IQGAP3

Chr 1

IQ motif containing GTPase activating protein 3

NCBI Gene: 128239 ENSG00000183856 UniProt: Q86VI3 OMIM: 621092

Enables calmodulin binding activity and myosin VI light chain binding activity. Predicted to be involved in mitotic actomyosin contractile ring assembly actin filament organization. Predicted to act upstream of or within several processes, including G1/S transition of mitotic cell cycle; intracellular signaling cassette; and regulation of macromolecule metabolic process. Predicted to be located in cytosol. Predicted to be active in cell cortex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.85

Clinical Summary— IQGAP3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 248 VUS of 339 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.81

OE 0.69 (0.57–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.64Z-score

OE missense 0.94 (0.89–0.99)

869 obs / 923.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.57–0.85)

0≤0.351.4

Missense OE?0.94 (0.89–0.99)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 67 / 96.8Missense obs/exp: 869 / 923.9Syn Z: 1.71

This gene — mechanism propensity

0.6454th %ile

GOF

0.73top 25%

LOF

0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

339 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS248

Likely Benign40

Benign13

Likely Pathogenic

248

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	1	0	1
VUS	3	244	1	0	248
Likely Benign	0	19	4	17	40
Benign	0	7	1	5	13
Total	3	270	7	22	302

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap IQGAP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →