ABCC2 V417I - GET-Evidence

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Curation:
Currentness:

ABCC2 V417I

(ABCC2 Val417Ile)


Short summary

Associated with increased activity of the intestinal efflux transporter ABCC2, evidenced by gene-dose related decrease of oral absorption and increased residual clearance of talinolol.

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

  • A @ chr10:101563815: 19.2% (2069/10758) in EVS
  • A @ chr10:101553804: 17.2% (22/128) in GET-Evidence
  • Frequency shown in summary reports: 19.2% (2069/10758)

Publications
 

Izzedine H, Hulot JS, Villard E, Goyenvalle C, Dominguez S, Ghosn J, Valantin MA, Lechat P, Deray AG. Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy. J Infect Dis. 2006 Dec 1;194(11):1481-91. Epub 2006 Oct 26. PubMed PMID: 17083032.

 

Haenisch S, May K, Wegner D, Caliebe A, Cascorbi I, Siegmund W. Influence of genetic polymorphisms on intestinal expression and rifampicin-type induction of ABCC2 and on bioavailability of talinolol. Pharmacogenet Genomics. 2008 Apr;18(4):357-65. PubMed PMID: 18334920.

Participants with at least one variant allele of V417I (n=13) had about 20% lower AUC and bioavailability (AUC: 2730±654 ng×h/ml vs. 3420±708 ng×h/ml, P<0.05; F: 60.3%±14.0% vs. 75.1%±12.0%, P<0.05).

Kim WJ, Lee JH, Yi J, Cho YJ, Heo K, Lee SH, Kim SW, Kim MK, Kim KH, In Lee B, Lee MG. A nonsynonymous variation in MRP2/ABCC2 is associated with neurological adverse drug reactions of carbamazepine in patients with epilepsy. Pharmacogenet Genomics. 2010 Apr;20(4):249-56. PubMed PMID: 20216337.

 

Genomes
 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het A @ chr10:101563815

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het A @ chr10:101563815

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het A @ chr10:101563815

 

hu2DBF2D - CGI sample GS01173-DNA_G02 from PGP sample 67180598
het A @ chr10:101563815

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het A @ chr10:101563815

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het A @ chr10:101563815

 

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
hom A @ chr10:101563815

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het A @ chr10:101563815

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het A @ chr10:101563815

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
het A @ chr10:101563815

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het A @ chr10:101563815

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
hom A @ chr10:101563815

 

GS06985 - var-GS06985-1100-36-ASM
hom A @ chr10:101553805

 

GS18501 - var-GS18501-1100-36-ASM
het A @ chr10:101553805

 

GS18502 - var-GS18502-1100-36-ASM
het A @ chr10:101553805

 

GS18504 - var-GS18504-1100-36-ASM
hom A @ chr10:101553805

 

GS18505 - var-GS18505-1100-36-ASM
het A @ chr10:101553805

 

GS19238 - var-GS19238-1100-36-ASM
het A @ chr10:101553805

 

GS20509 - var-GS20509-1100-36-ASM
het A @ chr10:101553805

 

GS21767 - var-GS21767-1100-36-ASM
het A @ chr10:101553805

 

NA12878

 

Other external references
 

    dbSNP
  • rs2273697
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [carbamazepine]
    Risk or phenotype-associated allele: A. Phenotype: This SNP showed a strong association with the neurological adverse drug reaction caused (ADR) by carbamazepine (P=0.005). The study results indicate that the c.1249A variant is an independent risk factor of carbamazepine CNS ADR. Study size: 146 patients with epilepsy who had been prescribed carbamazepine. Study population: Korean.
    www.ncbi.nlm.nih.gov/pubmed/20216337
  • Common variant, mostly found to have no association, but there was one exception.
    www.ncbi.nlm.nih.gov/pubmed/17083032
  • [talinolol]
    The A allele of this variant is associated in a gene dose dependent manner with the following phenotypes: 1) increased residual clearance of intravenous talinolol and 2) lower bioavailablilty of orally administered talinolol in healthy German subjects. However, this variant is not associated with alterations in intestinal ABCC2 mRNA or protein levels.
    www.ncbi.nlm.nih.gov/pubmed/18334920
    PolyPhen-2
  • Score: 0.001 (benign)
    Web search results (39 hits -- see all)
  • ABCC2 [PharmGKB]
    rs2273697 at chr10:101553805 in ABCC2. The A allele of this variant is ... is not associated with alterations in intestinal ABCC2 mRNA or protein levels. ...
    www.pharmgkb.org/do/serve?objId=PA116
  • Influence of genetic polymorphisms on intestinal expression ...
    OBJECTIVES: To evaluate whether ABCC2 gene polymorphisms are associated with ... The variant ABCC2 1249G>A (V417I), however, was associated with lower oral ...
    www.ncbi.nlm.nih.gov/pubmed/18334920
  • Pharma DMET - SNPedia
    ... noncore snp rs17216198 ABCC2 ABCC2_21214G>A(V417I) ABCC2_21214G>A(V417I) core snp rs2273697 ABCC2 ABCC2_21399G>T(A478A) ABCC2_21399G>A(A478A) noncore ...
    www.snpedia.com/index.php/Pharma_DMET
  • Pharmacogenetic Assessment of Toxicity and Outcome After ...
    ABCC2 IVS12+148A>G. Pac, Doc, Carb. 892. 338. 422. 132. 0.62. 0.38. ABCC2 V417I. Pac, Doc, Carb ... Abbreviations: SCOTROC1, Scottish Randomised Trial in Ovarian Cancer; ...
    jco.ascopubs.org/cgi/content/full/25/29/4528/T2
  • Pharmacogenetic Assessment of Toxicity and Outcome After ...
    ABCC2 IVS12 148A G. Pac, Doc, Carb. 892. 338. 422. 132. 0.62. 0.38. ABCC2 V417I. Pac, Doc, Carb ... tribution of transporters ABCC2 and ABCG2 to both carboplatin and ...
    jco.ascopubs.org/cgi/reprint/25/29/4528.pdf
  • Characterization of the cellular localization, expression ...
    ... has been reported for multidrug resistance-associated protein 2 (MRP2/ABCC2). The purpose of the current ... although the wild-type and V417I MRP2 were exclusively localized in ...
    www.ncbi.nlm.nih.gov/pubmed/15180328
  • A Gynecologic Oncology Group study of associations between ...
    ... between polymorphisms in ABC transporter genes (ABCB1, ABCC2, ... C3435T, synonymous-RS1045642), ABCC2 (G1249A, V417I-RS2273697), and ABCG2 (C421A, Q141K ...
    meeting.ascopubs.org/cgi/content/abstract/27/15S/5567
  • SpringerProtocols: Search Results
    Studies of ABCC2 (mutations in this gene have been observed in patients with ... Summary: (ABCC2) 1249G >A (V417I) Associated with risk of tenofovir-induced proximal ...
    springerprotocols.com/cdp/search/searchResultPage?text=ABCC2
  • IMIS Homepage
    The variant ABCC2 1249G>A (V417I), however, was associated with lower oral ... Intestinal ABCC2 mRNA and protein expression were upregulated by rifampicin ...
    uni-kiel.de/medinfo/.../caliebe/publikationen/index_en.html
  • HIGHLIGHTS FROM AAPS PUBLICATIONS
    2 (MRP2/ABCC2). The purpose of the present. study was to characterize the localization, ... observed V417I substitution may not affect the. in vivo function of ...
    aapspharmaceutica.com/publications/newsmagazine/.../096.pdf

Other in silico analyses
 

  • NBLOSUM100 score = –4
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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