CYP3A5
Chr 7Multicytochrome P450 family 3 subfamily A member 5
Also known as: CP35, CYPIIIA5, P450PCN3, PCN3
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein metabolizes drugs as well as the steroid hormones testosterone and progesterone. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Two pseudogenes of this gene have been identified within this cluster on chromosome 7. Expression of this gene is widely variable among populations, and a single nucleotide polymorphism that affects transcript splicing has been associated with susceptibility to hypertensions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
78 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 18 | 0 | 18 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 33 | 7 | 0 | 40 |
Likely Benign | 3 | 4 | 6 | 3 | 16 |
Benign | 1 | 0 | 1 | 1 | 3 |
| Total | 4 | 37 | 33 | 4 | 78 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →CYP3A5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Tacrolimus and Personalized Therapy to Prevent Acute Rejection Episodes
RECRUITINGDORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection
RECRUITINGEffectiveness and Cost-effectiveness of a Pre-emptive Genotyping Strategy in Patients Receiving Tacrolimus
RECRUITINGUtilising Genotype Informed Bayesian Dosing of Tacrolimus in Children Post Solid Organ Transplantation.
RECRUITINGBiological Collection for the Purpose of Exploring Genetic and Clinical-biological Factors Associated With Variability in Response to Mavacamten in the Treatment of Obstructive Hypertrophic Cardiomyopathy
NOT YET RECRUITINGAnalysis of the Effect of Donor CYP3A5 Gene Polymorphism on Early Tacrolimus Concentration and Postoperative Acute Renal Injury After Liver Transplantation
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools