Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT0QHQ1)

• DOT Name: Fibrinogen-like protein 1 (FGL1)
• Synonyms: HP-041; Hepassocin; HPS; Hepatocyte-derived fibrinogen-related protein 1; HFREP-1; Liver fibrinogen-related protein 1; LFIRE-1
• Gene Name: FGL1
• Related Disease:
  Chediak-Higashi syndrome
  Hepatocellular carcinoma
  Advanced cancer
  Albinism
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Griscelli syndrome
  Hantavirus infection
  Hermansky-Pudlak syndrome
  Hyperlipidemia
  Hypopigmentation of the skin
  Lung adenocarcinoma
  Neoplasm
  Nephropathy
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Obesity
  Ocular albinism
  Oculocutaneous albinism
  Polyp
  Pulmonary fibrosis
  Usher syndrome type 1B
  Bartter disease type 3
  Bartter syndrome
  Gastric cancer
  Hemophagocytic syndrome
  Nephrocalcinosis
  Stomach cancer
  Hyperglycemia
  Fatty liver disease
  Type-1/2 diabetes
• UniProt ID: FGL1_HUMAN
• PDB ID: 7TZ2
• Pfam ID: PF00147
• Sequence:
  MAKVFSFILVTTALTMGREISALEDCAQEQMRLRAQVRLLETRVKQQQVKIKQLLQENEV
  QFLDKGDENTVIDLGSKRQYADCSEIFNDGYKLSGFYKIKPLQSPAEFSVYCDMSDGGGW
  TVIQRRSDGSENFNRGWKDYENGFGNFVQKHGEYWLGNKNLHFLTTQEDYTLKIDLADFE
  KNSRYAQYKNFKVGDEKNFYELNIGEYSGTAGDSLAGNFHPEVQWWASHQRMKFSTWDRD
  HDNYEGNCAEEDQSGWWFNRCHSANLNGVYYSGPYTAKTDNGIVWYTWHGWWYSLKSVVM
  KIRPNDFIPNVI
• Function: Immune suppressive molecule that inhibits antigen-specific T-cell activation by acting as a major ligand of LAG3. Responsible for LAG3 T-cell inhibitory function. Binds LAG3 independently from MHC class II (MHC-II). Secreted by, and promotes growth of, hepatocytes.
• Tissue Specificity: Under normal conditions, liver-specific.

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chediak-Higashi syndrome	DISPJLLO	Definitive	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Albinism	DIS5D82I	Strong	Genetic Variation	[4]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Griscelli syndrome	DISTHCOQ	Strong	Genetic Variation	[9]
Hantavirus infection	DISZFTMH	Strong	Genetic Variation	[10]
Hermansky-Pudlak syndrome	DISCY0HQ	Strong	Genetic Variation	[11]
Hyperlipidemia	DIS61J3S	Strong	Altered Expression	[12]
Hypopigmentation of the skin	DIS39YKC	Strong	Altered Expression	[11]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Nephropathy	DISXWP4P	Strong	Biomarker	[11]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[14]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[14]
Obesity	DIS47Y1K	Strong	Biomarker	[15]
Ocular albinism	DIS5IHK1	Strong	Genetic Variation	[9]
Oculocutaneous albinism	DISJS7CU	Strong	Biomarker	[16]
Polyp	DISRSLYF	Strong	Biomarker	[8]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[17]
Usher syndrome type 1B	DISWTUHR	Strong	Genetic Variation	[9]
Bartter disease type 3	DISJJPTS	moderate	Biomarker	[18]
Bartter syndrome	DIS7D44B	moderate	Genetic Variation	[18]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[19]
Hemophagocytic syndrome	DIS3TMN4	moderate	Biomarker	[20]
Nephrocalcinosis	DIS5ZVJP	moderate	Biomarker	[18]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[19]
Hyperglycemia	DIS0BZB5	Disputed	Biomarker	[21]
Fatty liver disease	DIS485QZ	Limited	Biomarker	[15]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Fibrinogen-like protein 1 (FGL1).	[23]

12 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 Fibrinogen-like protein 1 (FGL1).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fibrinogen-like protein 1 (FGL1).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fibrinogen-like protein 1 (FGL1).	[26]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fibrinogen-like protein 1 (FGL1).	[27]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fibrinogen-like protein 1 (FGL1).	[28]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fibrinogen-like protein 1 (FGL1).	[29]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fibrinogen-like protein 1 (FGL1).	[29]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Fibrinogen-like protein 1 (FGL1).	[30]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Fibrinogen-like protein 1 (FGL1).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fibrinogen-like protein 1 (FGL1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fibrinogen-like protein 1 (FGL1).	[33]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Fibrinogen-like protein 1 (FGL1).	[34]

References

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• [13] Loss of FGL1 induces epithelialmesenchymal transition and angiogenesis in LKB1 mutant lung adenocarcinoma.Int J Oncol. 2019 Sep;55(3):697-707. doi: 10.3892/ijo.2019.4838. Epub 2019 Jul 15.
• [14] Overexpression of Hepassocin in Diabetic Patients with Nonalcoholic Fatty Liver Disease May Facilitate Increased Hepatic Lipid Accumulation.Endocr Metab Immune Disord Drug Targets. 2019;19(2):185-188. doi: 10.2174/1871530318666180716100543.
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• [16] Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. J Invest Dermatol. 2013 Jul;133(7):1834-40. doi: 10.1038/jid.2013.49. Epub 2013 Jan 30.
• [17] Identification of molecular signatures involved in radiation-induced lung fibrosis.J Mol Med (Berl). 2019 Jan;97(1):37-47. doi: 10.1007/s00109-018-1715-9. Epub 2018 Nov 7.
• [18] Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome.J Am Soc Nephrol. 2000 Aug;11(8):1449-1459. doi: 10.1681/ASN.V1181449.
• [19] Fibrinogenlikeprotein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis.Mol Med Rep. 2018 Aug;18(2):1465-1472. doi: 10.3892/mmr.2018.9097. Epub 2018 May 29.
• [20] Nontuberculous Mycobacterium infection complicated with Haemophagocytic syndrome: a case report and literature review.BMC Infect Dis. 2019 May 9;19(1):399. doi: 10.1186/s12879-019-4061-9.
• [21] The Hepatic Protection Effects of Hepassocin in Hyperglycemic Crisis.J Clin Endocrinol Metab. 2017 Jul 1;102(7):2407-2415. doi: 10.1210/jc.2016-3287.
• [22] A novel hepatokine, HFREP1, plays a crucial role in the development of insulin resistance and type 2 diabetes.Diabetologia. 2016 Aug;59(8):1732-42. doi: 10.1007/s00125-016-3991-7. Epub 2016 May 25.
• [23] 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.
• [24] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [25] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [26] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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• [32] Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
• [33] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [34] 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.