CausalSentinel

Protein Dossier — ITIH2 (Inter-alpha-trypsin inhibitor heavy chain H2)

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
Non-cancer illness code self-reported: hypertension -0.0188 0.00747 0.0116 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.127 0.057 0.0261 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.0712 0.0335 0.0334 Wald ratio 1 cis NA
Cough on most days 0.0431 0.0211 0.0405 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis -0.0741 0.0372 0.0464 Wald ratio 1 cis NA
Sodium in urine -0.00802 0.00423 0.0578 Wald ratio 1 cis NA
Pulse rate -0.0144 0.00761 0.0593 Wald ratio 1 cis NA
Forearm bone mineral density -0.0507 0.0275 0.0654 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.0616 0.0337 0.0675 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.00803 0.0044 0.0681 Wald ratio 1 cis NA
Lung cancer -0.0501 0.0276 0.0697 Wald ratio 1 cis NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone -0.096 0.0536 0.0732 Wald ratio 1 cis NA
…and 83 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

73 association rows across 54 traits (69 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 PTX3 levels 9e-562 rs10795566 2 GCST90859797 no MR -> candidate analysis
Inter-alpha-trypsin inhibitor heavy chain H2 levels 6e-490 rs4463754 4 GCST90247969 no MR -> candidate analysis
Serum levels of protein ITIH2 2e-272 rs73621240 1 GCST90090631 no MR -> candidate analysis
Pentraxin-related protein PTX3 levels 1e-239 rs35524242 1 GCST90012037 no MR -> candidate analysis
ERP44 protein levels 3e-211 rs3802589 4 GCST90469150 no MR -> candidate analysis
Blood protein levels 1e-142 rs73621225 4 GCST006585 no MR -> candidate analysis
NAD-dependent protein deacetylase sirtuin-2 levels 3e-119 rs41290289 2 GCST90248584 no MR -> candidate analysis
Serum levels of protein SIRT2 2e-84 rs6602268 2 GCST90088884 no MR -> candidate analysis
Inter-alpha-trypsin inhibitor heavy chain H1 levels 4e-68 rs73621263 1 GCST90247968 no MR -> candidate analysis
Osteopontin levels 3e-67 rs7913729 1 GCST90248798 no MR -> candidate analysis
Angiogenic factor with G patch and FHA domains 1 levels 9e-62 rs41290289 1 GCST90246457 no MR -> candidate analysis
Carbonic anhydrase 4 levels 6e-60 rs41290289 2 GCST90246864 no MR -> candidate analysis
…and 42 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 133 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
acute tonsillitis 0.563 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.431 common-variant locus no MR -> candidate analysis
metabolic dysfunction-associated steatotic liver disease 0.431 common-variant locus no MR -> candidate analysis
adverse effect 0.421 common-variant locus no MR -> candidate analysis
diaphragm disorder 0.419 common-variant locus no MR -> candidate analysis
response to antibiotic 0.08 common-variant locus no MR -> candidate analysis
poisoning 0.08 common-variant locus no MR -> candidate analysis
intracranial hemorrhage 0.079 common-variant locus no MR -> candidate analysis
Abnormal pupillary function 0.078 common-variant locus no MR -> candidate analysis
Cachexia 0.056 common-variant locus no MR -> candidate analysis
allergic asthma 0.039 common-variant locus no MR -> candidate analysis
tympanic membrane perforation 0.031 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 12 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 (Inter-alpha-trypsin inhibitor heavy chain H2)
gnomAD constraint pLI=6.1e-35, LOEUF=1.16 — LoF-tolerant
GWAS Catalog 71 unique SNPs / 141 rows
ClinVar 191 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance