Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT45M743)

• DOT Name: Calcyphosin-2 (CAPS2)
• Synonyms: Calcyphosine-2
• Gene Name: CAPS2
• Related Disease:
  Autism
  Autism spectrum disorder
  Neuralgia
  Pervasive developmental disorder
  Anxiety
  Anxiety disorder
  Neurodevelopmental disorder
  Intellectual disability
• UniProt ID: CAYP2_HUMAN
• Pfam ID: PF13499
• Sequence:
  MDLEVKGVAATSRSQIQPFFGRKKPLQQRWTSESWTNQNSCPPVVPRLDLGSLVDSDDED
  NFSYIPLSTANLPNSSSTLGWVTPCQTPYTQYHLNKLDQNIIPENLPAPTDKCKLKYQQC
  KTEIKEGYKQYSQRNAENTKSNVTHKQSPRNKIDEKCVQDEEANTDDLTTLDRKAILQQG
  YADNSCDKQQRARKLDAEIVAAEKKKQIVAEQVMIDHLSRAVISDPEQNLAIEQKESDHI
  LPDSKMTPLRFRKRTLHETKIRTHSTLTENVLSHKLQFDGRIVSRNGRDACRELIGFFFT
  HDQSLTIYEYRQFGKNRTNVLPFIQKSIYSHQCGRRKGKQYRLGDFYVGATLTFLSSDHL
  SLPESIKENTLLKLRITNIDQIALDSLKTASMEQEDDIIIQETNDRLVFKAIQDVLKEKL
  HKRGVRILTGLGKYFQQLDKEGNGLLDKADFKQALKVFHLEVSEKDFESAWLILNDNGNG
  KVDYGEFKRGIIGEMNEYRKSYVRKAFMKLDFNKSGSVPIINIRKCYCAKKHSQVISG
• Tissue Specificity: Abundantly expressed in many tissues. Expressed in brain, colon, heart, kidney, liver, lung, liver, pancreas, placenta, skeletal muscle, testis and thymus. Highest expression in colon, testis, lung, placenta and brain.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Neuralgia	DISWO58J	Strong	Biomarker	[3]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[4]
Anxiety	DISIJDBA	moderate	Biomarker	[1]
Anxiety disorder	DISBI2BT	moderate	Biomarker	[1]
Neurodevelopmental disorder	DIS372XH	moderate	Biomarker	[1]
Intellectual disability	DISMBNXP	Limited	Autosomal recessive	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Calcyphosin-2 (CAPS2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calcyphosin-2 (CAPS2).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Calcyphosin-2 (CAPS2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Calcyphosin-2 (CAPS2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calcyphosin-2 (CAPS2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Calcyphosin-2 (CAPS2).	[14]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Calcyphosin-2 (CAPS2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Calcyphosin-2 (CAPS2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Calcyphosin-2 (CAPS2).	[12]

References

• [1] Ca(2+)-dependent activator protein for secretion 2 and autistic-like phenotypes.Neurosci Res. 2010 Jul;67(3):197-202. doi: 10.1016/j.neures.2010.03.006. Epub 2010 Mar 17.
• [2] CAPS2 deficiency affects environmental enrichment-induced adult neurogenesis and differentiation/survival of newborn neurons in the hippocampal dentate gyrus.Neurosci Lett. 2017 Nov 20;661:121-125. doi: 10.1016/j.neulet.2017.09.047. Epub 2017 Sep 27.
• [3] Paralogs of the Calcium-Dependent Activator Protein for Secretion Differentially Regulate Synaptic Transmission and Peptide Secretion in Sensory Neurons.Front Cell Neurosci. 2018 Sep 11;12:304. doi: 10.3389/fncel.2018.00304. eCollection 2018.
• [4] Mouse models of mutations and variations in autism spectrum disorder-associated genes: mice expressing Caps2/Cadps2 copy number and alternative splicing variants.Int J Environ Res Public Health. 2013 Nov 27;10(12):6335-53. doi: 10.3390/ijerph10126335.
• [5] 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.
• [6] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] 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.
• [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.
• [14] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.