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HelpTest ID: 3A5Q Cytochrome P450 3A5 Genotype, Varies
Ordering Guidance
Testing is available as the single gene assay (this test) and as a part of a psychotropic or focused pharmacogenomics panel.
If multiple pharmacogenomic genotype testing is desired, order PGXQP / Focused Pharmacogenomics Panel, Varies.
If genotype testing for psychotropic medications is desired, order PSYQP / Psychotropic Pharmacogenomics Gene Panel, Varies.
Additional Testing Requirements
In general, most drugs metabolized by CYP3A5 are also metabolized by CYP3A4 and usually to a greater degree than CYP3A5. For this reason, substrates of these 2 enzymes are sometimes listed together in publications and genotyping of both genes might be needed to fully understand the metabolism of these drugs and predict phenotype. If CYP3A4 genotyping is needed, order 3A4Q / Cytochrome P450 3A4 Genotype, Varies.
Specimen Required
Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor or liver transplant will interfere with testing. For more information about testing patients who have received a hematopoietic stem cell or liver transplant ,call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Cord blood
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send cord blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 2 Swabs
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days
Additional information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
Specimen Type: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2mL with skirted conical base
Acceptable: Matrix tube, 1 mL
Collection Instructions:
1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated
Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-Neurology Specialty Testing Client Test Request (T732)
-Therapeutics Test Request (T831)
-Renal Diagnostics Test Request (T830)
Useful For
Aids in optimizing treatment with tacrolimus and other drugs metabolized by cytochrome P450 3A5
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) With Allelic Discrimination Analysis
Reporting Name
CYP3A5 Genotype, VSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | |
Clinical Information
CYP3A5 is a member of the CYP3A family of genes located on chromosome 7. The cytochrome P450 (CYP) 3A subfamily of enzymes responsible for the metabolism of more than 50% of medications that undergo hepatic metabolism and first-pass metabolism in intestinal epithelial cells. The CYP3A5 expression level and enzymatic activity can be modulated by genetic variation. The frequency of CYP3A5 alleles varies by ancestral background. For example, in individuals of European descent the most common allele is the CYP3A5*3 allele (c.219-237A>G), which results in a splicing defect and absence of enzyme activity. In individuals of African descent, the *1 allele is most common which has fully functional enzyme activity. In addition to the *3 allele, other alleles also are associated with reduced or no enzyme activity, including the *6, *7, *8, and *9 alleles.
CYP3A5 testing is commonly ordered for patients receiving tacrolimus. Tacrolimus is an immunosuppressive calcineurin inhibitor used in transplant recipients. Tacrolimus has a low therapeutic index with a wide range of adverse effects and large interindividual variability in its pharmacokinetics, particularly in the dose required to reach target trough blood concentrations. Thus, routine therapeutic drug monitoring is used in clinical practice.
Tacrolimus dose requirements are most closely associated with CYP3A5 genotype even though the drug is metabolized by both CYP3A4 and CYP3A5. According to existing literature and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, individuals with at least one copy of fully functional CYP3A5 (ie, *1/*1 or *1/*3) require a higher dose of tacrolimus to reach the targeted whole blood concentration than those without a copy of a fully functional CYP3A5 allele (ie, *3/*3).(1-4) CYP3A5 genotyping may predict dose requirements for tacrolimus but does not replace the need for therapeutic drug monitoring to guide tacrolimus dose adjustments. For a patient with the CYP3A5*3/*3 genotype, initiating tacrolimus therapy with a standard (normal) dose is recommended. One of the complications in interpreting CYP3A5 genotyping results and the effect of genotype on drug dosing is the fact that most individuals involved in drug trials have been of European decent. Individuals of European decent are more likely to have the CYP3A5*3/*3 genotype, which predicts a poor metabolizer phenotype. Dosing requirements were derived from these clinical trials so individuals with 1 or 2 copies of CYP3A5*1, will functionally behave as though they have increased activity and may require higher doses of CYP3A5 metabolized drugs.
The following table displays the CYP3A5 variants detected by this assay, the corresponding star allele, and the effect on CYP3A5 enzyme activity:
|
CYP3A5 allele |
cDNA nucleotide change (NM_000777.4) |
Effect on enzyme activity |
|
*1 |
None (wild type) |
Normal activity |
|
*3 |
c.219-237A>G |
No activity |
|
*6 |
c.624G>A |
No activity |
|
*7 |
c.1035dup |
No activity |
|
*8 |
c.82C>T |
Reduced activity |
|
*9 |
c.1009G>A |
Reduced activity |
Reference Values
An interpretive report will be provided.
Interpretation
The interpretive report includes an overview of the findings as well as the associated clinical significance.
The genotype, with associated star alleles, is assigned using standard allelic nomenclature as published by Pharmacogene Variation (PharmVar) Consortium.(5)
For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables. This resource also includes information regarding enzyme inhibitors and inducers.
Clinical Reference
1. Birdwell KA, Decker B, Barbarino JM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015;98(1):19-24. doi:10.1002/cpt.113
2. Thervet E, Loriot MA, Barbier S, et al. Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin Pharmacol Ther. 2010;87(6):721-726. doi:10.1038/clpt.2010.17
3. Lamba J, Hebert JM, Schuetz EG, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenet Genomics. 2012;22(7):555-558. doi:10.1097/FPC.0b013e328351d47f
4. Clinical Pharmacogenetics Implementation Consortium (CPIC). Accessed May 15, 2025. https://cpicpgx.org/
5. PharmVar: Pharmacogene Variation Consortium. Updated April 29, 2025. Accessed May 15, 2025. Available at www.pharmvar.org/
6. Lee SJ, Usmani KA, Chanas B, et al. Genetic findings and functional studies of human CYP3A5 single nucleotide polymorphisms in different ethnic groups. Pharmacogenetics. 2003;13(8):461-472. doi:10.1097/00008571-200308000-00004
Day(s) Performed
Varies
Report Available
3 to 8 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81231-CYP3A5
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| 3A5Q | CYP3A5 Genotype, V | 81140-6 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 610117 | CYP3A5 Genotype | 81140-6 |
| 610118 | CYP3A5 Phenotype | 79717-5 |
| 610119 | Interpretation | 69047-9 |
| 610120 | Additional Information | 48767-8 |
| 610121 | Method | 85069-3 |
| 610122 | Disclaimer | 62364-5 |
| 610123 | Reviewed by | 18771-6 |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
For any cord blood specimen that is received, maternal cell contamination testing may be performed at an additional charge.
mml-pgxsingle