Protein Dossier — CFI (Complement factor I)
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 |
| Amyotrophic lateral sclerosis |
-0.161 |
0.0574 |
0.00513 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
-0.0331 |
0.0122 |
0.00672 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hiatus hernia |
-0.15 |
0.0603 |
0.0131 |
Wald ratio |
1 |
cis |
NA |
| Fractured or broken bones in last 5 years |
0.0484 |
0.0234 |
0.0387 |
Wald ratio |
1 |
cis |
NA |
| Invasive mucinous ovarian cancer |
-0.262 |
0.129 |
0.0425 |
Wald ratio |
1 |
cis |
NA |
| Thalamus volume |
-40.8 |
20.3 |
0.0445 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Other bones |
0.0633 |
0.0322 |
0.0494 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis |
0.188 |
0.0966 |
0.0514 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting |
0.201 |
0.104 |
0.0529 |
Wald ratio |
1 |
cis |
NA |
| Pancreatic cancer |
-0.301 |
0.157 |
0.0546 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: uterine fibroids |
0.11 |
0.0572 |
0.0557 |
Wald ratio |
1 |
cis |
NA |
| Red blood cell count |
-0.0132 |
0.00706 |
0.0624 |
Wald ratio |
1 |
cis |
NA |
| …and 98 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2567_5_6 |
Factor I |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
44 association rows across 30 traits (39 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 |
| CFI protein levels |
4e-210 |
rs10033900 |
4 |
GCST90468730 |
no MR -> candidate analysis |
| Complement factor I levels |
7e-85 |
rs7439493 |
6 |
GCST90246997 |
no MR -> candidate analysis |
| Serum levels of protein CFI |
8e-54 |
rs10033900 |
1 |
GCST90087960 |
no MR -> candidate analysis |
| Complement factor I levels (CFI.2567.5.6) |
9e-37 |
rs7439493 |
1 |
GCST90240782 |
no MR -> candidate analysis |
| Circulating complement factor I levels |
9e-37 |
rs7439493 |
1 |
GCST90105032 |
no MR -> candidate analysis |
| Blood protein levels |
4e-34 |
rs10033900 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Atrial fibrillation |
5e-27 |
rs186391417 |
2 |
GCST90624412 |
MR: beta=0.0729, p=0.296 (cis) |
| Macular degeneration, dry (PheCode 362.21) |
9e-27 |
rs141853578 |
2 |
GCST90480043 |
no MR -> candidate analysis |
| Degeneration of macula and posterior pole of retina (PheCode |
1e-18 |
rs141853578 |
2 |
GCST90475849 |
no MR -> candidate analysis |
| Age-related macular degeneration or COVID-19 infection (MTAG |
2e-18 |
rs10033900 |
1 |
GCST90250834 |
no MR -> candidate analysis |
| Age-related macular degeneration or COVID-19 hospitalization |
3e-18 |
rs10033900 |
1 |
GCST90250833 |
no MR -> candidate analysis |
| Age-related macular degeneration or COVID-19 critical illnes |
4e-18 |
rs10033900 |
1 |
GCST90250832 |
no MR -> candidate analysis |
| …and 18 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 435 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 |
| complement factor I deficiency |
0.866 |
— |
established (curated) |
no MR -> candidate analysis |
| atypical hemolytic-uremic syndrome with I factor anomaly |
0.937 |
— |
established (curated) |
no MR -> candidate analysis |
| age-related macular degeneration |
0.803 |
0.241 |
established (curated) |
no MR -> candidate analysis |
| atypical hemolytic-uremic syndrome |
0.895 |
— |
established (curated) |
no MR -> candidate analysis |
| macular degeneration |
0.931 |
— |
common-variant locus |
no MR -> candidate analysis |
| retinal disorder |
0.733 |
0.193 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| degeneration of macula and posterior pole |
0.673 |
0.193 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| COVID-19 |
0.778 |
— |
common-variant locus |
no MR -> candidate analysis |
| wet macular degeneration |
0.749 |
— |
common-variant locus |
no MR -> candidate analysis |
| dry age related macular degeneration |
0.609 |
— |
common-variant locus |
no MR -> candidate analysis |
| atypical hemolytic uremic syndrome with complement gene abnormality |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| Familial drusen |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| atrophic macular degeneration |
0.572 |
— |
common-variant locus |
no MR -> candidate analysis |
| peroxisome biogenesis disorder 4A (Zellweger) |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| C3 glomerulonephritis |
0.297 |
— |
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), 2 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=3.4e-19, LOEUF=1.03 — LoF-tolerant |
| GWAS Catalog |
36 unique SNPs / 72 rows |
| ClinVar |
851 records; 5 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 435 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘CFI’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 851 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 30 traits by best p-value, aggregated from 44 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/P05156 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000205403/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/CFI — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CFI — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CFI%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CFI — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:48:49 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none