JAG2

Chr 14AR

jagged canonical Notch ligand 2

NCBI Gene: 3714ENSG00000184916UniProt: Q9Y219

Putative Notch ligand involved in the mediation of Notch signaling. Involved in limb development (By similarity)

Primary Disease Associations & Inheritance

Muscular dystrophy, limb-girdle, autosomal recessive 27MIM #619566
AR
454
ClinVar variants
62
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— JAG2
⚡
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.
📋
ClinVar Variants
62 Pathogenic / Likely Pathogenic· 273 VUS of 454 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.
0.14LOEUF
pLI 1.000
Z-score 6.95
OE 0.06 (0.03–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
2.20Z-score
OE missense 0.78 (0.73–0.83)
626 obs / 801.0 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.0.06 (0.03–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.73–0.83)
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.1.16
0≤1.21.6
LoF obs/exp: 4 / 63.9Missense obs/exp: 626 / 801.0Syn Z: -2.34

ClinVar Variant Classifications

454 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic5
VUS273
Likely Benign74
Benign23
Conflicting4
57
Pathogenic
5
Likely Pathogenic
273
VUS
74
Likely Benign
23
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
56
0
57
Likely Pathogenic
0
2
3
0
5
VUS
2
250
21
0
273
Likely Benign
0
14
15
45
74
Benign
0
5
3
15
23
Conflicting
—4
Total32719860436

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

View in ClinVar →

Protein Context — Lollipop Plot

JAG2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

JAG2-related muscular dystrophy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
JAGGED 2; JAG2
MIM #602570 · *

Muscular dystrophy, limb-girdle, autosomal recessive 27

MIM #619566

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Endothelial upregulation of mechanosensitive channel Piezo1 in pulmonary hypertension.
Wang Z et al.·Am J Physiol Cell Physiol
2021
Jagged2 targeting in lung cancer activates anti-tumor immunity via Notch-induced functional reprogramming of tumor-associated macrophages.
Mandula JK et al.·Immunity
2024Functional
Immunosuppressive JAG2(+) tumor-associated neutrophils hamper PD-1 blockade response in ovarian cancer by mediating the differentiation of effector regulatory T cells.
Wang C et al.·Cancer Commun (Lond)
2025
Precision medicine for human cancers with Notch signaling dysregulation (Review).
Katoh M et al.·Int J Mol Med
2020Review
Spatially-resolved analyses of muscle invasive bladder cancer microenvironment unveil a distinct fibroblast cluster associated with prognosis.
Feng C et al.·Front Immunol
2024
Notch signaling pathway in osteogenesis, bone development, metabolism, and diseases.
Dilawar M et al.·FASEB J
2025Review
Notch in skeletal physiology and disease.
Canalis E·Osteoporos Int
2018Review
Low SVEP1 in intrahepatic cholangiocarcinoma mediates phenotype switching-driven metastasis by Jag2/Notch1/Hes5.
Chen L et al.·Cell Death Dis
2025
The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.
Chen W et al.·Cardiovasc Diabetol
2024Review
The Notch signaling pathway in skeletal muscle health and disease.
Vargas-Franco D et al.·Muscle Nerve
2022Review
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools