Details of Drug Off-Target (DOT)

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

• DOT Name: Plexin-A3 (PLXNA3)
• Synonyms: Plexin-4; Semaphorin receptor SEX
• Gene Name: PLXNA3
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Advanced cancer
  Alzheimer disease
  Alzheimer disease 3
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Cataract
  Cystic fibrosis
  Depression
  Endometrial carcinoma
  Endometrium neoplasm
  Focal segmental glomerulosclerosis
  Hepatocellular carcinoma
  High blood pressure
  Major depressive disorder
  Mood disorder
  Multiple sclerosis
  Obesity
  Osteoporosis
  Sleep disorder
  Toxic epidermal necrolysis
  Type-1/2 diabetes
  Sexually transmitted infection
  Li-Fraumeni syndrome
  Diphtheria
  Meniere disease
  Neoplasm
  Type-1 diabetes
• UniProt ID: PLXA3_HUMAN
• Pfam ID: PF08337 ; PF20170 ; PF01437 ; PF01403 ; PF01833 ; PF18020 ; PF17960
• Sequence:
  MPSVCLLLLLFLAVGGALGNRPFRAFVVTDTTLTHLAVHRVTGEVFVGAVNRVFKLAPNL
  TELRAHVTGPVEDNARCYPPPSMRVCAHRLAPVDNINKLLLIDYAARRLVACGSIWQGIC
  QFLRLDDLFKLGEPHHRKEHYLSGAQEPDSMAGVIVEQGQGPSKLFVGTAVDGKSEYFPT
  LSSRKLISDEDSADMFSLVYQDEFVSSQIKIPSDTLSLYPAFDIYYIYGFVSASFVYFLT
  LQLDTQQTLLDTAGEKFFTSKIVRMCAGDSEFYSYVEFPIGCSWRGVEYRLVQSAHLAKP
  GLLLAQALGVPADEDVLFTIFSQGQKNRASPPRQTILCLFTLSNINAHIRRRIQSCYRGE
  GTLALPWLLNKELPCINTPMQINGNFCGLVLNQPLGGLHVIEGLPLLADSTDGMASVAAY
  TYRQHSVVFIGTRSGSLKKVRVDGFQDAHLYETVPVVDGSPILRDLLFSPDHRHIYLLSE
  KQVSQLPVETCEQYQSCAACLGSGDPHCGWCVLRHRCCREGACLGASAPHGFAEELSKCV
  QVRVRPNNVSVTSPGVQLTVTLHNVPDLSAGVSCAFEAAAENEAVLLPSGELLCPSPSLQ
  ELRALTRGHGATRTVRLQLLSKETGVRFAGADFVFYNCSVLQSCMSCVGSPYPCHWCKYR
  HTCTSRPHECSFQEGRVHSPEGCPEILPSGDLLIPVGVMQPLTLRAKNLPQPQSGQKNYE
  CVVRVQGRQQRVPAVRFNSSSVQCQNASYSYEGDEHGDTELDFSVVWDGDFPIDKPPSFR
  ALLYKCWAQRPSCGLCLKADPRFNCGWCISEHRCQLRTHCPAPKTNWMHLSQKGTRCSHP
  RITQIHPLVGPKEGGTRVTIVGENLGLLSREVGLRVAGVRCNSIPAEYISAERIVCEMEE
  SLVPSPPPGPVELCVGDCSADFRTQSEQVYSFVTPTFDQVSPSRGPASGGTRLTISGSSL
  DAGSRVTVTVRDSECQFVRRDAKAIVCISPLSTLGPSQAPITLAIDRANISSPGLIYTYT
  QDPTVTRLEPTWSIINGSTAITVSGTHLLTVQEPRVRAKYRGIETTNTCQVINDTAMLCK
  APGIFLGRPQPRAQGEHPDEFGFLLDHVQTARSLNRSSFTYYPDPSFEPLGPSGVLDVKP
  GSHVVLKGKNLIPAAAGSSRLNYTVLIGGQPCSLTVSDTQLLCDSPSQTGRQPVMVLVGG
  LEFWLGTLHISAERALTLPAMMGLAAGGGLLLLAITAVLVAYKRKTQDADRTLKRLQLQM
  DNLESRVALECKEAFAELQTDINELTNHMDEVQIPFLDYRTYAVRVLFPGIEAHPVLKEL
  DTPPNVEKALRLFGQLLHSRAFVLTFIHTLEAQSSFSMRDRGTVASLTMVALQSRLDYAT
  GLLKQLLADLIEKNLESKNHPKLLLRRTESVAEKMLTNWFTFLLHKFLKECAGEPLFLLY
  CAIKQQMEKGPIDAITGEARYSLSEDKLIRQQIDYKTLTLHCVCPENEGSAQVPVKVLNC
  DSITQAKDKLLDTVYKGIPYSQRPKAEDMDLEWRQGRMTRIILQDEDVTTKIECDWKRLN
  SLAHYQVTDGSLVALVPKQVSAYNMANSFTFTRSLSRYESLLRTASSPDSLRSRAPMITP
  DQETGTKLWHLVKNHDHADHREGDRGSKMVSEIYLTRLLATKGTLQKFVDDLFETVFSTA
  HRGSALPLAIKYMFDFLDEQADQRQISDPDVRHTWKSNCLPLRFWVNVIKNPQFVFDIHK
  NSITDACLSVVAQTFMDSCSTSEHRLGKDSPSNKLLYAKDIPNYKSWVERYYRDIAKMAS
  ISDQDMDAYLVEQSRLHASDFSVLSALNELYFYVTKYRQEILTALDRDASCRKHKLRQKL
  EQIISLVSSDS
• Function: Coreceptor for SEMA3A and SEMA3F. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Regulates the migration of sympathetic neurons, but not of neural crest precursors. Required for normal dendrite spine morphology in pyramidal neurons. May play a role in regulating semaphorin-mediated programmed cell death in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.
• KEGG Pathway: Axon guidance (hsa04360)
• Reactome Pathway:
  SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion (R-HSA-399955)
  CRMPs in Sema3A signaling (R-HSA-399956)
  Sema3A PAK dependent Axon repulsion (R-HSA-399954)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Genetic Variation	[1]
Liver cancer	DISDE4BI	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[5]
Cataract	DISUD7SL	Strong	Biomarker	[6]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[7]
Depression	DIS3XJ69	Strong	Biomarker	[8]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[9]
Endometrium neoplasm	DIS6OS2L	Strong	Biomarker	[9]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[11]
High blood pressure	DISY2OHH	Strong	Biomarker	[12]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[3]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[13]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[14]
Obesity	DIS47Y1K	Strong	Biomarker	[15]
Osteoporosis	DISF2JE0	Strong	Biomarker	[16]
Sleep disorder	DIS3JP1U	Strong	Genetic Variation	[17]
Toxic epidermal necrolysis	DISIWPFR	Strong	Biomarker	[18]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[7]
Sexually transmitted infection	DISIVIAL	moderate	Biomarker	[19]
Li-Fraumeni syndrome	DISR64XA	Disputed	Biomarker	[20]
Diphtheria	DISZWM55	Limited	Biomarker	[21]
Meniere disease	DISC5R5F	Limited	Genetic Variation	[22]
Neoplasm	DISZKGEW	Limited	Biomarker	[23]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[24]

2 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 Plexin-A3 (PLXNA3).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Plexin-A3 (PLXNA3).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Plexin-A3 (PLXNA3).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Plexin-A3 (PLXNA3).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Plexin-A3 (PLXNA3).	[28]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Plexin-A3 (PLXNA3).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Plexin-A3 (PLXNA3).	[30]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Plexin-A3 (PLXNA3).	[31]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Plexin-A3 (PLXNA3).	[31]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Plexin-A3 (PLXNA3).	[32]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Plexin-A3 (PLXNA3).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Plexin-A3 (PLXNA3).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Plexin-A3 (PLXNA3).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Plexin-A3 (PLXNA3).	[37]

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