CausalSentinel

Protein Dossier — FARS2 (Phenylalanine–tRNA ligase, 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
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal 0.196 0.0665 0.00324 Wald ratio 1 trans NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.142 0.0588 0.0162 Wald ratio 1 trans NA
2hr glucose -0.174 0.0784 0.0263 Wald ratio 1 trans NA
Sleep duration 0.0161 0.00743 0.0298 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.197 0.0918 0.0319 Wald ratio 1 trans NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.133 0.0683 0.0522 Wald ratio 1 trans NA
Non-cancer illness code self-reported: enlarged prostate -0.192 0.0999 0.0541 Wald ratio 1 trans NA
Total cholesterol -0.0418 0.0219 0.0563 Wald ratio 1 trans NA
Diagnoses - main ICD10: R07 Pain in throat and chest -0.0876 0.0465 0.0596 Wald ratio 1 trans NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.124 0.0705 0.0795 Wald ratio 1 trans NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate -0.217 0.126 0.0838 Wald ratio 1 trans NA
Non-cancer illness code self-reported: depression -0.0723 0.0423 0.0872 Wald ratio 1 trans NA
…and 76 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

57 association rows across 47 traits (26 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
Core binding factor acute myeloid leukemia 3e-32 rs6937985; rs11243033; rs2145980; rs4959355; rs9504502 2 GCST008413 no MR -> candidate analysis
Severe COVID-19 infection 9e-18 rs9328292 1 GCST90255357 no MR -> candidate analysis
Height 6e-17 rs2753248 3 GCST90245848 MR: beta=0.0187, p=0.134 (trans)
GLIPR1 protein levels 3e-16 rs190047298 2 GCST90469357 no MR -> candidate analysis
Neoplasm of uncertain behavior of male genital organs (PheCo 1e-11 rs138520938 1 GCST90479804 no MR -> candidate analysis
Weight 8e-11 rs11459760 2 GCST90662910 MR: beta=0.0122, p=0.146 (trans)
Human milk oligosaccharide concentration (lacto-N-fucopentao 5e-10 rs74867963 1 GCST90027226 no MR -> candidate analysis
Body mass index 5e-10 rs9328321 1 GCST90255621 MR: beta=0.0129, p=0.175 (trans)
Gut microbiome abundance (class Tyzzerella sp. 3 (at 3 month 7e-10 rs11243009 1 GCST90568581 no MR -> candidate analysis
Gut microbial network clusters (Pink (at 1 year) x Household 9e-10 rs7768493 2 GCST90569453 no MR -> candidate analysis
Red cell distribution width 4e-9 rs6906241 1 GCST007074 no MR -> candidate analysis
Klebsiella abundance in stool 5e-9 rs72825715 1 GCST90032447 no MR -> candidate analysis
…and 35 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 155 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
combined oxidative phosphorylation defect type 14 0.891 established (curated) no MR -> candidate analysis
hereditary spastic paraplegia 77 0.811 established (curated) no MR -> candidate analysis
hereditary disease 0.828 established (curated) no MR -> candidate analysis
Leigh syndrome 0.669 established (curated) no MR -> candidate analysis
autosomal dominant Alport syndrome 0.608 established (curated) no MR -> candidate analysis
COVID-19 0.5 common-variant locus no MR -> candidate analysis
severe acute respiratory syndrome 0.5 common-variant locus no MR -> candidate analysis
tooth agenesis 0.456 common-variant locus no MR -> candidate analysis
obesity disorder 0.439 common-variant locus no MR -> candidate analysis
male reproductive organ cancer 0.44 common-variant locus no MR -> candidate analysis
nephrotic syndrome 0.435 common-variant locus no MR -> candidate analysis
Global developmental delay 0.426 established (curated) no MR -> candidate analysis
gastrointestinal disease 0.433 common-variant locus no MR -> candidate analysis
Vertigo 0.431 common-variant locus no MR -> candidate analysis
mitochondrial encephalomyopathy 0.426 established (curated) no MR -> candidate analysis

Of the 15 rows above, 15 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 0 known modulators (Phenylalanine–tRNA ligase, mitochondrial)
gnomAD constraint pLI=2.2e-12, LOEUF=1.12 — LoF-tolerant
GWAS Catalog 63 unique SNPs / 121 rows
ClinVar 712 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance