IQGAP1

protein-coding

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

Gene summary

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]

MANE transcript

NM_003870.4

Inheritance

—

ClinVar variants

U:171B:16

Top phenotype

IQGAP1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr15:90,388,242-90,502,239

External References & Databases

Ensembl (ENSG00000140575)

Transcript & Mutation Effects

hg38 • Region Span ~114.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IQGAP1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 147

not providedTotal: 15

IQGAP1-related disorderTotal: 7

CIC-rearranged sarcomaTotal: 1

IQGAP1-associated immune conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003870.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	5 clinvar	2 clinvar	9
missense			155 clinvar	7 clinvar	2 clinvar	164
nonsense			6 clinvar			6
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	171	12	4	187

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003870.4	RefSeq	NP_003861.1	38	MANE Select
ENST00000268182.10	Ensembl	ENSP00000268182.5	38	MANE Select
ENST00000559809.2	Ensembl	ENSP00000484647.1	2	Standard
ENST00000560373.1	Ensembl	ENSP00000480393.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Adherens junction - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Proteoglycans in cancer - Homo sapiens (human)
Angiogenesis overview
VEGFA-VEGFR2 Signaling Pathway

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

Molecular Function

GTPase inhibitor activity
GTPase activator activity
calcium ion binding
protein binding
calmodulin binding

Cellular Component

ruffle
nucleus
cytoplasm
cytosol
microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000268182
Coding exons: 38
Length: 114026
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.44	680	885	0.769	0.0000473	10909
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.000068	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.291

Intolerance Scores

LoFtool: 0.402
RVIS EVS: -1.23
RVIS percentile EVS: 5.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.834

Gene Damage Prediction

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