CYP3A5
protein-codingcytochrome P450 family 3 subfamily A member 5, the group of Cytochrome P450 family 3
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: Selection and dosing of many medications may be affected by the presence of variants
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CYP3A5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000777.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 4 | ||||
| missense | 38 | 5 | 43 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 3 | 4 | |||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 48 | 12 | 0 | 60 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000768.1 | 13 | MANE Select | |
| Ensembl | ENSP00000222982.4 | 13 | MANE Select | |
| RefSeq | NP_001177413.1 | 5 | Standard | |
| RefSeq | NP_001278758.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Artemisinin and Derivatives Pathway, Pharmacokinetics
- Benzodiazepine Pathway, Pharmacokinetics
- Retinol metabolism - Homo sapiens (human)
- Steroid hormone biosynthesis - Homo sapiens (human)
- Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Biological Process
- lipid hydroxylation
- xenobiotic metabolic process
- steroid metabolic process
- alkaloid catabolic process
- drug catabolic process
Molecular Function
- monooxygenase activity
- iron ion binding
- oxidoreductase activity
- oxygen binding
- heme binding
Cellular Component
- endoplasmic reticulum membrane
- organelle membrane
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000222982
- Coding exons
- 13
- Length
- 31805
- Individuals with no LoFs
- 122011
- Homozygous LoFs
- 93
- Heterozygous LoFs
- 3644
- Defined
- 125748
- p
- 0.0150
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.17 | 216 | 270 | 0.800 | 0.0000136 | 3285 |
| Missense (PolyPhen) | 55 | 69.339 | 0.7932 | 912 | ||
| Synonymous | 0.629 | 92 | 100 | 0.920 | 0.00000524 | 965 |
| Loss of Function | 0.0330 | 25 | 25.2 | 0.993 | 0.00000121 | 322 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.10 | 0.10 | notable |
| Latino/Admixed American | 0.0098 | 0.0097 | notable |
| Ashkenazi Jewish | 0.0074 | 0.0075 | notable |
| East Asian | 0.0079 | 0.0079 | notable |
| Finnish | 0.0039 | 0.0039 | notable |
| European (Non-Finnish) | 0.011 | 0.011 | notable |
| South Asian | 0.0068 | 0.0067 | notable |
| Other | 0.011 | 0.011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.;
Intolerance Scores
- LoFtool
- 0.909
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.330
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |