CausalSentinel

Protein Dossier — CFHR4 (Complement factor H-related protein 4)

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
Systolic blood pressure automated reading -0.0227 0.00442 2.75e-07 Wald ratio 1 cis NA
Forearm bone mineral density -0.133 0.0283 2.47e-06 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0177 0.00442 6.28e-05 Wald ratio 1 cis NA
Lumbar spine bone mineral density -0.0569 0.0155 2.50e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.0753 0.0245 0.00211 Wald ratio 1 cis NA
Femoral neck bone mineral density -0.0367 0.0133 0.00589 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis -0.0498 0.0187 0.00766 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.00928 0.00354 0.00884 Wald ratio 1 cis NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis -0.202 0.0779 0.00936 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma -0.0314 0.0125 0.0119 Wald ratio 1 cis NA
HDL cholesterol -0.0209 0.00855 0.0144 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years 0.0318 0.013 0.0149 Wald ratio 1 cis NA
…and 110 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

209 association rows across 104 traits (201 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
Complement factor H-related protein 1 levels 4e-993 rs67908756 3 GCST90246993 no MR -> candidate analysis
Complement factor H-related protein 4 levels 8e-666 rs4915363 4 GCST90246995 no MR -> candidate analysis
Alpha-N-acetylglucosaminidase levels 2e-428 rs67908756 1 GCST90248587 no MR -> candidate analysis
Age-related macular degeneration (MTAG) 6e-414 rs7542235 1 GCST010284 no MR -> candidate analysis
CFHR5 plasma levels 3e-396 rs10737681 1 GCST90244658 no MR -> candidate analysis
Blood protein levels 7e-381 rs57809726 65 GCST006585 no MR -> candidate analysis
Leucine-rich repeat-containing protein 19 levels (LRRC19.701 1e-307 rs7519758 2 GCST90241776 no MR -> candidate analysis
Age-related macular degeneration or COVID-19 critical illnes 4e-291 rs60642321 1 GCST90250832 no MR -> candidate analysis
Age-related macular degeneration or COVID-19 infection (MTAG 8e-291 rs60642321 1 GCST90250834 no MR -> candidate analysis
Age-related macular degeneration or COVID-19 hospitalization 9e-291 rs60642321 1 GCST90250833 no MR -> candidate analysis
CFHR2 protein levels 1e-275 rs61820760 8 GCST90468726 no MR -> candidate analysis
CFHR4 protein levels 3e-268 rs184080912 10 GCST90468727 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 72 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
age-related macular degeneration 0.634 established (curated) no MR -> candidate analysis
retinal disorder 0.676 common-variant locus no MR -> candidate analysis
macular degeneration 0.665 common-variant locus no MR -> candidate analysis
placental abruption 0.388 common-variant locus no MR -> candidate analysis
kidney disorder 0.198 established (curated) no MR -> candidate analysis
degeneration of macula and posterior pole 0.158 common-variant locus no MR -> candidate analysis
COVID-19 0.15 common-variant locus no MR -> candidate analysis
meningococcal infection 0.084 common-variant locus no MR -> candidate analysis
wet macular degeneration 0.072 common-variant locus no MR -> candidate analysis
Visual impairment 0.058 common-variant locus no MR -> candidate analysis
lymphatic system disorder 0.056 common-variant locus no MR -> candidate analysis
maculopapular eruption 0.045 common-variant locus no MR -> candidate analysis
retinitis pigmentosa 0.045 common-variant locus no MR -> candidate analysis
hypotensive disorder 0.033 common-variant locus no MR -> candidate analysis
heart disorder 0.031 common-variant locus 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=1.5e-20, LOEUF=1.14 — LoF-tolerant
GWAS Catalog 128 unique SNPs / 330 rows
ClinVar 247 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance