CausalSentinel

Protein Dossier — MATN4 (Matrilin-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
Mean cell haemoglobin -0.181 0.057 0.00154 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.168 0.0574 0.00345 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.772 0.292 0.00829 Wald ratio 1 cis NA
Sodium in urine -0.0303 0.0119 0.0107 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0387 0.0156 0.0129 Wald ratio 1 cis NA
Eye problems or disorders: Cataract -0.2 0.0814 0.0142 Wald ratio 1 cis NA
Schizophrenia 0.127 0.0535 0.0172 Wald ratio 1 cis NA
Amygdala volume 27.4 11.6 0.0179 Wald ratio 1 cis NA
Eczema 0.191 0.084 0.0228 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.209 0.0929 0.0242 Wald ratio 1 cis NA
Depressive symptoms -0.0392 0.0174 0.0244 Wald ratio 1 cis NA
Mean platelet volume -0.0135 0.00609 0.0268 Wald ratio 1 cis NA
…and 104 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

13 association rows across 9 traits (11 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
WFDC12 protein levels 1e-61 rs77289229 4 GCST90471073 no MR -> candidate analysis
Matrilin-4 levels 4e-53 rs11086958 1 GCST90248424 no MR -> candidate analysis
Serum levels of protein MATN4 2e-38 rs2076023 1 GCST90089650 no MR -> candidate analysis
Blood protein levels 2e-23 rs11086957 2 GCST006585 no MR -> candidate analysis
Height 2e-19 rs2227275 1 GCST90245848 MR: beta=-0.0348, p=0.0353 (cis)
Matrilin-4 levels (MATN4.7083.74.3) 3e-16 rs11697677 1 GCST90241887 no MR -> candidate analysis
SDC4 protein levels 5e-14 rs117801728 1 GCST90470559 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 2e-9 rs56365005 1 GCST90838669 no MR -> candidate analysis
Parental longevity (mother’s age at death) 6e-6 rs371025208 1 GCST003393 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 53 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
holoprosencephaly 0.474 established (curated) no MR -> candidate analysis
Global developmental delay 0.426 established (curated) no MR -> candidate analysis
Meningomyelocele 0.426 established (curated) no MR -> candidate analysis
Proptosis 0.426 established (curated) no MR -> candidate analysis
Seizure 0.426 established (curated) no MR -> candidate analysis
diabetes insipidus 0.426 established (curated) no MR -> candidate analysis
microcephaly 0.426 established (curated) no MR -> candidate analysis
Oligomenorrhea 0.152 0.152 exploratory rare-variant signal no MR -> candidate analysis

Of the 8 rows above, 8 have no MR estimate in this resource. Across all retrieved diseases for this gene: 1 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=1.7e-10, LOEUF=0.953 — LoF-tolerant
GWAS Catalog 62 unique SNPs / 123 rows
ClinVar 134 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance