ANKK1 E713K - GET-Evidence

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Curation:
Currentness:

ANKK1 E713K

(ANKK1 Glu713Lys)


Short summary

 

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr11:113270828: 23.7% (2430/10274) in EVS
  • A @ chr11:112776037: 34.4% (42/122) in GET-Evidence
  • Frequency shown in summary reports: 23.7% (2430/10274)

Publications
 

Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH, Cohn JB. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990 Apr 18;263(15):2055-60. PubMed PMID: 1969501.

 

Mihara K, Kondo T, Suzuki A, Yasui N, Nagashima U, Ono S, Otani K, Kaneko S. Prolactin response to nemonapride, a selective antagonist for D2 like dopamine receptors, in schizophrenic patients in relation to Taq1A polymorphism of DRD2 gene. Psychopharmacology (Berl). 2000 Apr;149(3):246-50. PubMed PMID: 10823405.

 

Johnstone EC, Yudkin PL, Hey K, Roberts SJ, Welch SJ, Murphy MF, Griffiths SE, Walton RT. Genetic variation in dopaminergic pathways and short-term effectiveness of the nicotine patch. Pharmacogenetics. 2004 Feb;14(2):83-90. PubMed PMID: 15077009.

 

Young RM, Lawford BR, Barnes M, Burton SC, Ritchie T, Ward WK, Noble EP. Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele. Br J Psychiatry. 2004 Aug;185:147-51. PubMed PMID: 15286066.

 

Swan GE, Valdes AM, Ring HZ, Khroyan TV, Jack LM, Ton CC, Curry SJ, McAfee T. Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR. Pharmacogenomics J. 2005;5(1):21-9. PubMed PMID: 15492764.

 

Zai CC, De Luca V, Hwang RW, Voineskos A, Müller DJ, Remington G, Kennedy JL. Meta-analysis of two dopamine D2 receptor gene polymorphisms with tardive dyskinesia in schizophrenia patients. Mol Psychiatry. 2007 Sep;12(9):794-5. PubMed PMID: 17767146.

 

Smith L, Watson M, Gates S, Ball D, Foxcroft D. Meta-analysis of the association of the Taq1A polymorphism with the risk of alcohol dependency: a HuGE gene-disease association review. Am J Epidemiol. 2008 Jan 15;167(2):125-38. Epub 2007 Nov 7. Review. PubMed PMID: 17989061.

 

David SP, Strong DR, Munafò MR, Brown RA, Lloyd-Richardson EE, Wileyto PE, Evins EA, Shields PG, Lerman C, Niaura R. Bupropion efficacy for smoking cessation is influenced by the DRD2 Taq1A polymorphism: analysis of pooled data from two clinical trials. Nicotine Tob Res. 2007 Dec;9(12):1251-7. PubMed PMID: 18058343; PubMed Central PMCID: PMC2128730.

 

Alenius M, Wadelius M, Dahl ML, Hartvig P, Lindström L, Hammarlund-Udenaes M. Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting. J Psychiatr Res. 2008 Sep;42(11):884-93. Epub 2007 Dec 20. PubMed PMID: 18086475.

 

Bakker PR, van Harten PN, van Os J. Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions. Mol Psychiatry. 2008 May;13(5):544-56. Epub 2008 Jan 8. PubMed PMID: 18180754.

 

Styn MA, Nukui T, Romkes M, Perkins K, Land SR, Weissfeld JL. The impact of genetic variation in DRD2 and SLC6A3 on smoking cessation in a cohort of participants 1 year after enrollment in a lung cancer screening study. Am J Med Genet B Neuropsychiatr Genet. 2009 Mar 5;150B(2):254-61. PubMed PMID: 18563706; PubMed Central PMCID: PMC2730224.

 

Ikeda M, Yamanouchi Y, Kinoshita Y, Kitajima T, Yoshimura R, Hashimoto S, O'Donovan MC, Nakamura J, Ozaki N, Iwata N. Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia. Pharmacogenomics. 2008 Oct;9(10):1437-43. PubMed PMID: 18855532.

 

Shen YC, Chen SF, Chen CH, Lin CC, Chen SJ, Chen YJ, Luu SU. Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients. J Psychiatr Res. 2009 Mar;43(6):600-6. Epub 2008 Oct 15. PubMed PMID: 18926547.

 

Stice E, Spoor S, Bohon C, Small DM. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008 Oct 17;322(5900):449-52. PubMed PMID: 18927395; PubMed Central PMCID: PMC2681095.

 

Munafò MR, Johnstone EC, Murphy MF, Aveyard P. Lack of association of DRD2 rs1800497 (Taq1A) polymorphism with smoking cessation in a nicotine replacement therapy randomized trial. Nicotine Tob Res. 2009 Apr;11(4):404-7. Epub 2009 Mar 8. PubMed PMID: 19273465.

 

Calarge CA, Ellingrod VL, Acion L, Miller DD, Moline J, Tansey MJ, Schlechte JA. Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents. Pharmacogenet Genomics. 2009 May;19(5):373-82. PubMed PMID: 19339912; PubMed Central PMCID: PMC2699901.

 

Kraschewski A, Reese J, Anghelescu I, Winterer G, Schmidt LG, Gallinat J, Finckh U, Rommelspacher H, Wernicke C. Association of the dopamine D2 receptor gene with alcohol dependence: haplotypes and subgroups of alcoholics as key factors for understanding receptor function. Pharmacogenet Genomics. 2009 Jul;19(7):513-27. PubMed PMID: 19603545.

 

Zhang JP, Lencz T, Malhotra AK. D2 Receptor Genetic Variation and Clinical Response to Antipsychotic Drug Treatment: A Meta-Analysis. Am J Psychiatry. 2010 Mar 1. [Epub ahead of print] PubMed PMID: 20194480.

 

Genomes
 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het A @ chr11:113270828

 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het A @ chr11:113270828

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het A @ chr11:113270828

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het A @ chr11:113270828

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
het A @ chr11:113270828

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
het A @ chr11:113270828

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het A @ chr11:113270828

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het A @ chr11:113270828

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
hom A @ chr11:113270828

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
het A @ chr11:113270828

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het A @ chr11:113270828

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
het A @ chr11:113270828

 

hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
het A @ chr11:113270828

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het A @ chr11:113270828

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het A @ chr11:113270828

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het A @ chr11:113270828

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het A @ chr11:113270828

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
hom A @ chr11:113270828

 

huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het A @ chr11:113270828

 

huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
het A @ chr11:113270828

 

GS06994 - var-GS06994-1100-36-ASM
het A @ chr11:112776038

 

GS10851 - var-GS10851-1100-36-ASM
het A @ chr11:112776038

 

GS12004 - var-GS12004-1100-36-ASM
het A @ chr11:112776038

 

GS18501 - var-GS18501-1100-36-ASM
het A @ chr11:112776038

 

GS18502 - var-GS18502-1100-36-ASM
hom A @ chr11:112776038

 

GS18504 - var-GS18504-1100-36-ASM
het A @ chr11:112776038

 

GS18517 - var-GS18517-1100-36-ASM
hom A @ chr11:112776038

 

GS18526 - var-GS18526-1100-36-ASM
het A @ chr11:112776038

 

GS18537 - var-GS18537-1100-36-ASM
het A @ chr11:112776038

 

GS18555 - var-GS18555-1100-36-ASM
hom A @ chr11:112776038

 

GS18558 - var-GS18558-1100-36-ASM
hom A @ chr11:112776038

 

GS18940 - var-GS18940-1100-36-ASM
hom A @ chr11:112776038

 

GS18942 - var-GS18942-1100-36-ASM
het A @ chr11:112776038

 

GS19025 - var-GS19025-1100-36-ASM
het A @ chr11:112776038

 

GS19026 - var-GS19026-1100-36-ASM
hom A @ chr11:112776038

 

GS19129 - var-GS19129-1100-36-ASM
het A @ chr11:112776038

 

GS19669 - var-GS19669-1100-36-ASM
het A @ chr11:112776038

 

GS19670 - var-GS19670-1100-36-ASM
het A @ chr11:112776038

 

GS19701 - var-GS19701-1100-36-ASM
hom A @ chr11:112776038

 

GS19703 - var-GS19703-1100-36-ASM
het A @ chr11:112776038

 

GS19704 - var-GS19704-1100-36-ASM
het A @ chr11:112776038

 

GS19735 - var-GS19735-1100-36-ASM
het A @ chr11:112776038

 

Other external references
 

    dbSNP
  • rs1800497
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Schizophrenia]
    [aripiprazole]
    Phenotype: Compared with patients who had the A2/A2 (C/C) genotype, the positive and negative syndrome scale (PANSS) positive scores of A1/A1 (T/T) patients were 3.71 lower (p = 0.01) and of A1/A2 patients were 1.36 lower (p = 0.03) after 4-week aripiprazole treatment. These results suggest that A1 carriers are associated with superior therapeutic response on positive symptoms. Study size: 128 schizophrenic patients. Study population: Chinese.
    www.ncbi.nlm.nih.gov/pubmed/18926547
  • [Hyperprolactinemia]
    [nemonapride]
    Risk or phenotype-associated allele: T. Phenotype: In schizophrenic patients treated with nemonapride, the delta prolactin at 1 and 3 weeks was significantly (P<0.05) higher in female patients with the A1 allele than in males with or with no A1 allele. The delta prolactin at 3 weeks was also significantly (P<0.05) higher in the female patients with the A1 allele than in those with no A1 allele. Study size: 25 schizophrenic inpatients. Study population: Japanese.
    www.ncbi.nlm.nih.gov/pubmed/10823405
  • [tardive dyskinesia]
    Risk or phenotype-associated genotype: C/C. Phenotype: This meta-analysis suggests multiple genetic influences on tardive dyskinesia, including the Taq1A SNP. For Taq1A using the A1 allele as reference category, the study showed a risk-increasing effect for the A2 variant (OR=1.30, 95% CI: 1.03-1.65, P=0.026), and for A2-A2 homozygotes using A1-A1 as reference category (OR=1.80, 95% CI: 1.03-3.15, P=0.037).
    www.ncbi.nlm.nih.gov/pubmed/18180754
  • [Alcoholism]
    [ethanol]
    Risk or phenotype-associated genotype: T. Phenotype: The A1 allele is associated with 24 (69%) of 35 alcoholics, but it associated with only 7 (20%) of 35 nonalcoholics. The absence of the A1 allele is associated with 28 (80%) of 35 nonalcoholics and with only 11 (31%) of 35 alcoholics. Study size: 35 alcoholics and 35 nonalcoholics. Study population: 46 whites; 24 blacks
    www.ncbi.nlm.nih.gov/pubmed/1969501
  • [Schizophrenia]
    [aripiprazole; Bromperidol; chlorpromazine; clozapine; haloperidol; nemonapride; risperidone]
    Phenotype: A meta-analysis, including eight individual studies, was not able to detect an association between clinical response to antipsychotics and the Taq1A variant. Study size: meta-analysis included 8 individual studies, 748 patients total.
    www.ncbi.nlm.nih.gov/pubmed/20194480
  • [Alcoholism]
    [ethanol]
    Phenotype: In this case-control study the polymorphisms -141C Ins/Del (rs1799732); C957T (rs6277); A1385G (rs6276); and TaqIA (rs1800497) were genotyped. The haplotypes I-C-G-A2 and I-C-A-A1 occurred with a higher frequency in alcoholics [P=0.026, odds ratio (OR): 1.340; P=0.010, OR: 1.521, respectively]. Study size: 360 alcoholics and 368 controls. Study population:Caucasian individuals of German origin.
    www.ncbi.nlm.nih.gov/pubmed/19603545
  • [bupropion]
    Associated with 12-month smoking cessation outcomes following treatment with a combination of bupropion and behavioral counseling in women.
    www.pharmgkb.org/search/annotatedGene/drd2/v
  • [Tobacco Use Disorder]
    [bupropion]
    This variant (A2/A2 genotype) is associated with improved response to bupropion efficacy for smoking cessation.
    www.ncbi.nlm.nih.gov/pubmed/18058343
  • [Schizophrenia]
    [risperidone]
    This SNP is significant predictor of treatment response to risperidone in first-episode schizophrenia.
    www.ncbi.nlm.nih.gov/pubmed/18855532
  • [Obesity]
    In blood oxygen level-dependent functional magnetic resonance imaging studies, obese college-aged women and adolescent girls showed a blunted striatal response to chocolate milkshake tasting (vs. tasting of a tasteless solution) when compared to lean women and girls, and the genotype at this SNP affected the extent of this response. This SNP is known as the TaqIA allele of DRD2 even though it is more than 10 KB downstream from the gene boundary.
    www.ncbi.nlm.nih.gov/pubmed/18927395
  • [Hyperprolactinemia]
    [risperidone]
    Risk or phenotype-associated allele: T. Phenotype: Carriers of one or two copies of the T allele of this variant (also known as Taq1A A1) were at higher risk of developing hyperprolactinemia than those with two copies of the C allele (also known as Taq1A A2). This variant is a SNP located about 9.5 kb downstream of the DRD2 coding region, and results in a Glu (C allele) to Lys (T allele) amino acid substitution in the ANKK1 protein. Study size: 90. Study population/ethnicity: 7-17-year-old patients chronically treated with risperidone; non-Hispanic Caucasians. Significance metric(s): OR = 3.1; p < 0.05. Type of association: CO.
    www.ncbi.nlm.nih.gov/pubmed/19339912
  • Risk or phenotype-associated genotype: T/T. Phenotype: Patients with one or two A1 alleles (T/T) had a greater risk of significant side effects, particularly if they were male. Study size: 116. Study population: Caucasians.
    www.ncbi.nlm.nih.gov/pubmed/18086475
  • [tardive dyskinesia]
    Risk or phenotype-associated genotype: C/C. Phenotype: A meta-analysis showed that compared to tardive dyskinesia (TD)-negative patients, TD-positive patients had a higher A2 allele frequency (P = 0.003), with an effect-size of 1.30 (95% CI: 1.09-1.55), and higher A2/A2 genotype frequency (P = 0.001), with an effect-size of 1.50 (95% CI: 1.17-1.92). Study size: 1256 schizophrenia patients.
    www.ncbi.nlm.nih.gov/pubmed/17767146
  • [Tobacco Use Disorder]
    Phenotype: This study found no association between the Taq1A polymorphism and response to nicotine replacement therapy.
    www.ncbi.nlm.nih.gov/pubmed/19273465
  • [Tobacco Use Disorder]
    [bupropion]
    Risk or phenotype-associated genotype: T. Phenotype: Compared to women who carry both A2 (CC) alleles, women with at least one A1 (T) allele were more likely to report having stopped taking bupropion due to medication side effects (odds ratio (OR)=1.91, 95% confidence interval (CI)=1.01-3.60; P<0.04) and at 12 months were somewhat more likely to report smoking (OR=0.76, 95% CI=0.56-1.03; P<0.076). Significant associations or trends were not observed in men. Study size: 451 participants. Study population: Caucasian.
    www.ncbi.nlm.nih.gov/pubmed/15492764
  • [Alcoholism]
    [ethanol]
    Risk or phenotype-associated genotype: T. Phenotype: This meta-analysis included 44 studies with 9,382 participants. For all studies combined, when we assumed the dominant model of gene action (A1A1 + A1A2 vs. A2A2), a small but significant association of alcohol dependency with being homozygote or heterozygote for the A1 allele was detected. The odds ratio was 1.38 (95 percent confidence interval (CI): 1.20, 1.58) when random effects were used. Study size: 5,273 cases and 3,995 controls.
    www.ncbi.nlm.nih.gov/pubmed/17989061
  • [Tobacco Use Disorder]
    Risk or phenotype-associated allele: T (A1). Phenotype: In a smoking cessation study the TaqIA SNP was significantly associated with being abstinent at 1 year (P = 0.01). Participants who carried at least one minor allele (A1) were less likely to quit compared to A2A2 homozygous (Odds Ratio: 0.47, 95% CI: 0.24-0.94). Study size: 881. metric(s): OR =0.47, 95% CI: 0.24-0.94.
    www.ncbi.nlm.nih.gov/pubmed/18563706
  • [Hyperprolactinemia]
    [clozapine; olanzapine; risperidone]
    Risk or phenotype-associated allele: T. Phenotype: In the combined medication group patients with the A1 (T) allele had 40% higher prolactin levels than patients without this allele. Study size: 144 schizophrenic patients. Study population: White patients.
    www.ncbi.nlm.nih.gov/pubmed/15286066
  • [Tobacco Use Disorder]
    Risk associated genotype: C/C. Phenotype: In a randomized controlled trial investigating the short-term effectiveness of the nicotine patch, after 1 week of the trial the patch was more effective for smokers with CT/TT genotype (OR 2.80, 95% CI 1.70-4.61) than with CC (OR 1.41, 0.94-2.12; P for difference in ORs 0.04). Study size: 1532.
    www.ncbi.nlm.nih.gov/pubmed/15077009
    PolyPhen-2
  • Score: 0 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

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