SCAP
protein-codingSREBF chaperone, the group of WD repeat domain containing
Gene summary
This gene encodes a protein with a sterol sensing domain (SSD) and seven WD domains. In the presence of cholesterol, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi. The SREBPs are then proteolytically cleaved and regulate sterol biosynthesis. 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 ~63.4 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 SCAP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012235.4. 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 | 4 | 6 | 6 | 16 | ||
| missense | 197 | 6 | 203 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 212 | 12 | 6 | 230 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036367.2 | 22 | MANE Select | |
| Ensembl | ENSP00000265565.5 | 22 | MANE Select | |
| RefSeq | NP_001306973.1 | 17 | Standard | |
| Ensembl | ENSP00000324296.6 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| scap | Danio rerio | Structure: liver Quality: fatty abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sterol Regulatory Element-Binding Proteins (SREBP) signalling
- RAGE
- Metabolism of lipids
- Regulation of cholesterol biosynthesis by SREBP (SREBF)
- Metabolism
Biological Process
- response to hypoxia
- immune response
- aging
- cholesterol metabolic process
- response to insulin
Molecular Function
- protein binding
- sterol binding
- protein-containing complex binding
- unfolded protein binding
Cellular Component
- Golgi membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- Golgi apparatus
- ER to Golgi transport vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265565
- Coding exons
- 22
- Length
- 63414
- Individuals with no LoFs
- 125694
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 54
- Defined
- 125748
- p
- 0.000215
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.57 | 590 | 794 | 0.743 | 0.0000506 | 8154 |
| Missense (PolyPhen) | 144 | 241.26 | 0.59687 | 2457 | ||
| Synonymous | 0.360 | 340 | 349 | 0.975 | 0.0000229 | 2797 |
| Loss of Function | 4.43 | 20 | 55.7 | 0.359 | 0.00000275 | 607 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00021 | 0.00020 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00032 | 0.00031 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Escort protein required for cholesterol as well as lipid homeostasis. Regulates export of the SCAP/SREBF complex from the ER upon low cholesterol. Formation of a ternary complex with INSIG at high sterol concentrations leads to masking of an ER-export signal in SCAP and retention of the complex in the ER. Low sterol concentrations trigger release of INSIG, a conformational change in the SSC domain of SCAP, unmasking of the ER export signal, recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of SREBF in the Golgi, release of the transcription factor fragment of SREBF from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.161
Intolerance Scores
- LoFtool
- 0.285
- RVIS EVS
- -2.19
- RVIS percentile EVS
- 1.39
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.941
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |