Details of Drug Off-Target (DOT)

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

• DOT Name: Heterogeneous nuclear ribonucleoprotein H (HNRNPH1)
• Synonyms: hnRNP H
• Gene Name: HNRNPH1
• Related Disease:
  Prostate carcinoma
  Advanced cancer
  Amyotrophic lateral sclerosis
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Heroin dependence
  Intellectual disability
  Neoplasm
  Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects
  Obesity
  Congenital myasthenic syndrome
  Frontotemporal dementia
  Rhabdomyosarcoma
  T-cell acute lymphoblastic leukaemia
  Acute myelogenous leukaemia
  Myotonic dystrophy type 1
  Prostate cancer
  Prostate neoplasm
• UniProt ID: HNRH1_HUMAN
• PDB ID: 2LXU; 6DHS; 7ZUG
• Pfam ID: PF00076 ; PF08080
• Sequence:
  MMLGTEGGEGFVVKVRGLPWSCSADEVQRFFSDCKIQNGAQGIRFIYTREGRPSGEAFVE
  LESEDEVKLALKKDRETMGHRYVEVFKSNNVEMDWVLKHTGPNSPDTANDGFVRLRGLPF
  GCSKEEIVQFFSGLEIVPNGITLPVDFQGRSTGEAFVQFASQEIAEKALKKHKERIGHRY
  IEIFKSSRAEVRTHYDPPRKLMAMQRPGPYDRPGAGRGYNSIGRGAGFERMRRGAYGGGY
  GGYDDYNGYNDGYGFGSDRFGRDLNYCFSGMSDHRYGDGGSTFQSTTGHCVHMRGLPYRA
  TENDIYNFFSPLNPVRVHIEIGPDGRVTGEADVEFATHEDAVAAMSKDKANMQHRYVELF
  LNSTAGASGGAYEHRYVELFLNSTAGASGGAYGSQMMGGMGLSNQSSYGGPASQQLSGGY
  GGGYGGQSSMSGYDQVLQENSSDFQSNIA
• Function: This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Mediates pre-mRNA alternative splicing regulation. Inhibits, together with CUGBP1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Binds to the IR RNA. Binds poly(RG).
• Tissue Specificity: Expressed ubiquitously.
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  FGFR2 alternative splicing (R-HSA-6803529)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[5]
Heroin dependence	DISQ1H57	Strong	Genetic Variation	[6]
Intellectual disability	DISMBNXP	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects	DISF3SNU	Strong	Autosomal dominant	[7]
Obesity	DIS47Y1K	Strong	Biomarker	[8]
Congenital myasthenic syndrome	DISJLG2T	moderate	Biomarker	[9]
Frontotemporal dementia	DISKYHXL	moderate	Biomarker	[3]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[10]
T-cell acute lymphoblastic leukaemia	DIS17AI2	moderate	FusionGene	[11]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[12]
Myotonic dystrophy type 1	DISJC0OX	Limited	Altered Expression	[13]
Prostate cancer	DISF190Y	Limited	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Heterogeneous nuclear ribonucleoprotein H (HNRNPH1) affects the response to substance of Methotrexate.	[35]
Sulforaphane	DMQY3L0	Investigative	Heterogeneous nuclear ribonucleoprotein H (HNRNPH1) affects the binding of Sulforaphane.	[36]

21 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 Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[18]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[20]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[22]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[23]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[19]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[24]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[25]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[26]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[28]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[32]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[34]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[27]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Heterogeneous nuclear ribonucleoprotein H (HNRNPH1).	[33]

References

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• [2] Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis.Nat Commun. 2018 Aug 17;9(1):3315. doi: 10.1038/s41467-018-05748-7.
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• [23] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
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