Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ6GN0Q)

• DOT Name: Protein FAM13A (FAM13A)
• Gene Name: FAM13A
• Related Disease:
  Chronic obstructive pulmonary disease
  Breast cancer
  Breast carcinoma
  Cystic fibrosis
  Hyperlipidemia
  Liver cirrhosis
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Major depressive disorder
  Non-small-cell lung cancer
  Obstructive lung disease
  Pulmonary disease
  Asthma
  Idiopathic interstitial pneumonia
  Obesity
  Neoplasm
  Chronic bronchitis
  Pulmonary fibrosis
• UniProt ID: FA13A_HUMAN
• Pfam ID: PF00620
• Sequence:
  MGAGALAICQSKAAVRLKEDMKKIVAVPLNEQKDFTYQKLFGVSLQELERQGLTENGIPA
  VVWNIVEYLTQHGLTQEGLFRVNGNVKVVEQLRLKFESGVPVELGKDGDVCSAASLLKLF
  LRELPDSLITSALQPRFIQLFQDGRNDVQESSLRDLIKELPDTHYCLLKYLCQFLTKVAK
  HHVQNRMNVHNLATVFGPNCFHVPPGLEGMKEQDLCNKIMAKILENYNTLFEVEYTENDH
  LRCENLARLIIVKEVYYKNSLPILLTRGLERDMPKPPPKTKIPKSRSEGSIQAHRVLQPE
  LSDGIPQLSLRLSYRKACLEDMNSAEGAISAKLVPSSQEDERPLSPFYLSAHVPQVSNVS
  ATGELLERTIRSAVEQHLFDVNNSGGQSSEDSESGTLSASSATSARQRRRQSKEQDEVRH
  GRDKGLINKENTPSGFNHLDDCILNTQEVEKVHKNTFGCAGERSKPKRQKSSTKLSELHD
  NQDGLVNMESLNSTRSHERTGPDDFEWMSDERKGNEKDGGHTQHFESPTMKIQEHPSLSD
  TKQQRNQDAGDQEESFVSEVPQSDLTALCDEKNWEEPIPAFSSWQRENSDSDEAHLSPQA
  GRLIRQLLDEDSDPMLSPRFYAYGQSRQYLDDTEVPPSPPNSHSFMRRRSSSLGSYDDEQ
  EDLTPAQLTRRIQSLKKKIRKFEDRFEEEKKYRPSHSDKAANPEVLKWTNDLAKFRRQLK
  ESKLKISEEDLTPRMRQRSNTLPKSFGSQLEKEDEKKQELVDKAIKPSVEATLESIQRKL
  QEKRAESSRPEDIKDMTKDQIANEKVALQKALLYYESIHGRPVTKNERQVMKPLYDRYRL
  VKQILSRANTIPIIGSPSSKRRSPLLQPIIEGETASFFKEIKEEEEGSEDDSNVKPDFMV
  TLKTDFSARCFLDQFEDDADGFISPMDDKIPSKCSQDTGLSNLHAASIPELLEHLQEMRE
  EKKRIRKKLRDFEDNFFRQNGRNVQKEDRTPMAEEYSEYKHIKAKLRLLEVLISKRDTDS
  KSM
• Tissue Specificity: Isoform 1 is widely expressed, with highest expression in skeletal muscle, thymus, brain and lung. Isoform 3 is less abundant than isoform 1 and predominantly expressed in kidney, pancreas, liver, lung and thymus.
• Reactome Pathway:
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Definitive	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[3]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[4]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[5]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[6]
Lung cancer	DISCM4YA	Strong	Altered Expression	[7]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[7]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[8]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[8]
Obstructive lung disease	DIS4IIDZ	Strong	Genetic Variation	[10]
Pulmonary disease	DIS6060I	Strong	Biomarker	[5]
Asthma	DISW9QNS	moderate	Biomarker	[5]
Idiopathic interstitial pneumonia	DISH7LPY	moderate	Genetic Variation	[11]
Obesity	DIS47Y1K	moderate	Biomarker	[12]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[13]
Chronic bronchitis	DISS8O8V	Limited	Biomarker	[14]
Pulmonary fibrosis	DISQKVLA	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Protein FAM13A (FAM13A) affects the response to substance of Cisplatin.	[36]

21 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 Protein FAM13A (FAM13A).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM13A (FAM13A).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein FAM13A (FAM13A).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein FAM13A (FAM13A).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein FAM13A (FAM13A).	[19]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein FAM13A (FAM13A).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein FAM13A (FAM13A).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein FAM13A (FAM13A).	[21]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Protein FAM13A (FAM13A).	[23]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Protein FAM13A (FAM13A).	[24]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Protein FAM13A (FAM13A).	[25]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Protein FAM13A (FAM13A).	[26]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Protein FAM13A (FAM13A).	[27]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Protein FAM13A (FAM13A).	[28]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein FAM13A (FAM13A).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein FAM13A (FAM13A).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein FAM13A (FAM13A).	[32]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Protein FAM13A (FAM13A).	[33]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Protein FAM13A (FAM13A).	[34]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Protein FAM13A (FAM13A).	[20]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Protein FAM13A (FAM13A).	[35]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Protein FAM13A (FAM13A).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein FAM13A (FAM13A).	[29]

References

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• [2] Role of Polymorphisms of FAM13A, PHLDB1, and CYP24A1 in Breast Cancer Risk.Curr Mol Med. 2019;19(8):579-588. doi: 10.2174/1566524019666190619125109.
• [3] FAM13A is a modifier gene of cystic fibrosis lung phenotype regulating rhoa activity, actin cytoskeleton dynamics and epithelial-mesenchymal transition.J Cyst Fibros. 2018 Mar;17(2):190-203. doi: 10.1016/j.jcf.2017.11.003. Epub 2017 Nov 26.
• [4] Weighted Gene Co-Expression Network Analysis Identifies Specific Modules and Hub Genes Related to Hyperlipidemia.Cell Physiol Biochem. 2018;48(3):1151-1163. doi: 10.1159/000491982. Epub 2018 Jul 25.
• [5] High expression of FAM13A was associated with increasing the liver cirrhosis risk.Mol Genet Genomic Med. 2019 Mar;7(3):e543. doi: 10.1002/mgg3.543. Epub 2019 Jan 2.
• [6] A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population.Nat Genet. 2012 Jul 15;44(8):900-3. doi: 10.1038/ng.2353.
• [7] FAM13A as a Novel Hypoxia-Induced Gene in Non-Small Cell Lung Cancer.J Cancer. 2017 Oct 23;8(19):3933-3938. doi: 10.7150/jca.20342. eCollection 2017.
• [8] FAM13A is associated with non-small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival.Oncoimmunology. 2016 Dec 14;6(1):e1256526. doi: 10.1080/2162402X.2016.1256526. eCollection 2017.
• [9] GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.Am J Psychiatry. 2019 Aug 1;176(8):651-660. doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.
• [10] Genome-wide association study on the FEV(1)/FVC ratio in never-smokers identifies HHIP and FAM13A.J Allergy Clin Immunol. 2017 Feb;139(2):533-540. doi: 10.1016/j.jaci.2016.06.062. Epub 2016 Sep 6.
• [11] FAM13A polymorphism as a prognostic factor in patients with idiopathic pulmonary fibrosis.Respir Med. 2017 Feb;123:105-109. doi: 10.1016/j.rmed.2016.12.007. Epub 2016 Dec 22.
• [12] Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity.Int J Obes (Lond). 2019 Jun;43(6):1269-1280. doi: 10.1038/s41366-018-0222-y. Epub 2018 Oct 9.
• [13] Therapeutic predictors of neoadjuvant endocrine therapy response in estrogen receptor-positive breast cancer with reference to optimal gene expression profiling.Breast Cancer Res Treat. 2018 Nov;172(2):353-362. doi: 10.1007/s10549-018-4933-5. Epub 2018 Aug 27.
• [14] Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.Respir Res. 2014 Sep 21;15(1):113. doi: 10.1186/s12931-014-0113-2.
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• [16] 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.
• [17] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [18] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [19] 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.
• [20] 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.
• [21] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [22] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] 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.
• [25] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [26] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [27] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [28] ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model. Int J Cancer. 2006 Jan 15;118(2):483-9. doi: 10.1002/ijc.21340.
• [29] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [30] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [31] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [32] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [33] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [34] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.
• [35] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [36] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.