Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKQH7E5)

• DOT Name: Spermatid nuclear transition protein 1 (TNP1)
• Synonyms: STP-1; TP-1
• Gene Name: TNP1
• Related Disease:
  Azoospermia
  Male infertility
  Arthritis
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Neoplasm
  Rheumatic disorder
• UniProt ID: STP1_HUMAN
• Pfam ID: PF02079
• Sequence: MSTSRKLKSHGMRRSKSRSPHKGVKRGGSKRKYRKGNLKSRKRGDDANRNYRSHL
• Function: Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals. In condensing spermatids, loaded onto the nucleosomes, where it promotes the recruitment and processing of protamines, which are responsible for histone eviction.
• Tissue Specificity: Expressed by spermatids (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Biomarker	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Arthritis	DIST1YEL	Limited	Biomarker	[3]
Autoimmune disease	DISORMTM	Limited	Biomarker	[3]
Breast cancer	DIS7DPX1	Limited	Biomarker	[4]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]
Rheumatic disorder	DIS77ACK	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Spermatid nuclear transition protein 1 (TNP1).	[6]

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 increases the methylation of Spermatid nuclear transition protein 1 (TNP1).	[7]

References

• [1] Could analysis of testis-specific genes, as biomarkers in seminal plasma, predict presence of focal spermatogenesis in non-obstructive azoospermia?.Andrologia. 2020 Mar;52(2):e13483. doi: 10.1111/and.13483. Epub 2019 Dec 3.
• [2] DNA methylation changes at infertility genes in newborn twins conceived by in vitro fertilisation.Genome Med. 2017 Mar 24;9(1):28. doi: 10.1186/s13073-017-0413-5.
• [3] Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35.J Med Genet. 1996 Aug;33(8):672-7. doi: 10.1136/jmg.33.8.672.
• [4] Harnessing copper-palladium alloy tetrapod nanoparticle-induced pro-survival autophagy for optimized photothermal therapy of drug-resistant cancer.Nat Commun. 2018 Oct 12;9(1):4236. doi: 10.1038/s41467-018-06529-y.
• [5] hTERT is a critical determinant of telomerase activity in renal-cell carcinoma.Int J Cancer. 1998 Nov 23;78(5):539-43. doi: 10.1002/(sici)1097-0215(19981123)78:5<539::aid-ijc2>3.0.co;2-i.
• [6] 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.
• [7] 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.