Details of Drug Off-Target (DOT)

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

• DOT Name: Stomatin-like protein 3 (STOML3)
• Synonyms: SLP-3
• Gene Name: STOML3
• Related Disease:
  Hereditary stomatocytosis
  Advanced cancer
  Bardet biedl syndrome
  Epithelial ovarian cancer
  Gliosarcoma
  Insulinoma
  Intellectual disability
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Angelman syndrome
  Nervous system inflammation
  Prader-Willi syndrome
• UniProt ID: STML3_HUMAN
• Pfam ID: PF01145
• Sequence:
  MDSRVSSPEKQDKENFVGVNNKRLGVCGWILFSLSFLLVIITFPISIWMCLKIIKEYERA
  VVFRLGRIQADKAKGPGLILVLPCIDVFVKVDLRTVTCNIPPQEILTRDSVTTQVDGVVY
  YRIYSAVSAVANVNDVHQATFLLAQTTLRNVLGTQTLSQILAGREEIAHSIQTLLDDATE
  LWGIRVARVEIKDVRIPVQLQRSMAAEAEATREARAKVLAAEGEMNASKSLKSASMVLAE
  SPIALQLRYLQTLSTVATEKNSTIVFPLPMNILEGIGGVSYDNHKKLPNKA
• Function: Required for the function of many mechanoreceptors. Modulate mechanotransduction channels and acid-sensing ion channels (ASIC) proteins. Potentiates PIEZO1 and PIEZO2 function by increasing their sensitivity to mechanical stimulations.
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary stomatocytosis	DIS4TC4I	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Bardet biedl syndrome	DISTBNZW	Strong	Genetic Variation	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[2]
Gliosarcoma	DIS985MG	Strong	Biomarker	[4]
Insulinoma	DISIU1JS	Strong	Biomarker	[5]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[2]
Angelman syndrome	DIS4QVXO	Limited	Biomarker	[7]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[8]
Prader-Willi syndrome	DISYWMLU	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Stomatin-like protein 3 (STOML3).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Stomatin-like protein 3 (STOML3).	[10]

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] Evaluation of the potential of a new ribavirin analog impairing the dissemination of ovarian cancer cells.PLoS One. 2019 Dec 11;14(12):e0225860. doi: 10.1371/journal.pone.0225860. eCollection 2019.
• [3] Loss of Bardet Biedl syndrome proteins causes defects in peripheral sensory innervation and function.Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17524-9. doi: 10.1073/pnas.0706618104. Epub 2007 Oct 24.
• [4] Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in gliosarcoma.Am J Pathol. 2012 May;180(5):1816-23. doi: 10.1016/j.ajpath.2012.01.027.
• [5] Chromosome 1q loss of heterozygosity frequently occurs in sporadic insulinomas and is associated with tumor malignancy.Int J Cancer. 2005 Nov 1;117(2):234-40. doi: 10.1002/ijc.21175.
• [6] Haploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability. Orphanet J Rare Dis. 2013 Jan 7;8:3. doi: 10.1186/1750-1172-8-3.
• [7] Mechanisms of imprinting of the Prader-Willi/Angelman region.Am J Med Genet A. 2008 Aug 15;146A(16):2041-52. doi: 10.1002/ajmg.a.32364.
• [8] Gene Expression Profile of Olfactory Transduction Signaling in an Animal Model of Human Multiple Sclerosis.Exp Neurobiol. 2019 Feb;28(1):74-84. doi: 10.5607/en.2019.28.1.74. Epub 2019 Feb 28.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.