Protein Dossier — TIE1 (Tyrosine-protein kinase receptor Tie-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 |
| Non-cancer illness code self-reported: hypertension |
-0.0105 |
0.00291 |
3.13e-04 |
Inverse variance weighted |
2 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
-0.0105 |
0.00291 |
3.13e-04 |
Inverse variance weighted |
2 |
trans |
NA |
| Forced vital capacity (FVC) |
-0.0156 |
0.00538 |
0.00374 |
Inverse variance weighted |
2 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.0156 |
0.00538 |
0.00374 |
Inverse variance weighted |
2 |
trans |
NA |
| Hirschsprung’s disease |
-1.19 |
0.431 |
0.00561 |
Inverse variance weighted |
2 |
cis |
NA |
| Hirschsprung’s disease |
-1.19 |
0.431 |
0.00561 |
Inverse variance weighted |
2 |
trans |
NA |
| Diagnoses - main ICD10: K80 Cholelithiasis |
0.00256 |
0.000946 |
0.0067 |
Inverse variance weighted |
2 |
cis |
NA |
| Diagnoses - main ICD10: K80 Cholelithiasis |
0.00256 |
0.000946 |
0.0067 |
Inverse variance weighted |
2 |
trans |
NA |
| HDL cholesterol |
0.027 |
0.0108 |
0.0123 |
Inverse variance weighted |
2 |
cis |
NA |
| HDL cholesterol |
0.027 |
0.0108 |
0.0123 |
Inverse variance weighted |
2 |
trans |
NA |
| Non-cancer illness code self-reported: diverticular disease or diverticulitis |
0.00172 |
0.000706 |
0.0151 |
Inverse variance weighted |
2 |
cis |
NA |
| Non-cancer illness code self-reported: diverticular disease or diverticulitis |
0.00172 |
0.000706 |
0.0151 |
Inverse variance weighted |
2 |
trans |
NA |
| …and 197 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2844_53_2 |
sTie-1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
52 association rows across 36 traits (50 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 |
| Circulating TIE1 levels |
7e-256 |
rs4660729 |
2 |
GCST90860467 |
no MR -> candidate analysis |
| NOTCH1/TIE1 protein level ratio |
6e-249 |
rs3120044 |
1 |
GCST90315546 |
no MR -> candidate analysis |
| TIE1 protein levels |
4e-243 |
rs3768046 |
1 |
GCST90470863 |
no MR -> candidate analysis |
| Tyrosine-protein kinase receptor Tie-1, soluble levels |
2e-83 |
rs3120276 |
2 |
GCST90250042 |
no MR -> candidate analysis |
| Height |
1e-39 |
rs2275180 |
1 |
GCST90245848 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein TIE1 levels |
1e-33 |
rs3768046 |
1 |
GCST90944914 |
no MR -> candidate analysis |
| Serum levels of protein TIE1 |
1e-30 |
rs3768046 |
1 |
GCST90088101 |
no MR -> candidate analysis |
| Platelet count |
8e-28 |
rs140190628 |
2 |
GCST90002402 |
MR: beta=-1.94, p=0.0915 (cis) |
| Tyrosine-protein kinase receptor Tie-1, soluble levels (TIE1 |
5e-24 |
rs2275180 |
1 |
GCST90243207 |
no MR -> candidate analysis |
| Hemoglobin concentration |
2e-21 |
rs4660253 |
4 |
GCST90002310 |
no MR -> candidate analysis |
| Hemoglobin levels |
2e-20 |
rs3120047 |
2 |
GCST90662903 |
no MR -> candidate analysis |
| Hemoglobin |
1e-17 |
rs4660253 |
2 |
GCST90002384 |
no MR -> candidate analysis |
| …and 24 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 551 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 |
| lymphatic malformation 11 |
0.706 |
— |
established (curated) |
no MR -> candidate analysis |
| cardiovascular disorder |
0.327 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypertensive disorder |
0.106 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 3 rows above, 3 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 |
1 known modulators (Tyrosine-protein kinase receptor Tie-1) |
| gnomAD constraint |
pLI=3.8e-20, LOEUF=0.813 — LoF-tolerant |
| GWAS Catalog |
76 unique SNPs / 152 rows |
| ClinVar |
221 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 551 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 ‘TIE1’ and resolved to ‘Tyrosine-protein kinase receptor Tie-1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 221 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 36 traits by best p-value, aggregated from 52 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/P35590 — 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/ENSG00000066056/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5274/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/TIE1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/TIE1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=TIE1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/TIE1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:21:12 · 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