CausalSentinel

Protein Dossier — MUL1 (Mitochondrial ubiquitin ligase activator of NFKB 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
Glioma 0.581 0.167 5.03e-04 Wald ratio 1 trans NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus -0.277 0.106 0.00911 Wald ratio 1 trans NA
Endometrioid ovarian cancer -0.25 0.105 0.0176 Wald ratio 1 trans NA
Non-cancer illness code self-reported: uterine fibroids -0.18 0.0879 0.0401 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bladder problem (not cancer) -0.338 0.172 0.0486 Wald ratio 1 trans NA
Serum cystatin C (eGFRcys) 0.0143 0.00736 0.052 Wald ratio 1 trans NA
Iron -0.0729 0.0378 0.0539 Wald ratio 1 trans NA
Non-cancer illness code self-reported: sleep apnoea 0.242 0.13 0.0628 Wald ratio 1 trans NA
Microalbuminuria -0.153 0.0862 0.075 Wald ratio 1 trans NA
Non-cancer illness code self-reported: depression -0.0698 0.0398 0.0799 Wald ratio 1 trans NA
Neo-openness to experience 0.481 0.282 0.0882 Wald ratio 1 trans NA
Cancer code self-reported: prostate cancer -0.23 0.136 0.0901 Wald ratio 1 trans NA
…and 89 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

7 association rows across 6 traits (7 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
CDA protein levels 6e-18 rs114564927 2 GCST90468660 no MR -> candidate analysis
General cognitive ability 8e-10 rs10916805 1 GCST006269 no MR -> candidate analysis
Verbal-numerical reasoning 4e-9 rs12076947 1 GCST90011298 no MR -> candidate analysis
Forced vital capacity (FVC) 4e-9 rs609210 1 GCST90705071 no MR -> candidate analysis
Protein quantitative trait loci (liver) 9e-9 rs7544348 1 GCST011427 no MR -> candidate analysis
Height 2e-8 rs501108 1 GCST007841 MR: beta=-0.0181, p=0.118 (trans)

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

Top diseases by Open Targets association (of 129 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
jaw disease 0.337 common-variant locus no MR -> candidate analysis
intelligence 0.105 common-variant locus MR: beta=0.0534, p=0.274 (trans)
mathematical ability 0.052 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 2 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=9.5e-10, LOEUF=1.19 — LoF-tolerant
GWAS Catalog 66 unique SNPs / 131 rows
ClinVar 92 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance