{{Rsnum
|rsid=776746
|Gene=CYP3A5
|Chromosome=7
|position=99672916
|Orientation=minus
|GMAF=0.3118
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=CYP3A5,ZSCAN25
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 0.0 | 7.2 | 92.8
| HCB | 10.3 | 38.2 | 51.5
| JPT | 4.4 | 42.5 | 53.1
| YRI | 68.0 | 31.3 | 0.7
| ASW | 36.8 | 54.4 | 8.8
| CHB | 10.3 | 38.2 | 51.5
| CHD | 5.5 | 38.5 | 56.0
| GIH | 5.9 | 37.6 | 56.4
| LWK | 75.5 | 21.8 | 2.7
| MEX | 3.5 | 40.4 | 56.1
| MKK | 25.6 | 51.3 | 23.1
| TSI | 0.0 | 10.8 | 89.2
| HapMapRevision=28
}}

[[rs776746]], also known as 6986G>A, 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.

{{PharmGKB
|RSID=rs776746
|Name_s=CYP3A5*3, intron 3 splicing defect, c.219-237A>G; rs776746 G alllele
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:19865079
|Annotation=Risk or phenotype-associated allele: CYP3A5*3/*3 (rs776746 GG) genotype. Phenotype: Tacrolimus clearance was significantly lower in patients with the nonfunctional CYP3A5 enzyme encoded by the CYP3A5*3/*3 genotype (rs776746 GG) in comparison to carriers of the wild-type CYP3A5*1 ((rs776746 A) allele (p = 0.013).At 1 month after transplantation, creatinine clearance was higher in patients with the CYP3A5*1 allele than in those with CYP3A5*3/*3 (117.5 24.4 vs. 97.2 28.4 ml/min), but not to a statistically significant extent (p = 0.06). Tacrolimus clearance was significantly higher in patients with low (<33%) versus normal hematocrit levels (p = 0.007). The individualization of tacrolimus dosage should be based on weight, hematocrit level, and CYP3A5 polymorphism to maintain therapeutic range. However, interindividual and residual variability remained large even when genetic information was taken into account. In a simulated estimation, 20% of the patients received an overdose (C(0) > 20 ng/ml), and 19% received too low a dose (C(0) < 5 ng/ml), thereby reinforcing the need for monitoring. A standard dosage of 0.15 mg/kg twice daily was associated with underdosing in children with the CYP3A5*1 ((rs776746 A) allele, thus higher dosages (0.2-0.3 mg/kg twice daily) are recommended primarily in children with body weight <20 kg and low hematocrit levels. In contrast, for children with CYP3A5*3/*3 (rs776746 GG) genotype, the lower dosage of 0.1 mg/kg twice daily should be recommended, primarily in those with body weight >40 kg. Study size: 50. Study population/ethnicity: Pediatric kidney transplant patients (29 males) of 10 years mean age (2-18 y.o. range) recruited from nine French centers from 2005 to 2008. Significance metric(s): p = (0.007 - 0.013) Type of association: GN, PK.
|Drugs=tacrolimus
|Drug Classes=
|Diseases=Organ Transplantation; Transplantation
|Curation Level=Curated
|PharmGKB Accession ID=PA165110648
}}

{{PMID Auto
|PMID=20617557
|Title=Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy
}}
{{PMID Auto
|PMID=20685352
|Title=Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy
}}

{{PharmGKB
|RSID=rs776746
|Name_s=CYP3A5*3; CYP3A5:6986A>G
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/cyp3a5/variant.jsp#ImportantVariantInformationforCYP3A5-3
|Annotation=Nonfunctional variant of CYP3A5.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145175
}}

{{PharmGKB
|RSID=rs776746
|Name_s=CYP3A5*3; CYP3A5:6986A>G
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:19516253
|Annotation=A study in healthy Korean subjects indicates that CYP2C19 polymorphisms play an important role in the metabolism of cilostazol only in individuals with the CYP3A5*3/*3 genotype.
|Drugs=cilostazol
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165106756
}}

{{PharmGKB
|RSID=rs776746
|Name_s=rs776746 A>G; CYP3A5*3; Splicing defect
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:20212519
|Annotation=Risk or phenotype-associated allele: A. Phenotype: This variant was associated with reduced risk for neurotoxicity with paclitaxel treatment. Study size: 132. Study population/ethnicity: Patients with Neoplasms receiving paclitaxel; Spain. Significance metric(s): HR = 0.55 (0.33-0.94); p = 0.027. Type of association: PK; TOX.
|Drugs=paclitaxel
|Drug Classes=
|Diseases=Drug Toxicity; Neurotoxicity Syndromes
|Curation Level=Curated
|PharmGKB Accession ID=PA165291997
}}

{{PharmGKB
|RSID=rs776746
|Name_s=CYP3A5*3
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:20368718
|Annotation=Phenotype/associated allele: A meta-analysis of articles in PubMed in which dose-adjusted blood concentrations of Cyclosporine were measured in renal transplant patients implied that patients carrying the CYP3A5*3/*3 genotype will require a lower dose of Cyclosporine to reach target levels compared with CYP3A5*1/*1 or *1/*3 carriers. Study size: 15 studies ; 1742 subjects. Study population/ethnicity: France, the Netherlands, Belgium, United States, Germany, China, India ,Singapore and Malaysia. Type of association: PK.
|Drugs=cyclosporine
|Drug Classes=
|Diseases=Organ Transplantation; Transplantation
|Curation Level=Curated
|PharmGKB Accession ID=PA165363222
}}

{{PharmGKB
|RSID=rs776746
|Name_s=CYP3A5*1, intron 3 splicing defect, c.219-237G>A; rs776746 A alllele
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:14515059
|Annotation=Risk or phenotype-associated allele: CYP3A5*1, rs776746 AA genotype. Phenotype: Genotype frequencies were not in Hardy-Weinberg equilibrium for CYP3A5, where a greater than expected number of CYP3A5*1 (rs776746 AA) homozygotes was observed among cases (p = 0.006). CYP3A5*1 (rs776746 AA) homozygotes showed a non-significant increase in risk for lung cancer (OR = 5.24, p = 0.14). Study size: 1562 cancer cases, 432 controls. Study population/ethnicity: A case-control study was conducted in 801 Caucasian lung cancer patients that included 330 adenocarcinomas, 260 squamous cell carcinomas, 171 small cell lung cancers and 432 Caucasian hospital-based controls. Significance metric(s): Not significant, p = 0.14. Type of association: GN; PK
|Drugs=
|Drug Classes=
|Diseases=Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell
|Curation Level=Curated
|PharmGKB Accession ID=PA165110780
}}

{{PharmGKB
|RSID=rs776746
|Name_s=CYP3A5*3, intron 3 splicing defect, c.219-237A>G; rs776746 G alllele
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:12966368
|Annotation=Risk or phenotype-associated allele: CYP3A5*3/*3 (rs776746 GG) genotype. Phenotype: In kidney transplant patients, tacrolimus dose-adjusted trough levels were higher in patients carrying the CYP3A5*3/*3 (rs776746 GG) genotype (n = 45) than in carriers of the CYP3A5*1/*3 (rs776746 GA) plus CYP3A5*1/*1 (rs776746 AA) genotypes combined (n = 17), as follows: median and range, 94 (34-398) versus 61 (37-163) ng/mL per mg/kg (p < 0.0001). Thus, patients with the CYP3A5*3/*3 genotype require less tacrolimus to reach target predose concentrations compared with CYP3A5*1 (rs776746 A) allele carriers. Study size: 64. Study population/ethnicity: Renal transplant recipients from the outpatient clinic of the Erasmus Medical Center in Rotterdam in the Netherlands, who had received a renal graft at least 1 year before the start of the study and were administered tacrolimus. Significance metric(s): p < 0.0001 Type of association: GN; PK.
|Drugs=tacrolimus
|Drug Classes=
|Diseases=Organ Transplantation; Transplantation
|Curation Level=Curated
|PharmGKB Accession ID=PA165110654
}}

{{PharmGKB
|RSID=rs776746
|Name_s=CYP3A5*1, intron 3 splicing defect, c.219-237G>A; rs776746 A alllele
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:14515059
|Annotation=Risk or phenotype-associated allele: CYP3A5*1, rs776746 AA genotype. Phenotype: Genotype frequencies were not in Hardy-Weinberg equilibrium for CYP3A5, where a greater than expected number of CYP3A5*1 (rs776746 AA) homozygotes was observed among cases (p = 0.006). CYP3A5*1 (rs776746 AA) homozygotes showed a non-significant increase in risk for lung cancer (OR = 5.24, p = 0.14). Study size: 1562 cancer cases, 432 controls. Study population/ethnicity: A case-control study was conducted in 801 Caucasian lung cancer patients that included 330 adenocarcinomas, 260 squamous cell carcinomas, 171 small cell lung cancers, and 432 Caucasian hospital-based controls. Significance metric(s): Not significant, p = 0.14. Type of association: GN; PK; CO
|Drugs=
|Drug Classes=
|Diseases=Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell
|Curation Level=Curated
|PharmGKB Accession ID=PA165111316
}}

{{PharmGKB
|RSID=rs776746
|Name_s=CYP3A5*3C, g.6986A>G, rs776746 G allele, splice variant
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:15122075
|Annotation=Risk or phenotype-associated allele: CYP3A5*3C, g.6986A>G, rs776746 G allele, splice variant. Phenotype: There was no significant association between systemic exposure of tipifarnib (AUC levels) and CYP3A5*3C genotype. Study size: 28 (16 male). Study population/ethnicity: Caucasian cancer patients, aged 34-75. Significance metric(s): Not significant, p = 0.52. Type of association: GN; PK
|Drugs=Tipifarnib
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165111319
}}

{{PharmGKB
|RSID=rs776746
|Name_s=g.6986A>G
|Gene_s=CYP3A5, CYP3A
|Feature=Intron, NA
|Evidence=PubMed ID:20017669
|Annotation=Risk or phenotype-associated allele: G. Phenotype: This variant is statistically correlated with the mean of maximum transaminase values (ALT) in patients from Mozambique, with higher ALT mean value for G genotype carriers. Study size: 156. Study population/ethnicity: HIV infected patients from Mozambique. Significance metric(s): p= 0.019. Type of association: GN; CO
|Drugs=nevirapine
|Drug Classes=
|Diseases=Drug Toxicity; HIV Infections
|Curation Level=Curated
|PharmGKB Accession ID=PA165111625
}}
{{PMID Auto
|PMID=21206424
|Title=Novel Polymorphisms Associated With Tacrolimus Trough Concentrations: Results From a Multicenter Kidney Transplant Consortium
|OA=1
}}

{{PMID Auto
|PMID=22015057
|Title=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 Auto
|PMID=22120734
|Title=Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia
}}

{{PMID Auto
|PMID=21806386
|Title=Pharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patients
}}

{{PMID Auto
|PMID=22108237
|Title=The use of a DNA biobank linked to electronic medical records to characterize pharmacogenomic predictors of tacrolimus dose requirement in kidney transplant recipients.
|OA=1
}}

{{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|OA=1
}} Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk.

{{PMID|18248681|OA=1
}} Prevalence of common disease-associated variants in Asian Indians.

{{PMID|18547414|OA=1
}} Genotyping panel for assessing response to cancer chemotherapy.

{{PMID|18566991|OA=1
}} Joint effects of inflammation and androgen metabolism on prostate cancer severity.

{{PMID|18784455|OA=1
}} The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis.

{{PMID|18825162|OA=1
}} Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African Americans.

{{PMID|19076156|OA=1
}} Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6 and CYP3A) affect the pharmacokinetics of thiotepa and tepa.

{{PMID|19154420|OA=1
}} 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|OA=1
}} 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|OA=1
}} Explaining variability in ciclosporin exposure in adult kidney transplant recipients.

{{PMID|20389299|OA=1
}} Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.

{{PMID|20459744|OA=1
}} Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.

{{PMID|20538623|OA=1
}} 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|OA=1
}} 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|OA=1
}} 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.

{{GET Evidence
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs776746
|overall_frequency_n=47
|overall_frequency_d=128
|overall_frequency=0.367188
|n_genomes=28
|n_genomes_annotated=0
|n_haplomes=44
|n_articles=7
|n_articles_annotated=0
|in_pharmgkb=Y
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23146479
|Title=Effect of CYP3A5, CYP3A4, and ABCB1 Genotypes as Determinants of Tacrolimus Dose and Clinical Outcomes After Heart Transplantation
}}

{{PMID Auto
|PMID=23149441
|Title=Impact of Tacrolimus Intraindividual Variability and CYP3A5 Genetic Polymorphism on Acute Rejection in Kidney Transplantation
}}

{{PMID Auto
|PMID=24297552
|Title=Utilization of an emr-biorepository to identify the genetic predictors of calcineurin-inhibitor toxicity in heart transplant recipients
}}

{{PMID Auto
|PMID=24352002
|Title=Significant association between CYP3A5 polymorphism and blood concentration of tacrolimus in patients with connective tissue diseases
}}

{{PMID Auto
|PMID=24368493
|Title=Interaction between ALOX5AP and CYP3A5 gene variants significantly increases the risk for cerebral infarctions in Chinese
}}

{{PMID Auto
|PMID=24427273
|Title=Global Pharmacogenomics: Distribution of CYP3A5 Polymorphisms and Phenotypes in the Brazilian Population
|OA=1
}}

{{PMID Auto
|PMID=23130019
|Title=Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.
|OA=1
}}

{{PMID Auto
|PMID=23133420
|Title=Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
|OA=1
}}

{{PMID Auto
|PMID=23143606
|Title=Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese breast cancer patients.
}}

{{PMID Auto
|PMID=23501331
|Title=Effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and CYP3A activity in hypercholeresterolemic patients.
}}

{{PMID Auto
|PMID=23584898
|Title=CYP3A5*3 polymorphism and cancer risk: a meta-analysis and meta-regression.
}}

{{PMID Auto
|PMID=23734777
|Title=Lack of strong effect modification by NFE2L2/CYP3A5/ABO of the risk of venous thrombosis associated with oral hormone therapy.
}}

{{PMID Auto
|PMID=23991193
|Title=Novel single nucleotide polymorphisms in interleukin 6 affect tacrolimus metabolism in liver transplant patients
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}