ABCG2 Q141K - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

ABCG2 Q141K

(ABCG2 Gln141Lys)


Short summary

Significantly altered kintetics and increase plasma AUC with diflomotecan and rosuvastatin.

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

Impact

Insufficiently evaluated pharmacogenetic

(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

  • T @ chr4:89052323: 8.2% (882/10758) in EVS
  • T @ chr4:89271346: 11.7% (15/128) in GET-Evidence
  • Frequency shown in summary reports: 8.2% (882/10758)

Publications
 

Sparreboom A, Gelderblom H, Marsh S, Ahluwalia R, Obach R, Principe P, Twelves C, Verweij J, McLeod HL. Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype. Clin Pharmacol Ther. 2004 Jul;76(1):38-44. PubMed PMID: 15229462.

 

Zhang W, Yu BN, He YJ, Fan L, Li Q, Liu ZQ, Wang A, Liu YL, Tan ZR, Fen-Jiang, Huang YF, Zhou HH. Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. Clin Chim Acta. 2006 Nov;373(1-2):99-103. Epub 2006 May 13. PubMed PMID: 16784736.

 

Cusatis G, Gregorc V, Li J, Spreafico A, Ingersoll RG, Verweij J, Ludovini V, Villa E, Hidalgo M, Sparreboom A, Baker SD. Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J Natl Cancer Inst. 2006 Dec 6;98(23):1739-42. PubMed PMID: 17148776.

 

Kim HS, Sunwoo YE, Ryu JY, Kang HJ, Jung HE, Song IS, Kim EY, Shim JC, Shon JH, Shin JG. The effect of ABCG2 V12M, Q141K and Q126X, known functional variants in vitro, on the disposition of lamivudine. Br J Clin Pharmacol. 2007 Nov;64(5):645-54. Epub 2007 May 17. PubMed PMID: 17509035; PubMed Central PMCID: PMC2203270.

 

Petain A, Kattygnarath D, Azard J, Chatelut E, Delbaldo C, Geoerger B, Barrois M, Séronie-Vivien S, LeCesne A, Vassal G; Innovative Therapies with Children with Cancer European consortium. Population pharmacokinetics and pharmacogenetics of imatinib in children and adults. Clin Cancer Res. 2008 Nov 1;14(21):7102-9. PubMed PMID: 18981009.

 

Keskitalo JE, Zolk O, Fromm MF, Kurkinen KJ, Neuvonen PJ, Niemi M. ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther. 2009 Aug;86(2):197-203. Epub 2009 May 27. PubMed PMID: 19474787.

 

Woodward OM, Köttgen A, Coresh J, Boerwinkle E, Guggino WB, Köttgen M. Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10338-42. Epub 2009 Jun 8. PubMed PMID: 19506252; PubMed Central PMCID: PMC2700910.

 

Tomlinson B, Hu M, Lee VW, Lui SS, Chu TT, Poon EW, Ko GT, Baum L, Tam LS, Li EK. ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin. Clin Pharmacol Ther. 2010 May;87(5):558-62. Epub 2010 Feb 3. PubMed PMID: 20130569.

 

Genomes
 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr4:89052323

 

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het T @ chr4:89052323

 

 

 

 

GS06985 - var-GS06985-1100-36-ASM
het T @ chr4:89271347

 

GS18537 - var-GS18537-1100-36-ASM
hom T @ chr4:89271347

 

GS18555 - var-GS18555-1100-36-ASM
hom T @ chr4:89271347

 

GS18940 - var-GS18940-1100-36-ASM
het T @ chr4:89271347

 

GS18942 - var-GS18942-1100-36-ASM
het T @ chr4:89271347

 

GS18956 - var-GS18956-1100-36-ASM
het T @ chr4:89271347

 

GS19649 - var-GS19649-1100-36-ASM
het T @ chr4:89271347

 

GS19735 - var-GS19735-1100-36-ASM
het T @ chr4:89271347

 

Other external references
 

    dbSNP
  • rs2231142
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GWAS
  • Serum uric acid (rs2231142-T)
    Kolz 5-Jun-09 in PLoS Genet
    OR or beta: 0.14 [0.096-0.181] mg/dl increase
    Risk allele frequency: 0.11
    p-value: 1.00E-10 (women)
    Initial sample: 12,328 European males, 15,813 European females
    Replication sample: NR
    www.ncbi.nlm.nih.gov/pubmed/19503597
  • Serum uric acid (rs2231142-T)
    Kolz 5-Jun-09 in PLoS Genet
    OR or beta: 0.22 [0.171-0.270] mg/dl increase
    Risk allele frequency: 0.11
    p-value: 2.00E-18 (men)
    Initial sample: 12,328 European males, 15,813 European females
    Replication sample: NR
    www.ncbi.nlm.nih.gov/pubmed/19503597
  • Serum urate (rs2231142-?)
    Dehghan 1-Oct-08 in Lancet
    OR or beta: 0.24 [0.20-0.28] SD increase in serum
    Risk allele frequency: 0.11
    p-value: 3.00E-60 (whites)
    Initial sample: 11,847 individuals
    Replication sample: 14,867 individuals
    www.ncbi.nlm.nih.gov/pubmed/18834626
    PolyPhen-2
  • Score: 0.548 (possibly damaging)

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

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