Details of Drug Off-Target (DOT)

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

• DOT Name: Coiled-coil domain-containing protein 91 (CCDC91)
• Synonyms: GGA-binding partner; p56 accessory protein
• Gene Name: CCDC91
• Related Disease:
  Angiomyolipoma
  Chronic obstructive pulmonary disease
  Cognitive impairment
  Drug dependence
  Myopia
  Polycystic ovarian syndrome
  Status epilepticus seizure
  Substance abuse
  Substance dependence
  Cervical carcinoma
  Autism spectrum disorder
• UniProt ID: CCD91_HUMAN
• PDB ID: 1OM9
• Sequence:
  MDDDDFGGFEAAETFDGGSGETQTTSPAIPWAAFPAVSGVHLSPSSPEIVLDRDHSSSIG
  CLSSDAIISSPENTHAANSIVSQTIPKAQIQQSTHTHLDISLFPLGLTDEKSNGTIALVD
  DSEDPGANVSNIQLQQKISSLEIKLKVSEEEKQRIKQDVESLMEKHNVLEKGFLKEKEQE
  AISFQDRYKELQEKHKQELEDMRKAGHEALSIIVDEYKALLQSSVKQQVEAIEKQYISAI
  EKQAHKCEELLNAQHQRLLEMLDTEKELLKEKIKEALIQQSQEQKEILEKCLEEERQRNK
  EALVSAAKLEKEAVKDAVLKVVEEERKNLEKAHAEERELWKTEHAKDQEKVSQEIQKAIQ
  EQRKISQETVKAAIIEEQKRSEKAVEEAVKRTRDELIEYIKEQKRLDQVIRQRSLSSLEL
  FLSCAQKQLSALIATEPVDIE
• Function: Involved in the regulation of membrane traffic through the trans-Golgi network (TGN). Functions in close cooperation with the GGAs in the sorting of hydrolases to lysosomes.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angiomyolipoma	DIS2L71N	Strong	Biomarker	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[3]
Drug dependence	DIS9IXRC	Strong	Biomarker	[4]
Myopia	DISK5S60	Strong	Biomarker	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[6]
Status epilepticus seizure	DISY3BIC	Strong	Genetic Variation	[7]
Substance abuse	DIS327VW	Strong	Biomarker	[4]
Substance dependence	DISDRAAR	Strong	Biomarker	[4]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[8]
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[9]

3 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 Coiled-coil domain-containing protein 91 (CCDC91).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Coiled-coil domain-containing protein 91 (CCDC91).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Coiled-coil domain-containing protein 91 (CCDC91).	[16]

5 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 Coiled-coil domain-containing protein 91 (CCDC91).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Coiled-coil domain-containing protein 91 (CCDC91).	[13]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Coiled-coil domain-containing protein 91 (CCDC91).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coiled-coil domain-containing protein 91 (CCDC91).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Coiled-coil domain-containing protein 91 (CCDC91).	[17]

References

• [1] Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma.Lancet. 2003 Apr 19;361(9366):1348-9. doi: 10.1016/S0140-6736(03)13044-9.
• [2] Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
• [3] Key role of soluble epoxide hydrolase in the neurodevelopmental disorders of offspring after maternal immune activation.Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7083-7088. doi: 10.1073/pnas.1819234116. Epub 2019 Mar 19.
• [4] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [5] Genetic deletion of the adenosine A2A receptor confers postnatal development of relative myopia in mice.Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4362-70. doi: 10.1167/iovs.09-3998. Epub 2010 May 19.
• [6] Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.Nat Commun. 2015 Aug 18;6:7502. doi: 10.1038/ncomms8502.
• [7] Altered Synaptic Drive onto Birthdated Dentate Granule Cells in Experimental Temporal Lobe Epilepsy.J Neurosci. 2019 Sep 18;39(38):7604-7614. doi: 10.1523/JNEUROSCI.0654-18.2019. Epub 2019 Jul 3.
• [8] Identification of a promoter in position 56 within the long control region of human papillomavirus type 18.Arch Virol. 2001;146(11):2069-84. doi: 10.1007/s007050170021.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] 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.
• [14] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] 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.
• [17] 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.