Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9MVWO0)

• DOT Name: RING finger and SPRY domain-containing protein 1 (RSPRY1)
• Gene Name: RSPRY1
• Related Disease:
  Craniosynostosis
  Intellectual disability
  Progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome
  Osteochondrodysplasia
  Pyle disease
  Skeletal dysplasia
  Spondyloepimetaphyseal dysplasia
• UniProt ID: RSPRY_HUMAN
• Pfam ID: PF00622 ; PF13920
• Sequence:
  MIVFGWAVFLASRSLGQGLLLTLEEHIAHFLGTGGAATTMGNSCICRDDSGTDDSVDTQQ
  QQAENSAVPTADTRSQPRDPVRPPRRGRGPHEPRRKKQNVDGLVLDTLAVIRTLVDNDQE
  PPYSMITLHEMAETDEGWLDVVQSLIRVIPLEDPLGPAVITLLLDECPLPTKDALQKLTE
  ILNLNGEVACQDSSHPAKHRNTSAVLGCLAEKLAGPASIGLLSPGILEYLLQCLKLQSHP
  TVMLFALIALEKFAQTSENKLTISESSISDRLVTLESWANDPDYLKRQVGFCAQWSLDNL
  FLKEGRQLTYEKVNLSSIRAMLNSNDVSEYLKISPHGLEARCDASSFESVRCTFCVDAGV
  WYYEVTVVTSGVMQIGWATRDSKFLNHEGYGIGDDEYSCAYDGCRQLIWYNARSKPHIHP
  CWKEGDTVGFLLDLNEKQMIFFLNGNQLPPEKQVFSSTVSGFFAAASFMSYQQCEFNFGA
  KPFKYPPSMKFSTFNDYAFLTAEEKIILPRHRRLALLKQVSIRENCCSLCCDEVADTQLK
  PCGHSDLCMDCALQLETCPLCRKEIVSRIRQISHIS

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Craniosynostosis	DIS6J405	Strong	Biomarker	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]
Progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome	DISKRQXV	Strong	Autosomal recessive	[2]
Osteochondrodysplasia	DIS9SPWW	Limited	Biomarker	[1]
Pyle disease	DISJ2YQ3	Limited	Biomarker	[1]
Skeletal dysplasia	DIS5Z8U6	Limited	Biomarker	[1]
Spondyloepimetaphyseal dysplasia	DISO4L5A	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of RING finger and SPRY domain-containing protein 1 (RSPRY1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of RING finger and SPRY domain-containing protein 1 (RSPRY1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RING finger and SPRY domain-containing protein 1 (RSPRY1).	[4]

References

• [1] Further delineation of spondyloepimetaphyseal dysplasia Faden-Alkuraya type: A RSPRY1-associated spondylo-epi-metaphyseal dysplasia with cono-brachydactyly and craniosynostosis.Am J Med Genet A. 2018 Sep;176(9):2009-2016. doi: 10.1002/ajmg.a.40427. Epub 2018 Jul 31.
• [2] Identification of a Recognizable Progressive Skeletal Dysplasia Caused by RSPRY1 Mutations. Am J Hum Genet. 2015 Oct 1;97(4):608-15. doi: 10.1016/j.ajhg.2015.08.007. Epub 2015 Sep 10.
• [3] 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.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.