rs776746

minus

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

Reference

GRCh38 38.1/141

Chromosome

7

Position

99672916

Gene	CYP3A5, ZSCAN25

is a	snp
is	mentioned by
dbSNP	rs776746
dbSNP (classic)	rs776746
ClinGen	rs776746
ebi	rs776746
HLI	rs776746
Exac	rs776746
Gnomad	rs776746
Varsome	rs776746
LitVar	rs776746
Map	rs776746
PheGenI	rs776746
Biobank	rs776746
1000 genomes	rs776746
hgdp	rs776746
ensembl	rs776746
geneview	rs776746
scholar	rs776746
google	rs776746
pharmgkb	rs776746
gwascentral	rs776746
openSNP	rs776746
23andMe	rs776746
SNPshot	rs776746
SNPdbe	rs776746
MSV3d	rs776746
GWAS Ctlg	rs776746

GMAF

0.3118

Max Magnitude

2.5

?

(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 21206424 ] 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 22108237 ] 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 17615053 ] Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk.

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

[PMID 18547414 ] Genotyping panel for assessing response to cancer chemotherapy.

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

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

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

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

[PMID 19154420 ] 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 19694740 ] 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 20354687 ] Explaining variability in ciclosporin exposure in adult kidney transplant recipients.

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

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

[PMID 20538623 ] 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 21359226 ] 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 21671989 ] 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 24297552 ] 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 24427273 ] Global Pharmacogenomics: Distribution of CYP3A5 Polymorphisms and Phenotypes in the Brazilian Population

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

[PMID 23133420 ] 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 23734777 ] Lack of strong effect modification by NFE2L2/CYP3A5/ABO of the risk of venous thrombosis associated with oral hormone therapy.

[PMID 23991193 ] 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 25992585 ] 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 26325438 ] Influence of ADME genomic variants on tacrolimus/sirolimus blood levels and GVHD after allogeneic hematopoietic cell transplantation

ClinVar
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
Gene	CYP3A5 ZSCAN25
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 27788239 ] Interaction between Darunavir and Etravirine Is Partly Mediated by CYP3A5 Polymorphism.

[PMID 32256016 ] Importance of genetic polymorphisms in liver transplantation outcomes.

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