CYP39A1
protein-codingcytochrome P450 family 39 subfamily A member 1, the group of Cytochrome P450 family 39
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 is involved in the conversion of cholesterol to bile acids. Its substrates include the oxysterols 25-hydroxycholesterol, 27-hydroxycholesterol and 24-hydroxycholesterol. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~103.3 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 CYP39A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016593.5. 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 | 1 | 2 | 3 | |||
| missense | 54 | 8 | 62 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 58 | 10 | 0 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057677.2 | 12 | MANE Select | |
| Ensembl | ENSP00000275016.2 | 12 | MANE Select | |
| RefSeq | NP_001265667.1 | 12 | Standard | |
| RefSeq | NP_001265668.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Primary bile acid biosynthesis - Homo sapiens (human)
- 27-Hydroxylase Deficiency
- Bile Acid Biosynthesis
- Congenital Bile Acid Synthesis Defect Type II
- Cerebrotendinous Xanthomatosis (CTX)
Biological Process
- bile acid biosynthetic process
- cholesterol catabolic process
- digestion
- sterol metabolic process
- bile acid catabolic process
Molecular Function
- iron ion binding
- steroid 7-alpha-hydroxylase activity
- oxysterol 7-alpha-hydroxylase activity
- 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
- ENST00000275016
- Coding exons
- 12
- Length
- 102983
- Individuals with no LoFs
- 125612
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 136
- Defined
- 125748
- p
- 0.000541
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0649 | 235 | 232 | 1.01 | 0.0000106 | 3077 |
| Missense (PolyPhen) | 61 | 66.85 | 0.9125 | 893 | ||
| Synonymous | -0.941 | 95 | 84.0 | 1.13 | 0.00000405 | 849 |
| Loss of Function | 0.0977 | 24 | 24.5 | 0.979 | 0.00000112 | 328 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000091 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00029 | 0.00029 | rare |
| South Asian | 0.0026 | 0.0026 | notable |
| Other | 0.0010 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the bile acid metabolism. Has a preference for 24-hydroxycholesterol, and converts it into a 7-alpha- hydroxylated product. {ECO:0000269|PubMed:10748047}.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.428
- RVIS EVS
- 2.18
- RVIS percentile EVS
- 98.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00228
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |