CYP4F12
protein-codingcytochrome P450 family 4 subfamily F member 12, the group of Cytochrome P450 family 4
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. This protein likely localizes to the endoplasmic reticulum. When expressed in yeast the enzyme is capable of oxdizing arachidonic acid. It can also catalyze the epoxidation of 22:6n-3 and 22:5n-3 polyunsaturated long-chain fatty acids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. 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 ~24.2 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 CYP4F12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_023944.4. 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 | 1 | ||||
| missense | 87 | 6 | 93 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 89 | 7 | 0 | 96 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_076433.3 | 12 | MANE Select | |
| Ensembl | ENSP00000448998.1 | 12 | MANE Select | |
| Ensembl | ENSP00000321821.9 | 12 | Standard | |
| Ensembl | ENSP00000321821.9 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pregnane X Receptor pathway
- Nuclear Receptors Meta-Pathway
- Liver steatosis AOP
- Oxidation by Cytochrome P450
- Tryptophan metabolism
Biological Process
- very long-chain fatty acid metabolic process
- long-chain fatty acid metabolic process
- renal water homeostasis
- pressure natriuresis
- drug metabolic process
Molecular Function
- monooxygenase activity
- iron ion binding
- arachidonic acid epoxygenase activity
- alkane 1-monooxygenase activity
- heme binding
Cellular Component
- cytoplasm
- endoplasmic reticulum membrane
- integral component of membrane
- apical plasma membrane
- organelle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000550308
- Coding exons
- 12
- Length
- 24418
- Individuals with no LoFs
- 125270
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 478
- Defined
- 125748
- p
- 0.00190
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.762 | 365 | 326 | 1.12 | 0.0000199 | 3422 |
| Missense (PolyPhen) | 104 | 94.748 | 1.0976 | 1050 | ||
| Synonymous | -0.449 | 136 | 130 | 1.05 | 0.00000790 | 1010 |
| Loss of Function | 0.0432 | 26 | 26.2 | 0.991 | 0.00000138 | 271 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.015 | 0.013 | notable |
| Latino/Admixed American | 0.0039 | 0.0037 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00061 | 0.00061 | rare |
| South Asian | 0.0018 | 0.0017 | notable |
| Other | 0.0012 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes leukotriene B4 omega-hydroxylation and arachidonic acid omega-hydroxylation but with an activity much lower than that of CYP4F2. Catalyzes the hydroxylation of the antihistamine ebastine.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.442
- RVIS EVS
- 3.74
- RVIS percentile EVS
- 99.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0495
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |