IQGAP2

protein-coding

IQ motif containing GTPase activating protein 2, the group of IQ motif containing GTPase activating protein family

Gene summary

This gene encodes a member of the IQGAP family. The encoded protein contains three IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. This protein interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. It also acts as a tumor suppressor and has been found to play a role in regulating innate antiviral responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

MANE transcript

NM_006633.5

Inheritance

—

ClinVar variants

U:225B:19

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr5:76,403,285-76,708,132

External References & Databases

Ensembl (ENSG00000145703)

Transcript & Mutation Effects

hg38 • Region Span ~304.8 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 IQGAP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 261

not providedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006633.5. 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			1 clinvar	2 clinvar	4 clinvar	7
missense			216 clinvar	7 clinvar	6 clinvar	229
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	225	9	10	244

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006633.5	RefSeq	NP_006624.3	36	MANE Select
ENST00000274364.11	Ensembl	ENSP00000274364.6	36	MANE Select
NM_001285460.2	RefSeq	NP_001272389.2	34	Standard
NM_001285461.2	RefSeq	NP_001272390.2	24	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
iqgap2	Danio rerio	Structure: glomerular basement membrane Quality: increased width abnormal

Gene / Model

Organism

Observed Phenotype

iqgap2

Danio rerio

Structure: glomerular basement membrane

Quality: increased width

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of actin cytoskeleton - Homo sapiens (human)
G13 Signaling Pathway
Neutrophil degranulation
Signal Transduction
Innate Immune System

Biological Process

signal transduction
negative regulation of GTPase activity
Arp2/3 complex-mediated actin nucleation
neutrophil degranulation
thrombin-activated receptor signaling pathway

Molecular Function

actin binding
GTPase inhibitor activity
calmodulin binding
phosphatidylinositol-3,4,5-trisphosphate binding
Rho GTPase binding

Cellular Component

cytoplasm
cytosol
plasma membrane
microvillus
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000274364
Coding exons: 36
Length: 304884
Individuals with no LoFs: 125474
Homozygous LoFs: 0
Heterozygous LoFs: 274
Defined: 125748
p: 0.00109

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	718	815	0.881	0.0000423	10359
Missense (PolyPhen)		239	288.46	0.82853		3587
Synonymous	0.362	302	310	0.974	0.0000173	2889
Loss of Function	3.16	56	88.0	0.636	0.00000455	1123

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.0062	0.0062	notable
East Asian	0.0015	0.0015	notable
Finnish	0.00088	0.00088	rare
European (Non-Finnish)	0.00081	0.00080	rare
South Asian	0.00061	0.00059	rare
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin.;

Recessive Scores

pRec: 0.252

Intolerance Scores

LoFtool: 0.492
RVIS EVS: 0.39
RVIS percentile EVS: 76.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.785

Gene Damage Prediction

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