CYP8B1
protein-codingcytochrome P450 family 8 subfamily B member 1, the group of Cytochrome P450 family 8
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 membrane protein catalyzes the conversion of 7 alpha-hydroxy-4-cholesten-3-one into 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one. The balance between these two steroids determines the relative amounts of cholic acid and chenodeoxycholic acid both of which are secreted in the bile and affect the solubility of cholesterol. This gene is unique among the cytochrome P450 genes in that it is intronless. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.9 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 CYP8B1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004391.3. 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 | 2 | 3 | 5 | |||
| missense | 52 | 5 | 3 | 60 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 52 | 7 | 6 | 65 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004382.2 | 1 | MANE Select | |
| Ensembl | ENSP00000318867.4 | 1 | MANE Select | |
| Ensembl | ENSP00000404499.1 | 2 | Standard | |
| Ensembl | ENSP00000404499.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Primary bile acid biosynthesis - Homo sapiens (human)
- PPAR signaling pathway - Homo sapiens (human)
- 27-Hydroxylase Deficiency
- Bile Acid Biosynthesis
- Congenital Bile Acid Synthesis Defect Type II
Biological Process
- bile acid biosynthetic process
- sterol metabolic process
- oxidation-reduction process
Molecular Function
- iron ion binding
- sterol 12-alpha-hydroxylase activity
- oxygen binding
- heme binding
- 7alpha-hydroxycholest-4-en-3-one 12alpha-hydroxylase activity
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
- organelle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316161
- Coding exons
- 1
- Length
- 20137
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0712 | 278 | 281 | 0.988 | 0.0000162 | 3297 |
| Missense (PolyPhen) | 111 | 112.64 | 0.9854 | 1378 | ||
| Synonymous | 0.546 | 104 | 111 | 0.934 | 0.00000608 | 1006 |
| Loss of Function | 1.08 | 9 | 13.2 | 0.681 | 7.13e-7 | 149 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in bile acid synthesis and is responsible for the conversion of 7 alpha-hydroxy-4-cholesten-3-one into 7 alpha, 12 alpha-dihydroxy-4-cholesten-3-one. Responsible for the balance between formation of cholic acid and chenodeoxycholic acid. Has a rather broad substrate specificity including a number of 7-alpha- hydroxylated C27 steroids. {ECO:0000250|UniProtKB:O02766}.;
Intolerance Scores
- LoFtool
- 0.609
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00289
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |