CausalSentinel

Protein Dossier — ITIH5 (Inter-alpha-trypsin inhibitor heavy chain H5)

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: L03 Cellulitis 0.229 0.0776 0.00321 Wald ratio 1 cis NA
Rheumatoid arthritis 0.159 0.0581 0.00611 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.173 0.0695 0.0128 Wald ratio 1 cis NA
Alcohol intake frequency -0.0319 0.0129 0.0132 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.227 0.095 0.0171 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina 0.101 0.0442 0.0217 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.142 0.0631 0.025 Wald ratio 1 cis NA
Myocardial infarction -0.0821 0.0368 0.0258 Wald ratio 1 cis NA
Amygdala volume 17 8.35 0.0415 Wald ratio 1 cis NA
Neuroticism 0.0248 0.0124 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.211 0.106 0.046 Wald ratio 1 cis NA
Happiness 0.0207 0.0108 0.055 Wald ratio 1 cis NA
…and 52 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

51 association rows across 37 traits (46 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
Cytohesin-4 levels 4e-395 rs41298373 1 GCST90421923 no MR -> candidate analysis
Bone mineral density mean 2e-238 rs61836574 1 GCST90321120 no MR -> candidate analysis
ER degradation-enhancing alpha-mannosidase-like 2 levels 2e-212 rs41298373 1 GCST90424081 no MR -> candidate analysis
Blood protein levels 1e-142 rs73621225 5 GCST006585 no MR -> candidate analysis
Inter-alpha-trypsin inhibitor heavy chain H5 levels 1e-81 rs6602258 6 GCST90247972 no MR -> candidate analysis
Vertex-wise sulcal depth 3e-64 rs41298373 1 GCST90095129 no MR -> candidate analysis
ITIH5 protein levels 1e-50 rs41298373 1 GCST90469652 no MR -> candidate analysis
Brain morphology (MOSTest) 1e-42 rs41298373 2 GCST90239729 no MR -> candidate analysis
Left–right brain asymmetry 5e-38 rs41298373 1 GCST90010427 no MR -> candidate analysis
Vertex-wise cortical surface area 1e-30 rs41298373 1 GCST90095130 no MR -> candidate analysis
Cortical surface area (MOSTest) 5e-30 rs41298373 1 GCST010701 no MR -> candidate analysis
Inter-alpha-trypsin inhibitor heavy chain H5 levels (ITIH5.8 2e-29 rs7909223 4 GCST90241536 no MR -> candidate analysis
…and 25 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 291 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
macular holes 0.588 common-variant locus no MR -> candidate analysis
tympanic membrane perforation 0.473 common-variant locus no MR -> candidate analysis
Hypernatremia 0.468 common-variant locus no MR -> candidate analysis
Genetic renal or urinary tract malformation 0.431 common-variant locus no MR -> candidate analysis
Abnormal pupillary function 0.419 common-variant locus no MR -> candidate analysis
pneumonitis 0.416 common-variant locus no MR -> candidate analysis
stricture 0.416 common-variant locus no MR -> candidate analysis
Cachexia 0.397 common-variant locus no MR -> candidate analysis
intracranial hemorrhage 0.396 common-variant locus no MR -> candidate analysis
poisoning 0.088 common-variant locus no MR -> candidate analysis
response to antibiotic 0.088 common-variant locus no MR -> candidate analysis
allergic rhinitis 0.081 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=6e-19, LOEUF=1.03 — LoF-tolerant
GWAS Catalog 66 unique SNPs / 132 rows
ClinVar 225 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance