Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC3N1F6)

• DOT Name: Carbonic anhydrase-related protein 10 (CA10)
• Synonyms: Carbonic anhydrase-related protein X; CA-RP X; CARP X; Cerebral protein 15
• Gene Name: CA10
• Related Disease:
  Narcolepsy
  Asthma
  Breast cancer
  Breast carcinoma
  Cholangiocarcinoma
  Cholelithiasis
  Enterovirus infection
  G6PD deficiency
  Glioma
  Hand, foot and mouth disease
  Hashimoto thyroiditis
  Intrahepatic cholangiocarcinoma
  Obstructive lung disease
  Gastrointestinal stromal tumour
  Osteoporosis
• UniProt ID: CAH10_HUMAN
• Pfam ID: PF00194
• Sequence:
  MEIVWEVLFLLQANFIVCISAQQNSPKIHEGWWAYKEVVQGSFVPVPSFWGLVNSAWNLC
  SVGKRQSPVNIETSHMIFDPFLTPLRINTGGRKVSGTMYNTGRHVSLRLDKEHLVNISGG
  PMTYSHRLEEIRLHFGSEDSQGSEHLLNGQAFSGEVQLIHYNHELYTNVTEAAKSPNGLV
  VVSIFIKVSDSSNPFLNRMLNRDTITRITYKNDAYLLQGLNIEELYPETSSFITYDGSMT
  IPPCYETASWIIMNKPVYITRMQMHSLRLLSQNQPSQIFLSMSDNFRPVQPLNNRCIRTN
  INFSLQGKDCPNNRAQKLQYRVNEWLLK
• Function: Does not have a catalytic activity.
• Tissue Specificity: Strong expression in brain and central nervous system.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[1]
Asthma	DISW9QNS	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[4]
Cholelithiasis	DISERLZB	Strong	Genetic Variation	[5]
Enterovirus infection	DISH2UDP	Strong	Genetic Variation	[6]
G6PD deficiency	DISYF1GO	Strong	Genetic Variation	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Hand, foot and mouth disease	DISKJHLL	Strong	Biomarker	[9]
Hashimoto thyroiditis	DIS77CDF	Strong	Genetic Variation	[10]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[11]
Obstructive lung disease	DIS4IIDZ	Strong	Genetic Variation	[2]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Altered Expression	[12]
Osteoporosis	DISF2JE0	Limited	Biomarker	[13]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Carbonic anhydrase-related protein 10 (CA10) increases the Metabolic disorder ADR of Chlorothiazide.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carbonic anhydrase-related protein 10 (CA10).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Carbonic anhydrase-related protein 10 (CA10).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Carbonic anhydrase-related protein 10 (CA10).	[17]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Carbonic anhydrase-related protein 10 (CA10).	[18]

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 increases the methylation of Carbonic anhydrase-related protein 10 (CA10).	[16]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] Polymorphisms in recent GWA identified asthma genes CA10, SGK493, and CTNNA3 are associated with disease severity and treatment response in childhood asthma.Immunogenetics. 2014 Mar;66(3):143-51. doi: 10.1007/s00251-013-0755-0. Epub 2014 Jan 10.
• [3] Association of repeat polymorphisms in the estrogen receptors alpha, beta (ESR1, ESR2) and androgen receptor (AR) genes with the occurrence of breast cancer.Breast. 2008 Apr;17(2):159-66. doi: 10.1016/j.breast.2007.08.007. Epub 2007 Sep 29.
• [4] Development of a Theranostic Convergence Bioradiopharmaceutical for Immuno-PET Based Radioimmunotherapy of L1CAM in Cholangiocarcinoma Model.Clin Cancer Res. 2019 Oct 15;25(20):6148-6159. doi: 10.1158/1078-0432.CCR-19-1157. Epub 2019 Jul 23.
• [5] A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.Nat Genet. 2007 Aug;39(8):995-9. doi: 10.1038/ng2101. Epub 2007 Jul 15.
• [6] Molecular characteristics of hand, foot, and mouth disease for hospitalized pediatric patients in Yunnan, China.Medicine (Baltimore). 2018 Aug;97(31):e11610. doi: 10.1097/MD.0000000000011610.
• [7] G6PD (AC)n and (CTT)n microsatellites in Mexican Mestizos with common G6PD African variants.Blood Cells Mol Dis. 2007 May-Jun;38(3):238-41. doi: 10.1016/j.bcmd.2006.11.005. Epub 2007 Jan 12.
• [8] CA10 and CA11 negatively regulate neuronal activity-dependent growth of gliomas.Mol Oncol. 2019 May;13(5):1018-1032. doi: 10.1002/1878-0261.12445. Epub 2019 Mar 20.
• [9] Construction and characterization of an infectious cDNA clone of coxsackievirus A 10.Virol J. 2019 Aug 6;16(1):98. doi: 10.1186/s12985-019-1201-1.
• [10] Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto's thyroiditis.Sci Rep. 2019 Mar 29;9(1):5360. doi: 10.1038/s41598-019-41850-6.
• [11] A chimeric antibody to L1 cell adhesion molecule shows therapeutic effect in an intrahepatic cholangiocarcinoma model.Exp Mol Med. 2012 Apr 30;44(4):293-302. doi: 10.3858/emm.2012.44.4.027.
• [12] Overexpression of carbonic anhydrase-related protein XI promotes proliferation and invasion of gastrointestinal stromal tumors.Virchows Arch. 2005 Jul;447(1):66-73. doi: 10.1007/s00428-005-1225-3. Epub 2005 Jun 8.
• [13] A genome-wide association study of copy-number variation identifies putative loci associated with osteoarthritis in Koreans.BMC Musculoskelet Disord. 2015 Apr 4;16:76. doi: 10.1186/s12891-015-0531-4.
• [14] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [15] 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.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [19] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.