Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC8R6EH)

• DOT Name: Stomatin (STOM)
• Synonyms: Erythrocyte band 7 integral membrane protein; Erythrocyte membrane protein band 7.2; Protein 7.2b
• Gene Name: STOM
• Related Disease:
  Carcinoma of esophagus
  Cataract
  Cervical cancer
  Cervical carcinoma
  Childhood onset GLUT1 deficiency syndrome 2
  Cleft lip/palate
  Colorectal carcinoma
  Dehydrated hereditary stomatocytosis
  Gallbladder cancer
  Gallbladder carcinoma
  Gastric adenocarcinoma
  GLUT1 deficiency syndrome
  Movement disorder
  Nephrotic syndrome
  Non-small-cell lung cancer
  Osteoporosis
  Overhydrated hereditary stomatocytosis
  Recessive X-linked ichthyosis
  Sarcoma
  Soft tissue sarcoma
  Advanced cancer
  Cryohydrocytosis
  Neoplasm
• UniProt ID: STOM_HUMAN
• PDB ID: 7WH3
• Pfam ID: PF01145
• Sequence:
  MAEKRHTRDSEAQRLPDSFKDSPSKGLGPCGWILVAFSFLFTVITFPISIWMCIKIIKEY
  ERAIIFRLGRILQGGAKGPGLFFILPCTDSFIKVDMRTISFDIPPQEILTKDSVTISVDG
  VVYYRVQNATLAVANITNADSATRLLAQTTLRNVLGTKNLSQILSDREEIAHNMQSTLDD
  ATDAWGIKVERVEIKDVKLPVQLQRAMAAEAEASREARAKVIAAEGEMNASRALKEASMV
  ITESPAALQLRYLQTLTTIAAEKNSTIVFPLPIDMLQGIIGAKHSHLG
• Function: Regulates ion channel activity and transmembrane ion transport. Regulates ASIC2 and ASIC3 channel activity.
• Tissue Specificity: Detected in erythrocytes (at protein level). Widely expressed.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOH GTPase cycle (R-HSA-9013407)
  RHOJ GTPase cycle (R-HSA-9013409)
  Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[1]
Cataract	DISUD7SL	Strong	Genetic Variation	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Childhood onset GLUT1 deficiency syndrome 2	DISXPRXM	Strong	Biomarker	[4]
Cleft lip/palate	DIS14IG3	Strong	Genetic Variation	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Dehydrated hereditary stomatocytosis	DISGQT6H	Strong	Genetic Variation	[7]
Gallbladder cancer	DISXJUAF	Strong	Altered Expression	[6]
Gallbladder carcinoma	DISD6ACL	Strong	Altered Expression	[6]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[8]
GLUT1 deficiency syndrome	DIS8OXEB	Strong	Genetic Variation	[2]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[2]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[10]
Osteoporosis	DISF2JE0	Strong	Biomarker	[11]
Overhydrated hereditary stomatocytosis	DIS6TF7I	Strong	Altered Expression	[12]
Recessive X-linked ichthyosis	DISZY56W	Strong	Biomarker	[10]
Sarcoma	DISZDG3U	Strong	Biomarker	[10]
Soft tissue sarcoma	DISSN8XB	Strong	Biomarker	[10]
Advanced cancer	DISAT1Z9	Disputed	Biomarker	[13]
Cryohydrocytosis	DISMQHL3	Limited	Genetic Variation	[14]
Neoplasm	DISZKGEW	Limited	Biomarker	[15]

22 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 Stomatin (STOM).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Stomatin (STOM).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Stomatin (STOM).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Stomatin (STOM).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Stomatin (STOM).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Stomatin (STOM).	[21]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Stomatin (STOM).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Stomatin (STOM).	[23]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Stomatin (STOM).	[24]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Stomatin (STOM).	[25]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Stomatin (STOM).	[26]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Stomatin (STOM).	[27]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Stomatin (STOM).	[28]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Stomatin (STOM).	[29]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Stomatin (STOM).	[29]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Stomatin (STOM).	[29]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Stomatin (STOM).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Stomatin (STOM).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Stomatin (STOM).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Stomatin (STOM).	[33]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Stomatin (STOM).	[34]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Stomatin (STOM).	[35]

References

• [1] miRNA-1207-5p is associated with cancer progression by targeting stomatin-like protein 2 in esophageal carcinoma.Int J Oncol. 2015 May;46(5):2163-71. doi: 10.3892/ijo.2015.2900. Epub 2015 Feb 19.
• [2] Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome. Blood. 2011 Nov 10;118(19):5267-77. doi: 10.1182/blood-2010-12-326645. Epub 2011 Jul 26.
• [3] Stomatin-like protein 2 expression is associated with clinical survival in patients with cervical cancer.Int J Clin Exp Pathol. 2015 Feb 1;8(2):1804-9. eCollection 2015.
• [4] Glucide metabolism disorders (excluding glycogen myopathies).Handb Clin Neurol. 2013;113:1689-94. doi: 10.1016/B978-0-444-59565-2.00036-8.
• [5] Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate.Am J Med Genet A. 2010 Jul;152A(7):1701-10. doi: 10.1002/ajmg.a.33482.
• [6] Enhanced SLP-2 promotes invasion and metastasis by regulating Wnt/-catenin signal pathway in colorectal cancer and predicts poor prognosis.Pathol Res Pract. 2019 Jan;215(1):57-67. doi: 10.1016/j.prp.2018.10.018. Epub 2018 Oct 24.
• [7] Exclusion of the stomatin, alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis.Am J Hematol. 1999 Jan;60(1):72-4. doi: 10.1002/(sici)1096-8652(199901)60:1<72::aid-ajh13>3.0.co;2-8.
• [8] Increased expression of stomatin-like protein 2 (STOML2) predicts decreased survival in gastric adenocarcinoma: a retrospective study.Med Oncol. 2014 Jan;31(1):763. doi: 10.1007/s12032-013-0763-9. Epub 2013 Nov 21.
• [9] The curious genomic path from leaky red cell to nephrotic kidney.Nephron Physiol. 2003;93(2):p29-33. doi: 10.1159/000068527.
• [10] Simultaneous expression of flotillin-1, flotillin-2, stomatin and caveolin-1 in non-small cell lung cancer and soft tissue sarcomas.BMC Cancer. 2014 Feb 17;14:100. doi: 10.1186/1471-2407-14-100.
• [11] Lipid raft-associated stomatin enhances cell fusion.FASEB J. 2017 Jan;31(1):47-59. doi: 10.1096/fj.201600643R. Epub 2016 Sep 23.
• [12] The "stomatin" gene and protein in overhydrated hereditary stomatocytosis.Blood. 2003 Sep 15;102(6):2268-77. doi: 10.1182/blood-2002-06-1705. Epub 2003 May 15.
• [13] Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation.APMIS. 2016 Apr;124(4):271-7. doi: 10.1111/apm.12505. Epub 2016 Jan 11.
• [14] The Molecular Basis for Altered Cation Permeability in Hereditary Stomatocytic Human Red Blood Cells.Front Physiol. 2018 Apr 16;9:367. doi: 10.3389/fphys.2018.00367. eCollection 2018.
• [15] Stomatin-like protein 2 is associated with the clinicopathological features of human papillary thyroid cancer and is regulated by TGF- in thyroid cancer cells.Oncol Rep. 2014 Jan;31(1):153-60. doi: 10.3892/or.2013.2833. Epub 2013 Nov 4.
• [16] 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.
• [17] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [18] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [19] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [20] 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.
• [21] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [22] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [23] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [24] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [25] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [26] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [27] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [28] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [29] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [30] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [31] 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.
• [32] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [33] 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.
• [34] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [35] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.