Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTED6WB8)

• DOT Name: Speriolin-like protein (SPATC1L)
• Synonyms: Spermatogenesis and centriole-associated protein 1-like protein
• Gene Name: SPATC1L
• Related Disease:
  Aortic aneurysm
  Atrial fibrillation
  Lung cancer
  Lung carcinoma
  Deafness
• UniProt ID: SPC1L_HUMAN
• Pfam ID: PF15059 ; PF15058
• Sequence:
  MAEGGELMSRLLSENADLKKQVRLLKENQMLRRLLSQSCQEGGGHDLLPPRAHAYPEAGS
  PGSGVPDFGRFTSVADTPSQLQTSSLEDLLCSHAPLSSEDDTSPGCAAPSQAPFKAFLSP
  PEPHSHRGTDRKLSPLLSPLQDSLVDKTLLEPREMVRPKKVCFSESSLPTGDRTRRSYYL
  NEIQSFAGAEKDARVVGEIAFQLDRRILAYVFPGVTRLYGFTVANIPEKIEQTSTKSLDG
  SVDERKLRELTQRYLALSARLEKLGYSRDVHPAFSEFLINTYGILKQRPDLRANPLHSSP
  AALRKLVIDVVPPKFLGDSLLLLNCLCELSKEDGKPLFAW

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aortic aneurysm	DISQ5KRA	Strong	Genetic Variation	[1]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[2]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[3]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[3]
Deafness	DISKCLH4	Limited	Autosomal dominant	[4]

4 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 Speriolin-like protein (SPATC1L).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Speriolin-like protein (SPATC1L).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Speriolin-like protein (SPATC1L).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Speriolin-like protein (SPATC1L).	[9]

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 Speriolin-like protein (SPATC1L).	[8]

References

• [1] Identification of EGFLAM, SPATC1L and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals by exome-wide association studies.Int J Mol Med. 2017 May;39(5):1091-1100. doi: 10.3892/ijmm.2017.2927. Epub 2017 Mar 21.
• [2] Identification of TNFSF13, SPATC1L, SLC22A25 and SALL4 as novel susceptibility loci for atrial fibrillation by an exomewide association study.Mol Med Rep. 2017 Nov;16(5):5823-5832. doi: 10.3892/mmr.2017.7334. Epub 2017 Aug 23.
• [3] Genome-wide analysis of expression quantitative trait loci identified potential lung cancer susceptibility variants among Asian populations.Carcinogenesis. 2019 Apr 29;40(2):263-268. doi: 10.1093/carcin/bgy165.
• [4] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [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.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.