CausalSentinel

Protein Dossier — MTRF1L (Peptide chain release factor 1-like, mitochondrial)

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
PGC cross-disorder traits 0.284 0.0726 9.35e-05 Wald ratio 1 cis NA
Bipolar disorder 0.544 0.14 1.06e-04 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) 0.0365 0.0126 0.00377 Wald ratio 1 cis NA
Major depressive disorder 0.358 0.128 0.00522 Wald ratio 1 cis NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.795 0.305 0.00903 Wald ratio 1 cis NA
Haemoglobin concentration 0.086 0.0333 0.00983 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0296 0.0119 0.0131 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis -0.297 0.129 0.0218 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.35 0.159 0.0274 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids -0.385 0.18 0.0323 Wald ratio 1 cis NA
Non-cancer illness code self-reported: retinal detachment 0.382 0.18 0.0338 Wald ratio 1 cis NA
Schizophrenia 0.129 0.0636 0.0425 Wald ratio 1 cis NA
…and 93 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 7 traits (6 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
Peptide chain release factor 1-like, mitochondrial levels 8e-521 rs12206911 1 GCST90248896 no MR -> candidate analysis
Chronotype 3e-27 rs62436127 1 GCST007576 no MR -> candidate analysis
Morning person 3e-27 rs62436127 1 GCST007565 no MR -> candidate analysis
Morningness 1e-18 rs62436127 1 GCST007983 no MR -> candidate analysis
Hepatocyte nuclear factor 1-alpha protein levels (SomaScan I 9e-12 rs2038332 1 GCST90442591 no MR -> candidate analysis
Morning vs. evening chronotype 2e-8 rs62436127 1 GCST003429 no MR -> candidate analysis
Amygdala volume 9e-6 rs9479479 1 GCST009259 MR: beta=-10.1, p=0.471 (cis)

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

Top diseases by Open Targets association (of 104 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
ovarian benign neoplasm 0.459 common-variant locus no MR -> candidate analysis
fallopian tube disorder 0.153 common-variant locus no MR -> candidate analysis
ovarian disorder 0.153 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.108 common-variant locus no MR -> candidate analysis
schizophrenia 0.057 common-variant locus MR: beta=0.129, p=0.0425 (cis)
diabetes mellitus 0.093 common-variant locus no MR -> candidate analysis
tooth disorder 0.091 common-variant locus no MR -> candidate analysis
eye disorder 0.091 common-variant locus no MR -> candidate analysis
placenta praevia 0.09 common-variant locus no MR -> candidate analysis
hyperaldosteronism 0.084 common-variant locus no MR -> candidate analysis
corneal dystrophy 0.078 common-variant locus no MR -> candidate analysis
mathematical ability 0.078 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 11 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=8.1e-08, LOEUF=0.989 — LoF-tolerant
GWAS Catalog 79 unique SNPs / 158 rows
ClinVar 83 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance