Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT05B7BT)

• DOT Name: Sorting nexin-10 (SNX10)
• Gene Name: SNX10
• Related Disease:
  Adrenoleukodystrophy
  Autosomal recessive osteopetrosis 8
  Bone disease
  Colitis
  Colorectal carcinoma
  Fatty liver disease
  Gastric adenocarcinoma
  Inflammatory bowel disease
  Liver cancer
  Osteopetrosis
  Osteoporosis
  Bacterial infection
  Infantile malignant osteopetrosis
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Neoplasm
• UniProt ID: SNX10_HUMAN
• PDB ID: 4ON3; 4PZG; 6KOK
• Pfam ID: PF00787
• Sequence:
  MFPEQQKEEFVSVWVRDPRIQKEDFWHSYIDYEICIHTNSMCFTMKTSCVRRRYREFVWL
  RQRLQSNALLVQLPELPSKNLFFNMNNRQHVDQRRQGLEDFLRKVLQNALLLSDSSLHLF
  LQSHLNSEDIEACVSGQTKYSVEEAIHKFALMNRRFPEEDEEGKKENDIDYDSESSSSGL
  GHSSDDSSSHGCKVNTAPQES
• Function: Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. Plays a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium. Required for the localization to the cilium of V-ATPase subunit ATP6V1D and ATP6V0D1, and RAB8A. Involved in osteoclast differentiation and therefore bone resorption.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adrenoleukodystrophy	DISTUD1F	Strong	Biomarker	[1]
Autosomal recessive osteopetrosis 8	DISYR83H	Strong	Autosomal recessive	[2]
Bone disease	DISE1F82	Strong	Altered Expression	[3]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[1]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[6]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[4]
Liver cancer	DISDE4BI	Strong	Altered Expression	[7]
Osteopetrosis	DIS7GHNM	Strong	Genetic Variation	[8]
Osteoporosis	DISF2JE0	Strong	Altered Expression	[3]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[9]
Infantile malignant osteopetrosis	DIS8C3LZ	Supportive	Autosomal recessive	[10]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[7]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Sorting nexin-10 (SNX10) affects the response to substance of Paclitaxel.	[26]
Vinblastine	DM5TVS3	Approved	Sorting nexin-10 (SNX10) affects the response to substance of Vinblastine.	[26]
Apilimod dimesylate	DM4N2O0	Phase 2	Sorting nexin-10 (SNX10) affects the response to substance of Apilimod dimesylate.	[27]

15 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 Sorting nexin-10 (SNX10).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sorting nexin-10 (SNX10).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sorting nexin-10 (SNX10).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sorting nexin-10 (SNX10).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sorting nexin-10 (SNX10).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sorting nexin-10 (SNX10).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Sorting nexin-10 (SNX10).	[17]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sorting nexin-10 (SNX10).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Sorting nexin-10 (SNX10).	[19]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Sorting nexin-10 (SNX10).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sorting nexin-10 (SNX10).	[21]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Sorting nexin-10 (SNX10).	[21]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Sorting nexin-10 (SNX10).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sorting nexin-10 (SNX10).	[24]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Sorting nexin-10 (SNX10).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sorting nexin-10 (SNX10).	[23]

References

• [1] SNX10 mediates alcohol-induced liver injury and steatosis by regulating the activation of chaperone-mediated autophagy.J Hepatol. 2018 Jul;69(1):129-141. doi: 10.1016/j.jhep.2018.01.038. Epub 2018 Feb 13.
• [2] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [3] SNX10 is required for osteoclast formation and resorption activity.J Cell Biochem. 2012 May;113(5):1608-15. doi: 10.1002/jcb.24029.
• [4] Sorting nexin 10 acting as a novel regulator of macrophage polarization mediates inflammatory response in experimental mouse colitis.Sci Rep. 2016 Feb 9;6:20630. doi: 10.1038/srep20630.
• [5] SNX10 (sorting nexin 10) inhibits colorectal cancer initiation and progression by controlling autophagic degradation of SRC.Autophagy. 2020 Apr;16(4):735-749. doi: 10.1080/15548627.2019.1632122. Epub 2019 Jul 4.
• [6] Prognostic value of sorting nexin 10 weak expression in stomach adenocarcinoma revealed by weighted gene co-expression network analysis.World J Gastroenterol. 2018 Nov 21;24(43):4906-4919. doi: 10.3748/wjg.v24.i43.4906.
• [7] Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats.Tumour Biol. 2017 Apr;39(4):1010428317695932. doi: 10.1177/1010428317695932.
• [8] SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts.Sci Rep. 2017 Jun 7;7(1):3012. doi: 10.1038/s41598-017-02533-2.
• [9] SNX10 promotes phagosome maturation in macrophages and protects mice against Listeria monocytogenes infection.Oncotarget. 2017 Jul 27;8(33):53935-53947. doi: 10.18632/oncotarget.19644. eCollection 2017 Aug 15.
• [10] An SNX10 mutation causes malignant osteopetrosis of infancy. J Med Genet. 2012 Apr;49(4):221-6. doi: 10.1136/jmedgenet-2011-100520.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [15] 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.
• [16] 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.
• [17] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [20] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [21] 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.
• [22] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [23] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [24] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [25] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [26] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [27] Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017 Mar 30;129(13):1768-1778. doi: 10.1182/blood-2016-09-736892. Epub 2017 Jan 19.