SLCO1B1 N130D - GET-Evidence

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

To be considered sufficiently evaluated a variant must have both "variant evidence" and "clinical importance" scores filled in.

Please help improve GET-Evidence by evaluating evidence for this variant!

Curation:
Currentness:

SLCO1B1 N130D

(SLCO1B1 Asn130Asp)


Short summary

Low plasma AUC but no change in in-vitro transport with pravastatin.

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

  • G @ chr12:21329738: 52.8% (5659/10722) in EVS
  • G @ chr12:21221004: 60.3% (76/126) in GET-Evidence
  • Frequency shown in summary reports: 52.8% (5659/10722)

Publications
 

Kalliokoski A, Backman JT, Neuvonen PJ, Niemi M. Effects of the SLCO1B1*1B haplotype on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinide. Pharmacogenet Genomics. 2008 Nov;18(11):937-42. PubMed PMID: 18854776.

 

Picard N, Yee SW, Woillard JB, Lebranchu Y, Le Meur Y, Giacomini KM, Marquet P. The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics. Clin Pharmacol Ther. 2010 Jan;87(1):100-8. Epub 2009 Nov 4. PubMed PMID: 19890249; PubMed Central PMCID: PMC2884029.

 

Kroetz DL, Yee SW, Giacomini KM. The pharmacogenomics of membrane transporters project: research at the interface of genomics and transporter pharmacology. Clin Pharmacol Ther. 2010 Jan;87(1):109-16. Epub 2009 Nov 25. Review. PubMed PMID: 19940846; PubMed Central PMCID: PMC2923224.

 

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het G @ chr12:21329738

 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
hom G @ chr12:21329738

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het G @ chr12:21329738

 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het G @ chr12:21329738

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
hom G @ chr12:21329738

 

 

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het G @ chr12:21329738

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
het G @ chr12:21329738

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het G @ chr12:21329738

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het G @ chr12:21329738

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het G @ chr12:21329738

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het G @ chr12:21329738

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
hom G @ chr12:21329738

 

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
het G @ chr12:21329738

 

hu7A4AD1 - CGI sample GS01669-DNA_C05 from PGP sample 42408046
het G @ chr12:21329738

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
hom G @ chr12:21329738

 

hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
hom G @ chr12:21329738

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het G @ chr12:21329738

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
hom G @ chr12:21329738

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het G @ chr12:21329738

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
hom G @ chr12:21329738

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het G @ chr12:21329738

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het G @ chr12:21329738

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
hom G @ chr12:21329738

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
hom G @ chr12:21329738

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het G @ chr12:21329738

 

huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
het G @ chr12:21329738

 

GS06985 - var-GS06985-1100-36-ASM
hom G @ chr12:21221005

 

GS06994 - var-GS06994-1100-36-ASM
het G @ chr12:21221005

 

GS07357 - var-GS07357-1100-36-ASM
het G @ chr12:21221005

 

GS10851 - var-GS10851-1100-36-ASM
het G @ chr12:21221005

 

GS12004 - var-GS12004-1100-36-ASM
hom G @ chr12:21221005

 

GS18501 - var-GS18501-1100-36-ASM
hom G @ chr12:21221005

 

GS18502 - var-GS18502-1100-36-ASM
hom G @ chr12:21221005

 

GS18504 - var-GS18504-1100-36-ASM
hom G @ chr12:21221005

 

GS18505 - var-GS18505-1100-36-ASM
het G @ chr12:21221005

 

GS18508 - var-GS18508-1100-36-ASM
het G @ chr12:21221005

 

GS18517 - var-GS18517-1100-36-ASM
hom G @ chr12:21221005

 

GS18526 - var-GS18526-1100-36-ASM
het G @ chr12:21221005

 

GS18537 - var-GS18537-1100-36-ASM
hom G @ chr12:21221005

 

GS18555 - var-GS18555-1100-36-ASM
hom G @ chr12:21221005

 

GS18558 - var-GS18558-1100-36-ASM
het G @ chr12:21221005

 

GS18940 - var-GS18940-1100-36-ASM
hom G @ chr12:21221005

 

GS18942 - var-GS18942-1100-36-ASM
hom G @ chr12:21221005

 

GS18947 - var-GS18947-1100-36-ASM
het G @ chr12:21221005

 

GS19017 - var-GS19017-1100-36-ASM
het G @ chr12:21221005

 

GS19025 - var-GS19025-1100-36-ASM
hom G @ chr12:21221005

 

GS19026 - var-GS19026-1100-36-ASM
hom G @ chr12:21221005

 

GS19129 - var-GS19129-1100-36-ASM
hom G @ chr12:21221005

 

GS19238 - var-GS19238-1100-36-ASM
hom G @ chr12:21221005

 

GS19239 - var-GS19239-1100-36-ASM
hom G @ chr12:21221005

 

GS19240 - var-GS19240-1100-36-ASM
hom G @ chr12:21221005

 

GS19648 - var-GS19648-1100-36-ASM
het G @ chr12:21221005

 

GS19649 - var-GS19649-1100-36-ASM
het G @ chr12:21221005

 

GS19700 - var-GS19700-1100-36-ASM
het G @ chr12:21221005

 

GS19701 - var-GS19701-1100-36-ASM
het G @ chr12:21221005

 

GS19703 - var-GS19703-1100-36-ASM
het G @ chr12:21221005

 

GS19704 - var-GS19704-1100-36-ASM
hom G @ chr12:21221005

 

GS19735 - var-GS19735-1100-36-ASM
het G @ chr12:21221005

 

GS20502 - var-GS20502-1100-36-ASM
het G @ chr12:21221005

 

GS20509 - var-GS20509-1100-36-ASM
het G @ chr12:21221005

 

GS21767 - var-GS21767-1100-36-ASM
hom G @ chr12:21221005

 

Other external references
 

    dbSNP
  • rs2306283
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Organ Transplantation]
    [mycophenolate mofetil; mycophenolic acid; sirolimus; tacrolimus]
    Risk or phenotype-associated allele: SLCO1B1*15 defined by rs2306283 Asn130Asp (338A>G) and rs4149056 Val174Ala (521T>C). Phenotype: SLCO1B1*15 allele was associated with higher mycophenolic acid (MPA) AUC(0-12 hours) (p = 0.0246) and lower ratio of MPAG (MPA glucuronide)/MPA (p = 0.0267), but no association with MPAG AUC(0-9 h). Study size: 70. Study population/ethnicity: Caucasian cohort from the SOPHIE study cotreated with mycophenylate mofetil (MMF) and either sirolimus or tacrolimus. Significance metric(s): p < 0.03. Type of association: GN; PK
    www.ncbi.nlm.nih.gov/pubmed/19890249
  • [Neoplasms]
    Approximately 50% of the variation in absolute neutrophil count nadir in cancer patients is explained by rs3765129, rs2306283 and UGT1a1*93; the AUCs of irinotecan, SN-38, SN-38 glucuronide, and APC are influenced by rs3740066, rs2306283, rs35605, rs10276036, and rs717620 .
    www.ncbi.nlm.nih.gov/pubmed/19940846
  • [pravastatin]
    Associated with decreased pravastatin plasma AUC.
    www.pharmgkb.org/search/annotatedGene/slco1b
  • [nateglinide; repaglinide]
    Homozygosity for the G allele of this SNP was associated with reduced plasma concentrations of repaglinide, but not nateglinide, in healthy volunteers dosed separately with each of these drugs.
    www.ncbi.nlm.nih.gov/pubmed/18854776
  • [pravastatin]
    Variant with G allele showed mixed results: NO change in in vitro transport of estrone sulfate but decreased plasma AUC of pravastatin, endogenous bile acids
    www.ncbi.nlm.nih.gov/pubmed/11477075; PubMed ID:15116054; PubMed ID:19387419

Other in silico analyses
 

  • NBLOSUM100 score = –1
  • GET-Evidence autoscore = 1

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in