Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSIO2QA)

• DOT Name: Stomatin-like protein 1 (STOML1)
• Synonyms: SLP-1; EPB72-like protein 1; Protein unc-24 homolog; Stomatin-related protein; STORP
• Gene Name: STOML1
• Related Disease:
  Hereditary stomatocytosis
  Coronary heart disease
  Breast cancer
  Breast carcinoma
  Kennedy disease
  Neoplasm
  Schistosomiasis
• UniProt ID: STML1_HUMAN
• Pfam ID: PF01145 ; PF02036
• Sequence:
  MLGRSGYRALPLGDFDRFQQSSFGFLGSQKGCLSPERGGVGTGADVPQSWPSCLCHGLIS
  FLGFLLLLVTFPISGWFALKIVPTYERMIVFRLGRIRTPQGPGMVLLLPFIDSFQRVDLR
  TRAFNVPPCKLASKDGAVLSVGADVQFRIWDPVLSVMTVKDLNTATRMTAQNAMTKALLK
  RPLREIQMEKLKISDQLLLEINDVTRAWGLEVDRVELAVEAVLQPPQDSPAGPNLDSTLQ
  QLALHFLGGSMNSMAGGAPSPGPADTVEMVSEVEPPAPQVGARSSPKQPLAEGLLTALQP
  FLSEALVSQVGACYQFNVVLPSGTQSAYFLDLTTGRGRVGHGVPDGIPDVVVEMAEADLR
  ALLCRELRPLGAYMSGRLKVKGDLAMAMKLEAVLRALK
• Function: May play a role in cholesterol transfer to late endosomes. May play a role in modulating membrane acid-sensing ion channels. Can specifically inhibit proton-gated current of ASIC1 isoform 1. Can increase inactivation speed of ASIC3. May be involved in regulation of proton sensing in dorsal root ganglions. May play a role in protecting FBXW7 isoform 3 from degradation.
• Tissue Specificity: Ubiquitously expressed at low levels. Expression is highest in brain.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary stomatocytosis	DIS4TC4I	Definitive	Biomarker	[1]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[3]
Kennedy disease	DISXZVM1	Limited	Altered Expression	[4]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]
Schistosomiasis	DIS6PD44	Limited	Biomarker	[6]

2 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 Stomatin-like protein 1 (STOML1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Stomatin-like protein 1 (STOML1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Stomatin-like protein 1 (STOML1).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Stomatin-like protein 1 (STOML1).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Stomatin-like protein 1 (STOML1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Stomatin-like protein 1 (STOML1).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Stomatin-like protein 1 (STOML1).	[13]

References

• [1] A novel gene STORP (STOmatin-Related Protein) is localized 2 kb upstream of the promyelocytic gene on chromosome 15q22.Eur J Haematol. 2000 Feb;64(2):104-13. doi: 10.1034/j.1600-0609.2000.90054.x.
• [2] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [3] A lymph node metastasis-related protein-coding genes combining with long noncoding RNA signature for breast cancer survival prediction.J Cell Physiol. 2019 Nov;234(11):20036-20045. doi: 10.1002/jcp.28600. Epub 2019 Apr 4.
• [4] CD24 cell surface expression in Mvt1 mammary cancer cells serves as a biomarker for sensitivity to anti-IGF1R therapy.Breast Cancer Res. 2016 May 14;18(1):51. doi: 10.1186/s13058-016-0711-7.
• [5] Identification of tissue- and cancer-selective promoters for the introduction of genes into human ovarian cancer cells.Gynecol Oncol. 2002 Jun;85(3):451-8. doi: 10.1006/gyno.2002.6644.
• [6] Saposin-like proteins are expressed in the gastrodermis of Schistosoma mansoni and are immunogenic in natural infections.Int J Infect Dis. 2008 Nov;12(6):e39-47. doi: 10.1016/j.ijid.2007.10.007. Epub 2008 Jun 20.
• [7] 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.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.