Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC4LRBU)

• DOT Name: Myelin protein zero-like protein 3 (MPZL3)
• Gene Name: MPZL3
• Related Disease:
  Alopecia
  Dermatitis
  Lung adenocarcinoma
  Non-small-cell lung cancer
  Seborrhoeic dermatitis
• UniProt ID: MPZL3_HUMAN
• Pfam ID: PF07686
• Sequence:
  MQQRGAAGSRGCALFPLLGVLFFQGVYIVFSLEIRADAHVRGYVGEKIKLKCTFKSTSDV
  TDKLTIDWTYRPPSSSHTVSIFHYQSFQYPTTAGTFRDRISWVGNVYKGDASISISNPTI
  KDNGTFSCAVKNPPDVHHNIPMTELTVTERGFGTMLSSVALLSILVFVPSAVVVALLLVR
  MGRKAAGLKKRSRSGYKKSSIEVSDDTDQEEEEACMARLCVRCAECLDSDYEETY
• Function: Mediates homophilic cell-cell adhesion.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia	DIS37HU4	Strong	Genetic Variation	[1]
Dermatitis	DISY5SZC	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[3]
Seborrhoeic dermatitis	DISNWVJU	Strong	Biomarker	[4]

11 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 Myelin protein zero-like protein 3 (MPZL3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myelin protein zero-like protein 3 (MPZL3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Myelin protein zero-like protein 3 (MPZL3).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Myelin protein zero-like protein 3 (MPZL3).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Myelin protein zero-like protein 3 (MPZL3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Myelin protein zero-like protein 3 (MPZL3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Myelin protein zero-like protein 3 (MPZL3).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myelin protein zero-like protein 3 (MPZL3).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Myelin protein zero-like protein 3 (MPZL3).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Myelin protein zero-like protein 3 (MPZL3).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Myelin protein zero-like protein 3 (MPZL3).	[15]

References

• [1] The human orthologue of murine Mpzl3 with predicted adhesive and immune functions is a potential candidate gene for immune-related hereditary hair loss.Exp Dermatol. 2009 Mar;18(3):261-3. doi: 10.1111/j.1600-0625.2008.00797.x. Epub 2008 Oct 22.
• [2] Increased IL-17-expressing T cells in seborrhoeic dermatitis-like lesions of the Mpzl3 knockout mice.Exp Dermatol. 2018 Dec;27(12):1408-1411. doi: 10.1111/exd.13798.
• [3] Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations.Lancet Respir Med. 2019 Oct;7(10):881-891. doi: 10.1016/S2213-2600(19)30144-4. Epub 2019 Jul 17.
• [4] Seborrheic dermatitis-Looking beyond Malassezia.Exp Dermatol. 2019 Sep;28(9):991-1001. doi: 10.1111/exd.14006. Epub 2019 Aug 19.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.