Protein Dossier — RET (Proto-oncogene tyrosine-protein kinase receptor Ret)
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 |
| Hirschsprung’s disease |
-1.83 |
0.513 |
3.69e-04 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: small intestine or small bowel cancer |
0.749 |
0.259 |
0.00378 |
Wald ratio |
1 |
cis |
NA |
| Alzheimer’s disease |
0.193 |
0.0723 |
0.0077 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: D25 Leiomyoma of uterus |
0.204 |
0.0775 |
0.00848 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K57 Diverticular disease of intestine |
0.158 |
0.0646 |
0.0144 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Diabetes related eye disease |
0.246 |
0.109 |
0.0242 |
Wald ratio |
1 |
cis |
NA |
| Depressive symptoms |
-0.0325 |
0.0145 |
0.0244 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: prostate cancer |
0.224 |
0.101 |
0.0268 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hiatus hernia |
0.133 |
0.0617 |
0.0306 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K43 Ventral hernia |
0.266 |
0.125 |
0.0342 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I48 Atrial fibrillation and flutter |
-0.276 |
0.137 |
0.0433 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] |
0.148 |
0.0774 |
0.055 |
Wald ratio |
1 |
cis |
NA |
| …and 56 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3220_40_2 |
RET |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
34 association rows across 19 traits (28 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 RET levels |
8e-469 |
rs2435366 |
1 |
GCST90860059 |
no MR -> candidate analysis |
| Proto-oncogene tyrosine-protein kinase receptor Ret levels |
2e-145 |
rs10900296 |
5 |
GCST90249073 |
no MR -> candidate analysis |
| Hirschsprung disease |
2e-101 |
rs2505994 |
8 |
GCST005289 |
no MR -> candidate analysis |
| Serum levels of protein RET |
5e-89 |
rs1800858 |
1 |
GCST90088279 |
no MR -> candidate analysis |
| RET protein levels |
1e-59 |
rs3026734 |
4 |
GCST90470458 |
no MR -> candidate analysis |
| Blood protein levels |
4e-56 |
rs2505535 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Body mass index |
1e-13 |
rs2472738 |
1 |
GCST90662912 |
MR: beta=0.0107, p=0.317 (cis) |
| Cerebellar grey matter morphology (MOSTest) |
4e-12 |
rs10900298 |
1 |
GCST90728589 |
no MR -> candidate analysis |
| Anomalies of pupillary function (PheCode 379.4) |
2e-11 |
rs192917207 |
1 |
GCST90480099 |
no MR -> candidate analysis |
| Height |
3e-9 |
rs715106 |
1 |
GCST90245848 |
no MR -> candidate analysis |
| Gut microbial network clusters (Pink (at 1 year) x Any Breas |
1e-8 |
rs2163189 |
1 |
GCST90569458 |
no MR -> candidate analysis |
| Weight |
2e-8 |
rs1864401 |
1 |
GCST90018729 |
MR: beta=0.0213, p=0.19 (cis) |
| …and 7 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 1945 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 |
| medullary thyroid gland carcinoma |
0.935 |
— |
established (curated) |
no MR -> candidate analysis |
| multiple endocrine neoplasia type 2A |
0.944 |
— |
established (curated) |
no MR -> candidate analysis |
| multiple endocrine neoplasia type 2B |
0.887 |
— |
established (curated) |
no MR -> candidate analysis |
| Hirschsprung disease |
0.844 |
— |
established (curated) |
no MR -> candidate analysis |
| pheochromocytoma |
0.927 |
— |
established (curated) |
no MR -> candidate analysis |
| multiple endocrine neoplasia type 2 |
0.909 |
— |
established (curated) |
no MR -> candidate analysis |
| familial medullary thyroid carcinoma |
0.871 |
— |
established (curated) |
no MR -> candidate analysis |
| hepatocellular carcinoma |
0.426 |
— |
established (curated) |
no MR -> candidate analysis |
| multiple endocrine neoplasia |
0.682 |
— |
established (curated) |
no MR -> candidate analysis |
| colorectal cancer |
0.547 |
— |
established (curated) |
no MR -> candidate analysis |
| renal agenesis |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| renal hypodysplasia/aplasia 1 |
0.683 |
— |
established (curated) |
no MR -> candidate analysis |
| Ondine syndrome |
0.789 |
— |
established (curated) |
no MR -> candidate analysis |
| neoplasm |
0.277 |
— |
established (curated) |
MR: beta=0.11, p=0.162 (cis) |
| Inherited cancer-predisposing syndrome |
0.943 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 15 rows above, 14 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 |
15 known modulators (Proto-oncogene tyrosine-protein kinase receptor Ret) |
| gnomAD constraint |
pLI=1, LOEUF=0.236 — LoF-INTOLERANT |
| GWAS Catalog |
45 unique SNPs / 90 rows |
| ClinVar |
4466 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1945 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 ‘RET’ and resolved to ‘Proto-oncogene tyrosine-protein kinase receptor Ret’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 4466 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 19 of 19 traits by best p-value, aggregated from 34 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/P07949 — 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/ENSG00000165731/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2041/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/RET — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/RET — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=RET%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/RET — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:48:00 · 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