CausalSentinel

Protein Dossier — MILR1 (Allergin-1)

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
Body mass index (BMI) 0.0268 0.0103 0.00934 Wald ratio 1 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.279 0.11 0.0112 Wald ratio 1 trans NA
Lung cancer -0.178 0.0733 0.0152 Wald ratio 1 trans NA
Diagnoses - main ICD10: J33 Nasal polyp 0.258 0.118 0.0281 Wald ratio 1 trans NA
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.61 0.736 0.0283 Wald ratio 1 trans NA
Diagnoses - main ICD10: K20 Oesophagitis 0.189 0.0869 0.0298 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bone disorder 0.342 0.161 0.0336 Wald ratio 1 trans NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.202 0.0962 0.0357 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.132 0.0653 0.0432 Wald ratio 1 trans NA
Weight 0.0179 0.0091 0.0493 Wald ratio 1 trans NA
Lung adenocarcinoma -0.211 0.111 0.0587 Wald ratio 1 trans NA
Fractured bone site(s): Wrist -0.161 0.0871 0.0652 Wald ratio 1 trans NA
…and 68 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

33 association rows across 31 traits (30 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 MILR1 levels 2e-754 rs138176943 1 GCST90860202 no MR -> candidate analysis
MILR1 protein levels 2e-56 rs536767372 1 GCST90469907 no MR -> candidate analysis
Cerebrospinal fluid protein MILR1 levels 3e-35 rs138176943 1 GCST90942449 no MR -> candidate analysis
Sex hormone-binding globulin levels adjusted for BMI and hee 4e-28 rs17650301 1 GCST90399398 no MR -> candidate analysis
Height 2e-27 rs113252144 1 GCST007841 no MR -> candidate analysis
Sex hormone-binding globulin levels and heel estimated bone 3e-26 rs17650301 1 GCST90399396 no MR -> candidate analysis
Mitochondrial DNA heteroplasmy (chrM:16183:A:AC case-only he 5e-25 rs17850455 1 GCST90268483 no MR -> candidate analysis
Standing height (UKB data field 50) 6e-25 rs113252144 1 GCST90468178 no MR -> candidate analysis
Heel bone mineral density 3e-23 rs17650301 3 GCST007066 no MR -> candidate analysis
Estimated bone mineral density 4e-22 rs17650301 1 GCST90726625 no MR -> candidate analysis
Height (baseline) 6e-22 rs113252144 1 GCST90565843 no MR -> candidate analysis
Age at menopause 6e-20 rs17650301 1 GCST007079 no MR -> candidate analysis
…and 19 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 163 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
progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 0.833 established (curated) no MR -> candidate analysis
mitochondrial dna depletion syndrome 16B (neuroophthalmic type) 0.699 established (curated) no MR -> candidate analysis
mitochondrial DNA depletion syndrome 16 (hepatic type) 0.534 established (curated) no MR -> candidate analysis
hereditary spastic paraplegia 0.278 established (curated) no MR -> candidate analysis
asthma 0.087 common-variant locus MR: beta=-0.0402, p=0.182 (trans)

Of the 5 rows above, 4 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=2.8e-15, LOEUF=2.26 — LoF-tolerant
GWAS Catalog 47 unique SNPs / 80 rows
ClinVar 586 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance