IQGAP2: A Scaffold Protein with Emerging Roles in Cancer and Liver Disease
IQGAP2 (IQ Motif Containing GTPase Activating Protein 2) is a scaffold protein that regulates cell adhesion, proliferation, and cytoskeletal dynamics. It is frequently downregulated in hepatocellular carcinoma and other cancers, suggesting a tumor suppressor role.
Gene Information Card
| Symbol | IQGAP2 |
|---|---|
| Full Name | IQ Motif Containing GTPase Activating Protein 2 |
| Gene Type | Protein Coding |
| Chromosomal Location | 5q23.3 |
| NCBI Gene ID | 10758 ncbi.nlm.nih.gov/gene/10758 |
| Ensembl ID | ENSG00000148357 |
| UniProt ID | Q13576 |
| OMIM ID | 605401 |
| HGNC ID | 6111 |
| Aliases | KIAA0036, p68 |
Description
IQGAP2 is a member of the IQGAP family of scaffold proteins. It contains multiple protein-protein interaction domains, including calponin homology (CH) domains, a coiled-coil region, IQ motifs, a RasGAP-related domain (GRD), and a RasGAP C-terminus (RGCT) domain. Unlike its homolog IQGAP1, IQGAP2 is often downregulated in various cancers, particularly hepatocellular carcinoma (HCC), where it functions as a tumor suppressor. It plays a role in regulating cell proliferation, migration, and cytoskeletal organization by modulating signaling pathways such as Wnt/β-catenin and MAPK. IQGAP2 is also involved in liver metabolism and platelet function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular Carcinoma | Loss of IQGAP2 expression leads to increased Wnt/β-catenin signaling and cell proliferation, promoting tumorigenesis. | Multiple studies show reduced IQGAP2 mRNA and protein levels in HCC tissues compared to normal liver. Low expression correlates with poor prognosis. |
| Gastric Cancer | Downregulation of IQGAP2 is associated with increased cell invasion and metastasis, potentially through dysregulation of the actin cytoskeleton and cell adhesion. | Clinical samples and cell line studies demonstrate decreased IQGAP2 expression in gastric cancer, correlating with advanced tumor stage. |
| Prostate Cancer | Reduced IQGAP2 expression is linked to increased cell migration and invasion, possibly via activation of the MAPK/ERK pathway. | Studies on prostate cancer cell lines and tissues show lower IQGAP2 levels in aggressive tumors. |
| Liver Cirrhosis | Altered IQGAP2 expression may contribute to hepatic fibrosis and the progression to cirrhosis. | Expression data from liver tissues show changes in IQGAP2 levels during fibrotic progression, though the exact mechanism is under investigation. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High expression in normal liver tissue. |
| Kidney | Medium | Moderate expression in kidney tissue. |
| Testis | Medium | Moderate expression in testis. |
| Lung | Low | Low expression in lung tissue. |
| Brain | Low | Low expression in brain tissue. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (Liver) | Low | Hepatocellular carcinoma cell line with reduced IQGAP2 expression. |
| Huh7 (Liver) | Low | Hepatocellular carcinoma cell line with reduced IQGAP2 expression. |
| MCF7 (Breast) | Medium | Breast cancer cell line with moderate expression. |
| A549 (Lung) | Low | Lung carcinoma cell line with low expression. |
| HEK293 (Kidney) | Medium | Embryonic kidney cell line with moderate expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2440C>T (p.Arg814Trp) | Missense | Rare | Potential impact on protein function; found in some cancer samples. |
| c.3130A>G (p.Ile1044Val) | Missense | Rare | Variant of uncertain significance; observed in population databases. |
| c.3595C>T (p.Arg1199Ter) | Nonsense | Very Rare | Predicted to result in a truncated protein, likely causing loss of function. |
| c.1234_1235insA (p.Thr412AsnfsTer5) | Frameshift | Very Rare | Predicted to cause premature termination and loss of function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations, including nonsense, frameshift, and large deletions, are the most common type observed in cancers. These mutations lead to reduced or absent IQGAP2 protein, which is associated with increased cell proliferation and tumor growth, particularly in hepatocellular carcinoma.
Gain of Function (GOF)
Gain-of-function mutations in IQGAP2 are not well-documented. The gene is primarily considered a tumor suppressor, and its inactivation, rather than activation, is linked to disease.
Dominant Negative (DN)
Dominant-negative effects are theoretically possible if a mutant IQGAP2 protein can interfere with the function of the wild-type protein or its binding partners. However, specific dominant-negative mutations have not been clearly characterized in the literature.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • calmodulin binding |
| • protein homodimerization activity | • actin binding |
| • protein kinase binding | • signal transducer activity |
| • cell adhesion | • cell migration |
| • regulation of cell growth | • Wnt signaling pathway |
| • cytoskeleton organization | • negative regulation of cell population proliferation |
Pathways
• Wnt signaling pathway
• MAPK signaling pathway
• Regulation of actin cytoskeleton
• Adherens junction
Protein Summary
The IQGAP2 protein is a large scaffold protein (approximately 180 kDa) that localizes to the cytoplasm and cell cortex. It contains multiple domains that allow it to interact with a variety of proteins, including actin, calmodulin, and small GTPases like Cdc42 and Rac1. Through these interactions, IQGAP2 regulates cytoskeletal dynamics, cell adhesion, and cell polarity. In the liver, it plays a critical role in maintaining normal hepatocyte function and suppressing tumor formation by inhibiting the Wnt/β-catenin signaling pathway. Its expression is often lost or reduced in cancers, contributing to malignant progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IQGAP2 Knockout HEK293 Cell Line | EDJ-KQ7167 | Human | 10788 | Details Get a Quote |
| IQGAP2 Knockout A-549 Cell Line | EDJ-KQ32086 | Human | 10788 | Details Get a Quote |
| IQGAP2 Knockout HCT 116 Cell Line | EDJ-KQ32087 | Human | 10788 | Details Get a Quote |
| IQGAP2 Knockout HeLa Cell Line | EDJ-KQ32088 | Human | 10788 | Details Get a Quote |
