Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT97M1TR)

• DOT Name: Neuron navigator 3 (NAV3)
• Synonyms: Pore membrane and/or filament-interacting-like protein 1; Steerin-3; Unc-53 homolog 3; unc53H3
• Gene Name: NAV3
• Related Disease:
  Adenoma
  Autism
  Carcinoma
  Colorectal carcinoma
  Marinesco-Sjogren syndrome
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Clear cell renal carcinoma
  Diabetic kidney disease
  Major depressive disorder
  Melanoma
  Mood disorder
  Mycosis fungoides
  Neoplasm
  Nervous system neoplasm
  Neuroblastoma
  Opioid dependence
  Osteoarthritis
  Ovarian neoplasm
  Papillary renal cell carcinoma
  Primary cutaneous T-cell lymphoma
  Renal cell carcinoma
  T-cell lymphoma
  Acute myelogenous leukaemia
  Endometrial carcinoma
  Lung cancer
  Sezary syndrome
• UniProt ID: NAV3_HUMAN
• Pfam ID: PF00004 ; PF00307
• Sequence:
  MPVLGVASKLRQPAVGSKPVHTALPIPNLGTTGSQHCSSRPLELTETESSMLSCQLALKS
  TCEFGEKKPLQGKAKEKEDSKIYTDWANHYLAKSGHKRLIKDLQQDIADGVLLAEIIQII
  ANEKVEDINGCPRSQSQMIENVDVCLSFLAARGVNVQGLSAEEIRNGNLKAILGLFFSLS
  RYKQQQHHQQQYYQSLVELQQRVTHASPPSEASQAKTQQDMQSSLAARYATQSNHSGIAT
  SQKKPTRLPGPSRVPAAGSSSKVQGASNLNRRSQSFNSIDKNKPPNYANGNEKDSSKGPQ
  SSSGVNGNVQPPSTAGQPPASAIPSPSASKPWRSKSMNVKHSATSTMLTVKQSSTATSPT
  PSSDRLKPPVSEGVKTAPSGQKSMLEKFKLVNARTALRPPQPPSSGPSDGGKDDDAFSES
  GEMEGFNSGLNSGGSTNSSPKVSPKLAPPKAGSKNLSNKKSLLQPKEKEEKNRDKNKVCT
  EKPVKEEKDQVTEMAPKKTSKIASLIPKGSKTTAAKKESLIPSSSGIPKPGSKVPTVKQT
  ISPGSTASKESEKFRTTKGSPSQSLSKPITMEKASASSCPAPLEGREAGQASPSGSCTMT
  VAQSSGQSTGNGAVQLPQQQQHSHPNTATVAPFIYRAHSENEGTALPSADSCTSPTKMDL
  SYSKTAKQCLEEISGEDPETRRMRTVKNIADLRQNLEETMSSLRGTQISHSTLETTFDST
  VTTEVNGRTIPNLTSRPTPMTWRLGQACPRLQAGDAPSLGAGYPRSGTSRFIHTDPSRFM
  YTTPLRRAAVSRLGNMSQIDMSEKASSDLDMSSEVDVGGYMSDGDILGKSLRTDDINSGY
  MTDGGLNLYTRSLNRIPDTATSRDIIQRGVHDVTVDADSWDDSSSVSSGLSDTLDNISTD
  DLNTTSSVSSYSNITVPSRKNTQLRTDSEKRSTTDETWDSPEELKKPEEDFDSHGDAGGK
  WKTVSSGLPEDPEKAGQKASLSVSQTGSWRRGMSAQGGAPSRQKAGTSALKTPGKTDDAK
  ASEKGKAPLKGSSLQRSPSDAGKSSGDEGKKPPSGIGRSTATSSFGFKKPSGVGSSAMIT
  SSGATITSGSATLGKIPKSAAIGGKSNAGRKTSLDGSQNQDDVVLHVSSKTTLQYRSLPR
  PSKSSTSGIPGRGGHRSSTSSIDSNVSSKSAGATTSKLREPTKIGSGRSSPVTVNQTDKE
  KEKVAVSDSESVSLSGSPKSSPTSASACGAQGLRQPGSKYPDIASPTFRRLFGAKAGGKS
  ASAPNTEGVKSSSVMPSPSTTLARQGSLESPSSGTGSMGSAGGLSGSSSPLFNKPSDLTT
  DVISLSHSLASSPASVHSFTSGGLVWAANMSSSSAGSKDTPSYQSMTSLHTSSESIDLPL
  SHHGSLSGLTTGTHEVQSLLMRTGSVRSTLSESMQLDRNTLPKKGLRYTPSSRQANQEEG
  KEWLRSHSTGGLQDTGNQSPLVSPSAMSSSAAGKYHFSNLVSPTNLSQFNLPGPSMMRSN
  SIPAQDSSFDLYDDSQLCGSATSLEERPRAISHSGSFRDSMEEVHGSSLSLVSSTSSLYS
  TAEEKAHSEQIHKLRRELVASQEKVATLTSQLSANAHLVAAFEKSLGNMTGRLQSLTMTA
  EQKESELIELRETIEMLKAQNSAAQAAIQGALNGPDHPPKDLRIRRQHSSESVSSINSAT
  SHSSIGSGNDADSKKKKKKNWVNSRGSELRSSFKQAFGKKKSTKPPSSHSDIEELTDSSL
  PASPKLPHNAGDCGSASMKPSQSASASPLVWPPKKRQNGPVIYKHRSRICECTEAEAEII
  LQLKSELREKELKLTDIRLEALSSAHHLDQIREAMNRMQNEIEILKAENDRLKAETGNTA
  KPTRPPSESSSSTSSSSSRQSLGLSLNNLNITEAVSSDILLDDAGDATGHKDGRSVKIIV
  SISKGYGRAKDQKSQAYLIGSIGVSGKTKWDVLDGVIRRLFKEYVFRIDTSTSLGLSSDC
  IASYCIGDLIRSHNLEVPELLPCGYLVGDNNIITVNLKGVEENSLDSFVFDTLIPKPITQ
  RYFNLLMEHHRIILSGPSGTGKTYLANKLAEYVITKSGRKKTEDAIATFNVDHKSSKELQ
  QYLANLAEQCSADNNGVELPVVIILDNLHHVGSLSDIFNGFLNCKYNKCPYIIGTMNQGV
  SSSPNLELHHNFRWVLCANHTEPVKGFLGRYLRRKLIEIEIERNIRNNDLVKIIDWIPKT
  WHHLNSFLETHSSSDVTIGPRLFLPCPMDVEGSRVWFMDLWNYSLVPYILEAVREGLQMY
  GKRTPWEDPSKWVLDTYPWSSATLPQESPALLQLRPEDVGYESCTSTKEATTSKHIPQTD
  TEGDPLMNMLMKLQEAANYSSTQSCDSESTSHHEDILDSSLESTL
• Function: Plays a role in cell migration. May be involved in neuron regeneration. May regulate IL2 production by T-cells.
• Tissue Specificity: Highly expressed in brain. Expressed at low levels in heart and placenta. Present in activated T-cells but not in resting T-cells (at protein level). Down-regulated in primary neuroblastoma.

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Definitive	Genetic Variation	[1]
Autism	DISV4V1Z	Definitive	Genetic Variation	[2]
Carcinoma	DISH9F1N	Definitive	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Genetic Variation	[1]
Marinesco-Sjogren syndrome	DISKEU0B	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Amyloidosis	DISHTAI2	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[6]
Diabetic kidney disease	DISJMWEY	Strong	Genetic Variation	[7]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[8]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[9]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[8]
Mycosis fungoides	DIS62RB8	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[3]
Nervous system neoplasm	DIS141UP	Strong	Genetic Variation	[3]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[3]
Opioid dependence	DIS6WEHK	Strong	Biomarker	[11]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[12]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[13]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[6]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Biomarker	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[6]
T-cell lymphoma	DISSXRTQ	Strong	Genetic Variation	[15]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[16]
Endometrial carcinoma	DISXR5CY	Limited	Genetic Variation	[17]
Lung cancer	DISCM4YA	Limited	Biomarker	[18]
Sezary syndrome	DISFMTC7	Limited	Genetic Variation	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Neuron navigator 3 (NAV3) affects the response to substance of Paclitaxel.	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Neuron navigator 3 (NAV3).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuron navigator 3 (NAV3).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neuron navigator 3 (NAV3).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Neuron navigator 3 (NAV3).	[23]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Neuron navigator 3 (NAV3).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Neuron navigator 3 (NAV3).	[25]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Neuron navigator 3 (NAV3).	[26]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Neuron navigator 3 (NAV3).	[27]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Neuron navigator 3 (NAV3).	[26]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Neuron navigator 3 (NAV3).	[28]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Neuron navigator 3 (NAV3).	[27]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Neuron navigator 3 (NAV3).	[30]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Neuron navigator 3 (NAV3).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Neuron navigator 3 (NAV3).	[32]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Neuron navigator 3 (NAV3).	[27]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Neuron navigator 3 (NAV3).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neuron navigator 3 (NAV3).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Neuron navigator 3 (NAV3).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neuron navigator 3 (NAV3).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Neuron navigator 3 (NAV3).	[38]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Neuron navigator 3 (NAV3).	[39]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Neuron navigator 3 (NAV3).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Neuron navigator 3 (NAV3).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Neuron navigator 3 (NAV3).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Neuron navigator 3 (NAV3).	[29]

References

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• [19] Primary cutaneous T-cell lymphomas do not show specific NAV3 gene deletion or translocation.J Invest Dermatol. 2008 Oct;128(10):2458-66. doi: 10.1038/jid.2008.113. Epub 2008 May 29.
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• [38] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [39] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [40] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
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