Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT37KCUL)

• DOT Name: Tetratricopeptide repeat protein 29 (TTC29)
• Synonyms: TPR repeat protein 29; Protein TBPP2A; Testis development protein NYD-SP14
• Gene Name: TTC29
• Related Disease:
  Male infertility
  Spermatogenic failure 42
  Obsolete non-syndromic male infertility due to sperm motility disorder
• UniProt ID: TTC29_HUMAN
• PDB ID: 8J07
• Pfam ID: PF13424 ; PF13432
• Sequence:
  MTTLPPLPMTRPKLTALARQKLPCSSRKIPRSQLIKEKDDIDHYLEVNFKGLSKEEVAAY
  RNSYKKNICVDMLRDGYHKSFTELFALMERWDALREAARVRSLFWLQKPLEEQPDKLDYL
  YHYLTRAEDAERKESFEDVHNNLYALACYFNNSEDKWVRNHFYERCFKIAQLIKIDCGKK
  EAEAHMHMGLLYEEDGQLLEAAEHYEAFHQLTQGRIWKDETGRSLNLLACESLLRTYRLL
  SDKMLENKEYKQAIKILIKASEIAKEGSDKKMEAEASYYLGLAHLAAEEYETALTVLDTY
  CKISTDLDDDLSLGRGYEAIAKVLQSQGEMTEAIKYLKKFVKIARNNFQSLDLVRASTML
  GDIYNEKGYYNKASECFQQAFDTTVELMSMPLMDETKVHYGIAKAHQMMLTVNNYIESAD
  LTSLNYLLSWKESRGNIEPDPVTEEFRGSTVEAVSQNSERLEELSRFPGDQKNET
• Function: Axonemal protein which is implicated in axonemal and/or peri-axonemal structures assembly and regulates flagella assembly and beating and therefore sperm motility.
• Tissue Specificity: Expressed in spermatozoa (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Genetic Variation	[1]
Spermatogenic failure 42	DISLH7U4	Strong	Autosomal recessive	[1]
Obsolete non-syndromic male infertility due to sperm motility disorder	DISG7641	Supportive	Autosomal recessive	[1]

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 Tetratricopeptide repeat protein 29 (TTC29).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tetratricopeptide repeat protein 29 (TTC29).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Tetratricopeptide repeat protein 29 (TTC29).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tetratricopeptide repeat protein 29 (TTC29).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tetratricopeptide repeat protein 29 (TTC29).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tetratricopeptide repeat protein 29 (TTC29).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tetratricopeptide repeat protein 29 (TTC29).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Tetratricopeptide repeat protein 29 (TTC29).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tetratricopeptide repeat protein 29 (TTC29).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tetratricopeptide repeat protein 29 (TTC29).	[10]

References

• [1] Mutations in TTC29, Encoding an Evolutionarily Conserved Axonemal Protein, Result in Asthenozoospermia and Male Infertility. Am J Hum Genet. 2019 Dec 5;105(6):1148-1167. doi: 10.1016/j.ajhg.2019.10.007. Epub 2019 Nov 14.
• [2] 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.
• [3] 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.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] 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.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] 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.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.