CausalSentinel

Protein Dossier — HAAO (3-hydroxyanthranilate 3,4-dioxygenase)

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
Eye problems or disorders: Glaucoma 0.0946 0.0264 3.38e-04 Wald ratio 1 trans NA
Squamous cell lung cancer -0.148 0.0423 4.65e-04 Wald ratio 1 trans NA
Eye problems or disorders: Injury or trauma resulting in loss of vision 0.135 0.0396 6.69e-04 Wald ratio 1 trans NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.148 0.0443 8.18e-04 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.00891 0.00284 0.00172 Wald ratio 1 trans NA
Packed cell volume -0.0978 0.0369 0.00814 Wald ratio 1 trans NA
Haemoglobin concentration -0.0322 0.0122 0.00848 Wald ratio 1 trans NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis -0.0926 0.036 0.01 Wald ratio 1 trans NA
Height 0.0126 0.0052 0.015 Wald ratio 1 trans NA
Percent emphysema -0.0319 0.0138 0.0205 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) 0.00688 0.003 0.0218 Wald ratio 1 trans NA
Serum creatinine (eGFRcrea) 0.00309 0.0014 0.0278 Wald ratio 1 trans NA
…and 87 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

10 association rows across 8 traits (7 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
Cerebrospinal fluid protein HAAO levels 4e-132 rs55802110 1 GCST90944346 no MR -> candidate analysis
Hypospadias 4e-34 rs3816183 1 GCST002563 no MR -> candidate analysis
Mean spheric corpuscular volume 2e-11 rs62143187 1 GCST90002397 no MR -> candidate analysis
Insomnia 1e-10 rs4953657 2 GCST90131901 no MR -> candidate analysis
Protein quantitative trait loci (liver) 3e-9 rs2278581 2 GCST011427 no MR -> candidate analysis
Educational attainment 8e-8 rs13016201 1 GCST90105038 no MR -> candidate analysis
Plasma anastrozole concentration in anastrozole-treated estr 1e-6 rs1065643 1 GCST007664 no MR -> candidate analysis
Cognitive resilience to Alzheimer’s disease pathology (combi 5e-6 rs2304661 1 GCST90239696 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 947 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
vertebral, cardiac, renal, and limb defects syndrome 1 0.808 established (curated) no MR -> candidate analysis
congenital vertebral-cardiac-renal anomalies syndrome 0.795 established (curated) no MR -> candidate analysis
hypertensive disorder 0.702 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.637 common-variant locus no MR -> candidate analysis
hypospadias 0.55 common-variant locus no MR -> candidate analysis
benign prostatic hyperplasia 0.559 common-variant locus no MR -> candidate analysis
Increased blood pressure 0.555 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.549 common-variant locus no MR -> candidate analysis
cerebral small vessel disease 0.475 common-variant locus no MR -> candidate analysis
bone fracture 0.458 common-variant locus no MR -> candidate analysis
prostate cancer 0.45 common-variant locus MR: beta=0.0665, p=0.0799 (trans)
essential hypertension 0.433 common-variant locus no MR -> candidate analysis
vein disorder 0.367 common-variant locus no MR -> candidate analysis
acute tonsillitis 0.367 common-variant locus no MR -> candidate analysis
placental abruption 0.354 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 (3-hydroxyanthranilate 3,4-dioxygenase)
gnomAD constraint pLI=4.4e-18, LOEUF=1.34 — LoF-tolerant
GWAS Catalog 41 unique SNPs / 82 rows
ClinVar 101 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance