CausalSentinel

Protein Dossier — FAH (Fumarylacetoacetase)

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: R04 Haemorrhage from respiratory passages -0.18 0.0771 0.0199 Wald ratio 1 cis NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus -0.098 0.0449 0.0291 Wald ratio 1 cis NA
Diagnoses - main ICD10: R35 Polyuria -0.196 0.0906 0.0301 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.0855 0.04 0.0327 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.0741 0.0358 0.0383 Wald ratio 1 cis NA
Birth weight -0.0142 0.00717 0.0471 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease 0.104 0.0536 0.0531 Wald ratio 1 cis NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone -0.112 0.0584 0.0544 Wald ratio 1 cis NA
Eye problems or disorders: Cataract -0.0475 0.0265 0.0734 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema -0.0375 0.0213 0.0775 Wald ratio 1 cis NA
Non-cancer illness code self-reported: retinal detachment -0.167 0.0959 0.0811 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0372 0.0214 0.0824 Wald ratio 1 cis NA
…and 63 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

16 association rows across 13 traits (11 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
Fumarylacetoacetase levels 1e-373 rs11555096 3 GCST90247541 no MR -> candidate analysis
Serum levels of protein FAH 4e-246 rs11555096 1 GCST90086736 no MR -> candidate analysis
Fumarylacetoacetase levels (FAH.11424.4.3) 2e-121 rs11555096 1 GCST90241211 no MR -> candidate analysis
Blood protein levels 4e-75 rs11555096 1 GCST006585 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 1e-11 rs28561542 1 GCST90468087 no MR -> candidate analysis
Mean platelet volume 1e-10 rs28561542 1 GCST90002346 no MR -> candidate analysis
Protein quantitative trait loci (liver) 4e-9 rs868712158 2 GCST011427 no MR -> candidate analysis
Dimethylglycine levels 4e-9 rs2043692 1 GCST90105033 no MR -> candidate analysis
Height 7e-8 rs7164048 1 GCST90245848 no MR -> candidate analysis
Palmitoyl dihydrosphingomyelin (d18:0/16:0) levels in elite 2e-6 rs8043254 1 GCST90134044 no MR -> candidate analysis
Schizophrenia 2e-6 rs34140486 1 GCST90128471 MR: beta=-0.0161, p=0.417 (cis)
Ischemic stroke 6e-6 rs116120594 1 GCST90482715 no MR -> candidate analysis
…and 1 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 1300 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
tyrosinemia type I 0.964 established (curated) no MR -> candidate analysis
Tyrosinemia type 1 0.897 established (curated) no MR -> candidate analysis
tyrosinemia 0.699 established (curated) no MR -> candidate analysis
hereditary disease 0.772 established (curated) no MR -> candidate analysis
tyrosinemia type II 0.559 established (curated) no MR -> candidate analysis
T-substance anomaly 0.559 established (curated) no MR -> candidate analysis
beta-mannosidosis 0.438 established (curated) no MR -> candidate analysis
type 2 diabetes mellitus 0.251 common-variant locus no MR -> candidate analysis
hepatoblastoma 0.182 established (curated) no MR -> candidate analysis
amino acid metabolism disease 0.152 0.152 exploratory rare-variant signal no MR -> candidate analysis
personality disorder 0.152 0.152 exploratory rare-variant signal no MR -> candidate analysis

Of the 11 rows above, 11 have no MR estimate in this resource. Across all retrieved diseases for this gene: 2 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 (Fumarylacetoacetase)
gnomAD constraint pLI=4.7e-14, LOEUF=1.07 — LoF-tolerant
GWAS Catalog 30 unique SNPs / 60 rows
ClinVar 940 records; 15 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance