Protein Dossier — GFRA1 (GDNF family receptor alpha-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: uterine fibroids |
0.162 |
0.0687 |
0.0183 |
Wald ratio |
1 |
cis |
NA |
| Urinary albumin-to-creatinine ratio |
0.0529 |
0.025 |
0.0339 |
Wald ratio |
1 |
cis |
NA |
| Body fat |
0.0473 |
0.0223 |
0.0341 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M23 Internal derangement of knee |
-0.169 |
0.0798 |
0.0347 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R55 Syncope and collapse |
-0.295 |
0.145 |
0.0423 |
Wald ratio |
1 |
cis |
NA |
| Primary sclerosing cholangitis |
0.252 |
0.125 |
0.0432 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: asthma |
-0.0595 |
0.0296 |
0.0443 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis |
-0.314 |
0.164 |
0.0546 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R35 Polyuria |
0.239 |
0.128 |
0.0616 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
0.0304 |
0.0165 |
0.0648 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: iron deficiency anaemia |
-0.378 |
0.21 |
0.0719 |
Wald ratio |
1 |
cis |
NA |
| Lung adenocarcinoma |
0.214 |
0.12 |
0.075 |
Wald ratio |
1 |
cis |
NA |
| …and 77 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3314_74_2 |
GFRa-1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
66 association rows across 36 traits (49 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 |
| GFRA1 protein levels |
9e-269 |
rs11197603 |
7 |
GCST90469328 |
no MR -> candidate analysis |
| CLMP/GFRA1 protein level ratio |
3e-236 |
rs2420255 |
1 |
GCST90314133 |
no MR -> candidate analysis |
| Circulating GFRA1 levels |
5e-219 |
rs2420255 |
6 |
GCST90859697 |
no MR -> candidate analysis |
| GFRA1/TNFRSF1A protein level ratio |
3e-218 |
rs2420255 |
1 |
GCST90314924 |
no MR -> candidate analysis |
| GDNF family receptor alpha-1 levels |
2e-59 |
rs1079261 |
7 |
GCST90247719 |
no MR -> candidate analysis |
| Serum levels of protein GFRA1 |
4e-39 |
rs4269847 |
1 |
GCST90088308 |
no MR -> candidate analysis |
| Height |
4e-29 |
rs2694767 |
4 |
GCST90245848 |
no MR -> candidate analysis |
| PNLIPRP2 protein levels |
4e-29 |
rs75834919 |
8 |
GCST90470274 |
no MR -> candidate analysis |
| Blood protein levels |
8e-23 |
rs4269847 |
1 |
GCST006585 |
no MR -> candidate analysis |
| GDNF family receptor alpha-1 levels (GFRA1.3314.74.2) |
2e-22 |
rs10885877 |
1 |
GCST90241246 |
no MR -> candidate analysis |
| IGF 1 (UKB data field 30770) |
2e-16 |
rs3858325 |
1 |
GCST90468078 |
no MR -> candidate analysis |
| PNLIPRP1 protein levels |
6e-16 |
rs140237349 |
1 |
GCST90470273 |
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 346 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 |
| renal hypodysplasia/aplasia 4 |
0.752 |
— |
established (curated) |
no MR -> candidate analysis |
| bilateral renal agenesis |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| smoking initiation |
0.574 |
— |
common-variant locus |
no MR -> candidate analysis |
| bone Paget disease |
0.517 |
— |
common-variant locus |
no MR -> candidate analysis |
| bile duct disorder |
0.461 |
— |
common-variant locus |
no MR -> candidate analysis |
| contracture |
0.461 |
— |
common-variant locus |
no MR -> candidate analysis |
| stroke disorder |
0.431 |
— |
common-variant locus |
no MR -> candidate analysis |
| ulcerative colitis |
0.431 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormal erythrocyte morphology |
0.431 |
— |
common-variant locus |
no MR -> candidate analysis |
| alcohol drinking |
0.431 |
— |
common-variant locus |
no MR -> candidate analysis |
| Hirschsprung disease |
0.182 |
— |
established (curated) |
no MR -> candidate analysis |
| ovarian neoplasm |
0.427 |
— |
common-variant locus |
no MR -> candidate analysis |
| thrombophilia |
0.423 |
— |
common-variant locus |
no MR -> candidate analysis |
| myasthenia gravis |
0.423 |
— |
common-variant locus |
no MR -> candidate analysis |
| ovarian dysfunction |
0.423 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 15 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 (GDNF family receptor alpha-1) |
| gnomAD constraint |
pLI=1, LOEUF=0.471 — LoF-INTOLERANT |
| GWAS Catalog |
66 unique SNPs / 128 rows |
| ClinVar |
116 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 346 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 ‘GFRA1’ and resolved to ‘GDNF family receptor alpha-1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 116 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 66 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/P56159 — 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/ENSG00000151892/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3833481/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/GFRA1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/GFRA1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=GFRA1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/GFRA1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:47:59 · 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