CYP51A1
protein-codingcytochrome P450 family 51 subfamily A member 1, the group of Cytochrome P450 family 51
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 endoplasmic reticulum protein participates in the synthesis of cholesterol by catalyzing the removal of the 14alpha-methyl group from lanosterol. Homologous genes are found in all three eukaryotic phyla, fungi, plants, and animals, suggesting that this is one of the oldest cytochrome P450 genes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
- CYP51
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005129
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CYP51A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000786.4. 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 | 5 | 3 | 8 | |||
| missense | 1 | 74 | 4 | 1 | 80 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 1 | 81 | 9 | 4 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000777.1 | 10 | MANE Select | |
| Ensembl | ENSP00000003100.8 | 10 | MANE Select | |
| RefSeq | NP_001139624.1 | 8 | Standard | |
| Ensembl | ENSP00000394268.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Steroid biosynthesis - Homo sapiens (human)
- Simvastatin Action Pathway
- Pravastatin Action Pathway
- Atorvastatin Action Pathway
- Hyper-IgD syndrome
Biological Process
- steroid biosynthetic process
- cholesterol biosynthetic process
- sterol metabolic process
- sterol biosynthetic process
- cholesterol biosynthetic process via 24,25-dihydrolanosterol
Molecular Function
- iron ion binding
- sterol 14-demethylase activity
- heme binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- plasma membrane
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000003100
- Coding exons
- 10
- Length
- 30802
- Individuals with no LoFs
- 125660
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 88
- Defined
- 125748
- p
- 0.000350
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.788 | 239 | 276 | 0.866 | 0.0000139 | 3330 |
| Missense (PolyPhen) | 54 | 91.267 | 0.59167 | 1183 | ||
| Synonymous | -0.0764 | 95 | 94.1 | 1.01 | 0.00000424 | 989 |
| Loss of Function | 1.52 | 14 | 21.7 | 0.647 | 9.12e-7 | 303 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00056 | 0.00055 | rare |
| Latino/Admixed American | 0.00075 | 0.00072 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol. {ECO:0000269|PubMed:20149798, ECO:0000269|PubMed:8619637}.;
Intolerance Scores
- LoFtool
- 0.390
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.402
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |