AGAP3

Chr 7

ArfGAP with GTPase domain, ankyrin repeat and PH domain 3

Also known as: AGAP-3, CENTG3, CRAG, MRIP-1, cnt-g3

NCBI Gene: 116988ENSG00000133612UniProt: Q96P47

This gene encodes an essential component of the N-methyl-D-aspartate (NMDA) receptor signaling complex which mediates long-term potentiation in synapses by linking activation of NMDA receptor to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking. The encoded protein contains an N-terminal GTPase-like domain, a pleckstrin homology domain, an ArfGAP domain and several C-terminal ankryn repeat domains. [provided by RefSeq, Apr 2017]

205
ClinVar variants
73
Pathogenic / LP
0.91
pLI score· haploinsufficient
0
Active trials
Clinical Summary— AGAP3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 121 VUS of 205 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.911
Z-score 4.95
OE 0.19 (0.11–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.99Z-score
OE missense 0.65 (0.60–0.71)
377 obs / 579.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.11–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.60–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 8 / 43.0Missense obs/exp: 377 / 579.7Syn Z: -0.46

ClinVar Variant Classifications

205 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic4
VUS121
Likely Benign8
Benign3
69
Pathogenic
4
Likely Pathogenic
121
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
69
0
69
Likely Pathogenic
0
0
4
0
4
VUS
1
112
8
0
121
Likely Benign
0
5
1
2
8
Benign
1
1
0
1
3
Total2118823205

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

View in ClinVar →

Protein Context — Lollipop Plot

AGAP3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of fusions with potential clinical significance in melanoma.
Moran JMT et al.·Mod Pathol
2022
CRMP5-associated GTPase (CRAG) Is a Candidate Driver Gene for Colorectal Cancer Carcinogenesis.
Shimizu D et al.·Anticancer Res
2019
Clinical, Morphologic, and Genomic Findings in Spitz Tumors With RET Fusion: A Series of 31 Cases.
Donati M et al.·Mod Pathol
2025Cohort
BRAF Fusion as a Novel Mechanism of Acquired Resistance to Vemurafenib in BRAF(V600E) Mutant Melanoma.
Kulkarni A et al.·Clin Cancer Res
2017Case report
Spectrum of BRAF Mutations and Gene Rearrangements in Ovarian Serous Carcinoma.
Chui MH et al.·JCO Precis Oncol
2021
Primary pigmented papillary epithelial tumor of the sella: case report and literature review.
Wu S et al.·Brain Tumor Pathol
2025Review
Gastrointestinal stromal tumors with BRAF gene fusions. A report of two cases showing low or absent KIT expression resulting in diagnostic pitfalls.
Torrence D et al.·Genes Chromosomes Cancer
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Pulmonary Erdheim-Chester Disease With BRAF-AGAP3 Fusion: Late-Onset Osteolytic Femoral Lesions Despite Long-Term Pulmonary Stabilization With Corticosteroid.
Nishino K et al.·Cureus
2024🔓 Open Access
Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study.
Højgaard K et al.·Mol Brain
2023🔓 Open Access
Whole transcriptome sequencing reveals HOXD11-AGAP3, a novel fusion transcript in the Indian acute leukemia cohort.
Desai SS et al.·Front Genet
2023🔓 Open AccessCohort
AGAP3: A novel BRAF fusion partner in pediatric pancreatic-type acinar cell carcinoma.
Paoli C et al.·Genes Chromosomes Cancer
2022🔓 Open Access
Critical role of CRAG, a splicing variant of centaurin-γ3/AGAP3, in ELK1-dependent SRF activation at PML bodies.
Nagashima S et al.·Sci Rep
2019🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools