Protein Dossier — CFH (Complement factor H)
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 |
| Forced vital capacity (FVC) |
-0.0206 |
0.00548 |
1.66e-04 |
Wald ratio |
1 |
cis |
NA |
| Sleep duration |
-0.0188 |
0.00521 |
3.21e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone |
0.206 |
0.0617 |
8.61e-04 |
Wald ratio |
1 |
cis |
NA |
| IgA nephropathy |
-0.702 |
0.229 |
0.00216 |
Wald ratio |
1 |
cis |
NA |
| Serum cystatin C (eGFRcys) |
0.0136 |
0.00491 |
0.00547 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: asthma |
0.0488 |
0.0178 |
0.00612 |
Wald ratio |
1 |
cis |
NA |
| Hearing difficulty or problems: Yes |
0.0298 |
0.0112 |
0.00775 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: enlarged prostate |
0.128 |
0.0504 |
0.0111 |
Wald ratio |
1 |
cis |
NA |
| Coronary heart disease |
-0.0636 |
0.0252 |
0.0117 |
Wald ratio |
1 |
cis |
NA |
| Diastolic blood pressure automated reading |
0.0168 |
0.00684 |
0.0143 |
Wald ratio |
1 |
cis |
NA |
| Body fat |
-0.036 |
0.0147 |
0.0145 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis |
0.197 |
0.0809 |
0.0149 |
Wald ratio |
1 |
cis |
NA |
| …and 107 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4159_130_1 |
Factor H |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
2077 association rows across 1877 traits (2029 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 |
| Ribosomal protein S6 kinase alpha-1 levels |
3e-2377 |
rs10801553 |
1 |
GCST90248212 |
no MR -> candidate analysis |
| Thiosulfate sulfurtransferase levels |
6e-1871 |
rs12033127 |
2 |
GCST90249867 |
no MR -> candidate analysis |
| NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitoc |
2e-1862 |
rs12033127 |
1 |
GCST90248580 |
no MR -> candidate analysis |
| Glycosyltransferase 8 domain-containing protein 1 levels |
1e-1005 |
rs34813609 |
1 |
GCST90247734 |
no MR -> candidate analysis |
| Advanced age-related macular degeneration |
1e-617 |
rs10922109 |
5 |
GCST003219 |
no MR -> candidate analysis |
| Leucine-rich repeat transmembrane neuronal protein 1 levels |
2e-561 |
rs12029785 |
1 |
GCST90248335 |
no MR -> candidate analysis |
| Alpha-N-acetylglucosaminidase levels |
3e-464 |
rs529541 |
2 |
GCST90248587 |
no MR -> candidate analysis |
| Age-related macular degeneration |
1e-434 |
rs10737680 |
18 |
GCST001884 |
no MR -> candidate analysis |
| Age-related macular degeneration (MTAG) |
4e-421 |
rs800292 |
1 |
GCST010284 |
no MR -> candidate analysis |
| Anaphase-promoting complex subunit 7 levels (ANAPC7.11690.47 |
4e-401 |
rs528298 |
2 |
GCST90240278 |
no MR -> candidate analysis |
| NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitoc |
6e-394 |
rs10801553 |
1 |
GCST90242029 |
no MR -> candidate analysis |
| Otoraplin levels |
7e-378 |
rs529541 |
1 |
GCST90248801 |
no MR -> candidate analysis |
| …and 1865 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 2174 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 H deficiency |
0.947 |
— |
established (curated) |
no MR -> candidate analysis |
| age-related macular degeneration |
0.832 |
0.152 |
established (curated) |
no MR -> candidate analysis |
| atypical hemolytic-uremic syndrome |
0.917 |
— |
established (curated) |
no MR -> candidate analysis |
| age related macular degeneration 4 |
0.851 |
— |
established (curated) |
no MR -> candidate analysis |
| Familial drusen |
0.845 |
— |
established (curated) |
no MR -> candidate analysis |
| retinal disorder |
0.813 |
0.312 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| degeneration of macula and posterior pole |
0.767 |
0.222 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| macular degeneration |
0.95 |
— |
common-variant locus |
no MR -> candidate analysis |
| dense deposit disease |
0.549 |
— |
established (curated) |
no MR -> candidate analysis |
| wet macular degeneration |
0.895 |
— |
common-variant locus |
no MR -> candidate analysis |
| atypical hemolytic-uremic syndrome with H factor anomaly |
0.91 |
— |
established (curated) |
no MR -> candidate analysis |
| dry age related macular degeneration |
0.863 |
— |
common-variant locus |
no MR -> candidate analysis |
| complement 3 glomerulopathy |
0.195 |
— |
established (curated) |
no MR -> candidate analysis |
| Visual impairment |
0.822 |
— |
common-variant locus |
no MR -> candidate analysis |
| Retinal dystrophy |
0.797 |
— |
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 |
0 known modulators (Complement factor H) |
| gnomAD constraint |
pLI=1, LOEUF=0.452 — LoF-INTOLERANT |
| GWAS Catalog |
175 unique SNPs / 469 rows |
| ClinVar |
1628 records; 8 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
4 clinical annotations across 3 drugs |
phenome — Top 30 of 2174 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘CFH’ and resolved to ‘Complement factor H’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 1628 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 1877 traits by best p-value, aggregated from 2077 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/P08603 — 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/ENSG00000000971/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4629/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/CFH — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CFH — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CFH%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=CFH — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/CFH — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:47:47 · 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