CausalSentinel

Protein Dossier — RNASE4 (Ribonuclease 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
Hirschsprung’s disease 1.56 0.324 1.40e-06 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0342 0.0108 0.00152 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.14 0.0461 0.00243 Wald ratio 1 cis NA
Haemoglobin concentration -0.0516 0.0178 0.00373 Wald ratio 1 cis NA
Juvenile idiopathic arthritis -0.389 0.139 0.00522 Wald ratio 1 cis NA
Height -0.0218 0.00846 0.00991 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertrophic cardiomyopathy (hcm or hocm) 0.658 0.256 0.0102 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression -0.0682 0.0289 0.0182 Wald ratio 1 cis NA
Diagnoses - main ICD10: M54 Dorsalgia 0.107 0.0457 0.0194 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.0591 0.0254 0.02 Wald ratio 1 cis NA
Nucleus accumbens volume 6.65 2.9 0.0217 Wald ratio 1 cis NA
Percent emphysema -0.0592 0.026 0.023 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

47 association rows across 18 traits (41 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 ANG levels 1e-1158 rs10220701 5 GCST90860430 no MR -> candidate analysis
ANG/F9 protein level ratio 6e-1118 rs17114671 1 GCST90313259 no MR -> candidate analysis
Angiogenin levels 3e-452 rs11851044 12 GCST90246501 no MR -> candidate analysis
RNASE4 protein levels 2e-247 rs143247343 5 GCST90470478 no MR -> candidate analysis
Serum levels of protein ANG 2e-86 rs36071889 3 GCST90088789 no MR -> candidate analysis
ANG protein levels 1e-69 rs552960263 5 GCST90468307 no MR -> candidate analysis
Ribonuclease 4 levels 8e-45 rs4470055 3 GCST90426424 no MR -> candidate analysis
Ribonuclease 4 levels (RNASE4.5644.60.3) 1e-36 rs184297073 2 GCST90242666 no MR -> candidate analysis
RNASE6 protein levels 4e-28 rs3748338 1 GCST90470479 no MR -> candidate analysis
Blood protein levels 1e-18 rs1888560 1 GCST006585 no MR -> candidate analysis
Protein quantitative trait loci 1e-17 rs34121942 1 GCST010900 no MR -> candidate analysis
Ribonuclease 4 level in Chronic kidney disease with hyperten 4e-15 rs944438 1 GCST90238008 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 107 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
amyotrophic lateral sclerosis 0.847 established (curated) no MR -> candidate analysis
schizophrenia 0.537 common-variant locus MR: beta=-0.0516, p=0.0677 (cis)
frontotemporal dementia 0.426 established (curated) no MR -> candidate analysis
hereditary disease 0.306 established (curated) no MR -> candidate analysis
frontotemporal dementia with motor neuron disease 0.195 established (curated) no MR -> candidate analysis

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 not available
GWAS Catalog 105 unique SNPs / 226 rows
ClinVar 172 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance