Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLKMW1O)

• DOT Name: Reelin (RELN)
• Synonyms: EC 3.4.21.-
• Gene Name: RELN
• Related Disease:
  Lissencephaly with cerebellar hypoplasia
  Norman-Roberts syndrome
  Advanced cancer
  Amyloidosis
  Bipolar depression
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Cerebellar ataxia
  Childhood epilepsy with centrotemporal spikes
  Cognitive impairment
  Colorectal carcinoma
  Dementia
  Depression
  Epilepsy
  Epilepsy, familial temporal lobe, 1
  Familial Alzheimer disease
  Familial temporal lobe epilepsy 7
  Hypothyroidism
  Lissencephaly spectrum disorders
  Major depressive disorder
  Mood disorder
  Multiple sclerosis
  Neoplasm
  Nervous system disease
  Neurodevelopmental disorder
  Non-insulin dependent diabetes
  Plasma cell myeloma
  Psychotic disorder
  Stomach cancer
  Temporal lobe epilepsy
  Venous thromboembolism
  Hepatocellular carcinoma
  Autosomal dominant epilepsy with auditory features
  Complex neurodevelopmental disorder
  Alzheimer disease
  Ankylosing spondylitis
  Classic Hodgkin lymphoma
  Colitis
  Hirschsprung disease
  Huntington disease
  Mental disorder
  Neuroblastoma
  Sjogren syndrome
  Status epilepticus seizure
• UniProt ID: RELN_HUMAN
• PDB ID: 8G21
• EC Number: 3.4.21.-
• Pfam ID: PF07974 ; PF18720 ; PF21471
• Sequence:
  MERSGWARQTFLLALLLGATLRARAAAGYYPRFSPFFFLCTHHGELEGDGEQGEVLISLH
  IAGNPTYYVPGQEYHVTISTSTFFDGLLVTGLYTSTSVQASQSIGGSSAFGFGIMSDHQF
  GNQFMCSVVASHVSHLPTTNLSFIWIAPPAGTGCVNFMATATHRGQVIFKDALAQQLCEQ
  GAPTDVTVHPHLAEIHSDSIILRDDFDSYHQLQLNPNIWVECNNCETGEQCGAIMHGNAV
  TFCEPYGPRELITTGLNTTTASVLQFSIGSGSCRFSYSDPSIIVLYAKNNSADWIQLEKI
  RAPSNVSTIIHILYLPEDAKGENVQFQWKQENLRVGEVYEACWALDNILIINSAHRQVVL
  EDSLDPVDTGNWLFFPGATVKHSCQSDGNSIYFHGNEGSEFNFATTRDVDLSTEDIQEQW
  SEEFESQPTGWDVLGAVIGTECGTIESGLSMVFLKDGERKLCTPSMDTTGYGNLRFYFVM
  GGICDPGNSHENDIILYAKIEGRKEHITLDTLSYSSYKVPSLVSVVINPELQTPATKFCL
  RQKNHQGHNRNVWAVDFFHVLPVLPSTMSHMIQFSINLGCGTHQPGNSVSLEFSTNHGRS
  WSLLHTECLPEICAGPHLPHSTVYSSENYSGWNRITIPLPNAALTRNTRIRWRQTGPILG
  NMWAIDNVYIGPSCLKFCSGRGQCTRHGCKCDPGFSGPACEMASQTFPMFISESFGSSRL
  SSYHNFYSIRGAEVSFGCGVLASGKALVFNKDGRRQLITSFLDSSQSRFLQFTLRLGSKS
  VLSTCRAPDQPGEGVLLHYSYDNGITWKLLEHYSYLSYHEPRIISVELPGDAKQFGIQFR
  WWQPYHSSQREDVWAIDEIIMTSVLFNSISLDFTNLVEVTQSLGFYLGNVQPYCGHDWTL
  CFTGDSKLASSMRYVETQSMQIGASYMIQFSLVMGCGQKYTPHMDNQVKLEYSTNHGLTW
  HLVQEECLPSMPSCQEFTSASIYHASEFTQWRRVIVLLPQKTWSSATRFRWSQSYYTAQD
  EWALDSIYIGQQCPNMCSGHGSCDHGICRCDQGYQGTECHPEAALPSTIMSDFENQNGWE
  SDWQEVIGGEIVKPEQGCGVISSGSSLYFSKAGKRQLVSWDLDTSWVDFVQFYIQIGGES
  ASCNKPDSREEGVLLQYSNNGGIQWHLLAEMYFSDFSKPRFVYLELPAAAKTPCTRFRWW
  QPVFSGEDYDQWAVDDIIILSEKQKQIIPVINPTLPQNFYEKPAFDYPMNQMSVWLMLAN
  EGMVKNETFCAATPSAMIFGKSDGDRFAVTRDLTLKPGYVLQFKLNIGCANQFSSTAPVL
  LQYSHDAGMSWFLVKEGCYPASAGKGCEGNSRELSEPTMYHTGDFEEWTRITIVIPRSLA
  SSKTRFRWIQESSSQKNVPPFGLDGVYISEPCPSYCSGHGDCISGVCFCDLGYTAAQGTC
  VSNVPNHNEMFDRFEGKLSPLWYKITGAQVGTGCGTLNDGKSLYFNGPGKREARTVPLDT
  RNIRLVQFYIQIGSKTSGITCIKPRTRNEGLIVQYSNDNGILWHLLRELDFMSFLEPQII
  SIDLPQDAKTPATAFRWWQPQHGKHSAQWALDDVLIGMNDSSQTGFQDKFDGSIDLQANW
  YRIQGGQVDIDCLSMDTALIFTENIGKPRYAETWDFHVSASTFLQFEMSMGCSKPFSNSH
  SVQLQYSLNNGKDWHLVTEECVPPTIGCLHYTESSIYTSERFQNWKRITVYLPLSTISPR
  TRFRWIQANYTVGADSWAIDNVVLASGCPWMCSGRGICDAGRCVCDRGFGGPYCVPVVPL
  PSILKDDFNGNLHPDLWPEVYGAERGNLNGETIKSGTSLIFKGEGLRMLISRDLDCTNTM
  YVQFSLRFIAKSTPERSHSILLQFSISGGITWHLMDEFYFPQTTNILFINVPLPYTAQTN
  ATRFRLWQPYNNGKKEEIWIVDDFIIDGNNVNNPVMLLDTFDFGPREDNWFFYPGGNIGL
  YCPYSSKGAPEEDSAMVFVSNEVGEHSITTRDLNVNENTIIQFEINVGCSTDSSSADPVR
  LEFSRDFGATWHLLLPLCYHSSSHVSSLCSTEHHPSSTYYAGTMQGWRREVVHFGKLHLC
  GSVRFRWYQGFYPAGSQPVTWAIDNVYIGPQCEEMCNGQGSCINGTKCICDPGYSGPTCK
  ISTKNPDFLKDDFEGQLESDRFLLMSGGKPSRKCGILSSGNNLFFNEDGLRMLMTRDLDL
  SHARFVQFFMRLGCGKGVPDPRSQPVLLQYSLNGGLSWSLLQEFLFSNSSNVGRYIALEI
  PLKARSGSTRLRWWQPSENGHFYSPWVIDQILIGGNISGNTVLEDDFTTLDSRKWLLHPG
  GTKMPVCGSTGDALVFIEKASTRYVVSTDVAVNEDSFLQIDFAASCSVTDSCYAIELEYS
  VDLGLSWHPLVRDCLPTNVECSRYHLQRILVSDTFNKWTRITLPLPPYTRSQATRFRWHQ
  PAPFDKQQTWAIDNVYIGDGCIDMCSGHGRCIQGNCVCDEQWGGLYCDDPETSLPTQLKD
  NFNRAPSSQNWLTVNGGKLSTVCGAVASGMALHFSGGCSRLLVTVDLNLTNAEFIQFYFM
  YGCLITPNNRNQGVLLEYSVNGGITWNLLMEIFYDQYSKPGFVNILLPPDAKEIATRFRW
  WQPRHDGLDQNDWAIDNVLISGSADQRTVMLDTFSSAPVPQHERSPADAGPVGRIAFDMF
  MEDKTSVNEHWLFHDDCTVERFCDSPDGVMLCGSHDGREVYAVTHDLTPTEGWIMQFKIS
  VGCKVSEKIAQNQIHVQYSTDFGVSWNYLVPQCLPADPKCSGSVSQPSVFFPTKGWKRIT
  YPLPESLVGNPVRFRFYQKYSDMQWAIDNFYLGPGCLDNCRGHGDCLREQCICDPGYSGP
  NCYLTHTLKTFLKERFDSEEIKPDLWMSLEGGSTCTECGILAEDTALYFGGSTVRQAVTQ
  DLDLRGAKFLQYWGRIGSENNMTSCHRPICRKEGVLLDYSTDGGITWTLLHEMDYQKYIS
  VRHDYILLPEDALTNTTRLRWWQPFVISNGIVVSGVERAQWALDNILIGGAEINPSQLVD
  TFDDEGTSHEENWSFYPNAVRTAGFCGNPSFHLYWPNKKKDKTHNALSSRELIIQPGYMM
  QFKIVVGCEATSCGDLHSVMLEYTKDARSDSWQLVQTQCLPSSSNSIGCSPFQFHEATIY
  NSVNSSSWKRITIQLPDHVSSSATQFRWIQKGEETEKQSWAIDHVYIGEACPKLCSGHGY
  CTTGAICICDESFQGDDCSVFSHDLPSYIKDNFESARVTEANWETIQGGVIGSGCGQLAP
  YAHGDSLYFNGCQIRQAATKPLDLTRASKIMFVLQIGSMSQTDSCNSDLSGPHAVDKAVL
  LQYSVNNGITWHVIAQHQPKDFTQAQRVSYNVPLEARMKGVLLRWWQPRHNGTGHDQWAL
  DHVEVVLVSTRKQNYMMNFSRQHGLRHFYNRRRRSLRRYP
• Function: Extracellular matrix serine protease that plays a role in layering of neurons in the cerebral cortex and cerebellum. Regulates microtubule function in neurons and neuronal migration. Affects migration of sympathetic preganglionic neurons in the spinal cord, where it seems to act as a barrier to neuronal migration. Enzymatic activity is important for the modulation of cell adhesion. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation.
• Tissue Specificity: Abundantly produced during brain ontogenesis by the Cajal-Retzius cells and other pioneer neurons located in the telencephalic marginal zone and by granule cells of the external granular layer of the cerebellum. In adult brain, preferentially expressed in GABAergic interneurons of prefrontal cortices, temporal cortex, hippocampus and glutamatergic granule cells of cerebellum. Expression is reduced to about 50% in patients with schizophrenia. Also expressed in fetal and adult liver.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Spinocerebellar ataxia (hsa05017)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway: Reelin signalling pathway (R-HSA-8866376)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lissencephaly with cerebellar hypoplasia	DISST6TU	Definitive	Autosomal recessive	[1]
Norman-Roberts syndrome	DISUXOK0	Definitive	Autosomal recessive	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Amyloidosis	DISHTAI2	Strong	Biomarker	[4]
Bipolar depression	DISA75FU	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[8]
Childhood epilepsy with centrotemporal spikes	DISKT2L5	Strong	CausalMutation	[9]
Cognitive impairment	DISH2ERD	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Dementia	DISXL1WY	Strong	Altered Expression	[12]
Depression	DIS3XJ69	Strong	Biomarker	[13]
Epilepsy	DISBB28L	Strong	Biomarker	[14]
Epilepsy, familial temporal lobe, 1	DISTRYUX	Strong	Genetic Variation	[15]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[16]
Familial temporal lobe epilepsy 7	DISSDHKG	Strong	Autosomal dominant	[17]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[18]
Lissencephaly spectrum disorders	DISBCZL7	Strong	Biomarker	[19]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[20]
Mood disorder	DISLVMWO	Strong	Altered Expression	[21]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[22]
Neoplasm	DISZKGEW	Strong	Altered Expression	[23]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[10]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[24]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[25]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[26]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[27]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[28]
Temporal lobe epilepsy	DISNOPXX	Strong	Altered Expression	[29]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[30]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[31]
Autosomal dominant epilepsy with auditory features	DISFZN2O	Supportive	Autosomal dominant	[32]
Complex neurodevelopmental disorder	DISB9AFI	Disputed	Autosomal dominant	[1]
Alzheimer disease	DISF8S70	Limited	Altered Expression	[33]
Ankylosing spondylitis	DISRC6IR	Limited	Autosomal dominant	[34]
Classic Hodgkin lymphoma	DISV1LU6	Limited	Biomarker	[35]
Colitis	DISAF7DD	Limited	Biomarker	[36]
Hirschsprung disease	DISUUSM1	Limited	Biomarker	[35]
Huntington disease	DISQPLA4	Limited	Biomarker	[35]
Mental disorder	DIS3J5R8	Limited	Biomarker	[37]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[38]
Sjogren syndrome	DISUBX7H	Limited	Genetic Variation	[39]
Status epilepticus seizure	DISY3BIC	Limited	Biomarker	[40]

4 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 Reelin (RELN).	[41]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Reelin (RELN).	[50]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Reelin (RELN).	[56]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Reelin (RELN).	[50]

19 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 Reelin (RELN).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Reelin (RELN).	[43]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Reelin (RELN).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Reelin (RELN).	[45]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Reelin (RELN).	[46]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Reelin (RELN).	[47]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Reelin (RELN).	[48]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the expression of Reelin (RELN).	[49]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Reelin (RELN).	[48]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Reelin (RELN).	[51]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Reelin (RELN).	[52]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Reelin (RELN).	[53]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Reelin (RELN).	[54]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Reelin (RELN).	[51]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Reelin (RELN).	[48]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Reelin (RELN).	[55]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Reelin (RELN).	[57]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Reelin (RELN).	[58]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Reelin (RELN).	[59]

References

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