CausalSentinel

Protein Dossier — IGDCC4 (Immunoglobulin superfamily DCC subclass member 4)

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: R55 Syncope and collapse 0.347 0.0951 2.62e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.4 0.129 0.00193 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate 0.252 0.0842 0.00278 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma 0.287 0.0996 0.00397 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.2 0.0722 0.00562 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0554 0.0229 0.0157 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.0286 0.012 0.0173 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.105 0.0466 0.0243 Wald ratio 1 cis NA
Potassium in urine 0.0283 0.0128 0.0265 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis 0.187 0.0843 0.0266 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.227 0.118 0.0551 Wald ratio 1 cis NA
Diagnoses - main ICD10: L03 Cellulitis 0.216 0.114 0.0596 Wald ratio 1 cis NA
…and 76 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

27 association rows across 18 traits (24 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
IGDCC4 protein levels 2e-270 rs12441796 4 GCST90469523 no MR -> candidate analysis
Immunoglobulin superfamily DCC subclass member 4 levels 3e-119 rs35223184 2 GCST90248005 no MR -> candidate analysis
Mean corpuscular volume 4e-101 rs113968785 2 GCST90056174 no MR -> candidate analysis
Mean corpuscular hemoglobin 2e-49 rs113968785 2 GCST90002390 no MR -> candidate analysis
Red blood cell count 2e-44 rs113968785 2 GCST90002403 no MR -> candidate analysis
Serum levels of protein IGDCC4 6e-36 rs143814405 1 GCST90090826 no MR -> candidate analysis
Immunoglobulin superfamily DCC subclass member 4 levels (IGD 4e-27 rs35223184 1 GCST90241477 no MR -> candidate analysis
Estimated bone mineral density 1e-26 rs35558920 1 GCST90726625 no MR -> candidate analysis
Heel bone mineral density 3e-25 rs28665840 1 GCST006979 MR: beta=-0.0167, p=0.303 (cis)
Glycated haemoglobin HbA1c levels (UKB data field 30750) 1e-22 rs1550026 1 GCST90468072 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 1e-22 rs686134 1 GCST90838663 no MR -> candidate analysis
Height (baseline) 1e-16 rs12904090 1 GCST90565843 no MR -> candidate analysis
…and 6 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 72 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
Abnormality of the skeletal system 0.839 common-variant locus no MR -> candidate analysis
intelligence 0.606 common-variant locus no MR -> candidate analysis
scleritis 0.463 common-variant locus no MR -> candidate analysis
crush injury 0.4 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.31 common-variant locus no MR -> candidate analysis
autism spectrum disorder 0.31 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.19 common-variant locus no MR -> candidate analysis
hypothyroidism 0.096 common-variant locus MR: beta=-0.0983, p=0.112 (cis)
response to xenobiotic stimulus 0.063 common-variant locus no MR -> candidate analysis
acquired polycythemia vera 0.045 common-variant locus no MR -> candidate analysis
schizophrenia 0.032 common-variant locus MR: beta=-0.0462, p=0.447 (cis)
mathematical ability 0.032 common-variant locus no MR -> candidate analysis

Of the 12 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=4.1e-14, LOEUF=0.751 — LoF-tolerant
GWAS Catalog 50 unique SNPs / 100 rows
ClinVar 260 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance