CausalSentinel

Protein Dossier — AFP (Alpha-fetoprotein)

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: B37 Candidiasis 1.07 0.272 8.11e-05 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia 0.28 0.0933 0.00272 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0583 0.0197 0.00316 Wald ratio 1 cis NA
Systemic lupus erythematosus 0.896 0.304 0.00322 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.401 0.142 0.00468 Wald ratio 1 cis NA
Transferrin -0.181 0.0658 0.00585 Wald ratio 1 cis NA
LDL cholesterol 0.0834 0.0337 0.0133 Wald ratio 1 cis NA
Bulimia nervosa -0.118 0.0535 0.0278 Wald ratio 1 cis NA
Endometrioid ovarian cancer 0.393 0.182 0.0306 Wald ratio 1 cis NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation 0.181 0.0894 0.0426 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0501 0.025 0.0454 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pneumothorax 0.778 0.415 0.0607 Wald ratio 1 cis NA
…and 102 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

23 association rows across 14 traits (22 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
AFP levels 1e-237 rs10031441 1 GCST90239635 no MR -> candidate analysis
AFP protein levels 6e-233 rs16849384 2 GCST90468250 no MR -> candidate analysis
alpha-Fetoprotein levels 7e-198 rs16849384 3 GCST90278615 no MR -> candidate analysis
CXCL1 protein levels 9e-52 rs13131508 2 GCST90468930 no MR -> candidate analysis
Afamin levels 8e-48 rs66841185 2 GCST90137699 no MR -> candidate analysis
Albumin levels 7e-35 rs72647032 4 GCST90501097 no MR -> candidate analysis
N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase levels 3e-29 rs72647033 1 GCST90248566 no MR -> candidate analysis
Height 1e-23 rs10020432 2 GCST90245848 MR: beta=0.0187, p=0.331 (cis)
Serum levels of protein AFM 4e-20 rs72853185 1 GCST90088767 no MR -> candidate analysis
Tumor biomarkers 3e-18 rs12506899 1 GCST001808 no MR -> candidate analysis
Insulin-like growth factor-binding protein 7 levels 1e-15 rs1289184022 1 GCST90179322 no MR -> candidate analysis
CXCL6 protein levels 4e-12 rs188410248 1 GCST90468933 no MR -> candidate analysis
…and 2 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 1575 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
Congenital deficiency in alpha-fetoprotein 0.67 established (curated) no MR -> candidate analysis
Hereditary persistence of alpha-fetoprotein 0.572 established (curated) no MR -> candidate analysis
primary ovarian failure 0.438 established (curated) no MR -> candidate analysis
escherichia coli infection 0.401 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 4 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 (Alpha-fetoprotein)
gnomAD constraint pLI=4.8e-18, LOEUF=0.998 — LoF-tolerant
GWAS Catalog 53 unique SNPs / 105 rows
ClinVar 132 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance