Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY2ILFT)

• DOT Name: Proline-rich protein 12 (PRR12)
• Gene Name: PRR12
• Related Disease:
  Neuroocular syndrome
  Intellectual disability
  Myositis disease
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Systemic sclerosis
  Neurodevelopmental disorder
• UniProt ID: PRR12_HUMAN
• Pfam ID: PF13926
• Sequence:
  MDRNYPSAGFGDPLGAGAGWSYERSAKASLVYGSSRTSHPETDILHRQAYAAPHPLQSYA
  TNHHPAGLSGLFDTGLHHAGSAGPDASVMNLISALESRGPQPGPSASSLLSQFRSPSWQT
  AMHTPGPTELFISGALPGSSTFPSSSALSAYQHPASFGSRPFPVPSSLSLQDPPFSPPAN
  GLLSPHDVLHLKPSQAPTVPSSLGFERLAGGGVLGPAGLGPAQTPPYRPGPPDPPPPPRH
  LPTQFNLLASSSAAAAAAEQSSPQLYNFSGAAPGPPPPERALPRQDTVIKHYQRPASAQP
  PPPPPPAHALQHYLSCGGSYPSMGHRANLACSPLGGGEPSPGAGEPSKAGPSGATAGASG
  RATGPEAAGGGGAGGGGGGYRPIIQSPGYKTGKGGYGAAAGGATRPPPPRSTATPKCQSL
  GGPAAAYATGKASGAGGAGGQAYSPGQPQGLLGPQAYGQGFGGGQAQDLSKAPSYSGGPP
  QPPSGPPPPGLATCQSYSPDQLQGQLYGVQGEPYPGPAAHSQGLPTASPSLSYSTGHSPA
  LSGHGGGWGPSSLGGGGEASPSHIIRPLQSPPATGRPPGVGSPGAPGKYLSSVLASAPFL
  APPGAGSYAAGAGGYKGKGDGSELLAGPGGPPAERTEDEEFLIQHLLQAPSPPRTSGADG
  LVGEDGAADASKGLGGSGGAGGPPGTPYELAKEDPQRYHLQSVIRTSASLDEGATAALEL
  GLGRLKEKKKGPERGGETPEGLATSVVHYGAGAKELGAFLQKSPPPPPPTAQSTQPTPHG
  LLLEAGGPDLPLVLPPPPPQLLPSVLSHAPSPSPSASKVGVHLLEPATRDGAPQPPPPPP
  PPPPPMPLQLEAHLRSHGLEPAAPSPRLRPEESLDPPGAMQELLGALEPLPPAPGDTGVG
  PPNSEGKDPAGAYRSPSPQGTKAPRFVPLTSICFPDSLLQDEERSFFPTMEEMFGGGAAD
  DYGKAGPPEDEGDPKAGAGPPPGPPAYDPYGPYCPGRASGAGPETPGLGLDPNKPPELPS
  TVNAEPLGLIQSGPHQAAPPPPPPPPPPPAPASEPKGGLTSPIFCSTKPKKLLKTSSFHL
  LRRRDPPFQTPKKLYAQEYEFEADEDKADVPADIRLNPRRLPDLVSSCRSRPALSPLGDI
  DFCPPNPGPDGPRRRGRKPTKAKRDGPPRPRGRPRIRPLEVPTTAGPASASTPTDGAKKP
  RGRGRGRGRKAEEAGGTRLEPLKPLKIKLSVPKAGEGLGTSSGDAISGTDHNSLDSSLTR
  EKIEAKIKEVEEKQPEMKSGFMASFLDFLKSGKRHPPLYQAGLTPPLSPPKSVPPSVPAR
  GLQPQPPATPAVPHPPPSGAFGLGGALEAAESEGLGLGCPSPCKRLDEELKRNLETLPSF
  SSDEEDSVAKNRDLQESISSAISALDDPPLAGPKDTSTPDGPPLAPAAAVPGPPPLPGLP
  SANSNGTPEPPLLEEKPPPTPPPAPTPQPQPPPPPPPPQPALPSPPPLVAPTPSSPPPPP
  LPPPPPPAMPSPPPPPPPAAAPLAAPPEEPAAPSPEDPELPDTRPLHLAKKQETAAVCGE
  TDEEAGESGGEGIFRERDEFVIRAEDIPSLKLALQTGREPPPIWRVQKALLQKFTPEIKD
  GQRQFCATSNYLGYFGDAKNRYQRLYVKFLENVNKKDYVRVCARKPWHRPPVPVRRSGQA
  KNPVSAGGSSAPPPKAPAPPPKPETPEKTTSEKPPEQTPETAMPEPPAPEKPSLLRPVEK
  EKEKEKVTRGERPLRGERATSGRQTRPERSLATGQPATSRLPKARPTKVKAEPPPKKRKK
  WLKEAGGNATAGGGPPGSSSDSESSPGAPSEDERAVPGRLLKTRAMREMYRSYVEMLVST
  ALDPDMIQALEDTHDELYLPPMRKIDGLLNEHKKKVLKRLSLSPALQDALHTFPQLQVEQ
  SGEGSPEEGAVRLRPAGEPYNRKTLSKLKRSVVRAQEFKVELEKSGYYTLYHSLHHYKYH
  TFLRCRDQTLAIEGGAEDLGQEEVVQQCMRNQPWLEQLFDSFSDLLAQAQAHSRCG

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroocular syndrome	DIS2XQ1N	Definitive	Autosomal dominant	[1]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[2]
Myositis disease	DISCIXF0	Strong	Genetic Variation	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[3]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[3]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[2]

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 Proline-rich protein 12 (PRR12).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Proline-rich protein 12 (PRR12).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Proline-rich protein 12 (PRR12).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Proline-rich protein 12 (PRR12).	[8]

3 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 Proline-rich protein 12 (PRR12).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Proline-rich protein 12 (PRR12).	[6]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Proline-rich protein 12 (PRR12).	[9]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] De novo apparent loss-of-function mutations in PRR12 in three patients with intellectual disability and iris abnormalities.Hum Genet. 2018 Mar;137(3):257-264. doi: 10.1007/s00439-018-1877-0. Epub 2018 Mar 19.
• [3] Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.Ann Rheum Dis. 2019 Mar;78(3):311-319. doi: 10.1136/annrheumdis-2018-214127. Epub 2018 Dec 20.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.