SCAP Gene: Structure, Function, and Clinical Significance
Comprehensive guide to the SCAP (SREBF chaperone) gene, its role in lipid metabolism, associated diseases, and expression profiles.
Gene Information Card
| Symbol | SCAP |
|---|---|
| Full Name | SREBF chaperone |
| Gene Type | protein-coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 22937 ncbi.nlm.nih.gov/gene/22937 |
| Ensembl ID | ENSG00000172534 |
| UniProt ID | Q12770 |
| OMIM ID | 601648 |
| HGNC ID | 10579 |
| Aliases | SREBP cleavage-activating protein; SREBP chaperone; FLJ22059 |
Description
The SCAP gene encodes the SREBF chaperone protein, a critical regulator of lipid homeostasis. SCAP functions as a sensor of sterol levels in the endoplasmic reticulum (ER) and controls the activation of SREBP transcription factors, which regulate genes involved in cholesterol and fatty acid synthesis. Mutations or dysregulation of SCAP can lead to metabolic disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypercholesterolemia | Altered SCAP function disrupts SREBP activation, leading to abnormal cholesterol metabolism. | OMIM: 601648; PubMed studies |
| Hepatocellular carcinoma | Overexpression of SCAP promotes lipogenesis and tumor growth via SREBP activation. | COSMIC; PubMed studies |
| Obesity and insulin resistance | SCAP-mediated SREBP activation contributes to lipid accumulation in adipose tissue and liver. | OMIM; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (nTPM ~50) | High expression consistent with role in lipid metabolism |
| Adipose tissue | Moderate (nTPM ~20) | Expressed in adipocytes |
| Brain | Low (nTPM ~5) | Low expression in neuronal tissues |
| Muscle | Low (nTPM ~3) | Minimal expression in skeletal muscle |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | High (nTPM ~60) | Liver cancer cell line; high SCAP expression |
| HeLa (cervical) | Moderate (nTPM ~25) | Cervical cancer cell line |
| A549 (lung) | Moderate (nTPM ~20) | Lung carcinoma cell line |
| MCF7 (breast) | Low (nTPM ~10) | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | Rare (<0.01%) | Alters sterol sensing; potential impact on SREBP activation |
| c.456C>T (p.Pro152Leu) | Missense | Not reported | Predicted damaging; may affect protein stability |
| c.789_790insA | Frameshift | Not reported | Loss of function; likely leads to truncated protein |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SCAP impair SREBP activation, leading to reduced lipid synthesis and potential developmental defects.
Gain of Function (GOF)
Gain-of-function mutations (e.g., overexpression) enhance SREBP activity, promoting lipogenesis and tumor progression.
Dominant Negative (DN)
Dominant-negative mutations may interfere with SCAP-SREBP interaction, disrupting sterol regulation.
View complete mutation data：
Gene Ontology (GO)
| • sterol sensor activity | • protein binding |
| • endoplasmic reticulum membrane | • Golgi apparatus |
| • regulation of cholesterol biosynthetic process | • SREBP signaling pathway |
Pathways
• SREBP signaling pathway
• Cholesterol metabolism
• Fatty acid biosynthesis
• Insulin signaling
Protein Summary
The SCAP protein is a multi-pass transmembrane protein localized to the ER membrane. It contains a sterol-sensing domain (SSD) that detects cholesterol levels. Under low sterol conditions, SCAP escorts SREBP from the ER to the Golgi, where proteolytic cleavage releases the active transcription factor. Under high sterol conditions, SCAP binds INSIG, retaining SREBP in the ER. This mechanism tightly regulates lipid synthesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCAP Knockout HEK293 Cell Line | EDJ-KQ3113 | Human | 22937 | Details Get a Quote |
| SCAPER Knockout HEK293 Cell Line | EDJ-KQ15184 | Human | 49855 | Details Get a Quote |
| SCAPER Knockout HCT 116 Cell Line | EDJ-KQ17926 | Human | 49855 | Details Get a Quote |
| SCAPER Knockout A-549 Cell Line | EDJ-KQ47976 | Human | 49855 | Details Get a Quote |
| SCAPER Knockout HeLa Cell Line | EDJ-KQ47977 | Human | 49855 | Details Get a Quote |
| SCAP Knockout A-549 Cell Line | EDJ-KQ24455 | Human | 22937 | Details Get a Quote |
| SCAP Knockout HCT 116 Cell Line | EDJ-KQ24456 | Human | 22937 | Details Get a Quote |
| SCAP Knockout HeLa Cell Line | EDJ-KQ24457 | Human | 22937 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
