Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOV7J85)

• DOT Name: Muscleblind-like protein 1 (MBNL1)
• Synonyms: Triplet-expansion RNA-binding protein
• Gene Name: MBNL1
• Related Disease:
  Rheumatoid arthritis
  Autism spectrum disorder
  Breast neoplasm
  Cataract
  Cervical cancer
  Cervical carcinoma
  Cholelithiasis
  Depression
  Familial prostate carcinoma
  Fuchs' endothelial dystrophy
  Huntington disease-like 2
  Myocardial infarction
  Myopathy
  Myotonic dystrophy type 2
  Myotonic syndrome
  Neoplasm
  Non-insulin dependent diabetes
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Schizophrenia
  Systemic lupus erythematosus
  Tetralogy of fallot
  Type-1/2 diabetes
  Werner syndrome
  Colorectal carcinoma
  Myotonic dystrophy
  Myotonic dystrophy type 1
  X-linked myotubular myopathy
• UniProt ID: MBNL1_HUMAN
• PDB ID: 3D2N; 3D2Q; 3D2S; 5U6H; 5U6L; 5U9B
• Pfam ID: PF00642 ; PF14608
• Sequence:
  MAVSVTPIRDTKWLTLEVCREFQRGTCSRPDTECKFAHPSKSCQVENGRVIACFDSLKGR
  CSRENCKYLHPPPHLKTQLEINGRNNLIQQKNMAMLAQQMQLANAMMPGAPLQPVPMFSV
  APSLATNASAAAFNPYLGPVSPSLVPAEILPTAPMLVTGNPGVPVPAAAAAAAQKLMRTD
  RLEVCREYQRGNCNRGENDCRFAHPADSTMIDTNDNTVTVCMDYIKGRCSREKCKYFHPP
  AHLQAKIKAAQYQVNQAAAAQAAATAAAMTQSAVKSLKRPLEATFDLGIPQAVLPPLPKR
  PALEKTNGATAVFNTGIFQYQQALANMQLQQHTAFLPPVPMVHGATPATVSAATTSATSV
  PFAATATANQIPIISAEHLTSHKYVTQM
• Function: Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. Regulates the TNNT2 exon 5 skipping through competition with U2AF2. Inhibits the formation of the spliceosome A complex on intron 4 of TNNT2 pre-mRNA. Binds to the stem-loop structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Binds to the 5'-YGCU(U/G)Y-3'consensus sequence. Binds to the IR RNA. Binds to expanded CUG repeat RNA, which folds into a hairpin structure containing GC base pairs and bulged, unpaired U residues. Together with RNA binding proteins RBPMS and RBFOX2, activates vascular smooth muscle cells alternative splicing events. Regulates NCOR2 alternative splicing.
• Tissue Specificity: Highly expressed in cardiac, skeletal muscle and during myoblast differentiation. Weakly expressed in other tissues (at protein level). Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[1]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Cataract	DISUD7SL	Strong	Biomarker	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[5]
Cholelithiasis	DISERLZB	Strong	Biomarker	[6]
Depression	DIS3XJ69	Strong	Biomarker	[7]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[8]
Fuchs' endothelial dystrophy	DISL7TXC	Strong	Biomarker	[9]
Huntington disease-like 2	DISM3G09	Strong	Biomarker	[10]
Myocardial infarction	DIS655KI	Strong	Biomarker	[11]
Myopathy	DISOWG27	Strong	Biomarker	[12]
Myotonic dystrophy type 2	DIS5ZWF1	Strong	Biomarker	[13]
Myotonic syndrome	DISPCJM5	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[16]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[8]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[8]
Schizophrenia	DISSRV2N	Strong	Biomarker	[17]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[18]
Tetralogy of fallot	DISMHFNW	moderate	Altered Expression	[19]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[20]
Werner syndrome	DISZY45W	moderate	Biomarker	[21]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[22]
Myotonic dystrophy	DISNBEMX	Limited	Altered Expression	[23]
Myotonic dystrophy type 1	DISJC0OX	Limited	Altered Expression	[24]
X-linked myotubular myopathy	DISJ95GS	Limited	Biomarker	[25]

18 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 Muscleblind-like protein 1 (MBNL1).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Muscleblind-like protein 1 (MBNL1).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Muscleblind-like protein 1 (MBNL1).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Muscleblind-like protein 1 (MBNL1).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Muscleblind-like protein 1 (MBNL1).	[30]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Muscleblind-like protein 1 (MBNL1).	[31]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Muscleblind-like protein 1 (MBNL1).	[32]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Muscleblind-like protein 1 (MBNL1).	[33]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Muscleblind-like protein 1 (MBNL1).	[34]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Muscleblind-like protein 1 (MBNL1).	[35]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Muscleblind-like protein 1 (MBNL1).	[36]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Muscleblind-like protein 1 (MBNL1).	[37]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Muscleblind-like protein 1 (MBNL1).	[38]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Muscleblind-like protein 1 (MBNL1).	[33]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Muscleblind-like protein 1 (MBNL1).	[40]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Muscleblind-like protein 1 (MBNL1).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Muscleblind-like protein 1 (MBNL1).	[43]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Muscleblind-like protein 1 (MBNL1).	[44]

2 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 Muscleblind-like protein 1 (MBNL1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Muscleblind-like protein 1 (MBNL1).	[42]

References

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