IQGAP1

Summary

IQGAP1 (IQ motif containing GTPase activating protein 1, HGNC:6110) is a protein-coding gene on chromosome 15q26.1, encoding Ras GTPase-activating-like protein IQGAP1 (P46940). Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton.

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.

Source: NCBI Gene 8826 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 210 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003870

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6110
Approved symbol	IQGAP1
Name	IQ motif containing GTPase activating protein 1
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	p195, KIAA0051, SAR1, HUMORFA01
Ensembl gene	ENSG00000140575
Ensembl biotype	protein_coding
OMIM	603379
Entrez	8826

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 retained_intron, 10 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000268182, ENST00000558003, ENST00000558491, ENST00000558957, ENST00000559031, ENST00000559674, ENST00000559682, ENST00000559809, ENST00000560020, ENST00000560218, ENST00000560373, ENST00000560418, ENST00000560733, ENST00000560738, ENST00000561086, ENST00000561132, ENST00000561461, ENST00000633485, ENST00000869272, ENST00000869273, ENST00000869274, ENST00000921153, ENST00000921154

RefSeq mRNA: 1 — MANE Select: NM_003870 NM_003870

CCDS: CCDS10362

Canonical transcript exons

ENST00000268182 — 38 exons

Exon	Start	End
ENSE00000943998	90440502	90440615
ENSE00000943999	90441506	90441684
ENSE00000944000	90443394	90443478
ENSE00000944001	90448573	90448736
ENSE00000944002	90449559	90449643
ENSE00000944003	90452775	90452938
ENSE00000944004	90453132	90453292
ENSE00000944005	90454428	90454552
ENSE00000944006	90456152	90456315
ENSE00000944007	90466001	90466091
ENSE00000944008	90466269	90466436
ENSE00000944009	90467450	90467592
ENSE00000944010	90472840	90473010
ENSE00000944011	90473715	90473798
ENSE00000944012	90473896	90473967
ENSE00000944013	90474064	90474133
ENSE00000944014	90474485	90474693
ENSE00000944017	90477665	90477889
ENSE00000944018	90481960	90482100
ENSE00000944019	90482197	90482281
ENSE00000944020	90483361	90483593
ENSE00000944022	90486030	90486132
ENSE00000944027	90494713	90494835
ENSE00001304261	90388242	90388396
ENSE00001317184	90499995	90502239
ENSE00001705272	90477067	90477230
ENSE00001799868	90439332	90439399
ENSE00002481794	90390774	90390873
ENSE00003470788	90497232	90497340
ENSE00003505414	90426110	90426266
ENSE00003557978	90429589	90429666
ENSE00003565166	90486954	90487089
ENSE00003635448	90476663	90476818
ENSE00003644754	90484220	90484352
ENSE00003648085	90433719	90433795
ENSE00003650935	90492545	90492711
ENSE00003665227	90487495	90487582
ENSE00003685728	90491333	90491545

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 166.2675 / max 2982.1330, expressed in 1828 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148442	159.7261	1828
148443	3.1293	1453
148459	1.3612	795
148452	0.7464	341
148457	0.5643	175
148460	0.3507	150
148458	0.1977	101
148451	0.1489	52
148455	0.0429	13

Top tissues by expression

300 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.59	gold quality
colonic epithelium	UBERON:0000397	98.95	gold quality
monocyte	CL:0000576	98.87	gold quality
tongue squamous epithelium	UBERON:0006919	98.87	gold quality
skin of hip	UBERON:0001554	98.81	gold quality
tendon	UBERON:0000043	98.80	gold quality
mononuclear cell	CL:0000842	98.78	gold quality
leukocyte	CL:0000738	98.76	gold quality
upper leg skin	UBERON:0004262	98.74	gold quality
right coronary artery	UBERON:0001625	98.72	gold quality
body of uterus	UBERON:0009853	98.69	gold quality
secondary oocyte	CL:0000655	98.63	gold quality
descending thoracic aorta	UBERON:0002345	98.63	gold quality
lower lobe of lung	UBERON:0008949	98.59	gold quality
popliteal artery	UBERON:0002250	98.54	gold quality
tibial artery	UBERON:0007610	98.54	gold quality
aorta	UBERON:0000947	98.53	gold quality
ascending aorta	UBERON:0001496	98.52	gold quality
thoracic aorta	UBERON:0001515	98.52	gold quality
artery	UBERON:0001637	98.52	gold quality
left coronary artery	UBERON:0001626	98.49	gold quality
blood	UBERON:0000178	98.41	gold quality
vagina	UBERON:0000996	98.41	gold quality
coronary artery	UBERON:0001621	98.41	gold quality
myometrium	UBERON:0001296	98.38	gold quality
skin of abdomen	UBERON:0001416	98.38	gold quality
mammalian vulva	UBERON:0000997	98.37	gold quality
right lung	UBERON:0002167	98.35	gold quality
synovial joint	UBERON:0002217	98.35	gold quality
skin of leg	UBERON:0001511	98.31	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1451.79
E-GEOD-75367	yes	315.05
E-HCAD-13	yes	21.03
E-CURD-112	yes	18.94
E-MTAB-10042	yes	4.14
E-GEOD-124858	no	858.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2, NFE2L2

miRNA regulators (miRDB)

116 targeting IQGAP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718

Literature-anchored findings (GeneRIF, showing 40)

