CYP3A4

Chr 7

cytochrome P450 family 3 subfamily A member 4

Also known as: CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4, HLP, NF-25

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs in use today, including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin, and chloroquine. The enzyme also metabolizes some steroids and carcinogens. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Previously another CYP3A gene, CYP3A3, was thought to exist; however, it is now thought that this sequence represents a transcript variant of CYP3A4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2020]

Primary Disease Associations & Inheritance

UniProtVitamin D-dependent rickets 3
58
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical SummaryCYP3A4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 26 VUS of 58 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.12LOEUF
pLI 0.000
Z-score 1.09
OE 0.76 (0.531.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.35Z-score
OE missense 1.06 (0.961.17)
281 obs / 264.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.76 (0.531.12)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.961.17)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
01.21.6
LoF obs/exp: 19 / 24.8Missense obs/exp: 281 / 264.9Syn Z: 0.38

ClinVar Variant Classifications

58 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS26
Likely Benign8
Benign3
20
Pathogenic
1
Likely Pathogenic
26
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
19
0
20
Likely Pathogenic
0
0
1
0
1
VUS
1
17
8
0
26
Likely Benign
1
2
2
3
8
Benign
0
0
2
1
3
Total22032458

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CYP3A4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

No OMIM entries found.

📖
GeneReview available — CYP3A4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Carcinoma, Renal Cell

Study to Evaluate the Safety and Efficacy of Bicalutamide in Combination with Sunitinib in Patients with TKIs-resistant RCC

RECRUITING
NCT06222593Phase PHASE1, PHASE2State University of New York at BuffaloStarted 2024-10-01
Bicalutamide in combination with Sunitinib
Opioid Use DisorderPregnancy Related

Predicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy

RECRUITING
NCT05942313Ilana HullStarted 2023-08-28
Buprenorphine/ Methadone exposure
Kidney Transplant Failure and RejectionImmunosuppression-related Infectious Disease

Tacrolimus Pharmacokinetic Subpopulations

RECRUITING
NCT04526431University Hospital, GrenobleStarted 2020-07-28
Dosage Forms Oral
Cancer

Pharmacokinetic Boosting of Olaparib to Improve Exposure, Tolerance and Cost-effectiveness

RECRUITING
NCT05078671Phase PHASE4Radboud University Medical CenterStarted 2021-12-15
OlaparibCobicistat
Metastatic MelanomaBRAF Gene Mutation

Nilotinib Plus Dabrafenib/Trametinib or Encorafenib/Binimetinib in Metastatic Melanoma

RECRUITING
NCT04903119Phase PHASE1Rina PlattnerStarted 2022-06-01
Nilotinib 100mgNilotinib 200mgNilotinib 300mg
Acute Myeloid LeukemiaAcute Lymphoblastic LeukemiaMixed Lineage Acute Leukemia

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

RECRUITING
NCT04065399Phase PHASE1, PHASE2Syndax PharmaceuticalsStarted 2019-11-05
revumenibcobicistat
Healthy Volunteer

A Study to Learn How Fluconazole, Carbamazepine and Itraconazole Affect How the Body Processes ASP3082 in Healthy Adults

RECRUITING
NCT07395024Phase PHASE1Astellas Pharma Global Development, Inc.Started 2026-02-03
SetidegrasibFluconazoleCarbamazepine
AnalgesiaCardiac Surgery

Precision Analgesia for Cardiac Surgery

NOT YET RECRUITING
NCT05612399Kathirvel SubramaniamStarted 2026-04-01
Waldenström Macroglobulinemia (WM)

Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia

NOT YET RECRUITING
NCT07169565Phase PHASE1Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2025-09-01
IbrutinibBendamustineRituximab
Intracerebral HemorrhageAtrial Fibrillation

Anticoagulation in ICH Survivors for Stroke Prevention and Recovery

RECRUITING
NCT03907046Phase PHASE3Yale UniversityStarted 2020-01-28
ApixabanAspirin
Obstructive Hypertrophic Cardiomyopathy (oHCM)

Biological 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 RECRUITING
NCT07439952Assistance Publique - Hôpitaux de ParisStarted 2026-02-05
MelanomaNon-Small-Cell Lung CancerThyroid Cancer

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.

RECRUITING
NCT05355701Phase PHASE1PfizerStarted 2022-07-05
PF-07799933binimetinibcetuximab