Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNO747E)

• DOT Name: Testis-expressed protein 101 (TEX101)
• Synonyms: Cell surface receptor NYD-SP8; Scleroderma-associated autoantigen; Spermatogenesis-related gene protein
• Gene Name: TEX101
• Related Disease:
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Azoospermia
  Hepatocellular carcinoma
  Male infertility
  Oligospermia
  Advanced cancer
  Neoplasm
• UniProt ID: TX101_HUMAN
• PDB ID: 7BPR
• Pfam ID: PF00021
• Sequence:
  MGTPRIQHLLILLVLGASLLTSGLELYCQKGLSMTVEADPANMFNWTTEEVETCDKGALC
  QETILIIKAGTETAILATKGCIPEGEEAITIVQHSSPPGLIVTSYSNYCEDSFCNDKDSL
  SQFWEFSETTASTVSTTLHCPTCVALGTCFSAPSLPCPNGTTRCYQGKLEITGGGIESSV
  EVKGCTAMIGCRLMSGILAVGPMFVREACPHQLLTQPRKTENGATCLPIPVWGLQLLLPL
  LLPSFIHFS
• Function: Plays a role in fertilization by controlling binding of sperm to zona pellucida and migration of spermatozoa into the oviduct. May play a role in signal transduction and promote protein tyrosine phosphorylation.
• Tissue Specificity: Detected in testis and spermatogonia. Not detected in spermatocytes. Detected in blood leukocytes.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Azoospermia	DIS94181	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Male infertility	DISY3YZZ	Strong	Biomarker	[4]
Oligospermia	DIS6YJF3	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Biomarker	[1]

2 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 Testis-expressed protein 101 (TEX101).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Testis-expressed protein 101 (TEX101).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Testis-expressed protein 101 (TEX101).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Testis-expressed protein 101 (TEX101).	[7]

References

• [1] Transcriptome analysis of the cancer/testis genes, DAZ1, AURKC, and TEX101, in breast tumors and six breast cancer cell lines.Tumour Biol. 2015 Sep;36(10):8201-6. doi: 10.1007/s13277-015-3546-4. Epub 2015 May 21.
• [2] Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility.BMC Med. 2017 Mar 23;15(1):60. doi: 10.1186/s12916-017-0817-5.
• [3] PSPC1-interchanged interactions with PTK6 and -catenin synergize oncogenic subcellular translocations and tumor progression.Nat Commun. 2019 Dec 16;10(1):5716. doi: 10.1038/s41467-019-13665-6.
• [4] Identification of TEX101-associated Proteins Through Proteomic Measurement of Human Spermatozoa Homozygous for the Missense Variant rs35033974.Mol Cell Proteomics. 2019 Feb;18(2):338-351. doi: 10.1074/mcp.RA118.001170. Epub 2018 Nov 14.
• [5] 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.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.