CausalSentinel

Protein Dossier — AIFM1 (Apoptosis-inducing factor 1, 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
Weight -0.0181 0.00513 4.12e-04 Wald ratio 1 trans NA
Body mass index (BMI) -0.0197 0.00581 6.77e-04 Wald ratio 1 trans NA
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.27 0.443 0.004 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.0125 0.00477 0.00881 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.113 0.0469 0.0164 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bone disorder 0.237 0.0989 0.0167 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension -0.0238 0.0101 0.0188 Wald ratio 1 trans NA
Heel bone mineral density (BMD) T-score automated 0.0174 0.00752 0.021 Wald ratio 1 trans NA
Non-cancer illness code self-reported: gout -0.127 0.0555 0.0219 Wald ratio 1 trans NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.154 0.0678 0.0227 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) 0.0114 0.00503 0.0235 Wald ratio 1 trans NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.0967 0.0441 0.0285 Wald ratio 1 trans NA
…and 64 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

6 association rows across 6 traits (4 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 4e-32 rs209999 1 GCST90018959 no MR -> candidate analysis
Hemoglobin A1c levels 3e-14 rs10622586 1 GCST90018958 no MR -> candidate analysis
Lung function (forced vital capacity) 2e-11 rs210034 1 GCST90244093 no MR -> candidate analysis
Forced vital capacity (FVC) 2e-11 rs209539 1 GCST90705071 MR: beta=0.0125, p=0.00881 (trans)
Facial morphology (factor 15, philtrum width) 1e-6 rs143386295 1 GCST004319 no MR -> candidate analysis
Bipolar disorder 5e-6 rs188076915 1 GCST008103 MR: beta=0.198, p=0.0356 (trans)

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

Top diseases by Open Targets association (of 2534 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
severe X-linked mitochondrial encephalomyopathy 0.847 established (curated) no MR -> candidate analysis
X-linked hereditary sensory and autonomic neuropathy with deafness 0.906 established (curated) no MR -> candidate analysis
X-linked Charcot-Marie-Tooth disease type 4 0.741 established (curated) no MR -> candidate analysis
spondyloepimetaphyseal dysplasia, Bieganski type 0.843 established (curated) no MR -> candidate analysis
Charcot-Marie-Tooth disease X-linked recessive 4 0.753 established (curated) no MR -> candidate analysis
X-linked hereditary sensory and autonomic neuropathy with hearing loss 0.947 established (curated) no MR -> candidate analysis
combined oxidative phosphorylation deficiency 0.852 established (curated) no MR -> candidate analysis
Charcot-Marie-Tooth disease 0.852 established (curated) no MR -> candidate analysis
auditory neuropathy 0.766 established (curated) no MR -> candidate analysis
Tip-toe gait 0.591 established (curated) no MR -> candidate analysis
dystonia 9 0.438 established (curated) no MR -> candidate analysis
Sensorineural hearing impairment 0.438 established (curated) no MR -> candidate analysis
ear malformation 0.438 established (curated) no MR -> candidate analysis
Foot dorsiflexor weakness 0.438 established (curated) no MR -> candidate analysis
Distal muscle weakness 0.438 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 (Apoptosis-inducing factor 1, mitochondrial)
gnomAD constraint pLI=1, LOEUF=0.15 — LoF-INTOLERANT
GWAS Catalog 12 unique SNPs / 24 rows
ClinVar 964 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance