Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPS77HO)

• DOT Name: Leucine-rich glioma-inactivated protein 1 (LGI1)
• Synonyms: Epitempin-1
• Gene Name: LGI1
• Related Disease:
  Autosomal dominant epilepsy with auditory features
  Advanced cancer
  Astrocytoma
  Attention deficit hyperactivity disorder
  Autoimmune disease
  Brain cancer
  Brain neoplasm
  Cerebellar ataxia
  Dementia
  Depression
  Encephalitis
  Epilepsy
  Epilepsy syndrome
  Epilepsy, familial temporal lobe, 1
  Epilepsy, idiopathic generalized
  Esophageal squamous cell carcinoma
  Fleck corneal dystrophy
  Focal epilepsy
  Glioma
  Herpes simplex encephalitis
  Listeriosis
  Malignant glioma
  Metastatic malignant neoplasm
  Movement disorder
  Neuroblastoma
  Non-small-cell lung cancer
  Sleep disorder
  Trichohepatoenteric syndrome
  Glioblastoma multiforme
  Nephrocalcinosis
  Temporal lobe epilepsy
  Adult glioblastoma
  Choreatic disease
  Cognitive impairment
  Epilepsy with generalized tonic-clonic seizures
  Myasthenia gravis
  Nervous system disease
  Psychotic disorder
  Tauopathy
• UniProt ID: LGI1_HUMAN
• PDB ID: 5Y2Z; 5Y30; 5Y31
• Pfam ID: PF03736 ; PF13855
• Sequence:
  MESERSKRMGNACIPLKRIAYFLCLLSALLLTEGKKPAKPKCPAVCTCTKDNALCENARS
  IPRTVPPDVISLSFVRSGFTEISEGSFLFTPSLQLLLFTSNSFDVISDDAFIGLPHLEYL
  FIENNNIKSISRHTFRGLKSLIHLSLANNNLQTLPKDIFKGLDSLTNVDLRGNSFNCDCK
  LKWLVEWLGHTNATVEDIYCEGPPEYKKRKINSLSSKDFDCIITEFAKSQDLPYQSLSID
  TFSYLNDEYVVIAQPFTGKCIFLEWDHVEKTFRNYDNITGTSTVVCKPIVIETQLYVIVA
  QLFGGSHIYKRDSFANKFIKIQDIEILKIRKPNDIETFKIENNWYFVVADSSKAGFTTIY
  KWNGNGFYSHQSLHAWYRDTDVEYLEIVRTPQTLRTPHLILSSSSQRPVIYQWNKATQLF
  TNQTDIPNMEDVYAVKHFSVKGDVYICLTRFIGDSKVMKWGGSSFQDIQRMPSRGSMVFQ
  PLQINNYQYAILGSDYSFTQVYNWDAEKAKFVKFQELNVQAPRSFTHVSINKRNFLFASS
  FKGNTQIYKHVIVDLSA
• Function: Regulates voltage-gated potassium channels assembled from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by precluding channel closure mediated by the KCNAB1 subunit. Ligand for ADAM22 that positively regulates synaptic transmission mediated by AMPA-type glutamate receptors. Plays a role in suppressing the production of MMP1/3 through the phosphatidylinositol 3-kinase/ERK pathway. May play a role in the control of neuroblastoma cell survival.
• Tissue Specificity: Predominantly expressed in neural tissues, especially in brain. Expression is reduced in low-grade brain tumors and significantly reduced or absent in malignant gliomas.; [Isoform 1]: Expressed in the occipital cortex and hippocampus; higher amounts are observed in the parietal and frontal cortices, putamen, and, particularly, in the temporal neocortex, where it is between 3 and 5 times more abundant than in the hippocampus (at protein level) . Expression is absent in the cerebellum .; [Isoform 3]: Abundantly expressed in the occipital cortex and weakly expressed in the hippocampus (at protein level).
• Reactome Pathway: LGI-ADAM interactions (R-HSA-5682910)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant epilepsy with auditory features	DISFZN2O	Definitive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Astrocytoma	DISL3V18	Strong	Altered Expression	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Brain cancer	DISBKFB7	Strong	Genetic Variation	[6]
Brain neoplasm	DISY3EKS	Strong	Genetic Variation	[6]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[7]
Dementia	DISXL1WY	Strong	Biomarker	[8]
Depression	DIS3XJ69	Strong	Biomarker	[9]
Encephalitis	DISLD1RL	Strong	Biomarker	[10]
Epilepsy	DISBB28L	Strong	Biomarker	[11]
Epilepsy syndrome	DISLYXJ3	Strong	Genetic Variation	[12]
Epilepsy, familial temporal lobe, 1	DISTRYUX	Strong	Autosomal dominant	[13]
Epilepsy, idiopathic generalized	DISODZC9	Strong	Biomarker	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[15]
Fleck corneal dystrophy	DISERQJ1	Strong	Genetic Variation	[16]
Focal epilepsy	DIS4LY5L	Strong	Genetic Variation	[17]
Glioma	DIS5RPEH	Strong	Genetic Variation	[18]
Herpes simplex encephalitis	DISGX28I	Strong	Biomarker	[19]
Listeriosis	DISKMQBM	Strong	Biomarker	[20]
Malignant glioma	DISFXKOV	Strong	Biomarker	[21]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[15]
Movement disorder	DISOJJ2D	Strong	Biomarker	[22]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[24]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[25]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[26]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[23]
Nephrocalcinosis	DIS5ZVJP	moderate	Genetic Variation	[27]
Temporal lobe epilepsy	DISNOPXX	moderate	Biomarker	[28]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[23]
Choreatic disease	DISH8K3M	Limited	Genetic Variation	[25]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[29]
Epilepsy with generalized tonic-clonic seizures	DISMG0FL	Limited	Therapeutic	[18]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[30]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[31]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[32]
Tauopathy	DISY2IPA	Limited	Biomarker	[33]

8 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 Leucine-rich glioma-inactivated protein 1 (LGI1).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich glioma-inactivated protein 1 (LGI1).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Leucine-rich glioma-inactivated protein 1 (LGI1).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Leucine-rich glioma-inactivated protein 1 (LGI1).	[37]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Leucine-rich glioma-inactivated protein 1 (LGI1).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Leucine-rich glioma-inactivated protein 1 (LGI1).	[36]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Leucine-rich glioma-inactivated protein 1 (LGI1).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Leucine-rich glioma-inactivated protein 1 (LGI1).	[41]

1 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 Leucine-rich glioma-inactivated protein 1 (LGI1).	[40]

References

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