Details of Drug Off-Target (DOT)

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

• DOT Name: Surfactant-associated protein 2 (SFTA2)
• Synonyms: Surfactant-associated protein G; SP-G
• Gene Name: SFTA2
• Related Disease:
  Hepatitis B virus infection
  Attention deficit hyperactivity disorder
  Bipolar disorder
  Hydrocephalus
  Lung adenocarcinoma
  Major depressive disorder
  Membranous glomerulonephritis
  Myasthenia gravis
  Rheumatoid arthritis
  Schizophrenia
  Squamous cell carcinoma
  Type-1 diabetes
  Vitiligo
  Small-cell lung cancer
  Chronic hepatitis B virus infection
  Lung cancer
  Systemic lupus erythematosus
• UniProt ID: SFTA2_HUMAN
• Pfam ID: PF15210
• Sequence:
  MGSGLPLVLLLTLLGSSHGTGPGMTLQLKLKESFLTNSSYESSFLELLEKLCLLLHLPSG
  TSVTLHHARSQHHVVCNT
• Function: Putative surfactant protein.
• Tissue Specificity: Predominantly expressed in lung, where it is detected in type II pneumocytes in the alveolus, and in nonciliated epithelium in bronchioli (at protein level). Also detected at lower levels in cervix, esophagus, stomach, testis and kidney.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Genetic Variation	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[2]
Hydrocephalus	DISIZUF7	Strong	Altered Expression	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Membranous glomerulonephritis	DISFSUKQ	Strong	Genetic Variation	[5]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[7]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[8]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[9]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[10]
Vitiligo	DISR05SL	Strong	Genetic Variation	[11]
Small-cell lung cancer	DISK3LZD	moderate	Genetic Variation	[12]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Genetic Variation	[13]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[14]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Surfactant-associated protein 2 (SFTA2).	[16]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Surfactant-associated protein 2 (SFTA2).	[17]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Surfactant-associated protein 2 (SFTA2).	[18]

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 increases the methylation of Surfactant-associated protein 2 (SFTA2).	[19]

References

• [1] A genome-wide association study identified new variants associated with the risk of chronic hepatitis B.Hum Mol Genet. 2013 Oct 15;22(20):4233-8. doi: 10.1093/hmg/ddt266. Epub 2013 Jun 10.
• [2] Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.Lancet. 2013 Apr 20;381(9875):1371-1379. doi: 10.1016/S0140-6736(12)62129-1. Epub 2013 Feb 28.
• [3] Localization, Occurrence, and CSF Changes of SP-G, a New Surface Active Protein with Assumable Immunoregulatory Functions in the CNS.Mol Neurobiol. 2019 Apr;56(4):2433-2439. doi: 10.1007/s12035-018-1247-x. Epub 2018 Jul 21.
• [4] Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma.Oncotarget. 2017 May 3;8(42):71759-71771. doi: 10.18632/oncotarget.17606. eCollection 2017 Sep 22.
• [5] Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.N Engl J Med. 2011 Feb 17;364(7):616-26. doi: 10.1056/NEJMoa1009742.
• [6] Risk for myasthenia gravis maps to a (151) ProAla change in TNIP1 and to human leukocyte antigen-B*08.Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.
• [7] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [8] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [9] A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer.Sci Rep. 2019 Mar 26;9(1):5207. doi: 10.1038/s41598-019-41585-4.
• [10] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [11] Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.Nat Genet. 2010 Jul;42(7):614-8. doi: 10.1038/ng.603. Epub 2010 Jun 6.
• [12] CD133+ cancer stem-like cells in small cell lung cancer are highly tumorigenic and chemoresistant but sensitive to a novel neuropeptide antagonist.Cancer Res. 2014 Mar 1;74(5):1554-65. doi: 10.1158/0008-5472.CAN-13-1541. Epub 2014 Jan 16.
• [13] Association of VARS2-SFTA2 polymorphisms with the risk of chronic hepatitis B in a Korean population.Liver Int. 2015 Aug;35(8):1934-40. doi: 10.1111/liv.12740. Epub 2015 Jan 10.
• [14] Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.Hum Mol Genet. 2012 Nov 15;21(22):4980-95. doi: 10.1093/hmg/dds334. Epub 2012 Aug 16.
• [15] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [16] 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.
• [17] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [18] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [19] 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.