INSIG2: Insulin Induced Gene 2 - A Key Regulator of Cholesterol and Lipid Metabolism
Comprehensive gene card for INSIG2, including genomic context, expression, mutations, and clinical significance in metabolic disorders.
Gene Information Card
| Symbol | INSIG2 |
|---|---|
| Full Name | Insulin Induced Gene 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q14.2 |
| NCBI Gene ID | 51141 ncbi.nlm.nih.gov/gene/51141 |
| Ensembl ID | ENSG00000125657 |
| UniProt ID | Q9Y5U4 |
| OMIM ID | 608660 |
| HGNC ID | HGNC:20425 |
| Aliases | INSIG-2, MGC1405 |
Description
INSIG2 encodes a protein that anchors in the endoplasmic reticulum membrane and regulates cholesterol and lipid metabolism by controlling the processing of sterol regulatory element-binding proteins (SREBPs). It binds to SCAP (SREBP cleavage-activating protein) and retains the SCAP-SREBP complex in the ER in the presence of sterols, thereby preventing SREBP activation and subsequent lipogenic gene expression. INSIG2 is induced by insulin and plays a critical role in maintaining lipid homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypercholesterolemia, susceptibility to | INSIG2 variants may alter SREBP regulation, leading to dysregulated cholesterol synthesis. | PMID: 16960695; GWAS catalog |
| Obesity, common | Polymorphisms in INSIG2 have been associated with body mass index (BMI) and obesity risk in multiple populations. | PMID: 16855265; meta-analysis |
| Type 2 diabetes | INSIG2 expression changes in insulin-resistant states; variants may contribute to diabetes susceptibility. | PMID: 19057616; ClinVar |
| Non-alcoholic fatty liver disease (NAFLD) | Dysregulation of INSIG2-mediated lipid metabolism may promote hepatic steatosis. | PMID: 23222517 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adipose tissue | 8.3 | Medium |
| Pancreas | 6.1 | Low |
| Skeletal muscle | 4.7 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver carcinoma) | 15.2 | High expression; used in lipid metabolism studies |
| 3T3-L1 (adipocyte) | 9.8 | Medium; induced during differentiation |
| HeLa (cervical carcinoma) | 5.4 | Low |
| HEK293 (embryonic kidney) | 4.1 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs7566605 (G>C) | SNP (intronic) | ~30% in European populations | Associated with increased BMI and obesity risk |
| c.256G>A (p.Val86Ile) | Missense | Rare | Unknown functional effect; reported in ClinVar |
| c.1-124C>T | Promoter variant | ~5% | May alter INSIG2 expression levels |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations have been reported in human disease; experimental knockdown in cells leads to increased SREBP processing and lipid accumulation.
Gain of Function (GOF)
Not described; overexpression in vitro reduces SREBP activation and lipogenesis.
Dominant Negative (DN)
Not reported for INSIG2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• SREBP signaling (Reactome: R-HSA-1655829)
• Cholesterol biosynthesis (KEGG: hsa00100)
• Insulin signaling (KEGG: hsa04910)
Protein Summary
INSIG2 is a 225-amino-acid transmembrane protein localized to the endoplasmic reticulum. It contains six transmembrane domains and a sterol-sensing domain. The protein binds to SCAP in a sterol-dependent manner, retaining the SCAP-SREBP complex in the ER and preventing SREBP cleavage. This regulation is crucial for controlling cholesterol and fatty acid synthesis. INSIG2 is induced by insulin and is expressed in liver, adipose, and other metabolic tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| INSIG2 Knockout HEK293 Cell Line | EDJ-KQ10942 | Human | 51141 | Details Get a Quote |
| INSIG2 Knockout A-549 Cell Line | EDJ-KQ38733 | Human | 51141 | Details Get a Quote |
| INSIG2 Knockout HCT 116 Cell Line | EDJ-KQ38734 | Human | 51141 | Details Get a Quote |
| INSIG2 Knockout HeLa Cell Line | EDJ-KQ38735 | Human | 51141 | Details Get a Quote |
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