CausalSentinel

Protein Dossier — METTL24 (Probable methyltransferase-like protein 24)

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: R11 Nausea and vomiting 0.519 0.162 0.00132 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders 0.403 0.148 0.00647 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0696 0.0263 0.0082 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0347 0.0136 0.0107 Wald ratio 1 cis NA
Cancer code self-reported: small intestine or small bowel cancer 0.902 0.37 0.0149 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0341 0.0143 0.0174 Wald ratio 1 cis NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.221 0.0933 0.018 Wald ratio 1 cis NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.373 0.164 0.0227 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.137 0.0644 0.0335 Wald ratio 1 cis NA
Non-cancer illness code self-reported: chronic obstructive airways disease or copd 0.378 0.204 0.0643 Wald ratio 1 cis NA
Squamous cell lung cancer 0.351 0.194 0.0704 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis 0.0898 0.0508 0.077 Wald ratio 1 cis NA
…and 66 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

25 association rows across 23 traits (18 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
USP8/WASF1 protein level ratio 6e-1016 rs7748253 1 GCST90315944 no MR -> candidate analysis
CEP43/WASF1 protein level ratio 4e-750 rs7748253 1 GCST90314023 no MR -> candidate analysis
MPHOSPH8/WASF1 protein level ratio 2e-687 rs7748253 1 GCST90315481 no MR -> candidate analysis
GYS1/WASF1 protein level ratio 7e-629 rs7748253 1 GCST90315006 no MR -> candidate analysis
ITGB1BP2/WASF1 protein level ratio 5e-599 rs7748253 1 GCST90315224 no MR -> candidate analysis
BAG6/WASF1 protein level ratio 1e-446 rs7748253 1 GCST90313452 no MR -> candidate analysis
IRAG2/WASF1 protein level ratio 1e-432 rs7748253 1 GCST90315192 no MR -> candidate analysis
STAT5B/WASF1 protein level ratio 3e-402 rs7748253 1 GCST90315889 no MR -> candidate analysis
Circulating WASF1 levels 6e-163 rs6939019 1 GCST90860560 no MR -> candidate analysis
Methyltransferase-like protein 24 levels 4e-63 rs2334321 2 GCST90427820 no MR -> candidate analysis
Platelet distribution width 2e-26 rs6939019 1 GCST90002401 no MR -> candidate analysis
WASF1 protein levels 4e-16 rs6568643 1 GCST90471067 no MR -> candidate analysis
…and 11 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 33 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
COVID-19 0.47 common-variant locus no MR -> candidate analysis
lung abscess 0.421 common-variant locus no MR -> candidate analysis
bronchopneumonia 0.421 common-variant locus no MR -> candidate analysis
digestive system disorder 0.406 common-variant locus no MR -> candidate analysis
response to xenobiotic stimulus 0.314 common-variant locus no MR -> candidate analysis
esophageal ulcer 0.314 common-variant locus no MR -> candidate analysis
Crohn disease 0.235 common-variant locus no MR -> candidate analysis
Oral leukoplakia 0.06 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.059 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.05 common-variant locus no MR -> candidate analysis
Nasal polyposis 0.044 common-variant locus no MR -> candidate analysis
fever of unknown origin 0.034 common-variant locus no MR -> candidate analysis
placental abruption 0.031 common-variant locus no MR -> candidate analysis

Of the 13 rows above, 13 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=1.6e-09, LOEUF=1.21 — LoF-tolerant
GWAS Catalog 58 unique SNPs / 116 rows
ClinVar 100 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance