Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC2S91N)

• DOT Name: Protein FAM3B (FAM3B)
• Synonyms: Cytokine-like protein 2-21; Pancreatic-derived factor; PANDER
• Gene Name: FAM3B
• Related Disease:
  Cognitive impairment
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Adenocarcinoma
  Carcinoma of esophagus
  Colon cancer
  Colon carcinoma
  Esophageal squamous cell carcinoma
  Fatty liver disease
  Hepatocellular carcinoma
  Hyperglycemia
  Lung carcinoma
  Metabolic disorder
  Neoplasm
  Neuroblastoma
  Obesity
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Skin and skin-structure infection
  Varicella zoster virus infection
  Cardiovascular disease
  Type-1/2 diabetes
• UniProt ID: FAM3B_HUMAN
• Pfam ID: PF15711
• Sequence:
  MRPLAGGLLKVVFVVFASLCAWYSGYLLAELIPDAPLSSAAYSIRSIGERPVLKAPVPKR
  QKCDHWTPCPSDTYAYRLLSGGGRSKYAKICFEDNLLMGEQLGNVARGINIAIVNYVTGN
  VTATRCFDMYEGDNSGPMTKFIQSAAPKSLLFMVTYDDGSTRLNNDAKNAIEALGSKEIR
  NMKFRSSWVFIAAKGLELPSEIQREKINHSDAKNNRYSGWPAEIQIEGCIPKERS
• Function: Induces apoptosis of alpha and beta cells in a dose- and time-dependent manner.
• Tissue Specificity: Highly expressed in the pancreas. Also found in the colon, kidney, prostate, small intestine and testis.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Genetic Variation	[1]
Non-alcoholic fatty liver disease	DISDG1NL	Definitive	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[6]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[7]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[10]
Obesity	DIS47Y1K	Strong	Altered Expression	[11]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[9]
Skin and skin-structure infection	DIS3F9EY	Strong	Biomarker	[12]
Varicella zoster virus infection	DIS7U38D	Strong	Biomarker	[12]
Cardiovascular disease	DIS2IQDX	Limited	Biomarker	[6]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[13]

3 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 Protein FAM3B (FAM3B).	[14]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein FAM3B (FAM3B).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein FAM3B (FAM3B).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM3B (FAM3B).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein FAM3B (FAM3B).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein FAM3B (FAM3B).	[17]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein FAM3B (FAM3B).	[19]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Protein FAM3B (FAM3B).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein FAM3B (FAM3B).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein FAM3B (FAM3B).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein FAM3B (FAM3B).	[24]

References

• [1] Genetic dissection of the Down syndrome critical region.Hum Mol Genet. 2015 Nov 15;24(22):6540-51. doi: 10.1093/hmg/ddv364. Epub 2015 Sep 15.
• [2] FAM3 gene family: A promising therapeutical target for NAFLD and type 2 diabetes.Metabolism. 2018 Apr;81:71-82. doi: 10.1016/j.metabol.2017.12.001. Epub 2017 Dec 6.
• [3] A non-secretory form of FAM3B promotes invasion and metastasis of human colon cancer cells by upregulating Slug expression.Cancer Lett. 2013 Jan 28;328(2):278-84. doi: 10.1016/j.canlet.2012.09.026. Epub 2012 Oct 8.
• [4] FAM3B promotes progression of oesophageal carcinoma via regulating the AKT-MDM2-p53 signalling axis and the epithelial-mesenchymal transition.J Cell Mol Med. 2019 Feb;23(2):1375-1385. doi: 10.1111/jcmm.14040. Epub 2018 Dec 18.
• [5] Pancreatic-derived factor promotes lipogenesis in the mouse liver: role of the Forkhead box 1 signaling pathway.Hepatology. 2011 Jun;53(6):1906-16. doi: 10.1002/hep.24295. Epub 2011 May 2.
• [6] FAM3B mediates high glucose-induced vascular smooth muscle cell proliferation and migration via inhibition of miR-322-5p.Sci Rep. 2017 May 23;7(1):2298. doi: 10.1038/s41598-017-02683-3.
• [7] Knockdown of FAM3B triggers cell apoptosis through p53-dependent pathway.Int J Biochem Cell Biol. 2013 Mar;45(3):684-91. doi: 10.1016/j.biocel.2012.12.003. Epub 2012 Dec 12.
• [8] Effects of circulating member B of the family with sequence similarity 3 on the risk of developing metabolic syndrome and its components: A 5-year prospective study.J Diabetes Investig. 2018 Jul;9(4):782-788. doi: 10.1111/jdi.12780. Epub 2018 Jan 3.
• [9] FAM3B/PANDER inhibits cell death and increases prostate tumor growth by modulating the expression of Bcl-2 and Bcl-X(L) cell survival genes.BMC Cancer. 2018 Jan 22;18(1):90. doi: 10.1186/s12885-017-3950-9.
• [10] Over-expression of CLN3P, the Batten disease protein, inhibits PANDER-induced apoptosis in neuroblastoma cells: further evidence that CLN3P has anti-apoptotic properties.Mol Genet Metab. 2006 Jun;88(2):178-83. doi: 10.1016/j.ymgme.2006.01.011. Epub 2006 Mar 3.
• [11] Family with sequence similarity 3 gene family and nonalcoholic fatty liver disease.J Gastroenterol Hepatol. 2013 Aug;28 Suppl 1:105-11. doi: 10.1111/jgh.12033.
• [12] ORF11 protein interacts with the ORF9 essential tegument protein in varicella-zoster virus infection.J Virol. 2013 May;87(9):5106-17. doi: 10.1128/JVI.00102-13. Epub 2013 Feb 20.
• [13] Association of serum pancreatic derived factor (PANDER) with beta-cell dysfunction in type 2 diabetes mellitus.J Diabetes Complications. 2017 Apr;31(4):748-752. doi: 10.1016/j.jdiacomp.2017.01.001. Epub 2017 Jan 20.
• [14] 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.
• [15] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [16] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [19] 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.
• [20] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [23] 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.
• [24] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.