CausalSentinel

Protein Dossier — A1CF (APOBEC1 complementation factor)

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
Serum creatinine (eGFRcrea) -0.014 0.00301 3.44e-06 Wald ratio 1 trans NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.339 0.0874 1.07e-04 Wald ratio 1 trans NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.148 0.0579 0.0107 Wald ratio 1 trans NA
Type 2 diabetes -0.105 0.0418 0.0121 Wald ratio 1 trans NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt -0.307 0.126 0.0149 Wald ratio 1 trans NA
Fracture resulting from simple fall -0.0537 0.0231 0.0199 Wald ratio 1 trans NA
Fractured or broken bones in last 5 years -0.0569 0.0271 0.0359 Wald ratio 1 trans NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.168 0.0833 0.0433 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma 0.121 0.0612 0.0486 Wald ratio 1 trans NA
Caudate volume 31.9 16.4 0.0515 Wald ratio 1 trans NA
Neo-openness to experience -0.429 0.224 0.0559 Wald ratio 1 trans NA
Haemoglobin concentration -0.04 0.0213 0.0603 Wald ratio 1 trans NA
…and 100 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

182 association rows across 104 traits (171 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
Serum urate levels 8e-95 rs10994860 4 GCST90455669 no MR -> candidate analysis
Gamma glutamyl transferase levels 1e-84 rs151068477 7 GCST90662899 no MR -> candidate analysis
Urate levels (UKB data field 30880) 3e-78 rs10994860 1 GCST90468107 no MR -> candidate analysis
Serum uric acid levels 8e-67 rs10994860 2 GCST90018977 no MR -> candidate analysis
Gamma glutamyltransferase levels (UKB data field 30730) 1e-59 rs151068477 2 GCST90468070 no MR -> candidate analysis
Creatinine levels 2e-54 rs11375604 4 GCST90662902 no MR -> candidate analysis
Estimated glomerular filtration rate (creatinine) 5e-54 rs10821905 4 GCST90103633 no MR -> candidate analysis
Urate levels 9e-51 rs17592117 8 GCST011119 no MR -> candidate analysis
Gamma glutamyl transpeptidase 2e-48 rs151068477 1 GCST90018954 no MR -> candidate analysis
Gout 5e-45 rs10994860 2 GCST90455676 no MR -> candidate analysis
Estimated glomerular filtration rate (creatinine, cystatin c 5e-44 rs10821907 1 GCST90428446 no MR -> candidate analysis
Creatinine levels (UKB data field 30700) 3e-43 rs10821907 1 GCST90468067 no MR -> candidate analysis
…and 92 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 431 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
gout 0.821 common-variant locus no MR -> candidate analysis
familial hyperlipidemia 0.67 common-variant locus no MR -> candidate analysis
colorectal cancer 0.534 established (curated) no MR -> candidate analysis
colorectal adenoma 0.519 common-variant locus no MR -> candidate analysis
renal dialysis 0.48 common-variant locus no MR -> candidate analysis
skull disorder 0.48 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.414 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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=1.1e-11, LOEUF=0.887 — LoF-tolerant
GWAS Catalog 57 unique SNPs / 114 rows
ClinVar 92 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance