Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0OM1O0)

DOT Name	Ankyrin repeat and protein kinase domain-containing protein 1 (ANKK1)
Synonyms	EC 2.7.11.1; Protein kinase PKK2; Sugen kinase 288; SgK288; X-kinase
Gene Name	ANKK1
Related Disease	Alcohol use disorder ( ) Bipolar disorder ( ) Alzheimer disease ( ) Alzheimer disease 3 ( ) Attention deficit hyperactivity disorder ( ) Bipolar I disorder ( ) Breast cancer ( ) Breast carcinoma ( ) Dementia ( ) Depression ( ) Drug dependence ( ) Impulse control disorder ( ) Language disorder ( ) Major depressive disorder ( ) Nicotine dependence ( ) Obesity ( ) Opioid dependence ( ) Parkinson disease ( ) Schizophrenia ( ) Substance dependence ( ) Tourette syndrome ( ) Melanoma ( ) Substance withdrawal syndrome ( ) Advanced cancer ( ) Anxiety ( ) Anxiety disorder ( ) Cocaine addiction ( ) Mental disorder ( ) Migraine disorder ( ) Nervous system disease ( ) Non-insulin dependent diabetes ( ) Post-traumatic stress disorder ( )
UniProt ID	ANKK1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.7.11.1
Pfam ID	PF00023 ; PF12796 ; PF13637 ; PF07714
Sequence	MAADPTELRLGSLPVFTRDDFEGDWRLVASGGFSQVFQARHRRWRTEYAIKCAPCLPPDA ASSDVNYLIEEAAKMKKIKFQHIVSIYGVCKQPLGIVMEFMANGSLEKVLSTHSLCWKLR FRIIHETSLAMNFLHSIKPPLLHLDLKPGNILLDSNMHVKISDFGLSKWMEQSTRMQYIE RSALRGMLSYIPPEMFLESNKAPGPKYDVYSFAIVIWELLTQKKPYSGFNMMMIIIRVAA GMRPSLQPVSDQWPSEAQQMVDLMKRCWDQDPKKRPCFLDITIETDILLSLLQSRVAVPE SKALARKVSCKLSLRQPGEVNEDISQELMDSDSGNYLKRALQLSDRKNLVPRDEELCIYE NKVTPLHFLVAQGSVEQVRLLLAHEVDVDCQTASGYTPLLIAAQDQQPDLCALLLAHGAD ANRVDEDGWAPLHFAAQNGDDGTARLLLDHGACVDAQEREGWTPLHLAAQNNFENVARLL VSRQADPNLHEAEGKTPLHVAAYFGHVSLVKLLTSQGAELDAQQRNLRTPLHLAVERGKV RAIQHLLKSGAVPDALDQSGYGPLHTAAARGKYLICKMLLRYGASLELPTHQGWTPLHLA AYKGHLEIIHLLAESHANMGALGAVNWTPLHLAARHGEEAVVSALLQCGADPNAAEQSGW TPLHLAVQRSTFLSVINLLEHHANVHARNKVGWTPAHLAALKGNTAILKVLVEAGAQLDV QDGVSCTPLQLALRSRKQGIMSFLEGKEPSVATLGGSKPGAEMEI
Tissue Specificity	Highly expressed in brain and weakly expressed in placenta and spinal cord.

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Alcohol use disorder	DISMB65Y	Definitive	Biomarker	[1]
Bipolar disorder	DISAM7J2	Definitive	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Alzheimer disease 3	DISVT69G	Strong	Genetic Variation	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[4]
Bipolar I disorder	DISD09EH	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Dementia	DISXL1WY	Strong	Genetic Variation	[7]
Depression	DIS3XJ69	Strong	Biomarker	[8]
Drug dependence	DIS9IXRC	Strong	Genetic Variation	[9]
Impulse control disorder	DISRIYJ5	Strong	Biomarker	[10]
Language disorder	DISTLKP7	Strong	Biomarker	[11]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[12]
Nicotine dependence	DISZD9W7	Strong	Genetic Variation	[13]
Obesity	DIS47Y1K	Strong	Genetic Variation	[14]
Opioid dependence	DIS6WEHK	Strong	Genetic Variation	[15]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[16]
Schizophrenia	DISSRV2N	Strong	Posttranslational Modification	[17]
Substance dependence	DISDRAAR	Strong	Genetic Variation	[18]
Tourette syndrome	DISX9D54	Strong	Genetic Variation	[19]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[20]
Substance withdrawal syndrome	DISTT24U	moderate	Genetic Variation	[21]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[22]
Anxiety	DISIJDBA	Limited	Biomarker	[23]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[23]
Cocaine addiction	DISHTRXG	Limited	Biomarker	[24]
Mental disorder	DIS3J5R8	Limited	Genetic Variation	[25]
Migraine disorder	DISFCQTG	Limited	Genetic Variation	[26]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[26]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[27]
Post-traumatic stress disorder	DISHL1EY	Limited	Genetic Variation	[28]
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⏷ Show the Full List of 32 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 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 Ankyrin repeat and protein kinase domain-containing protein 1 (ANKK1).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ankyrin repeat and protein kinase domain-containing protein 1 (ANKK1).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ankyrin repeat and protein kinase domain-containing protein 1 (ANKK1).	[31]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Ankyrin repeat and protein kinase domain-containing protein 1 (ANKK1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ankyrin repeat and protein kinase domain-containing protein 1 (ANKK1).	[33]
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References

1	The association between DRD2/ANKK1 and genetically informed measures of alcohol use and problems.Addict Biol. 2013 May;18(3):523-36. doi: 10.1111/j.1369-1600.2012.00490.x. Epub 2012 Sep 12.
2	The DRD2/ANKK1 gene is associated with response to add-on dextromethorphan treatment in bipolar disorder.J Affect Disord. 2012 May;138(3):295-300. doi: 10.1016/j.jad.2012.01.024. Epub 2012 Feb 11.
3	The association of DRD2 -141C and ANKK1 TaqIA polymorphisms with alcohol dependence in Korean population classified by the Lesch typology.Alcohol Alcohol. 2013 Jul-Aug;48(4):426-32. doi: 10.1093/alcalc/agt029. Epub 2013 Apr 4.
4	Attention, cognitive control and motivation in ADHD: Linking event-related brain potentials and DNA methylation patterns in boys at early school age.Sci Rep. 2017 Jun 19;7(1):3823. doi: 10.1038/s41598-017-03326-3.
5	The ALDH2 and DRD2/ANKK1 genes interacted in bipolar II but not bipolar I disorder.Pharmacogenet Genomics. 2010 Aug;20(8):500-6. doi: 10.1097/FPC.0b013e32833caa2b.
6	Moderating Effects of Genetic Polymorphisms on Improvements in Cognitive Impairment in Breast Cancer Survivors Participating in a 6-Week Mindfulness-Based Stress Reduction Program.Biol Res Nurs. 2015 Jul;17(4):393-404. doi: 10.1177/1099800415577633. Epub 2015 Apr 15.
7	Influence of the DRD2/ANKK1 Taq1A polymorphism on caudate volume in older adults without dementia.Brain Struct Funct. 2018 Jul;223(6):2653-2662. doi: 10.1007/s00429-018-1650-0. Epub 2018 Mar 21.
8	COMT and ANKK1 Genetics Interact With Depression to Influence Behavior Following Severe TBI: An Initial Assessment.Neurorehabil Neural Repair. 2016 Nov;30(10):920-930. doi: 10.1177/1545968316648409. Epub 2016 May 6.
9	Association between DRD2/ANKK1 TaqIA polymorphism and common illicit drug dependence: evidence from a meta-analysis.Hum Immunol. 2015 Jan;76(1):42-51. doi: 10.1016/j.humimm.2014.12.005. Epub 2014 Dec 11.
10	The addiction-related gene ANKK1 in Parkinsonian patients with impulse control disorder.Neurotox Res. 2015 Apr;27(3):205-8. doi: 10.1007/s12640-014-9504-x. Epub 2014 Dec 2.
11	Associations of prenatal nicotine exposure and the dopamine related genes ANKK1 and DRD2 to verbal language.PLoS One. 2013 May 15;8(5):e63762. doi: 10.1371/journal.pone.0063762. Print 2013.
12	DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder.Int J Neuropsychopharmacol. 2013 Oct;16(9):2095-101. doi: 10.1017/S146114571300045X. Epub 2013 May 20.
13	Association of ankyrin repeats & kinase domain containing 1 (ANKK1) gene polymorphism with co-morbid alcohol & nicotine dependence: A pilot study from a tertiary care treatment centre in north India.Indian J Med Res. 2017 Jan;145(1):33-38. doi: 10.4103/ijmr.IJMR_458_14.
14	Complete sequence of the ANKK1 gene in Mexican-Mestizo individuals with obesity, with or without binge eating disorder.Eur Psychiatry. 2018 Oct;54:59-64. doi: 10.1016/j.eurpsy.2018.07.010. Epub 2018 Aug 16.
15	Association between the traditional Chinese medicine pathological factors of opioid addiction and DRD2/ANKK1 TaqIA polymorphisms.BMC Complement Altern Med. 2015 Jul 3;15:209. doi: 10.1186/s12906-015-0727-z.
16	The influence of SLC6A3 and DRD2 polymorphisms on levodopa-therapy in patients with sporadic Parkinson's disease.J Pharm Pharmacol. 2019 Feb;71(2):206-212. doi: 10.1111/jphp.13031. Epub 2018 Oct 23.
17	DNA methylation of ANKK1 and response to aripiprazole in patients with acute schizophrenia: A preliminary study.J Psychiatr Res. 2018 May;100:84-87. doi: 10.1016/j.jpsychires.2018.02.018. Epub 2018 Feb 23.
18	Who gains? Genetic and neurophysiological correlates of BMI gain upon college entry in women.Appetite. 2014 Nov;82:160-5. doi: 10.1016/j.appet.2014.07.007. Epub 2014 Jul 15.
19	Association between DRD2/ANKK1 TaqIA Polymorphism and Susceptibility with Tourette Syndrome: A Meta-Analysis.PLoS One. 2015 Jun 25;10(6):e0131060. doi: 10.1371/journal.pone.0131060. eCollection 2015.
20	A pilot study of genetic variants in dopamine regulators with indoor tanning and melanoma.Exp Dermatol. 2013 Sep;22(9):576-81. doi: 10.1111/exd.12200.
21	Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction.Pharmacol Rep. 2012;64(5):1126-34. doi: 10.1016/s1734-1140(12)70909-x.
22	Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity.Diabetologia. 2016 Dec;59(12):2622-2631. doi: 10.1007/s00125-016-4095-0. Epub 2016 Sep 6.
23	The association of dopamine pathway gene score, nicotine dependence and smoking cessation in a rural male population of Shandong, China.Am J Addict. 2016 Sep;25(6):493-8. doi: 10.1111/ajad.12421. Epub 2016 Aug 4.
24	ANKK1 and DRD2 pharmacogenetics of disulfiram treatment for cocaine abuse.Pharmacogenet Genomics. 2013 Jul;23(7):333-40. doi: 10.1097/FPC.0b013e328361c39d.
25	DRD2/ANKK1 TaqI A polymorphism affects corticostriatal activity in response to negative affective facial stimuli.Behav Brain Res. 2011 Sep 30;223(1):36-41. doi: 10.1016/j.bbr.2011.04.007. Epub 2011 Apr 12.
26	Identification of a novel ANKK1 and other dopaminergic (DRD2 and DBH) gene variants in migraine susceptibility.Neuromolecular Med. 2013 Mar;15(1):61-73. doi: 10.1007/s12017-012-8195-9. Epub 2012 Aug 9.
27	Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and type 2 diabetes susceptibility.Diabet Med. 2014 Aug;31(8):1001-8. doi: 10.1111/dme.12464. Epub 2014 May 2.
28	Uncovering precision phenotype-biomarker associations in traumatic brain injury using topological data analysis.PLoS One. 2017 Mar 3;12(3):e0169490. doi: 10.1371/journal.pone.0169490. eCollection 2017.
29	Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
30	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
31	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
32	Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
33	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.