Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDQ7QAW)

• DOT Name: Semaphorin-6A (SEMA6A)
• Synonyms: Semaphorin VIA; Sema VIA; Semaphorin-6A-1; SEMA6A-1
• Gene Name: SEMA6A
• Related Disease:
  Melanoma
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Anca-associated vasculitis
  Arteriosclerosis
  Atherosclerosis
  Bladder cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Cerebral infarction
  Ehlers-Danlos syndrome
  Endometriosis
  Epithelial ovarian cancer
  Glioma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  High blood pressure
  Metabolic disorder
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Osteoarthritis
  Osteosarcoma
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Rheumatoid arthritis
  Schizophrenia
  Urinary bladder cancer
  Urinary bladder neoplasm
  Diabetic kidney disease
  Gallbladder carcinoma
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Stomach cancer
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Crohn disease
  Glioblastoma multiforme
  Mental disorder
  Myocardial infarction
  Nervous system disease
  Type-1/2 diabetes
• UniProt ID: SEM6A_HUMAN
• PDB ID: 6WTS
• Pfam ID: PF01437 ; PF01403
• Sequence:
  MRSEALLLYFTLLHFAGAGFPEDSEPISISHGNYTKQYPVFVGHKPGRNTTQRHRLDIQM
  IMIMNGTLYIAARDHIYTVDIDTSHTEEIYCSKKLTWKSRQADVDTCRMKGKHKDECHNF
  IKVLLKKNDDALFVCGTNAFNPSCRNYKMDTLEPFGDEFSGMARCPYDAKHANVALFADG
  KLYSATVTDFLAIDAVIYRSLGESPTLRTVKHDSKWLKEPYFVQAVDYGDYIYFFFREIA
  VEYNTMGKVVFPRVAQVCKNDMGGSQRVLEKQWTSFLKARLNCSVPGDSHFYFNILQAVT
  DVIRINGRDVVLATFSTPYNSIPGSAVCAYDMLDIASVFTGRFKEQKSPDSTWTPVPDER
  VPKPRPGCCAGSSSLERYATSNEFPDDTLNFIKTHPLMDEAVPSIFNRPWFLRTMVRYRL
  TKIAVDTAAGPYQNHTVVFLGSEKGIILKFLARIGNSGFLNDSLFLEEMSVYNSEKCSYD
  GVEDKRIMGMQLDRASSSLYVAFSTCVIKVPLGRCERHGKCKKTCIASRDPYCGWIKEGG
  ACSHLSPNSRLTFEQDIERGNTDGLGDCHNSFVALNGHSSSLLPSTTTSDSTAQEGYESR
  GGMLDWKHLLDSPDSTDPLGAVSSHNHQDKKGVIRESYLKGHDQLVPVTLLAIAVILAFV
  MGAVFSGITVYCVCDHRRKDVAVVQRKEKELTHSRRGSMSSVTKLSGLFGDTQSKDPKPE
  AILTPLMHNGKLATPGNTAKMLIKADQHHLDLTALPTPESTPTLQQKRKPSRGSREWERN
  QNLINACTKDMPPMGSPVIPTDLPLRASPSHIPSVVVLPITQQGYQHEYVDQPKMSEVAQ
  MALEDQAATLEYKTIKEHLSSKSPNHGVNLVENLDSLPPKVPQREASLGPPGASLSQTGL
  SKRLEMHHSSSYGVDYKRSYPTNSLTRSHQATTLKRNNTNSSNSSHLSRNQSFGRGDNPP
  PAPQRVDSIQVHSSQPSGQAVTVSRQPSLNAYNSLTRSGLKRTPSLKPDVPPKPSFAPLS
  TSMKPNDACT
• Function: Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation; (Microbial infection) Acts as a receptor for P.sordellii toxin TcsL in the in the vascular endothelium.
• KEGG Pathway: Axon guidance (hsa04360)
• Reactome Pathway: Other semaphorin interactions (R-HSA-416700)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Anca-associated vasculitis	DISU3CNU	Strong	Genetic Variation	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[10]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Genetic Variation	[11]
Endometriosis	DISX1AG8	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[13]
Glioma	DIS5RPEH	Strong	Altered Expression	[14]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
High blood pressure	DISY2OHH	Strong	Biomarker	[17]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[21]
Osteoarthritis	DIS05URM	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Parkinson disease	DISQVHKL	Strong	Biomarker	[23]
Prostate cancer	DISF190Y	Strong	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[24]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[25]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[26]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[27]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Diabetic kidney disease	DISJMWEY	moderate	Biomarker	[28]
Gallbladder carcinoma	DISD6ACL	moderate	Biomarker	[29]
Gastric cancer	DISXGOUK	moderate	Posttranslational Modification	[30]
Lung cancer	DISCM4YA	moderate	Biomarker	[19]
Lung carcinoma	DISTR26C	moderate	Biomarker	[19]
Stomach cancer	DISKIJSX	moderate	Posttranslational Modification	[30]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[31]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[32]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[33]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[2]
Mental disorder	DIS3J5R8	Limited	Genetic Variation	[34]
Myocardial infarction	DIS655KI	Limited	Biomarker	[35]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[36]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[37]

14 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 Semaphorin-6A (SEMA6A).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Semaphorin-6A (SEMA6A).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Semaphorin-6A (SEMA6A).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Semaphorin-6A (SEMA6A).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Semaphorin-6A (SEMA6A).	[42]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Semaphorin-6A (SEMA6A).	[43]
Marinol	DM70IK5	Approved	Marinol increases the expression of Semaphorin-6A (SEMA6A).	[44]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Semaphorin-6A (SEMA6A).	[45]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Semaphorin-6A (SEMA6A).	[46]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Semaphorin-6A (SEMA6A).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Semaphorin-6A (SEMA6A).	[49]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Semaphorin-6A (SEMA6A).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Semaphorin-6A (SEMA6A).	[52]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Semaphorin-6A (SEMA6A).	[53]

3 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 Semaphorin-6A (SEMA6A).	[48]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Semaphorin-6A (SEMA6A).	[51]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Semaphorin-6A (SEMA6A).	[51]

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