CYP1A1
protein-codingcytochrome P450 family 1 subfamily A member 1, the group of Cytochrome P450 family 1
Gene summary
This gene, CYP1A1, 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. This protein localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. The gene has been associated with lung cancer risk. A related family member, CYP1A2, is located approximately 25 kb away from CYP1A1 on chromosome 15. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]
- CYP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CYP1A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001319217.2. 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 | 1 | 6 | 1 | 8 | ||
| missense | 56 | 6 | 6 | 68 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 57 | 14 | 7 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001306146.1 | 6 | MANE Select | |
| Ensembl | ENSP00000369050.3 | 6 | MANE Select | |
| RefSeq | NP_000490.1 | 6 | Standard | |
| RefSeq | NP_001306145.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Amodiaquine Pathway, Pharmacokinetics
- Tryptophan metabolism - Homo sapiens (human)
- Retinol metabolism - Homo sapiens (human)
- Steroid hormone biosynthesis - Homo sapiens (human)
- Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Biological Process
- response to hypoxia
- lipid hydroxylation
- porphyrin-containing compound metabolic process
- aging
- steroid metabolic process
Molecular Function
- monooxygenase activity
- iron ion binding
- protein binding
- oxidoreductase activity
- oxidoreductase activity, acting on diphenols and related substances as donors
Cellular Component
- mitochondrion
- endoplasmic reticulum membrane
- organelle membrane
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379727
- Coding exons
- 6
- Length
- 6069
- Individuals with no LoFs
- 125219
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 527
- Defined
- 125748
- p
- 0.00211
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.357 | 322 | 304 | 1.06 | 0.0000179 | 3359 |
| Missense (PolyPhen) | 129 | 110.18 | 1.1708 | 1262 | ||
| Synonymous | -0.0685 | 123 | 122 | 1.01 | 0.00000667 | 1044 |
| Loss of Function | -1.11 | 23 | 17.9 | 1.28 | 9.33e-7 | 203 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00098 | 0.00098 | rare |
| Latino/Admixed American | 0.0022 | 0.0022 | notable |
| Ashkenazi Jewish | 0.00080 | 0.00079 | rare |
| East Asian | 0.0013 | 0.0012 | notable |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.0024 | 0.0024 | notable |
| South Asian | 0.0034 | 0.0033 | notable |
| Other | 0.0047 | 0.0041 | 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.;
Recessive Scores
- pRec
- 0.835
Intolerance Scores
- LoFtool
- 0.627
- RVIS EVS
- 0.62
- RVIS percentile EVS
- 83.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.671
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |