Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKLQU00)

• DOT Name: Retinoic acid-induced protein 1 (RAI1)
• Gene Name: RAI1
• Related Disease:
  Smith-Magenis syndrome
  Advanced cancer
  Anxiety disorder
  Breast carcinoma
  Charcot-Marie-Tooth disease type 1A
  Epilepsy
  Hereditary neuropathy with liability to pressure palsies
  Melanoma
  Mental disorder
  Non-insulin dependent diabetes
  Obstructive sleep apnea
  Peripheral neuropathy
  Sleep disorder
  Spinocerebellar ataxia type 2
  Trichohepatoenteric syndrome
  Fragile X syndrome
  Intellectual disability
  Neurodevelopmental disorder
  Potocki-Lupski syndrome
  Schizophrenia
  Autism
  Autism spectrum disorder
  Breast cancer
  Parkinson disease
• UniProt ID: RAI1_HUMAN
• Pfam ID: PF13771
• Sequence:
  MQSFRERCGFHGKQQNYQQTSQETSRLENYRQPSQAGLSCDRQRLLAKDYYNPQPYPSYE
  GGAGTPSGTAAAVAADKYHRGSKALPTQQGLQGRPAFPGYGVQDSSPYPGRYAGEESLQA
  WGAPQPPPPQPQPLPAGVAKYDENLMKKTAVPPSRQYAEQGAQVPFRTHSLHVQQPPPPQ
  QPLAYPKLQRQKLQNDIASPLPFPQGTHFPQHSQSFPTSSTYSSSVQGGGQGAHSYKSCT
  APTAQPHDRPLTASSSLAPGQRVQNLHAYQSGRLSYDQQQQQQQQQQQQQQALQSRHHAQ
  ETLHYQNLAKYQHYGQQGQGYCQPDAAVRTPEQYYQTFSPSSSHSPARSVGRSPSYSSTP
  SPLMPNLENFPYSQQPLSTGAFPAGITDHSHFMPLLNPSPTDATSSVDTQAGNCKPLQKD
  KLPENLLSDLSLQSLTALTSQVENISNTVQQLLLSKAAVPQKKGVKNLVSRTPEQHKSQH
  CSPEGSGYSAEPAGTPLSEPPSSTPQSTHAEPQEADYLSGSEDPLERSFLYCNQARGSPA
  RVNSNSKAKPESVSTCSVTSPDDMSTKSDDSFQSLHGSLPLDSFSKFVAGERDCPRLLLS
  ALAQEDLASEILGLQEAIGEKADKAWAEAPSLVKDSSKPPFSLENHSACLDSVAKSAWPR
  PGEPEALPDSLQLDKGGNAKDFSPGLFEDPSVAFATPDPKKTTGPLSFGTKPTLGVPAPD
  PTTAAFDCFPDTTAASSADSANPFAWPEENLGDACPRWGLHPGELTKGLEQGGKASDGIS
  KGDTHEASACLGFQEEDPPGEKVASLPGDFKQEEVGGVKEEAGGLLQCPEVAKADRWLED
  SRHCCSTADFGDLPLLPPTSRKEDLEAEEEYSSLCELLGSPEQRPGMQDPLSPKAPLICT
  KEEVEEVLDSKAGWGSPCHLSGESVILLGPTVGTESKVQSWFESSLSHMKPGEEGPDGER
  APGDSTTSDASLAQKPNKPAVPEAPIAKKEPVPRGKSLRSRRVHRGLPEAEDSPCRAPVL
  PKDLLLPESCTGPPQGQMEGAGAPGRGASEGLPRMCTRSLTALSEPRTPGPPGLTTTPAP
  PDKLGGKQRAAFKSGKRVGKPSPKAASSPSNPAALPVASDSSPMGSKTKETDSPSTPGKD
  QRSMILRSRTKTQEIFHSKRRRPSEGRLPNCRATKKLLDNSHLPATFKVSSSPQKEGRVS
  QRARVPKPGAGSKLSDRPLHALKRKSAFMAPVPTKKRNLVLRSRSSSSSNASGNGGDGKE
  ERPEGSPTLFKRMSSPKKAKPTKGNGEPATKLPPPETPDACLKLASRAAFQGAMKTKVLP
  PRKGRGLKLEAIVQKITSPSLKKFACKAPGASPGNPLSPSLSDKDRGLKGAGGSPVGVEE
  GLVNVGTGQKLPTSGADPLCRNPTNRSLKGKLMNSKKLSSTDCFKTEAFTSPEALQPGGT
  ALAPKKRSRKGRAGAHGLSKGPLEKRPYLGPALLLTPRDRASGTQGASEDNSGGGGKKPK
  MEELGLASQPPEGRPCQPQTRAQKQPGHTNYSSYSKRKRLTRGRAKNTTSSPCKGRAKRR
  RQQQVLPLDPAEPEIRLKYISSCKRLRSDSRTPAFSPFVRVEKRDAFTTICTVVNSPGDA
  PKPHRKPSSSASSSSSSSSFSLDAAGASLATLPGGSILQPRPSLPLSSTMHLGPVVSKAL
  STSCLVCCLCQNPANFKDLGDLCGPYYPEHCLPKKKPKLKEKVRPEGTCEEASLPLERTL
  KGPECAAAATAGKPPRPDGPADPAKQGPLRTSARGLSRRLQSCYCCDGREDGGEEAAPAD
  KGRKHECSKEAPAEPGGEAQEHWVHEACAVWTGGVYLVAGKLFGLQEAMKVAVDMMCSSC
  QEAGATIGCCHKGCLHTYHYPCASDAGCIFIEENFSLKCPKHKRLP
• Function: Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation.
• Tissue Specificity: Expressed in all tissues examined with higher expression in the heart and brain. No expression was seen in the corpus callosum of the brain.
• Reactome Pathway:
  Heme signaling (R-HSA-9707616)
  Circadian Clock (R-HSA-400253)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Smith-Magenis syndrome	DISG4G6X	Definitive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Charcot-Marie-Tooth disease type 1A	DISSRZG7	Strong	Genetic Variation	[5]
Epilepsy	DISBB28L	Strong	Biomarker	[6]
Hereditary neuropathy with liability to pressure palsies	DISY0X1V	Strong	Genetic Variation	[7]
Melanoma	DIS1RRCY	Strong	Biomarker	[8]
Mental disorder	DIS3J5R8	Strong	Altered Expression	[9]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[10]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[11]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[7]
Sleep disorder	DIS3JP1U	Strong	Genetic Variation	[12]
Spinocerebellar ataxia type 2	DISF7WDI	Strong	Biomarker	[13]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[14]
Fragile X syndrome	DISE8W3A	moderate	Genetic Variation	[12]
Intellectual disability	DISMBNXP	moderate	Biomarker	[15]
Neurodevelopmental disorder	DIS372XH	moderate	Genetic Variation	[12]
Potocki-Lupski syndrome	DISUOI38	Moderate	Autosomal dominant	[16]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[17]
Autism	DISV4V1Z	Limited	Biomarker	[18]
Autism spectrum disorder	DISXK8NV	Limited	Genetic Variation	[19]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[4]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[20]

6 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 Retinoic acid-induced protein 1 (RAI1).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Retinoic acid-induced protein 1 (RAI1).	[22]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Retinoic acid-induced protein 1 (RAI1).	[29]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Retinoic acid-induced protein 1 (RAI1).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Retinoic acid-induced protein 1 (RAI1).	[32]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Retinoic acid-induced protein 1 (RAI1).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Retinoic acid-induced protein 1 (RAI1).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Retinoic acid-induced protein 1 (RAI1).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Retinoic acid-induced protein 1 (RAI1).	[25]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Retinoic acid-induced protein 1 (RAI1).	[26]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Retinoic acid-induced protein 1 (RAI1).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Retinoic acid-induced protein 1 (RAI1).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Retinoic acid-induced protein 1 (RAI1).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Retinoic acid-induced protein 1 (RAI1).	[33]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Retinoic acid-induced protein 1 (RAI1).	[34]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Retinoic acid-induced protein 1 (RAI1).	[35]

References

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