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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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IQGAP2
IQ motif containing GTPase activating protein 2
Chromosome 5 · 5q13.3
NCBI Gene: 10788Ensembl: ENSG00000145703.17HGNC: HGNC:6111UniProt: B7Z7U6
109PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomephosphatidylinositol-3,4,5-trisphosphate bindingfilopodiumcell surfaceprostate carcinomaalcohol drinkingneurodegenerative diseaseEscherichia coli Infections
✦AI Summary

IQGAP2 is a scaffold protein that regulates cellular signaling and cytoskeletal dynamics through multiple molecular mechanisms. Primary Function: IQGAP2 binds activated CDC42 and RAC1 small GTPases but lacks intrinsic GTPase-activating activity, instead modulating their signaling through alternative mechanisms 1. The protein contains conserved domains including an N-terminal calponin homology motif for actin binding, IQ motifs for calmodulin interaction, and a RasGAP homology domain 1. Mechanism: IQGAP2 associates with calmodulin through its IQ-motifs in a calcium-dependent manner 2, and functions as a scaffold bridging receptor signaling to intracellular outcomes 3. Disease Relevance: IQGAP2 functions as a tumor suppressor in multiple cancers. Reduced IQGAP2 expression in breast cancer promotes epithelial-mesenchymal transition and inhibits apoptosis via MEK-ERK and p38 pathway dysregulation 4. Loss-of-function variants associate with altered blood cell traits 5, and reduced hippocampal IQGAP2 correlates with Alzheimer's disease 6. Clinical Significance: IQGAP2 deficiency increases blood-brain barrier permeability and leukocyte infiltration into the CNS 6, highlighting its role in immune privilege maintenance. The protein represents a therapeutic target for cancer intervention through restoration of tumor-suppressive functions.

Sources cited
1
IQGAP2 binds CDC42 and RAC1 GTPases but lacks GTPase-activating activity; contains calponin homology domain for actin binding and IQ motifs for calmodulin interaction
PMID: 8756646
2
IQGAP2 IQ-motifs bind calmodulin in calcium-dependent manner with varying interaction characteristics
PMID: 21299499
3
IQGAP2 functions as scaffold protein coupling receptor signaling to cellular outcomes alongside IQGAP1 and IQGAP3
PMID: 37071417
4
IQGAP2 acts as tumor suppressor in breast cancer; reduced expression promotes EMT and inhibits apoptosis through MEK-ERK and p38 pathways
PMID: 33846302
5
Loss-of-function variants in IQGAP2 associate with altered blood cell traits in large population study
PMID: 33087929
6
IQGAP2 deficiency increases blood-brain barrier permeability and CNS immune cell infiltration; reduced in Alzheimer's disease
PMID: 40071147
Disease Associationsⓘ20
prostate carcinomaOpen Targets
0.38Weak
alcohol drinkingOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.32Weak
Escherichia coli InfectionsOpen Targets
0.31Weak
cholelithiasisOpen Targets
0.30Weak
placental retentionOpen Targets
0.27Weak
Parkinson diseaseOpen Targets
0.20Weak
glomerulonephritisOpen Targets
0.18Weak
esophageal ulcerOpen Targets
0.18Weak
bronchial diseaseOpen Targets
0.17Weak
mood disorderOpen Targets
0.15Weak
Abnormality of the immune systemOpen Targets
0.14Weak
immune system diseaseOpen Targets
0.14Weak
ureteral disorderOpen Targets
0.13Weak
HypercholesterolemiaOpen Targets
0.13Weak
kidney diseaseOpen Targets
0.12Weak
benign neoplasm of adrenal glandOpen Targets
0.12Weak
malnutritionOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
pachyonychia congenitaOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CALM3Protein interaction100%CALML3Protein interaction100%CALML5Protein interaction100%CALML6Protein interaction99%CALML4Protein interaction99%CALM1Protein interaction94%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
87%
Lung
12%
Heart
8%
Ovary
7%
Brain
1%
Gene Interaction Network
Click a node to explore
IQGAP2CALM3CALML3CALML5CALML6CALML4CALM1
PROTEIN STRUCTURE
Preparing viewer…
PDB3IEZ · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.01LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.84 [0.71–1.01]
RankingsWhere IQGAP2 stands among ~20K protein-coding genes
  • #4,360of 20,598
    Most Researched109 · top quartile
  • #9,759of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedIQGAP2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Exome sequencing and characterization of 49,960 individuals in the UK Biobank.
PMID: 33087929
Nature · 2020
1.00
2
The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.
PMID: 37071417
J Cell Biol · 2023
0.90
3
Cloning and characterization of a novel transcript variant of IQGAP2 in human testis.
PMID: 15621655
DNA Seq · 2004
0.80
4
IQGAP1 gene silencing induces apoptosis and decreases the invasive capacity of human hepatocellular carcinoma cells.
PMID: 27488117
Tumour Biol · 2016
0.70
5
IQGAP2 regulates blood-brain barrier immune dynamics.
PMID: 40071147
iScience · 2025
0.60