Protein Dossier — FLT4 (Vascular endothelial growth factor receptor 3)
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 |
| HbA1C |
-0.0158 |
0.00508 |
0.00184 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: H25 Senile cataract |
0.00093 |
0.000299 |
0.00187 |
Inverse variance weighted |
2 |
trans |
NA |
| Diagnoses - main ICD10: H25 Senile cataract |
0.00093 |
0.000299 |
0.00187 |
Inverse variance weighted |
2 |
cis |
NA |
| Hirschsprung’s disease |
-0.577 |
0.196 |
0.00319 |
Wald ratio |
1 |
trans |
NA |
| Thalamus volume |
24.8 |
9.26 |
0.00733 |
Wald ratio |
1 |
trans |
NA |
| Type 2 diabetes |
-0.057 |
0.0214 |
0.00772 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: G47 Sleep disorders |
-0.000676 |
0.000261 |
0.00969 |
Inverse variance weighted |
2 |
trans |
NA |
| Diagnoses - main ICD10: G47 Sleep disorders |
-0.000676 |
0.000261 |
0.00969 |
Inverse variance weighted |
2 |
cis |
NA |
| Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms |
-0.00107 |
0.000416 |
0.00998 |
Inverse variance weighted |
2 |
trans |
NA |
| Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms |
-0.00107 |
0.000416 |
0.00998 |
Inverse variance weighted |
2 |
cis |
NA |
| Age at menopause |
-0.0726 |
0.0291 |
0.0124 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: vitiligo |
0.000141 |
5.69e-05 |
0.0129 |
Inverse variance weighted |
2 |
trans |
NA |
| …and 148 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2358_19_2 |
VEGF sR3 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
37 association rows across 24 traits (31 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 FLT4 levels |
3e-608 |
rs34221241 |
4 |
GCST90860081 |
no MR -> candidate analysis |
| FLT4/ICAM2 protein level ratio |
3e-516 |
rs34221241 |
1 |
GCST90314860 |
no MR -> candidate analysis |
| FLT4/KDR protein level ratio |
3e-498 |
rs34221241 |
1 |
GCST90314861 |
no MR -> candidate analysis |
| FLT4 protein levels |
7e-73 |
rs307813 |
7 |
GCST90469252 |
no MR -> candidate analysis |
| SCGB3A1 protein levels |
5e-71 |
rs307802 |
2 |
GCST90470542 |
no MR -> candidate analysis |
| Serum levels of protein FLT4 |
5e-33 |
rs34221241 |
1 |
GCST90087934 |
no MR -> candidate analysis |
| Secretoglobin family 3A member 1 levels |
1e-24 |
rs307802 |
1 |
GCST90249510 |
no MR -> candidate analysis |
| Vascular endothelial growth factor receptor 3 levels (FLT4.2 |
2e-19 |
rs34221241 |
1 |
GCST90243324 |
no MR -> candidate analysis |
| Vascular endothelial growth factor receptor 3 levels |
1e-17 |
rs34221241 |
2 |
GCST90161351 |
no MR -> candidate analysis |
| Hematological traits (multi-trait analysis) |
6e-16 |
rs10065018 |
1 |
GCST90838669 |
no MR -> candidate analysis |
| Platelet count |
3e-13 |
rs10065018 |
2 |
GCST90002357 |
MR: beta=-0.725, p=0.239 (trans) |
| Albumin levels |
6e-11 |
rs62407083 |
1 |
GCST90662901 |
no MR -> candidate analysis |
| …and 12 more traits (see JSON) |
|
|
|
|
|
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 980 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 1 |
0.951 |
— |
established (curated) |
no MR -> candidate analysis |
| congenital heart defects, multiple types, 7 |
0.891 |
— |
established (curated) |
no MR -> candidate analysis |
| Milroy disease |
0.852 |
— |
established (curated) |
no MR -> candidate analysis |
| capillary infantile hemangioma |
0.715 |
— |
established (curated) |
no MR -> candidate analysis |
| neoplasm |
0.195 |
— |
established (curated) |
MR: beta=-0.00107, p=0.00998 (trans) |
| colorectal cancer |
0.012 |
— |
established (curated) |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.834 |
— |
common-variant locus |
no MR -> candidate analysis |
| hereditary disease |
0.83 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 8 rows above, 7 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 (Vascular endothelial growth factor C) |
| gnomAD constraint |
pLI=1, LOEUF=0.249 — LoF-INTOLERANT |
| GWAS Catalog |
41 unique SNPs / 82 rows |
| ClinVar |
657 records; 8 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
2 clinical annotations across 1 drugs |
phenome — Top 30 of 980 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 ‘FLT4’ and resolved to ‘Vascular endothelial growth factor C’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 657 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 24 traits by best p-value, aggregated from 37 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/P35916 — 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/ENSG00000037280/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3714157/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/FLT4 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/FLT4 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=FLT4%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=FLT4 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/FLT4 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:41:54 · 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