Protein Dossier — JAG1 (Protein jagged-1)
MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
1. Published MR estimates (retrieved, not computed)
| Outcome |
beta |
se |
p |
method |
nSNP |
cis/trans |
coloc |
| Large vessel disease |
-0.573 |
0.157 |
2.60e-04 |
Wald ratio |
1 |
trans |
NA |
| Ulcerative colitis |
-0.159 |
0.0594 |
0.00735 |
Wald ratio |
1 |
trans |
NA |
| Fractured bone site(s): Arm |
0.234 |
0.0885 |
0.00825 |
Wald ratio |
1 |
trans |
NA |
| Height |
0.0328 |
0.0136 |
0.0164 |
Wald ratio |
1 |
trans |
NA |
| Heel bone mineral density (BMD) T-score automated |
-0.0335 |
0.0143 |
0.0189 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: B37 Candidiasis |
0.671 |
0.298 |
0.024 |
Wald ratio |
1 |
trans |
NA |
| Cardioembolic stroke |
0.307 |
0.147 |
0.0369 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: K57 Diverticular disease of intestine |
-0.197 |
0.0954 |
0.0391 |
Wald ratio |
1 |
trans |
NA |
| Packed cell volume |
-0.164 |
0.0801 |
0.0408 |
Wald ratio |
1 |
trans |
NA |
| Alzheimer’s disease |
-0.142 |
0.071 |
0.0448 |
Wald ratio |
1 |
trans |
NA |
| Parkinson’s disease |
-0.365 |
0.189 |
0.0532 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: muscle or soft tissue injuries |
0.203 |
0.108 |
0.06 |
Wald ratio |
1 |
trans |
NA |
| …and 107 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5092_51_3 |
JAG1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
125 association rows across 82 traits (120 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.
| Trait |
best p |
lead SNP |
n assoc |
study |
MR status |
| Estimated bone mineral density |
1e-89 |
rs141094380 |
3 |
GCST90726625 |
no MR -> candidate analysis |
| Heel bone mineral density |
1e-87 |
rs17457340 |
15 |
GCST006433 |
MR: beta=-0.0335, p=0.0189 (trans) |
| PSPN protein levels |
1e-34 |
rs549768142 |
1 |
GCST90470364 |
no MR -> candidate analysis |
| CALCA protein levels |
5e-26 |
rs3790163 |
1 |
GCST90468528 |
no MR -> candidate analysis |
| Brain morphology (MOSTest) |
4e-25 |
rs6077868 |
2 |
GCST90239729 |
no MR -> candidate analysis |
| High light scatter reticulocyte count (UKB data field 30300) |
4e-25 |
rs1997814 |
1 |
GCST90468076 |
no MR -> candidate analysis |
| Circulating CALCA levels |
4e-25 |
rs3790163 |
1 |
GCST90860308 |
no MR -> candidate analysis |
| High light scatter reticulocyte percentage (UKB data field 3 |
3e-23 |
rs1997814 |
1 |
GCST90468077 |
no MR -> candidate analysis |
| Immature reticulocyte fraction (UKB data field 30280) |
6e-21 |
rs1997814 |
1 |
GCST90468079 |
no MR -> candidate analysis |
| Lumbar spine bone mineral density |
3e-19 |
rs3790160 |
1 |
GCST001482 |
MR: beta=0.0342, p=0.393 (trans) |
| Subcortical volume (MOSTest) |
3e-19 |
rs6133987 |
1 |
GCST010702 |
no MR -> candidate analysis |
| Diastolic blood pressure (UKB data field 4079) |
3e-19 |
rs889509 |
1 |
GCST90468163 |
no MR -> candidate analysis |
| …and 70 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1880 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.
| Disease |
genetic assoc. |
burden (ExWAS) |
causal status |
MR status |
| Alagille syndrome due to a JAG1 point mutation |
0.945 |
— |
established (curated) |
no MR -> candidate analysis |
| Alagille syndrome |
0.791 |
— |
established (curated) |
no MR -> candidate analysis |
| Tetralogy of Fallot |
0.85 |
— |
established (curated) |
no MR -> candidate analysis |
| Charcot-Marie-Tooth disease, axonal, Type 2HH |
0.867 |
— |
established (curated) |
no MR -> candidate analysis |
| deafness, congenital heart defects, and posterior embryotoxon |
0.834 |
— |
established (curated) |
no MR -> candidate analysis |
| Abnormality of the cardiovascular system |
0.875 |
— |
established (curated) |
no MR -> candidate analysis |
| hypertensive disorder |
0.851 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.81 |
— |
common-variant locus |
no MR -> candidate analysis |
| Increased blood pressure |
0.789 |
— |
common-variant locus |
no MR -> candidate analysis |
| cataract |
0.754 |
— |
common-variant locus |
MR: beta=0.137, p=0.217 (trans) |
| migraine disorder |
0.762 |
— |
common-variant locus |
no MR -> candidate analysis |
| hereditary disease |
0.721 |
— |
established (curated) |
no MR -> candidate analysis |
| essential hypertension |
0.696 |
— |
common-variant locus |
no MR -> candidate analysis |
| keloid |
0.648 |
— |
common-variant locus |
no MR -> candidate analysis |
| osteoporosis |
0.638 |
— |
common-variant locus |
MR: beta=0.0665, p=0.425 (trans) |
Of the 15 rows above, 13 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.
5. Downstream annotation (druggability & safety preview)
| Layer |
Result |
| ChEMBL druggability |
0 known modulators (Protein jagged-1) |
| gnomAD constraint |
pLI=1, LOEUF=0.219 — LoF-INTOLERANT |
| GWAS Catalog |
109 unique SNPs / 223 rows |
| ClinVar |
2760 records; 12 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1880 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘JAG1’ and resolved to ‘Protein jagged-1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 2760 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 82 traits by best p-value, aggregated from 125 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/P78504 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000101384/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3217396/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/JAG1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/JAG1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=JAG1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/JAG1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:19:48 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none