SCUBE1
protein-codingsignal peptide, CUB domain and EGF like domain containing 1
Gene summary
This gene encodes a cell surface glycoprotein that is a member of the SCUBE (signal peptide, CUB domain, EGF (epidermal growth factor)-like protein) family. Family members have an amino-terminal signal peptide, nine copies of EGF-like repeats and a CUB domain at the carboxyl terminus. This protein is expressed in platelets and endothelial cells and may play an important role in vascular biology. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~146.1 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 SCUBE1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173050.5. 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 | 3 | 2 | 4 | 9 | ||
| missense | 167 | 7 | 1 | 175 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 171 | 9 | 5 | 185 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_766638.2 | 22 | MANE Select | |
| Ensembl | ENSP00000354080.3 | 22 | MANE Select | |
| Ensembl | ENSP00000290460.7 | 8 | Standard | |
| Ensembl | ENSP00000290460.7 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| scube1 | Danio rerio | Structure: blood cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- inflammatory response
- adult heart development
- blood coagulation
- post-embryonic development
- extracellular matrix disassembly
Molecular Function
- calcium ion binding
- identical protein binding
- protein heterodimerization activity
Cellular Component
- extracellular space
- plasma membrane
- external side of plasma membrane
- cell surface
- extrinsic component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360835
- Coding exons
- 22
- Length
- 146106
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 125748
- p
- 0.0000994
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.98 | 496 | 636 | 0.779 | 0.0000423 | 6479 |
| Missense (PolyPhen) | 180 | 266.52 | 0.67537 | 2701 | ||
| Synonymous | -0.353 | 276 | 269 | 1.03 | 0.0000206 | 1833 |
| Loss of Function | 5.56 | 10 | 54.2 | 0.185 | 0.00000268 | 600 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00015 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00013 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000094 | 0.000088 | rare |
| South Asian | 0.00026 | 0.00023 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Could function as an adhesive molecule and its matrix bound and soluble fragments may play a critical role in vascular biology. {ECO:0000269|PubMed:16753137}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.0505
- RVIS EVS
- -1.45
- RVIS percentile EVS
- 3.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.226
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |