Details of Drug Off-Target (DOT)

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

• DOT Name: Plexin-A2 (PLXNA2)
• Synonyms: Semaphorin receptor OCT
• Gene Name: PLXNA2
• Related Disease:
  Neuroblastoma
  Retinitis pigmentosa
  Vitelliform macular dystrophy
  Acute coronary syndrome
  Age-related macular degeneration
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Cataract
  Depression
  Diabetic macular edema
  Diabetic retinopathy
  Glaucoma/ocular hypertension
  Glycogen storage disease type II
  High blood pressure
  Keratoconus
  Mixed anxiety and depressive disorder
  Non-arteritic anterior ischemic optic neuropathy
  Non-hodgkin lymphoma
  Non-insulin dependent diabetes
  Non-proliferative diabetic retinopathy
  Occult macular dystrophy
  Open-angle glaucoma
  Optic neuritis
  OPTN-related open angle glaucoma
  Parkinson disease
  Polycystic ovarian syndrome
  Proliferative diabetic retinopathy
  Retinopathy
  Retinoschisis
  Schizophrenia
  Stargardt disease
  Type-1 diabetes
  Vascular disease
  Type-1/2 diabetes
  Neoplasm
  Acute myelogenous leukaemia
  Advanced cancer
  Disorder of orbital region
  Multiple sclerosis
  Severe early-childhood-onset retinal dystrophy
• UniProt ID: PLXA2_HUMAN
• PDB ID: 3Q3J
• Pfam ID: PF08337 ; PF20170 ; PF01437 ; PF01403 ; PF01833 ; PF18020 ; PF17960
• Sequence:
  MEQRRPWPRALEVDSRSVVLLSVVWVLLAPPAAGMPQFSTFHSENRDWTFNHLTVHQGTG
  AVYVGAINRVYKLTGNLTIQVAHKTGPEEDNKSCYPPLIVQPCSEVLTLTNNVNKLLIID
  YSENRLLACGSLYQGVCKLLRLDDLFILVEPSHKKEHYLSSVNKTGTMYGVIVRSEGEDG
  KLFIGTAVDGKQDYFPTLSSRKLPRDPESSAMLDYELHSDFVSSLIKIPSDTLALVSHFD
  IFYIYGFASGGFVYFLTVQPETPEGVAINSAGDLFYTSRIVRLCKDDPKFHSYVSLPFGC
  TRAGVEYRLLQAAYLAKPGDSLAQAFNITSQDDVLFAIFSKGQKQYHHPPDDSALCAFPI
  RAINLQIKERLQSCYQGEGNLELNWLLGKDVQCTKAPVPIDDNFCGLDINQPLGGSTPVE
  GLTLYTTSRDRMTSVASYVYNGYSVVFVGTKSGKLKKIRADGPPHGGVQYEMVSVLKDGS
  PILRDMAFSIDQRYLYVMSERQVTRVPVESCEQYTTCGECLSSGDPHCGWCALHNMCSRR
  DKCQQAWEPNRFAASISQCVSLAVHPSSISVSEHSRLLSLVVSDAPDLSAGIACAFGNLT
  EVEGQVSGSQVICISPGPKDVPVIPLDQDWFGLELQLRSKETGKIFVSTEFKFYNCSAHQ
  LCLSCVNSAFRCHWCKYRNLCTHDPTTCSFQEGRINISEDCPQLVPTEEILIPVGEVKPI
  TLKARNLPQPQSGQRGYECVLNIQGAIHRVPALRFNSSSVQCQNSSYQYDGMDISNLAVD
  FAVVWNGNFIIDNPQDLKVHLYKCAAQRESCGLCLKADRKFECGWCSGERRCTLHQHCTS
  PSSPWLDWSSHNVKCSNPQITEILTVSGPPEGGTRVTIHGVNLGLDFSEIAHHVQVAGVP
  CTPLPGEYIIAEQIVCEMGHALVGTTSGPVRLCIGECKPEFMTKSHQQYTFVNPSVLSLN
  PIRGPESGGTMVTITGHYLGAGSSVAVYLGNQTCEFYGRSMSEIVCVSPPSSNGLGPVPV
  SVSVDRAHVDSNLQFEYIDDPRVQRIEPEWSIASGHTPLTITGFNLDVIQEPRIRVKFNG
  KESVNVCKVVNTTTLTCLAPSLTTDYRPGLDTVERPDEFGFVFNNVQSLLIYNDTKFIYY
  PNPTFELLSPTGVLDQKPGSPIILKGKNLCPPASGGAKLNYTVLIGETPCAVTVSETQLL
  CEPPNLTGQHKVMVHVGGMVFSPGSVSVISDSLLTLPAIVSIAAGGSLLLIIVIIVLIAY
  KRKSRENDLTLKRLQMQMDNLESRVALECKEAFAELQTDINELTSDLDRSGIPYLDYRTY
  AMRVLFPGIEDHPVLRELEVQGNGQQHVEKALKLFAQLINNKVFLLTFIRTLELQRSFSM
  RDRGNVASLIMTGLQGRLEYATDVLKQLLSDLIDKNLENKNHPKLLLRRTESVAEKMLTN
  WFAFLLHKFLKECAGEPLFMLYCAIKQQMEKGPIDAITGEARYSLSEDKLIRQQIEYKTL
  ILNCVNPDNENSPEIPVKVLNCDTITQVKEKILDAVYKNVPYSQRPRAVDMDLEWRQGRI
  ARVVLQDEDITTKIEGDWKRLNTLMHYQVSDRSVVALVPKQTSSYNIPASASISRTSISR
  YDSSFRYTGSPDSLRSRAPMITPDLESGVKVWHLVKNHDHGDQKEGDRGSKMVSEIYLTR
  LLATKGTLQKFVDDLFETLFSTVHRGSALPLAIKYMFDFLDEQADRHSIHDTDVRHTWKS
  NCLPLRFWVNVIKNPQFVFDIHKGSITDACLSVVAQTFMDSCSTSEHRLGKDSPSNKLLY
  AKDIPSYKSWVERYYADIAKLPAISDQDMNAYLAEQSRLHAVEFNMLSALNEIYSYVSKY
  SEELIGALEQDEQARRQRLAYKVEQLINAMSIES
• Function: Coreceptor for SEMA3A and SEMA6A. Necessary for signaling by SEMA6A and class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. 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.
• Tissue Specificity: Detected in fetal brain.
• 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)
  Other semaphorin interactions (R-HSA-416700)
  Sema3A PAK dependent Axon repulsion (R-HSA-399954)

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[1]
Retinitis pigmentosa	DISCGPY8	Definitive	Biomarker	[2]
Vitelliform macular dystrophy	DISEFYYN	Definitive	Biomarker	[3]
Acute coronary syndrome	DIS7DYEW	Strong	Genetic Variation	[4]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Cataract	DISUD7SL	Strong	Biomarker	[8]
Depression	DIS3XJ69	Strong	Biomarker	[9]
Diabetic macular edema	DIS162FN	Strong	Biomarker	[10]
Diabetic retinopathy	DISHGUJM	Strong	Genetic Variation	[11]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Biomarker	[12]
Glycogen storage disease type II	DISXZPBC	Strong	Biomarker	[13]
High blood pressure	DISY2OHH	Strong	Biomarker	[14]
Keratoconus	DISOONXH	Strong	Biomarker	[15]
Mixed anxiety and depressive disorder	DISV809X	Strong	Genetic Variation	[16]
Non-arteritic anterior ischemic optic neuropathy	DIS53TUF	Strong	Biomarker	[17]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[18]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[19]
Non-proliferative diabetic retinopathy	DISPMG3Z	Strong	Biomarker	[20]
Occult macular dystrophy	DISG772R	Strong	Genetic Variation	[21]
Open-angle glaucoma	DISSZEE8	Strong	Biomarker	[22]
Optic neuritis	DISDYCHC	Strong	Biomarker	[23]
OPTN-related open angle glaucoma	DISDR98A	Strong	Biomarker	[17]
Parkinson disease	DISQVHKL	Strong	Biomarker	[24]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[25]
Proliferative diabetic retinopathy	DISQZ13G	Strong	Genetic Variation	[26]
Retinopathy	DISB4B0F	Strong	Biomarker	[27]
Retinoschisis	DISTTWND	Strong	Biomarker	[28]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[29]
Stargardt disease	DISPXOTO	Strong	Biomarker	[30]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[11]
Vascular disease	DISVS67S	Strong	Biomarker	[31]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[32]
Neoplasm	DISZKGEW	Disputed	Biomarker	[33]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[34]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[35]
Disorder of orbital region	DISH0ECJ	Limited	Biomarker	[36]
Multiple sclerosis	DISB2WZI	Limited	Genetic Variation	[37]
Severe early-childhood-onset retinal dystrophy	DISFDRFO	Limited	Biomarker	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Plexin-A2 (PLXNA2).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Plexin-A2 (PLXNA2).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Plexin-A2 (PLXNA2).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Plexin-A2 (PLXNA2).	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Plexin-A2 (PLXNA2).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Plexin-A2 (PLXNA2).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Plexin-A2 (PLXNA2).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Plexin-A2 (PLXNA2).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Plexin-A2 (PLXNA2).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Plexin-A2 (PLXNA2).	[45]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Plexin-A2 (PLXNA2).	[47]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Plexin-A2 (PLXNA2).	[48]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Plexin-A2 (PLXNA2).	[49]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Plexin-A2 (PLXNA2).	[50]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Plexin-A2 (PLXNA2).	[52]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Plexin-A2 (PLXNA2).	[53]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Plexin-A2 (PLXNA2).	[55]

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