Details of Drug Off-Target (DOT)

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

• DOT Name: Leucine-rich repeat-containing protein 34 (LRRC34)
• Gene Name: LRRC34
• Related Disease:
  Multiple sclerosis
  Small lymphocytic lymphoma
  Plasma cell myeloma
  Systemic sclerosis
  Thyroid gland carcinoma
• UniProt ID: LRC34_HUMAN
• PDB ID: 8J07
• Pfam ID: PF13516
• Sequence:
  MAAQPPRPVGERSMGSSREAARAPARSPAWASTQASTPGAALAVQRESPESGLQKHYSNL
  CMEKSQKINPFILHILQEVDEEIKKGLAAGITLNIAGNNRLVPVERVTGEDFWILSKILK
  NCLYINGLDVGYNLLCDVGAYYAAKLLQKQLNLIYLNLMFNDIGPEGGELIAKVLHKNRT
  LKYLRMTGNKIENKGGMFFAAMLQINSSLEKLDLGDCDLGMQSVIAFATVLTQNQAIKAI
  NLNRPILYSEQEESTVHVGRMLKENHCLVALHMCKHDIKNSGIQQLCDALYLNSSLRYLD
  VSCNKITHDGMVYLADVLKSNTTLEVIDLSFNRIENAGANYLSETLTSHNRSLKALSVVS
  NNIEGEGLVALSQSMKTNLTFSHIYIWGNKFDEATCIAYSDLIQMGCLKPDNTDVEPFVV
  DGRVYLAEVSNGLKKHYYWTSTYGESYDHSSNAGFALVPVGQQP
• Function: Highly expressed in stem cells where it may be involved in regulation of pluripotency. In embryonic stem cells (ESCs), important for normal expression of the pluripotency regulators POU5F1/OCT4 and KLF4. Also important for expression of the ectodermal marker gene NES and the endodermal marker gene GATA4. Promotes stem cell proliferation in vitro.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Definitive	Genetic Variation	[1]
Small lymphocytic lymphoma	DIS30POX	Definitive	Genetic Variation	[1]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[2]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[3]
Thyroid gland carcinoma	DISMNGZ0	Limited	Genetic Variation	[4]

6 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 Leucine-rich repeat-containing protein 34 (LRRC34).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat-containing protein 34 (LRRC34).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Leucine-rich repeat-containing protein 34 (LRRC34).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Leucine-rich repeat-containing protein 34 (LRRC34).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leucine-rich repeat-containing protein 34 (LRRC34).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Leucine-rich repeat-containing protein 34 (LRRC34).	[11]

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 affects the methylation of Leucine-rich repeat-containing protein 34 (LRRC34).	[9]

References

• [1] Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.Genet Epidemiol. 2019 Oct;43(7):844-863. doi: 10.1002/gepi.22242. Epub 2019 Aug 13.
• [2] Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.Nat Commun. 2016 Jul 1;7:12050. doi: 10.1038/ncomms12050.
• [3] Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients.Arthritis Res Ther. 2016 Jan 20;18:20. doi: 10.1186/s13075-016-0923-3.
• [4] A genome-wide association study yields five novel thyroid cancer risk loci.Nat Commun. 2017 Feb 14;8:14517. doi: 10.1038/ncomms14517.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] 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.
• [10] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [11] 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.