GPC2

Chr 7

glypican 2

NCBI Gene: 221914ENSG00000213420UniProt: Q8N158

Predicted to be involved in several processes, including positive regulation of neuron projection development; regulation of protein localization to membrane; and smoothened signaling pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

121
ClinVar variants
20
Pathogenic / LP
0.03
pLI score
1
Active trials
Clinical Summary— GPC2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 93 VUS of 121 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.032
Z-score 3.12
OE 0.30 (0.17–0.56)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.01Z-score
OE missense 0.84 (0.76–0.93)
262 obs / 312.2 exp
Tolerant

Mild missense constraint

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.0.30 (0.17–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.76–0.93)
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.0.90
0≤1.21.6
LoF obs/exp: 7 / 23.3Missense obs/exp: 262 / 312.2Syn Z: 0.87

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic2
VUS93
Likely Benign8
18
Pathogenic
2
Likely Pathogenic
93
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
2
0
2
VUS
0
85
8
0
93
Likely Benign
0
6
1
1
8
Benign
0
0
0
0
0
Total091291121

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

View in ClinVar →

Protein Context — Lollipop Plot

GPC2 · 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
GLYPICAN 2; GPC2
MIM #618446 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity.
Heitzeneder S et al.·Cancer Cell
2022
Reprogramming the neuroblastoma tumor immune microenvironment to enhance GPC2 CAR T cells.
Giudice AM et al.·Mol Ther
2025
D3-GPC2-Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer.
Giudice AM et al.·Clin Cancer Res
2025Functional
Antibody-gamma/delta T cell receptors targeting GPC2 regress neuroblastoma with low antigen density.
Quan A et al.·Cell Rep Med
2025
Glypicans as Cancer Therapeutic Targets.
Li N et al.·Trends Cancer
2018Review
Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors.
Foster JB et al.·J Immunother Cancer
2022
Association between GPC2 polymorphisms and neuroblastoma risk in Chinese children.
Li M et al.·J Clin Lab Anal
2023
Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma.
Sun M et al.·J Immunother Cancer
2023
An optimized bicistronic chimeric antigen receptor against GPC2 or CD276 overcomes heterogeneous expression in neuroblastoma.
Tian M et al.·J Clin Invest
2022
Fine-tuning CARs for best performance.
Hotblack A et al.·Cancer Cell
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Refractory NeuroblastomaRelapsed NeuroblastomaHigh-risk Neuroblastoma

GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma and Metastatic Retinoblastoma

RECRUITING
NCT05650749Phase PHASE1Stephan Grupp MD PhDStarted 2023-05-23
GPC2 CAR T cells

External Resources

Links to major genomics databases and tools