Protein Dossier — GFRA2 (GDNF family receptor alpha-2)
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 |
| Hearing difficulty or problems: Yes |
0.0528 |
0.0134 |
7.81e-05 |
Wald ratio |
1 |
cis |
NA |
| Potassium in urine |
0.0269 |
0.00829 |
0.0012 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypopituitarism |
0.691 |
0.238 |
0.00362 |
Wald ratio |
1 |
cis |
NA |
| Low grade serous ovarian cancer |
-0.463 |
0.173 |
0.00738 |
Wald ratio |
1 |
cis |
NA |
| Subjective well being |
-0.0271 |
0.0102 |
0.00766 |
Wald ratio |
1 |
cis |
NA |
| Fasting insulin |
0.0315 |
0.0118 |
0.00788 |
Wald ratio |
1 |
cis |
NA |
| Schizophrenia |
0.0931 |
0.0369 |
0.0116 |
Wald ratio |
1 |
cis |
NA |
| Hippocampus volume |
-40.6 |
16.1 |
0.0117 |
Wald ratio |
1 |
cis |
NA |
| Nucleus accumbens volume |
-8.85 |
3.79 |
0.0196 |
Wald ratio |
1 |
cis |
NA |
| Eczema |
-0.131 |
0.0573 |
0.0224 |
Wald ratio |
1 |
cis |
NA |
| Caudate volume |
-36.8 |
16.8 |
0.0283 |
Wald ratio |
1 |
cis |
NA |
| HOMA-IR |
0.0339 |
0.0159 |
0.0334 |
Wald ratio |
1 |
cis |
NA |
| …and 95 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2515_14_3 |
GFRa-2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
101 association rows across 60 traits (68 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 GFRA2 levels |
7e-447 |
rs2410696 |
10 |
GCST90860506 |
no MR -> candidate analysis |
| GDNF family receptor alpha-2 levels |
2e-141 |
rs15881 |
10 |
GCST90247720 |
no MR -> candidate analysis |
| GFRA2 protein levels |
2e-79 |
rs9644130 |
13 |
GCST90469329 |
no MR -> candidate analysis |
| Serum levels of protein GFRA2 |
2e-63 |
rs15881 |
3 |
GCST90087954 |
no MR -> candidate analysis |
| Blood protein levels |
5e-39 |
rs15881 |
1 |
GCST006585 |
no MR -> candidate analysis |
| GDNF family receptor alpha-2 levels (GFRA2.2515.14.3) |
4e-33 |
rs15881 |
3 |
GCST90241247 |
no MR -> candidate analysis |
| Monocyte percentage (UKB data field 30190) |
2e-18 |
rs1075417 |
1 |
GCST90468091 |
no MR -> candidate analysis |
| Monocyte count |
3e-18 |
rs12543924 |
4 |
GCST90002340 |
no MR -> candidate analysis |
| Lymphocyte count |
7e-17 |
rs533703709 |
1 |
GCST90002320 |
no MR -> candidate analysis |
| Monocyte count (UKB data field 30130) |
1e-14 |
rs7461577 |
1 |
GCST90468090 |
no MR -> candidate analysis |
| Monocyte percentage of white cells |
2e-13 |
rs1075417 |
1 |
GCST90002394 |
no MR -> candidate analysis |
| Bone mineral density mean |
3e-13 |
rs118062820 |
1 |
GCST90321120 |
no MR -> candidate analysis |
| …and 48 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 710 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 |
| poisoning |
0.535 |
— |
common-variant locus |
no MR -> candidate analysis |
| esophageal ulcer |
0.474 |
— |
common-variant locus |
no MR -> candidate analysis |
| temporomandibular joint disorder |
0.473 |
— |
common-variant locus |
no MR -> candidate analysis |
| device complication |
0.467 |
— |
common-variant locus |
no MR -> candidate analysis |
| injury |
0.439 |
— |
common-variant locus |
MR: beta=0.169, p=0.345 (cis) |
| alcohol drinking |
0.436 |
— |
common-variant locus |
no MR -> candidate analysis |
| vitiligo |
0.403 |
— |
common-variant locus |
no MR -> candidate analysis |
| stroke disorder |
0.363 |
— |
common-variant locus |
no MR -> candidate analysis |
| response to selective serotonin reuptake inhibitor |
0.363 |
— |
common-variant locus |
no MR -> candidate analysis |
| oral cavity neoplasm |
0.363 |
— |
common-variant locus |
no MR -> candidate analysis |
| Shock |
0.355 |
— |
common-variant locus |
no MR -> candidate analysis |
| crush injury |
0.355 |
— |
common-variant locus |
no MR -> candidate analysis |
| ankylosing spondylitis |
0.355 |
— |
common-variant locus |
no MR -> candidate analysis |
| Hodgkins lymphoma |
0.312 |
— |
common-variant locus |
no MR -> candidate analysis |
| tooth disorder |
0.239 |
— |
common-variant locus |
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 |
0 known modulators (GDNF family receptor alpha-2) |
| gnomAD constraint |
pLI=0.93, LOEUF=0.528 — LoF-INTOLERANT |
| GWAS Catalog |
95 unique SNPs / 161 rows |
| ClinVar |
163 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 710 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 ‘GFRA2’ and resolved to ‘GDNF family receptor alpha-2’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 163 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 60 traits by best p-value, aggregated from 101 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/O00451 — 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/ENSG00000168546/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL6066244/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/GFRA2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/GFRA2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=GFRA2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/GFRA2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:48:14 · 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