• IQGAP1 enhances the function of beta-catenin in the nucleus and that calmodulin regulates this stimulation (PMID:11734550)
• The mechanism for regulation of the F-actin binding activity of IQGAP1 by calcium/calmodulin (PMID:11809768)
• IQGAP1 has a crucial role in transducing Cdc42 signaling to the cytoskeleton (PMID:11948177)
• IQGAP1 is a potential target protein of S100B during processes of dynamic rearrangement of cell membrane morphology (PMID:12377780)
• interaction of calmodulin with IQ motifs (PMID:12446675)
• Identification and characterization of the Cdc42-binding site of IQGAP1. (PMID:12745076)
• IQGAP1 has a fundamental role in cell motility and invasion (PMID:12900413)
• Data suggest that cyclic AMP/protein kinase A may be coupled with calcium/calmodulin and guanosine triphosphatases through an IQGAP1/AKAP79 complex. (PMID:12938160)
• Rac1 enhances the accumulation of actin filaments, E-cadherin, and beta-catenin by acting on IQGAP1. (PMID:14699063)
• IQGAP1 binds ERK2 and modulates its activity (PMID:14970219)
• IQGAP1 functions as a VEGFR2-associated scaffold protein to organize ROS-dependent VEGF signaling, thus promoting EC migration & proliferation, which may contribute to repair & maintenance of the functional integrity of established blood vessels. (PMID:15217908)
• differential requirement for efficient GTP hydrolysis by the Sar1p GTPase in export of cargo from the endoplasmic reticulum (PMID:15252131)
• IQGAP1 might serve as an effector or sequester nucleotide-free Cdc42 to prevent signaling (PMID:15355962)
• We therefore propose that PP2A, especially PP2A-A, functions to maintain F-actin assembly to which beta1 integrin is anchored by recruitment of IQGAP1 to Rac-beta1 integrin. (PMID:15521075)
• IQGAP1 is expressed in podocytes at significant levels, and could be found at the immediate vicinity of the slit diaphragm (PMID:15634346)
• Data show that IQGAP1 is phosphorylated at multiple sites in intact cells and that phosphorylation of IQGAP1 will alter its ability to regulate the cytoskeleton of neuronal cells. (PMID:15695813)
• a specific sequence of IQGAP1 is necessary for its oligomerization; self-association is required for the normal cellular function of IQGAP1 (PMID:16105843)
• IQGAP1 interacts directly with MEK1 and MEK2 kinases. (PMID:16135787)
• IQGAP1 may function to link Nox2 to actin at the leading edge, thereby facilitating reactive oxygen species production at the site of injury, which may contribute to endothelial cell migration (PMID:16179592)
• GluR4 may regulate its synaptic targeting through phosphorylation-dependent interactions with alpha-Actinin-1 and IQGAP1 (PMID:16190873)
• We therefore propose that PP2A plays a crucial role in the maintenance of cell-cell adhesion through recruitment of IQGAP1 to the Rac-bound E-cadherin-catenins complex. (PMID:16245300)
• PTPmu may regulate Rho-GTPase-dependent functions of IQGAP1 (PMID:16380380)
• Findings suggest the involvement of IQGAP1 in the progression and spread of ovarian adenocarcinomas. (PMID:16387427)
• IQGAP1 represents a potential target for the design of new organ preservation strategies and prevention of Ischemia-reperfusion injury to improve transplantation outcome. (PMID:16622255)
• signal-induced relief of the autoinhibited fold of IQGAP1 allows activation of N-WASP to stimulate Arp2/3-dependent actin assembly (PMID:17085436)
• in motile cells beta-catenin is recruited by IQGAP1 and N-cadherin to active membrane ruffles, wherein beta-catenin mediates the internalization and possible recycling of the membrane-associated proteins N-cadherin and APC (PMID:17255093)
• IQGAP1 may link the calmodulin and Rap1 signaling pathways (PMID:17517894)
• These data suggest that IQGAP1 serves as a junction to integrate multiple signalling molecules to facilitate cell migration. (PMID:17544257)
• IQGAP1 modulates activation of B-Raf. (PMID:17563371)
• DIA1 and IQGAP1 interact in cell migration and phagocytic cup formation. (PMID:17620407)
• IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42 (PMID:17693642)
• that ALIX and TSG101/ESCRT-I also bind a series of proteins involved in cytokinesis, including CEP55, CD2AP, ROCK1, and IQGAP1. (PMID:17853893)
• IQGAP1 enhances mammary tumorigenesis, suggesting that it may be a target for therapeutic intervention. (PMID:17981797)
• The exocyst subunits Sec3 and Sec8 interact with the polarity protein IQGAP1 and that this interaction is triggered by active Cdc42 and RhoA, which are essential for matrix degradation. (PMID:18541705)
• the scaffold protein IQGAP1 couples Ca(2+) and calmodulin signaling to B-Raf function (PMID:18567582)
• IQGAP1 promotes cell proliferation and phosphorylation of IQGAP1 is involved in the process of wound closure in bronchial epithelial cells. (PMID:18575779)
• Only the first IQ motif of IQGAP1 interacts with MYL6B. The first and second IQ motifs of IQGAP1 interact with S100B in the presence of calcium ions. (PMID:18587628)
• IQGAP1, Ca(2+), and calmodulin are a novel signaling complex regulating actin pedestal formation by EPEC (PMID:18809683)
• IQGAP1 expression level seemed to be closely associated with the enhanced invasion and migration in ovarian cancer cell lines. (PMID:19036171)
• We identified IQGAP1 as a host cell interaction partner of the novel effector protein Ibe of EPEC and EHEC strains. [IQGAP1] (PMID:19134119)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	iqgap1	ENSDARG00000078888
mus_musculus	Iqgap1	ENSMUSG00000030536
rattus_norvegicus	Iqgap1	ENSRNOG00000012002
caenorhabditis_elegans	pes-7	WBGENE00003980

Paralogs (2): IQGAP2 (ENSG00000145703), IQGAP3 (ENSG00000183856)

Protein

Protein identifiers

Ras GTPase-activating-like protein IQGAP1 — P46940 (reviewed: P46940)

Alternative names: p195

All UniProt accessions (6): A0A087WWP1, A0A087X225, A0A0J9YXZ5, P46940, H0YKA5, H0YLE8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane. Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth. May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest.

Subunit / interactions. Interacts with CDC42; the interaction is demonstrated with IQGAP1 in GTP-bound and in nucleotide-free state. Interacts with RAC1. Does not interact with RHOA. Interacts with TSG101. Interacts with PAK6. Interacts with TMEM14B; this interaction increases IQGAP1 phosphorylation and induces its nuclear translocation. Interacts with SASH1. Interacts with PJVK. Interacts with SLC26A4; this interaction enhances the chloride-bicarbonate exchange activity of SLC26A4. Interacts with SVEP1. Interacts with ILK; the interaction is required for localization of IQGAP to the cell cortex. (Microbial infection) Interacts with ebolavirus vp40. (Microbial infection) Interacts with human cytomegalovirus protein UL5. (Microbial infection) Interacts with C.jejuni invasion antigen D (CiaD).

Subcellular location. Cell membrane. Nucleus. Cytoplasm. Cell cortex. Apical cell membrane. Basolateral cell membrane.

Tissue specificity. Expressed in the placenta, lung, and kidney. A lower level expression is seen in the heart, liver, skeletal muscle and pancreas.

Post-translational modifications. Phosphorylation of Ser-1443 by PKC/PRKCE prevents interaction between C1 and C2, allowing binding of nucleotide-free CDC42. Ser-1443 phosphorylation enhances the ability to promote neurite outgrowth.

Domain organisation. Regions C1 and C2 can either interact with nucleotide-free CDC42, or interact together, depending on the phosphorylation state of Ser-1443. When Ser-1443 is not phosphorylated, C1 and C2 interact, which prevents binding of nucleotide-free CDC42 and promotes binding of GTP-bound CDC42. Phosphorylation of Ser-1443 prevents interaction between C1 and C2, which opens the structure of the C-terminus and allows binding and sequestration of nucleotide-free CDC42 on both C1 and C2.

RefSeq proteins (1): NP_003861* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR000593	IQGAP_helical	Domain
IPR001202	WW_dom	Domain
IPR001715	CH_dom	Domain
IPR001936	RasGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR023152	RasGAP_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily

Pfam: PF00307, PF00612, PF00616, PF03836

UniProt features (82 total): helix 39, strand 11, turn 8, domain 7, modified residue 6, mutagenesis site 4, region of interest 3, initiator methionine 1, chain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3FAY	X-RAY DIFFRACTION	2.2
5L0O	X-RAY DIFFRACTION	2.36
3I6X	X-RAY DIFFRACTION	2.5
1X0H	SOLUTION NMR
2RR8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46940-F1	78.64	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 2, 2, 172, 330, 1441, 1443

Mutagenesis-validated functional residues (4):

Position	Phenotype
1441	abolishes neurite outgrowth promoting activity; when associated with a-1443.
1441	strongly enhances neurite outgrowth promoting activity; when associated with a-1443.
1443	abolishes neurite outgrowth promoting activity; when associated with a-1441.
1443	strongly enhances neurite outgrowth promoting activity; when associated with a-1441.

Function

Pathways and Gene Ontology

Reactome pathways

37 pathways

ID	Pathway
R-HSA-373753	Nephrin family interactions
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-5626467	RHO GTPases activate IQGAPs
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-6798695	Neutrophil degranulation
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013424	RHOV GTPase cycle
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-1430728	Metabolism
R-HSA-1500931	Cell-Cell communication
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-422356	Regulation of insulin secretion
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers

MSigDB gene sets: 435 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_MITOTIC_CYTOKINESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, GOBP_MEMBRANE_BIOGENESIS, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOCC_SECRETORY_GRANULE, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, HSIAO_HOUSEKEEPING_GENES, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, LANG_MYB_FAMILY_TARGETS

GO Biological Process (21): regulation of cytokine production (GO:0001817), signal transduction (GO:0007165), epidermal growth factor receptor signaling pathway (GO:0007173), regulation of mitotic cell cycle (GO:0007346), fibroblast growth factor receptor signaling pathway (GO:0008543), fibroblast migration (GO:0010761), cell migration (GO:0016477), regulation of actin cytoskeleton organization (GO:0032956), negative regulation of dephosphorylation (GO:0035305), cellular response to platelet-derived growth factor stimulus (GO:0036120), positive regulation of MAPK cascade (GO:0043410), platelet-derived growth factor receptor signaling pathway (GO:0048008), caveola assembly (GO:0070836), cellular response to calcium ion (GO:0071277), cellular response to epidermal growth factor stimulus (GO:0071364), podocyte development (GO:0072015), mitotic actomyosin contractile ring assembly actin filament organization (GO:1903479), MAPK cascade (GO:0000165), regulation of GTPase activity (GO:0043087), cellular response to fibroblast growth factor stimulus (GO:0044344), neuron projection extension (GO:1990138)

GO Molecular Function (16): MAP kinase scaffold activity (GO:0005078), GTPase inhibitor activity (GO:0005095), GTPase activator activity (GO:0005096), calcium ion binding (GO:0005509), calmodulin binding (GO:0005516), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), protein domain specific binding (GO:0019904), small GTPase binding (GO:0031267), protein serine/threonine kinase activator activity (GO:0043539), S100 protein binding (GO:0044548), cadherin binding (GO:0045296), actin filament binding (GO:0051015), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (29): ruffle (GO:0001726), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), actin filament (GO:0005884), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell cortex (GO:0005938), cytoplasmic side of plasma membrane (GO:0009898), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), axon (GO:0030424), growth cone (GO:0030426), midbody (GO:0030496), secretory granule membrane (GO:0030667), cortical actin cytoskeleton (GO:0030864), slit diaphragm (GO:0036057), cytoplasmic ribonucleoprotein granule (GO:0036464), neuron projection (GO:0043005), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904), cell-cell junction (GO:0005911), actin cytoskeleton (GO:0015629), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), cell leading edge (GO:0031252), plasma membrane bounded cell projection (GO:0120025)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
RHO GTPase cycle	8
Oncogenic MAPK signaling	5
Cell-Cell communication	1
Regulation of insulin secretion	1
RHO GTPase Effectors	1
RAF/MAP kinase cascade	1
Innate Immune System	1
Signaling by RAS mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular response to growth factor stimulus	3
GTPase activity	3
protein binding	3
cytoplasm	3
cell surface receptor protein tyrosine kinase signaling pathway	2
MAPK cascade	2
GTPase regulator activity	2
binding	2
polymeric cytoskeletal fiber	2
actin cytoskeleton	2
cell periphery	2
plasma membrane	2
plasma membrane region	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ERBB signaling pathway	1
mitotic cell cycle	1
regulation of cell cycle	1
cellular response to fibroblast growth factor stimulus	1
ameboidal-type cell migration	1
cell motility	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
dephosphorylation	1
regulation of dephosphorylation	1
negative regulation of phosphate metabolic process	1
response to platelet-derived growth factor	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
plasma membrane raft assembly	1
response to calcium ion	1
cellular response to metal ion	1

Protein interactions and networks

STRING

3228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IQGAP1	CLIP1	P30622	998
IQGAP1	CDC42	P21181	997
IQGAP1	CALM1	P02593	994
IQGAP1	CALML3	P27482	994
IQGAP1	CTNNB1	P35222	994
IQGAP1	CALML5	Q9NZT1	994
IQGAP1	CDH1	P12830	993
IQGAP1	CALML6	Q8TD86	993
IQGAP1	CALML4	Q96GE6	993
IQGAP1	AKT1	P31749	966
IQGAP1	MAP2K1	Q02750	962
IQGAP1	EXOC1	Q9NV70	960
IQGAP1	FLNA	P21333	937
IQGAP1	RACGAP1	Q9H0H5	937
IQGAP1	EXOC4	Q96A65	934

IntAct

382 interactions, top by confidence:

A	B	Type	Score
GRB2	EGFR	psi-mi:“MI:0914”(association)	0.980
IQGAP1	CDC42	psi-mi:“MI:0914”(association)	0.960
CDC42	IQGAP1	psi-mi:“MI:0403”(colocalization)	0.960
CDC42	IQGAP1	psi-mi:“MI:0915”(physical association)	0.960
IQGAP1	CDC42	psi-mi:“MI:0915”(physical association)	0.960
CDH2	CTNNB1	psi-mi:“MI:0914”(association)	0.930
RAC1	IQGAP1	psi-mi:“MI:0915”(physical association)	0.920
RAC1	IQGAP1	psi-mi:“MI:0403”(colocalization)	0.920
MAPK14	RPS6KA4	psi-mi:“MI:0914”(association)	0.870
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CXCR2	IQGAP1	psi-mi:“MI:0915”(physical association)	0.680
CXCR2	IQGAP1	psi-mi:“MI:0407”(direct interaction)	0.680
IQGAP1	CXCR2	psi-mi:“MI:0914”(association)	0.680

BioGRID (776): PDLIM7 (Two-hybrid), IQGAP1 (Affinity Capture-RNA), IQGAP1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), IQGAP1 (Biochemical Activity), IQGAP1 (Affinity Capture-MS), IQGAP1 (Protein-peptide), IQGAP1 (Protein-peptide), IQGAP1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS)

ESM2 similar proteins: A1Z3X3, A2AT37, A2VD00, A4GWN3, A4II09, A4VCH4, A7RWP6, B0W6N3, O43395, O49160, O75937, P23116, P32780, P46940, Q00004, Q14152, Q173M7, Q1JU68, Q2HJ41, Q2KIA6, Q40554, Q5EAV6, Q5R5F1, Q5RE03, Q5ZJ85, Q5ZMW3, Q62383, Q642C0, Q6DDM4, Q6GMH0, Q6GQ80, Q6NZB0, Q6PCR7, Q7KZ85, Q7ZY79, Q8BM39, Q8BMA6, Q8UVK2, Q8VZM1, Q922U1

Diamond homologs: O14188, P14318, P46940, Q10201, Q12280, Q24799, Q9JKF1, B9EUM5, O14185, P19966, P26932, P31232, P37397, P37802, P37803, P37804, P37805, P51911, Q01995, Q08091, Q08092, Q08093, Q08094, Q08290, Q08873, Q15052, Q15417, Q2HJ38, Q32L92, Q3SYU6, Q3ZBY2, Q4R5J4, Q54TK8, Q55E26, Q55GV9, Q5AH02, Q5E9F5, Q5R6R2, Q5RFN6, Q5XFX0

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
PRKCA	up-regulates	IQGAP1	phosphorylation
PRKCE	up-regulates	IQGAP1	phosphorylation
MET	“up-regulates activity”	IQGAP1	phosphorylation
SRC	“up-regulates activity”	IQGAP1	phosphorylation
NBEAL2	down-regulates	IQGAP1
IQGAP1	“down-regulates activity”	CDC42	binding
IQGAP1	“down-regulates activity”	RAC1	binding
CLASP2	“up-regulates activity”	IQGAP1	binding
MAP4K3	“up-regulates activity”	IQGAP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPases activate PAKs	6	28.1×	2e-05
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	6	25.7×	3e-05
VEGFR2 mediated vascular permeability	6	21.1×	7e-05
RHO GTPases activate IQGAPs	5	14.9×	1e-03
Parasite infection	5	14.9×	1e-03
Leishmania phagocytosis	5	14.9×	1e-03
RHO GTPases activate PKNs	5	13.7×	2e-03
RHO GTPases Activate WASPs and WAVEs	5	13.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell-cell adhesion mediated by cadherin	5	14.1×	5e-03
positive regulation of fibroblast proliferation	6	12.2×	4e-03
skeletal muscle tissue development	6	11.9×	4e-03
epidermal growth factor receptor signaling pathway	6	10.2×	5e-03
actin filament organization	9	7.3×	4e-03
actin cytoskeleton organization	10	5.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

210 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	145
Likely benign	13
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

5457 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90388392:TGGCT:T	donor_gain	1.0000
15:90388393:GGCTG:G	donor_gain	1.0000
15:90388396:TG:T	donor_loss	1.0000
15:90388397:G:GG	donor_gain	1.0000
15:90390772:A:AG	acceptor_gain	1.0000
15:90390772:AGCTG:A	acceptor_loss	1.0000
15:90390773:G:GA	acceptor_gain	1.0000
15:90390773:GCT:G	acceptor_gain	1.0000
15:90390871:GAG:G	donor_gain	1.0000
15:90426089:A:AG	acceptor_gain	1.0000
15:90426090:T:G	acceptor_gain	1.0000
15:90426102:T:A	acceptor_gain	1.0000
15:90426103:G:A	acceptor_gain	1.0000
15:90426105:T:TA	acceptor_gain	1.0000
15:90426106:GCAG:G	acceptor_loss	1.0000
15:90426107:CAG:C	acceptor_loss	1.0000
15:90426108:A:AG	acceptor_gain	1.0000
15:90426108:AG:A	acceptor_gain	1.0000
15:90426108:AGGT:A	acceptor_gain	1.0000
15:90426108:AGGTG:A	acceptor_gain	1.0000
15:90426109:G:GC	acceptor_gain	1.0000
15:90426109:GG:G	acceptor_gain	1.0000
15:90426109:GGT:G	acceptor_gain	1.0000
15:90426109:GGTG:G	acceptor_gain	1.0000
15:90426109:GGTGG:G	acceptor_gain	1.0000
15:90426263:CAAGG:C	donor_loss	1.0000
15:90426264:AAG:A	donor_gain	1.0000
15:90426265:AG:A	donor_gain	1.0000
15:90426266:GG:G	donor_gain	1.0000
15:90426267:G:GG	donor_gain	1.0000

AlphaMissense

10969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90390822:G:C	R35T	1.000
15:90390823:A:C	R35S	1.000
15:90390823:A:T	R35S	1.000
15:90390837:C:A	A40D	1.000
15:90390845:T:C	Y43H	1.000
15:90390849:T:C	L44P	1.000
15:90390851:T:C	C45R	1.000
15:90390852:G:A	C45Y	1.000
15:90390853:T:G	C45W	1.000
15:90390866:G:C	A50P	1.000
15:90426111:T:A	W53R	1.000
15:90426111:T:C	W53R	1.000
15:90426113:G:C	W53C	1.000
15:90426113:G:T	W53C	1.000
15:90426157:T:C	L68P	1.000
15:90426169:T:C	L72P	1.000
15:90426177:G:A	G75R	1.000
15:90426177:G:C	G75R	1.000
15:90426177:G:T	G75W	1.000
15:90426178:G:A	G75E	1.000
15:90426198:G:T	G82W	1.000
15:90429604:T:C	F110L	1.000
15:90429605:T:C	F110S	1.000
15:90429605:T:G	F110C	1.000
15:90429606:T:A	F110L	1.000
15:90429606:T:G	F110L	1.000
15:90429608:G:C	R111T	1.000
15:90429609:A:C	R111S	1.000
15:90429609:A:T	R111S	1.000
15:90429611:A:G	H112R	1.000

dbSNP variants (sampled 300 via entrez): RS1000010620 (15:90435419 T>C), RS1000019001 (15:90389824 G>C), RS1000055867 (15:90476101 A>G), RS1000064933 (15:90435101 G>A,C), RS1000068030 (15:90390108 T>C), RS1000151395 (15:90463990 G>C), RS1000204572 (15:90411634 C>A,G), RS1000215352 (15:90498639 G>C), RS1000220704 (15:90406692 A>G), RS1000229559 (15:90492073 A>G), RS1000230819 (15:90491085 A>T), RS1000281574 (15:90490902 G>A), RS1000292538 (15:90387734 AAG>A), RS1000312192 (15:90463919 G>A,C), RS1000360824 (15:90464208 G>A)

Disease associations

OMIM: gene MIM:603379 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): breast ductal adenocarcinoma (MONDO:0005590), CIC-rearranged sarcoma (MONDO:0956989)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST004618_39	White blood cell count (basophil)	2.000000e-16
GCST004627_157	Lymphocyte count	1.000000e-22
GCST004631_27	Basophil percentage of white cells	2.000000e-20
GCST004632_45	Lymphocyte percentage of white cells	1.000000e-18
GCST004634_43	Basophil percentage of granulocytes	1.000000e-13
GCST005038_92	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST005531_9	Multiple sclerosis	2.000000e-09
GCST006661_175	Male-pattern baldness	2.000000e-11
GCST006979_940	Heel bone mineral density	6.000000e-34
GCST009719_21	Allergic rhinitis	6.000000e-12
GCST009839_2	Chronic postoperative pain	4.000000e-06
GCST010730_5	Rheumatoid arthritis	2.000000e-08
GCST010984_39	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	2.000000e-11
GCST010985_18	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	2.000000e-11
GCST012489_127	Heel bone mineral density x serum urate levels interaction	7.000000e-10
GCST90002379_71	Basophil count	6.000000e-59
GCST90002380_34	Basophil percentage of white cells	2.000000e-73
GCST90002388_159	Lymphocyte count	6.000000e-63
GCST90002389_304	Lymphocyte percentage of white cells	2.000000e-47
GCST90002399_370	Neutrophil percentage of white cells	5.000000e-27
GCST90002404_374	Red cell distribution width	5.000000e-12
GCST90011769_1	Glaucoma (primary open-angle)	3.000000e-08

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0004587	lymphocyte count
EFO:0007992	basophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0009270	heel bone mineral density
EFO:0010640	chronic post-operative pain measurement
EFO:0004847	age at onset
EFO:0004531	urate measurement
EFO:0007990	neutrophil percentage of leukocytes
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295763 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.45	Kd	35.39	nM	CHEMBL5653589
7.45	ED50	35.39	nM	CHEMBL5653589
7.05	IC50	90	nM	MOLIBRESIB
5.33	Kd	4703	nM	CHEMBL3752910
5.33	ED50	4703	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 12 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148600: Binding affinity to human IQGAP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0354	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178553: Inhibition of IQGAP1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0900	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148600: Binding affinity to human IQGAP1 incubated for 45 mins by Kinobead based pull down assay	kd	4.7033	uM

CTD chemical–gene interactions

72 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	5
trichostatin A	affects cotreatment, increases expression	3
Quercetin	affects binding, decreases reaction, decreases expression, increases expression	3
methylmercuric chloride	increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
geldanamycin	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
arsenite	affects binding, decreases reaction, increases reaction	1
afimoxifene	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
cupric oxide	increases expression	1
artenimol	affects binding	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118597	Binding	Binding affinity to IQGAP1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8IL	Abcam HCT 116 IQGAP1 KO	Cancer cell line	Male
CVCL_B9KW	Abcam A-549 IQGAP1 KO	Cancer cell line	Male
CVCL_D2FW	Abcam MCF-7 IQGAP1 KO	Cancer cell line	Female
CVCL_SS77	HAP1 IQGAP1 (-) 1	Cancer cell line	Male
CVCL_SS78	HAP1 IQGAP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

14 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT06414434	PHASE1	ACTIVE_NOT_RECRUITING	BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT06820957	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body