IQGAP1

IQ motif containing GTPase activating protein 1, the group of IQ motif containing GTPase activating protein family

Basic information

Region (hg38): 15:90388241-90502239

Links

ENSG00000140575 ∙ NCBI:8826 ∙ OMIM:603379 ∙ HGNC:6110 ∙ Uniprot:P46940 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IQGAP1 gene.

• Inborn genetic diseases (45 variants)
• not provided (8 variants)
• IQGAP1-related condition (2 variants)
• IQGAP1-associated immune condition (1 variants)
• not specified (1 variants)
• CIC-DUX Sarcoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IQGAP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			47	2	2	51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	47	4	4

Variants in IQGAP1

This is a list of pathogenic ClinVar variants found in the IQGAP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-90388352-C-T		not specified	Uncertain significance (Mar 07, 2024)
15-90388381-C-T		not specified	Uncertain significance (Aug 04, 2023)
15-90388391-A-G		not specified	Uncertain significance (Sep 01, 2021)
15-90390776-G-A		not specified	Uncertain significance (Oct 25, 2022)
15-90390824-C-T		not specified	Uncertain significance (Oct 27, 2021)
15-90390833-G-A		not specified	Uncertain significance (May 03, 2023)
15-90426205-T-A		not specified	Uncertain significance (Jul 14, 2023)
15-90426247-G-A		not specified	Uncertain significance (Jun 09, 2022)
15-90429671-C-T			Benign (Jun 18, 2018)
15-90433743-A-G		not specified	Uncertain significance (May 23, 2023)
15-90440519-A-G		IQGAP1-related disorder	Uncertain significance (Feb 05, 2023)
15-90440554-G-A		not specified	Uncertain significance (Dec 15, 2022)
15-90440612-G-A		not specified	Uncertain significance (Feb 14, 2023)
15-90441492-G-GA		CIC-DUX Sarcoma	not provided (-)
15-90441630-C-T			Benign (May 09, 2018)
15-90441637-A-G			Benign (Jun 28, 2018)
15-90448593-A-G		not specified	Likely benign (Sep 16, 2021)
15-90448666-G-A		not specified	Uncertain significance (Dec 21, 2023)
15-90448718-T-G		not specified	Uncertain significance (Nov 17, 2022)
15-90449581-A-G		not specified	Uncertain significance (Jan 26, 2022)
15-90452780-G-A		not specified	Uncertain significance (Jan 26, 2022)
15-90452796-T-C		not specified	Uncertain significance (Jun 11, 2021)
15-90452853-C-A		not specified	Uncertain significance (Feb 10, 2022)
15-90452925-G-A		not specified	Likely benign (Dec 19, 2022)
15-90453172-T-C		IQGAP1-associated immune condition	Uncertain significance (Sep 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IQGAP1	protein_coding	protein_coding	ENST00000268182	38	114026

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00246	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.44	680	885	0.769	0.0000473	10909
Missense in Polyphen		110	213.05	0.51631		2619
Synonymous	-1.12	358	332	1.08	0.0000177	3069
Loss of Function	7.43	18	97.0	0.186	0.00000531	1132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000117	0.000117
Ashkenazi Jewish	0.000201	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.000329	0.000323
European (Non-Finnish)	0.000151	0.000149
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000681	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Binds to activated CDC42 but does not stimulate its GTPase activity. It associates with calmodulin. Could serve as an assembly scaffold for the organization of a multimolecular complex that would interface incoming signals to the reorganization of the actin cytoskeleton at the plasma membrane. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}.
• Pathway: Adherens junction - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Angiogenesis overview;VEGFA-VEGFR2 Signaling Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;EGF-EGFR Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;MAP2K and MAPK activation;Neutrophil degranulation;Disease;Signal Transduction;Innate Immune System;Immune System;Metabolism;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;RHO GTPases activate IQGAPs;RHO GTPase Effectors;Signaling by Rho GTPases;EGFR1;ErbB1 downstream signaling;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Posttranslational regulation of adherens junction stability and dissassembly;C-MYB transcription factor network;Integrin-linked kinase signaling;Integration of energy metabolism;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Nephrin family interactions;Cell-Cell communication;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;RAC1 signaling pathway;Nectin adhesion pathway;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;CDC42 signaling events;PDGFR-beta signaling pathway;Lissencephaly gene (LIS1) in neuronal migration and development;Signaling events mediated by VEGFR1 and VEGFR2;E-cadherin signaling in the nascent adherens junction (Consensus)

Recessive Scores

• pRec: 0.291

Intolerance Scores

• loftool: 0.402
• rvis_EVS: -1.23
• rvis_percentile_EVS: 5.54

Haploinsufficiency Scores

• pHI: 0.489
• hipred: Y
• hipred_score: 0.648
• ghis: 0.431

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.834

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Iqgap1
• Phenotype: digestive/alimentary phenotype; neoplasm; liver/biliary system phenotype

Gene ontology

• Biological process: regulation of cytokine production;signal transduction;epidermal growth factor receptor signaling pathway;regulation of mitotic cell cycle;fibroblast growth factor receptor signaling pathway;cell migration;negative regulation of GTPase activity;negative regulation of dephosphorylation;cellular response to platelet-derived growth factor stimulus;neutrophil degranulation;positive regulation of MAP kinase activity;positive regulation of GTPase activity;positive regulation of protein kinase activity;platelet-derived growth factor receptor signaling pathway;positive regulation of focal adhesion assembly;cellular response to calcium ion;cellular response to epidermal growth factor stimulus;glomerular visceral epithelial cell development;positive regulation of dendrite development;positive regulation of peptidyl-tyrosine autophosphorylation;positive regulation of cellular protein localization;positive regulation of vascular associated smooth muscle cell migration;neuron projection extension;response to angiotensin
• Cellular component: ruffle;nucleus;cytoplasm;cytosol;microtubule;actin filament;plasma membrane;focal adhesion;actin cytoskeleton;microtubule cytoskeleton;lateral plasma membrane;axon;growth cone;midbody;secretory granule membrane;extrinsic component of cytoplasmic side of plasma membrane;slit diaphragm;cytoplasmic ribonucleoprotein granule;neuron projection;membrane raft;extracellular exosome
• Molecular function: GTPase inhibitor activity;GTPase activator activity;calcium ion binding;protein binding;calmodulin binding;phosphatidylinositol-3,4,5-trisphosphate binding;protein kinase binding;protein phosphatase binding;protein domain specific binding;small GTPase binding;protein-containing complex scaffold activity;protein serine/threonine kinase activator activity;S100 protein binding;protein-containing complex binding;cadherin binding;Rac GTPase binding;mitogen-activated protein kinase binding