OSBPL8
protein-codingoxysterol binding protein like 8, the group of Pleckstrin homology domain containing|Oxysterol binding proteins
Gene summary
This gene encodes a member of a family of proteins containing an N-terminal pleckstrin homology domain and a highly conserved C-terminal oxysterol-binding protein-like sterol-binding domain. It binds mutliple lipid-containing molecules, including phosphatidylserine, phosphatidylinositol 4-phosphate (PI4P) and oxysterol, and promotes their exchange between the endoplasmic reticulum and the plasma membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~208.0 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 OSBPL8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020841.5. 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 | 1 | ||||
| missense | 71 | 3 | 74 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 77 | 3 | 0 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065892.1 | 23 | MANE Select | |
| Ensembl | ENSP00000261183.3 | 23 | MANE Select | |
| RefSeq | NP_001003712.1 | 21 | Standard | |
| RefSeq | NP_001306581.1 | 21 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- Metabolism
- Acyl chain remodelling of PS
- Glycerophospholipid biosynthesis
- Phospholipid metabolism
Biological Process
- negative regulation of sequestering of triglyceride
- phospholipid transport
- sterol transport
- negative regulation of cell migration
- activation of protein kinase B activity
Molecular Function
- phosphatidylserine binding
- phospholipid transporter activity
- lipid binding
- sterol transporter activity
- cholesterol binding
Cellular Component
- endoplasmic reticulum membrane
- cytosol
- membrane
- integral component of membrane
- nuclear membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261183
- Coding exons
- 23
- Length
- 208013
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125745
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.00 | 278 | 459 | 0.606 | 0.0000234 | 5845 |
| Missense (PolyPhen) | 75 | 185.12 | 0.40514 | 2331 | ||
| Synonymous | 0.400 | 144 | 150 | 0.959 | 0.00000743 | 1591 |
| Loss of Function | 5.04 | 15 | 55.5 | 0.270 | 0.00000295 | 686 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000098 | 0.000097 | rare |
| South Asian | 0.00061 | 0.00059 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner (PubMed:26206935). Binds oxysterol, 25- hydroxycholesterol and cholesterol (PubMed:17428193, PubMed:17991739, PubMed:21698267). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:17991739, ECO:0000269|PubMed:21698267, ECO:0000269|PubMed:26206935}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.560
- RVIS EVS
- -0.51
- RVIS percentile EVS
- 21.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.860
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |