CausalSentinel

Protein Dossier — EXOSC3 (Exosome complex component RRP40)

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
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.192 0.0607 0.00152 Wald ratio 1 trans NA
Forearm bone mineral density 0.192 0.064 0.00275 Wald ratio 1 trans NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus 0.168 0.0634 0.00808 Wald ratio 1 trans NA
Neuroticism 0.0391 0.015 0.00932 Wald ratio 1 trans NA
Diagnoses - main ICD10: M23 Internal derangement of knee 0.128 0.0502 0.0105 Wald ratio 1 trans NA
Hearing difficulty or problems: Yes 0.0358 0.0141 0.0111 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoarthritis 0.0639 0.0266 0.0162 Wald ratio 1 trans NA
Happiness 0.0246 0.0105 0.0192 Wald ratio 1 trans NA
Type 2 diabetes 0.259 0.113 0.0216 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hiatus hernia 0.11 0.0499 0.0268 Wald ratio 1 trans NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.106 0.0494 0.0326 Wald ratio 1 trans NA
Diagnoses - main ICD10: K35 Acute appendicitis -0.347 0.179 0.0523 Wald ratio 1 trans NA
…and 61 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

5 association rows across 5 traits (3 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
Height 2e-33 rs927631 1 GCST90245848 no MR -> candidate analysis
Reticulocyte count 2e-9 rs11330143 1 GCST90002405 no MR -> candidate analysis
Forced vital capacity (FVC) 2e-8 rs10973574 1 GCST90705071 no MR -> candidate analysis
Loneliness (linear analysis) 2e-6 rs78173384 1 GCST003772 no MR -> candidate analysis
Response to serotonin-norepinephrine reuptake inhibitors (re 9e-6 rs201857596 1 GCST012159 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 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
pontocerebellar hypoplasia type 1 0.872 established (curated) no MR -> candidate analysis
pontocerebellar hypoplasia 0.841 established (curated) no MR -> candidate analysis
Non-syndromic pontocerebellar hypoplasia 0.841 established (curated) no MR -> candidate analysis
hereditary disease 0.681 established (curated) no MR -> candidate analysis
microcephaly 0.559 established (curated) no MR -> candidate analysis
Hypotonia 0.559 established (curated) no MR -> candidate analysis
Abnormal cerebellum morphology 0.559 established (curated) no MR -> candidate analysis
Abnormality of the nervous system 0.559 established (curated) no MR -> candidate analysis
Paucity of anterior horn motor neurons 0.559 established (curated) no MR -> candidate analysis
Lissencephaly 0.559 established (curated) no MR -> candidate analysis
fetal akinesia deformation sequence 1 0.559 established (curated) no MR -> candidate analysis
congenital myopathy 0.559 established (curated) no MR -> candidate analysis
Severe intrauterine growth retardation 0.559 established (curated) no MR -> candidate analysis
Hypoplasia of the pons 0.559 established (curated) no MR -> candidate analysis

Of the 14 rows above, 14 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=3.4e-05, LOEUF=1.06 — LoF-tolerant
GWAS Catalog 21 unique SNPs / 39 rows
ClinVar 399 records; 7 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance