IQGAP1

Chr 15

IQ motif containing GTPase activating protein 1

Also known as: HUMORFA01, SAR1, p195

NCBI Gene: 8826ENSG00000140575UniProt: P46940

This gene encodes a member of the IQGAP family. The protein contains four IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. It interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. Expression of the protein is upregulated by gene amplification in two gastric cancer cell lines. [provided by RefSeq, Jul 2008]

208
ClinVar variants
39
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— IQGAP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 148 VUS of 208 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.998
Z-score 7.43
OE 0.19 (0.13–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.44Z-score
OE missense 0.77 (0.72–0.82)
680 obs / 884.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.13–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.72–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 18 / 97.0Missense obs/exp: 680 / 884.6Syn Z: -1.12

ClinVar Variant Classifications

208 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic4
VUS148
Likely Benign13
Benign7
Conflicting1
35
Pathogenic
4
Likely Pathogenic
148
VUS
13
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
4
0
4
VUS
0
143
5
0
148
Likely Benign
0
7
1
5
13
Benign
0
2
3
2
7
Conflicting
—1
Total0152487208

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IQGAP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MYL9 expressed in cancer-associated fibroblasts regulate the immune microenvironment of colorectal cancer and promotes tumor progression in an autocrine manner.
Deng S et al.·J Exp Clin Cancer Res
2023
Tight junction protein cingulin variant is associated with cancer susceptibility by overexpressed IQGAP1 and Rac1-dependent epithelial-mesenchymal transition.
Huang YT et al.·J Exp Clin Cancer Res
2024
IQGAP1 and RNA Splicing in the Context of Head and Neck via Phosphoproteomics.
Muehlbauer LK et al.·J Proteome Res
2022
IQGAP1 regulation and roles in cancer.
Johnson M et al.·Cell Signal
2009Review
IQGAP1‑siRNA inhibits proliferation and metastasis of U251 and U373 glioma cell lines.
Diao B et al.·Mol Med Rep
2017
Deciphering the SOX4/MAPK1 regulatory axis: a phosphoproteomic insight into IQGAP1 phosphorylation and pancreatic Cancer progression.
Song C et al.·J Transl Med
2024
Role of scaffold proteins in the heterogeneity of glioblastoma.
Iyer VJ et al.·Cell Commun Signal
2024Review
Exome sequencing findings in children with annular pancreas.
Pitsava G et al.·Mol Genet Genomic Med
2023
A novel pathway for stemness propagation and chemoresistance in non-small cell lung cancer via phosphorylated PKM2-loaded small extracellular vesicles.
Wang J et al.·Theranostics
2025
Identification of disulfidptosis-related genes and subgroups in spinal cord injury.
Tao Y et al.·Spinal Cord
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools