Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT38HXJP)

• DOT Name: Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1)
• Synonyms: CocoaCrisp; Cysteine-rich secretory protein 10; CRISP-10; LCCL domain-containing cysteine-rich secretory protein 1; Trypsin inhibitor Hl
• Gene Name: CRISPLD1
• Related Disease:
  Coronary atherosclerosis
  Coronary heart disease
• UniProt ID: CRLD1_HUMAN
• Pfam ID: PF00188 ; PF03815
• Sequence:
  MKCTAREWLRVTTVLFMARAIPAMVVPNATLLEKLLEKYMDEDGEWWIAKQRGKRAITDN
  DMQSILDLHNKLRSQVYPTASNMEYMTWDVELERSAESWAESCLWEHGPASLLPSIGQNL
  GAHWGRYRPPTFHVQSWYDEVKDFSYPYEHECNPYCPFRCSGPVCTHYTQVVWATSNRIG
  CAINLCHNMNIWGQIWPKAVYLVCNYSPKGNWWGHAPYKHGRPCSACPPSFGGGCRENLC
  YKEGSDRYYPPREEETNEIERQQSQVHDTHVRTRSDDSSRNEVISAQQMSQIVSCEVRLR
  DQCKGTTCNRYECPAGCLDSKAKVIGSVHYEMQSSICRAAIHYGIIDNDGGWVDITRQGR
  KHYFIKSNRNGIQTIGKYQSANSFTVSKVTVQAVTCETTVEQLCPFHKPASHCPRVYCPR
  NCMQANPHYARVIGTRVYSDLSSICRAAVHAGVVRNHGGYVDVMPVDKRKTYIASFQNGI
  FSESLQNPPGGKAFRVFAVV

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary atherosclerosis	DISKNDYU	Definitive	Genetic Variation	[1]
Coronary heart disease	DIS5OIP1	Definitive	Genetic Variation	[1]

2 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 Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[2]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[9]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[7]
ACYLINE	DM9GRTK	Phase 2	ACYLINE increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cysteine-rich secretory protein LCCL domain-containing 1 (CRISPLD1).	[13]

References

• [1] CRISPLD1 rs12115090 polymorphisms alters antiplatelet potency of clopidogrel in coronary artery disease patients in Chinese Han.Gene. 2018 Dec 15;678:226-232. doi: 10.1016/j.gene.2018.08.027. Epub 2018 Aug 7.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] 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.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [12] Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
• [13] 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.