CausalSentinel

Protein Dossier — GFRAL (GDNF family receptor alpha-like)

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
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.832 0.265 0.00167 Wald ratio 1 cis NA
Diagnoses - main ICD10: M54 Dorsalgia 0.25 0.082 0.00229 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.181 0.0726 0.0124 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.165 0.0701 0.0183 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0409 0.0174 0.019 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract 0.26 0.12 0.0307 Wald ratio 1 cis NA
Potassium in urine -0.0276 0.0137 0.043 Wald ratio 1 cis NA
Lung cancer -0.183 0.0932 0.0498 Wald ratio 1 cis NA
Fracture resulting from simple fall 0.0624 0.0332 0.0601 Wald ratio 1 cis NA
Non-cancer illness code self-reported: iron deficiency anaemia 0.269 0.145 0.063 Wald ratio 1 cis NA
Myocardial infarction 0.097 0.0552 0.0789 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0377 0.0224 0.0918 Wald ratio 1 cis NA
…and 48 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

44 association rows across 24 traits (38 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
GFRAL protein levels 2e-311 rs10948914 7 GCST90469331 no MR -> candidate analysis
GDNF family receptor alpha-like levels 5e-74 rs60761034 3 GCST90247722 no MR -> candidate analysis
Heel bone mineral density 2e-26 rs1502199 6 GCST006979 MR: beta=-0.0409, p=0.019 (cis)
Body size at age 10 2e-23 rs12110721 1 GCST010989 no MR -> candidate analysis
Estimated bone mineral density 1e-19 rs1502199 1 GCST90726625 no MR -> candidate analysis
Serum levels of protein GFRAL 1e-18 rs3846917 1 GCST90089569 no MR -> candidate analysis
Childhood body mass index 4e-18 rs12110721 2 GCST90301649 no MR -> candidate analysis
Morning person 8e-16 rs13203948 1 GCST007565 no MR -> candidate analysis
Morningness 2e-15 rs9396083 1 GCST007983 no MR -> candidate analysis
Blood protein levels 2e-14 rs1032772 1 GCST006585 no MR -> candidate analysis
Blood urea nitrogen levels 2e-12 rs143297173 1 GCST005986 no MR -> candidate analysis
Body mass index 4e-11 rs9370410 6 GCST90446645 MR: beta=-0.00972, p=0.47 (cis)
…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 137 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
Abnormality of the skeletal system 0.653 common-variant locus no MR -> candidate analysis
gout 0.516 common-variant locus MR: beta=0.0769, p=0.467 (cis)
skull disorder 0.482 common-variant locus no MR -> candidate analysis
preeclampsia 0.474 common-variant locus no MR -> candidate analysis
placental retention 0.436 common-variant locus no MR -> candidate analysis
placental abruption 0.435 common-variant locus no MR -> candidate analysis
frozen shoulder 0.434 common-variant locus no MR -> candidate analysis
polycystic ovary syndrome 0.424 common-variant locus no MR -> candidate analysis
aneurysm 0.099 common-variant locus no MR -> candidate analysis
circadian rhythm 0.094 common-variant locus no MR -> candidate analysis
hyperuricemia 0.076 common-variant locus no MR -> candidate analysis
dislocation 0.071 common-variant locus no MR -> candidate analysis
vesicoureteral reflux 0.07 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.067 common-variant locus no MR -> candidate analysis
muscular atrophy 0.067 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-like)
gnomAD constraint pLI=2.1e-10, LOEUF=1.05 — LoF-tolerant
GWAS Catalog 98 unique SNPs / 175 rows
ClinVar 83 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance