CausalSentinel

Protein Dossier — ARFIP1 (Arfaptin-1)

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
Height 0.0381 0.0142 0.00744 Wald ratio 1 cis NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.452 0.169 0.00754 Wald ratio 1 cis NA
Pulse rate -0.0429 0.0181 0.0175 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.169 0.0727 0.0197 Wald ratio 1 cis NA
Small vessel disease 0.338 0.154 0.0275 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma -0.0677 0.0307 0.0277 Wald ratio 1 cis NA
Non-cancer illness code self-reported: retinal detachment 0.283 0.138 0.04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.507 0.255 0.0463 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders 0.216 0.109 0.0476 Wald ratio 1 cis NA
Chronic kidney disease -0.13 0.0669 0.0527 Wald ratio 1 cis NA
HOMA-B 0.0502 0.0272 0.0649 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0883 0.049 0.0713 Wald ratio 1 cis NA
…and 92 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

31 association rows across 24 traits (31 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
Arfaptin-1 levels 5e-160 rs4619875 1 GCST90246566 no MR -> candidate analysis
ARFIP1 protein levels 3e-123 rs4619875 1 GCST90468349 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 1e-44 rs11099854 2 GCST90838669 no MR -> candidate analysis
Red cell distribution width 1e-38 rs4619875 4 GCST90002404 no MR -> candidate analysis
Red blood cell erythrocyte distribution width (UKB data fiel 1e-37 rs4619875 1 GCST90468099 no MR -> candidate analysis
Circulating MMP9 levels 1e-29 rs12509964 1 GCST90859917 no MR -> candidate analysis
red cell diameter width (RDW, mean, inv-norm transformed) 4e-23 rs4619875 2 GCST90476361 no MR -> candidate analysis
Height 6e-23 rs7664303 1 GCST90245848 MR: beta=0.0381, p=0.00744 (cis)
mean corpuscular hemoglobin concentration (MCHC, mean, inv-n 1e-22 rs4619875 2 GCST90475458 no MR -> candidate analysis
Arfaptin-1 levels (ARFIP1.13488.3.3) 7e-22 rs4619875 1 GCST90240329 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 8e-20 rs4619875 1 GCST90468087 no MR -> candidate analysis
red cell diameter width (RDW, minimum, inv-norm transformed) 8e-18 rs4619875 1 GCST90476365 no MR -> candidate analysis
…and 12 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 28 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
pneumoconiosis 0.425 common-variant locus no MR -> candidate analysis
Sjogren syndrome 0.425 common-variant locus no MR -> candidate analysis
alcohol drinking 0.172 common-variant locus no MR -> candidate analysis
urolithiasis 0.172 common-variant locus no MR -> candidate analysis
nervous system cancer 0.153 common-variant locus no MR -> candidate analysis
brain cancer 0.153 common-variant locus no MR -> candidate analysis
placenta praevia 0.035 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=0.00013, LOEUF=0.795 — LoF-tolerant
GWAS Catalog 31 unique SNPs / 62 rows
ClinVar 87 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance