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From SNPedia

Geno Mag Summary
(A;A) 0 reference allele
(A;G) 2 carrier of 1 nonfunctional CYP3A5 allele; drug metabolism affects
(G;G) 2.5 CYP3A5*3 homozygote; CYP3A5 non-expressor
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs776746
1000 genomesrs776746
GWAS Ctlgrs776746
Max Magnitude2.5
? (A;A) (A;G) (G;G) 28

rs776746, also known as 6986A>G, is a SNP encoding the (nonfunctional) CYP3A5*3 allele of the CYP3A5 gene.

CYP3A5*3 has been studied especially in connection with the metabolism of tacrolimus, an immunosuppressive drug used in organ transplantation. The optimal therapeutic dose is in a relatively narrow window, so blood concentration monitoring is recommended. CYP3A5*3 carriers tend to build up higher levels of tacrolimus than CYP3A5*1 carriers, unless their tacrolimus intake is reduced.

Carrying two non-expressing CYP3A5*3 alleles (in other words, the rs776746(G;G) genotype) is very common among Caucasians (over 85% of all), and is still relatively common (perhaps about half of all people) in many other populations other than those that are of African descent.

[PMID 20617557] Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy

[PMID 20685352] Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy

[PMID 21206424OA-icon.png] Novel Polymorphisms Associated With Tacrolimus Trough Concentrations: Results From a Multicenter Kidney Transplant Consortium

[PMID 22015057] Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study

[PMID 22120734] Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia

[PMID 21806386] Pharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patients

[PMID 22108237OA-icon.png] The use of a DNA biobank linked to electronic medical records to characterize pharmacogenomic predictors of tacrolimus dose requirement in kidney transplant recipients.

[PMID 16172230] Risk of testicular germ cell cancer in relation to variation in maternal and offspring cytochrome p450 genes involved in catechol estrogen metabolism.

[PMID 17615053OA-icon.png] Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk.

[PMID 18248681OA-icon.png] Prevalence of common disease-associated variants in Asian Indians.

[PMID 18547414OA-icon.png] Genotyping panel for assessing response to cancer chemotherapy.

[PMID 18566991OA-icon.png] Joint effects of inflammation and androgen metabolism on prostate cancer severity.

[PMID 18784455OA-icon.png] The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis.

[PMID 18825162OA-icon.png] Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African Americans.

[PMID 19076156OA-icon.png] Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6 and CYP3A) affect the pharmacokinetics of thiotepa and tepa.

[PMID 19154420OA-icon.png] The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC.

[PMID 19584153] Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia.

[PMID 19694740OA-icon.png] No significant effect of ABCB1 haplotypes on the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin.

[PMID 20170205] Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I.

[PMID 20214406] Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II.

[PMID 20354687OA-icon.png] Explaining variability in ciclosporin exposure in adult kidney transplant recipients.

[PMID 20389299OA-icon.png] Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.

[PMID 20459744OA-icon.png] Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.

[PMID 20538623OA-icon.png] Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver.

[PMID 21102498] Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients.

[PMID 21359226OA-icon.png] The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected.

[PMID 21480817] Pharmacogenetics of tacrolimus after renal transplantation: analysis of polymorphisms in genes encoding 16 drug metabolizing enzymes.

[PMID 21544031] Expression of CYP3A5 and P-glycoprotein in renal allografts with histological signs of calcineurin inhibitor nephrotoxicity.

[PMID 21671989OA-icon.png] Dosing equation for tacrolimus using genetic variants and clinical factors.

[PMID 21896346] Polymorphisms in genes that regulate cyclosporine metabolism affect cyclosporine blood levels and clinical outcomes in patients who receive allogeneic hematopoietic stem cell transplantation.

[PMID 22469198] Identification of Factors Affecting Tacrolimus Level and 5-Year Clinical Outcome in Kidney Transplant Patients.

[PMID 23146479] Effect of CYP3A5, CYP3A4, and ABCB1 Genotypes as Determinants of Tacrolimus Dose and Clinical Outcomes After Heart Transplantation

[PMID 23149441] Impact of Tacrolimus Intraindividual Variability and CYP3A5 Genetic Polymorphism on Acute Rejection in Kidney Transplantation

[PMID 24297552OA-icon.png] Utilization of an emr-biorepository to identify the genetic predictors of calcineurin-inhibitor toxicity in heart transplant recipients

[PMID 24352002] Significant association between CYP3A5 polymorphism and blood concentration of tacrolimus in patients with connective tissue diseases

[PMID 24368493] Interaction between ALOX5AP and CYP3A5 gene variants significantly increases the risk for cerebral infarctions in Chinese

[PMID 24427273OA-icon.png] Global Pharmacogenomics: Distribution of CYP3A5 Polymorphisms and Phenotypes in the Brazilian Population

[PMID 23130019OA-icon.png] Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.

[PMID 23133420OA-icon.png] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.

[PMID 23143606] Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese breast cancer patients.

[PMID 23501331] Effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and CYP3A activity in hypercholeresterolemic patients.

[PMID 23584898] CYP3A5*3 polymorphism and cancer risk: a meta-analysis and meta-regression.

[PMID 23734777OA-icon.png] Lack of strong effect modification by NFE2L2/CYP3A5/ABO of the risk of venous thrombosis associated with oral hormone therapy.

[PMID 23991193OA-icon.png] Novel single nucleotide polymorphisms in interleukin 6 affect tacrolimus metabolism in liver transplant patients

[PMID 25712187] Donor IL-18 rs5744247 polymorphism as a new biomarker of tacrolimus elimination in Chinese liver transplant patients during the early post-transplantation period: results from two cohort studies

[PMID 25992585OA-icon.png] Polymorphisms in CYP1B1, CYP3A5, GSTT1, and SULT1A1 Are Associated with Early Age Acute Leukemia

[PMID 26177348] Comparison of tacrolimus and cyclosporin A in CYP3A5 expressing Chinese de novo kidney transplant recipients: a 2-year prospective study

[PMID 26325438OA-icon.png] Influence of ADME genomic variants on tacrolimus/sirolimus blood levels and GVHD after allogeneic hematopoietic cell transplantation

Risk Rs776746(A;A)
Alt Rs776746(A;A)
Reference Rs776746(G;G)
Significance Drug-response
Disease sirolimus response - Dosage Cyclosporine response - Dosage tacrolimus response - Dosage tacrolimus response due to donor genotype - Dosage tacrolimus response - Efficacy
Variation info
CLNDBN sirolimus response - Dosage cyclosporine response - Dosage, Metabolism/PK tacrolimus response - Dosage, Metabolism/PK tacrolimus response due to donor genotype - Dosage, Metabolism/PK tacrolimus response - Efficacy
Reversed 1
HGVS NC_000007.13:g.99270539C>T
CLNSRC PharmGKB Clinical Annotation
CLNACC RCV000211230.1, RCV000211240.1, RCV000211322.1, RCV000211356.1, RCV000211409.1,

[PMID 27788239OA-icon.png] Interaction between Darunavir and Etravirine Is Partly Mediated by CYP3A5 Polymorphism.

[PMID 32256016OA-icon.png] Importance of genetic polymorphisms in liver transplantation outcomes.

[PMID 33564260OA-icon.png] Association of CYP3A5 Gene Polymorphisms and Amlodipine-Induced Peripheral Edema in Chinese Han Patients with Essential Hypertension.