSIRNLFGSGSLRASESNR
  VTGVYELSLCHVADAGSPGMQRRRRRVLDTSVAYVRGEENLAGWRPRSDSLILDHQWELE
  KLSLLQEVEKTRHYLLLREKLETAQRPVPEALSPAFSEDSESHGSSSASSPLSAEGRPSP
  LEAPNERQRELAVKCLRLLTHTFNREYTHSHVCVSASESKLSEMSVTLLRDPSMSPLGVA
  TLTPSSTCPSLVEGRYGATDLRTPQPCSRPASPEPELLPEADSKKLPSPARATETDKEPQ
  RLLVPDIQEIRVSPIVSKKGYLHFLEPHTSGWARRFVVVRRPYAYMYNSDKDTVERFVLN
  LATAQVEYSEDQQAMLKTPNTFAVCTEHRGILLQAASDKDMHDWLYAFNPLLAGTIRSKL
  SRRRSAQMRV
• Function: Motor for anterograde axonal transport of synaptic vesicle precursors. Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons. The interaction calcium-dependent with CALM1 increases vesicle motility and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites.
• Tissue Specificity: Expressed in neurons.
• 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

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary spastic paraplegia 10	DISYFO3L	Definitive	Genetic Variation	[1]
Intellectual disability, autosomal dominant 9	DISWARCU	Definitive	Autosomal dominant	[2]
Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability	DISFHDE1	Definitive	Genetic Variation	[3]
Molybdenum cofactor deficiency	DISKS8QN	Definitive	Genetic Variation	[4]
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[5]
Neuropathy, hereditary sensory, type 2C	DISOPFSN	Definitive	Autosomal recessive	[6]
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	DIS84UUI	Definitive	Genetic Variation	[3]
Syndromic intellectual disability	DISH7SDF	Definitive	Autosomal dominant	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Autism	DISV4V1Z	Strong	Biomarker	[9]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[10]
Autonomic neuropathy	DISI3WJ0	Strong	Genetic Variation	[11]
Charcot-Marie-Tooth disease type 2	DISR30O9	Strong	Biomarker	[2]
Complex hereditary spastic paraplegia	DIS9KXQY	Strong	Genetic Variation	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[13]
Hereditary spastic paraplegia	DISGZQV1	Strong	Genetic Variation	[14]
Hereditary spastic paraplegia 30	DIS97ZN9	Strong	Autosomal recessive	[15]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Nervous system disease	DISJ7GGT	Strong	Genetic Variation	[17]
Optic nerve disorder	DISSOQM8	Strong	CausalMutation	[18]
Peripheral neuropathy	DIS7KN5G	Strong	CausalMutation	[18]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[17]
Precancerous condition	DISV06FL	Strong	Biomarker	[16]
Tuberous sclerosis	DISEMUGZ	Strong	Genetic Variation	[19]
Vascular purpura	DIS6ZZMF	Strong	Biomarker	[20]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[21]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Genetic Variation	[22]
Peripheral sensory neuropathies	DISYWI6M	moderate	Genetic Variation	[23]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[24]
Hereditary sensory and autonomic neuropathy type 2	DIS4TP1G	Supportive	Autosomal recessive	[25]
PEHO syndrome	DISPO5IP	Supportive	Autosomal dominant	[18]
Benign neoplasm	DISDUXAD	Limited	Biomarker	[8]
Breast cancer	DIS7DPX1	Limited	Posttranslational Modification	[26]
Breast carcinoma	DIS2UE88	Limited	Posttranslational Modification	[26]
Paraplegia	DISSKWBI	Limited	Biomarker	[27]
Rett syndrome	DISGG5UV	Limited	Genetic Variation	[28]
Stroke	DISX6UHX	Limited	Biomarker	[29]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	Kinesin-like protein KIF1A (KIF1A) affects the response to substance of Daunorubicin.	[43]

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 Kinesin-like protein KIF1A (KIF1A).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Kinesin-like protein KIF1A (KIF1A).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Kinesin-like protein KIF1A (KIF1A).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kinesin-like protein KIF1A (KIF1A).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kinesin-like protein KIF1A (KIF1A).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Kinesin-like protein KIF1A (KIF1A).	[34]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Kinesin-like protein KIF1A (KIF1A).	[35]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Kinesin-like protein KIF1A (KIF1A).	[36]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Kinesin-like protein KIF1A (KIF1A).	[37]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Kinesin-like protein KIF1A (KIF1A).	[37]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Kinesin-like protein KIF1A (KIF1A).	[38]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kinesin-like protein KIF1A (KIF1A).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Kinesin-like protein KIF1A (KIF1A).	[41]

References

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• [16] Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy.Cancer Prev Res (Phila). 2010 Sep;3(9):1093-103. doi: 10.1158/1940-6207.CAPR-10-0115. Epub 2010 Aug 26.
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• [19] Characterization of a kinesin-related gene ATSV, within the tuberous sclerosis locus (TSC1) candidate region on chromosome 9Q34.Genomics. 1996 May 1;33(3):421-9. doi: 10.1006/geno.1996.0217.
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