Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNPKCX6)

• DOT Name: STING ER exit protein (STEEP1)
• Synonyms: STEEP
• Gene Name: STEEP1
• Related Disease:
  Intellectual disability, X-linked 107
  X-linked syndromic intellectual disability
• UniProt ID: STEEP_HUMAN
• PDB ID: 8C6J
• Sequence:
  MPKVVSRSVVCSDTRDREEYDDGEKPLHVYYCLCGQMVLVLDCQLEKLPMRPRDRSRVID
  AAKHAHKFCNTEDEETMYLRRPEGIERQYRKKCAKCGLPLFYQSQPKNAPVTFIVDGAVV
  KFGQGFGKTNIYTQKQEPPKKVMMTKRTKDMGKFSSVTVSTIDEEEEEIEAREVADSYAQ
  NAKVIEKQLERKGMSKRRLQELAELEAKKAKMKGTLIDNQFK
• Function: Molecular adapter that stimulates membrane curvature formation and subsequent endoplasmic reticulum exit site (ERES) establishment by recruiting PI3K complex I, leading to COPII vesicle-mediated transport. Promotes endoplasmic reticulum (ER) exit of cGAMP-activated STING1 oligomers.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability, X-linked 107	DISB4ZVY	Limited	X-linked	[1]
X-linked syndromic intellectual disability	DISG1YOH	Limited	X-linked	[2]

4 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 STING ER exit protein (STEEP1).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of STING ER exit protein (STEEP1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of STING ER exit protein (STEEP1).	[6]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of STING ER exit protein (STEEP1).	[7]

1 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 decreases the methylation of STING ER exit protein (STEEP1).	[5]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] CXorf56, a dendritic neuronal protein, identified as a new candidate gene for X-linked intellectual disability. Eur J Hum Genet. 2018 Apr;26(4):552-560. doi: 10.1038/s41431-017-0051-9. Epub 2018 Jan 26.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [7] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.