IQGAP1

Chr 15

IQ motif containing GTPase activating protein 1

Also known as: HUMORFA01, SAR1, p195

NCBI Gene: 8826 ENSG00000140575 UniProt: P46940 OMIM: 603379

This protein regulates actin cytoskeleton dynamics and assembly, binds to activated CDC42, associates with calmodulin, and promotes neurite outgrowth. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.28

Clinical Summary— IQGAP1

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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.

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ClinVar Variants

144 VUS of 207 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.19 (0.13–0.28)

0≤0.351.4

Missense OE?0.77 (0.72–0.82)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 18 / 97.0Missense obs/exp: 680 / 884.6Syn Z: -1.12

ClinVar Variant Classifications

207 submitted variants in ClinVar

ClinVar

Classification Summary

VUS144

Likely Benign12

Benign6

144

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	144	0	0	144
Likely Benign	7	0	5	12
Benign	2	2	2	6
Total	153	2	7	162

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap IQGAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →