CausalSentinel

Protein Dossier — ITIH1 (Inter-alpha-trypsin inhibitor heavy chain H1)

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: K43 Ventral hernia	0.00141	0.000444	0.00153	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: K43 Ventral hernia	0.00141	0.000444	0.00153	Inverse variance weighted	2	trans	NA
Neo-neuroticism	-1.04	0.365	0.00425	Wald ratio	1	trans	NA
Subjective well being	0.0283	0.0106	0.00766	Wald ratio	1	trans	NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema	0.00347	0.0014	0.0134	Inverse variance weighted	2	trans	NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema	0.00347	0.0014	0.0134	Inverse variance weighted	2	trans	NA
Forearm bone mineral density	-0.102	0.0417	0.0146	Inverse variance weighted	2	trans	NA
Forearm bone mineral density	-0.102	0.0417	0.0146	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: R11 Nausea and vomiting	0.000998	0.000419	0.0173	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: R11 Nausea and vomiting	0.000998	0.000419	0.0173	Inverse variance weighted	2	trans	NA
Pulse rate	-0.0269	0.0115	0.0194	Inverse variance weighted	2	trans	NA
Pulse rate	-0.0269	0.0115	0.0194	Inverse variance weighted	2	trans	NA
…and 170 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

131 association rows across 92 traits (111 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
Single Ig IL-1-related receptor levels	3e-1748	rs1042779	1	GCST90249554	no MR -> candidate analysis
Inter-alpha-trypsin inhibitor heavy chain H1 levels	1e-865	rs2286798	1	GCST90247968	no MR -> candidate analysis
Janus kinase and microtubule-interacting protein 3 levels	2e-500	rs1042779	1	GCST90248145	no MR -> candidate analysis
Blood protein levels	3e-321	rs678	13	GCST006585	no MR -> candidate analysis
Single Ig IL-1-related receptor levels (SIGIRR.8326.63.3)	2e-312	rs1042779	1	GCST90242826	no MR -> candidate analysis
Janus kinase and microtubule-interacting protein 3 levels (J	3e-285	rs1042779	1	GCST90241663	no MR -> candidate analysis
Serum levels of protein ITIH1	4e-277	rs2286798	1	GCST90089947	no MR -> candidate analysis
Arylamine N-acetyltransferase 1 levels	6e-240	rs678	1	GCST90246590	no MR -> candidate analysis
Inter-alpha-trypsin inhibitor heavy chain H1 levels (ITIH1.7	2e-171	rs1042779	1	GCST90241535	no MR -> candidate analysis
ITIH1 protein levels	3e-80	rs678	1	GCST90469649	no MR -> candidate analysis
Ubiquitin-conjugating enzyme E2 Q1 level in Chronic kidney d	1e-73	rs1042779	1	GCST90235839	no MR -> candidate analysis
Serum levels of protein C15orf48	9e-48	rs678	1	GCST90089403	no MR -> candidate analysis
…and 80 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 150 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
osteoarthritis, hip	0.709	—	common-variant locus	no MR -> candidate analysis
schizophrenia	0.585	—	common-variant locus	MR: beta=0.0278, p=0.33 (trans)
major depressive disorder	0.571	—	common-variant locus	MR: beta=-0.0579, p=0.483 (trans)
bipolar disorder	0.543	—	common-variant locus	MR: beta=-0.000556, p=0.103 (trans)
osteoarthritis	0.499	—	common-variant locus	MR: beta=-0.0716, p=0.479 (trans)
autism spectrum disorder	0.48	—	common-variant locus	no MR -> candidate analysis
attention deficit-hyperactivity disorder	0.463	—	common-variant locus	no MR -> candidate analysis
total hip arthroplasty	0.446	—	common-variant locus	no MR -> candidate analysis
psychiatric disorder	0.341	—	common-variant locus	no MR -> candidate analysis
eye disorder	0.341	—	common-variant locus	no MR -> candidate analysis
nervous system disorder	0.341	—	common-variant locus	no MR -> candidate analysis
Abnormality of the skeletal system	0.303	—	common-variant locus	no MR -> candidate analysis
anxiety disorder	0.285	—	common-variant locus	no MR -> candidate analysis
osteoarthritis, knee	0.283	—	common-variant locus	MR: beta=-0.0716, p=0.479 (trans)
carpal tunnel syndrome	0.282	—	common-variant locus	no MR -> candidate analysis

Of the 15 rows above, 10 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=6.8e-29, LOEUF=1.07 — LoF-tolerant
GWAS Catalog	173 unique SNPs / 444 rows
ClinVar	191 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 150 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.
• chembl — No ChEMBL target for ‘ITIH1’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 191 ClinVar records for this gene; it is a sample, not a rate.
• pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).
• gwas_traits — Top 20 of 92 traits by best p-value, aggregated from 131 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.

Sources

• uniprot: https://www.uniprot.org/uniprotkb/P19827 — UniProt release 2026_02 (10-June-2026)
• mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000055957/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/ITIH1 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/ITIH1 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=ITIH1%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/ITIH1 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T03:18:43 · Tier: A
• Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
• MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
• Tool errors this run: none

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