CausalSentinel

Protein Dossier — APOL1 (Apolipoprotein L1)

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
Haemoglobin concentration	-0.0315	0.0087	2.89e-04	Inverse variance weighted	3	cis	NA
Haemoglobin concentration	-0.0315	0.0087	2.89e-04	Inverse variance weighted	3	trans	NA
Haemoglobin concentration	-0.0315	0.0087	2.89e-04	Inverse variance weighted	3	trans	NA
Packed cell volume	-0.0814	0.0274	0.00301	Inverse variance weighted	2	trans	NA
Packed cell volume	-0.0814	0.0274	0.00301	Inverse variance weighted	2	trans	NA
Eye problems or disorders: Injury or trauma resulting in loss of vision	0.00188	0.000708	0.00777	Inverse variance weighted	3	cis	NA
Eye problems or disorders: Injury or trauma resulting in loss of vision	0.00188	0.000708	0.00777	Inverse variance weighted	3	trans	NA
Eye problems or disorders: Injury or trauma resulting in loss of vision	0.00188	0.000708	0.00777	Inverse variance weighted	3	trans	NA
Percent emphysema	-0.0294	0.0112	0.00844	Inverse variance weighted	2	trans	NA
Percent emphysema	-0.0294	0.0112	0.00844	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: R11 Nausea and vomiting	-0.000437	0.000178	0.0139	Inverse variance weighted	3	cis	NA
Diagnoses - main ICD10: R11 Nausea and vomiting	-0.000437	0.000178	0.0139	Inverse variance weighted	3	trans	NA
…and 250 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

92 association rows across 53 traits (86 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
Apolipoprotein L1 levels	1e-243	rs9610469	6	GCST90246552	no MR -> candidate analysis
APOL1 protein levels	1e-136	rs28360494	4	GCST90468341	no MR -> candidate analysis
Serum levels of protein APOL1	9e-116	rs4419330	3	GCST90086773	no MR -> candidate analysis
End stage renal disease (PheCode 585.32)	9e-46	rs9622363	2	GCST90480376	no MR -> candidate analysis
Apolipoprotein L1 level in Chronic kidney disease with hyper	1e-40	rs2239785	1	GCST90233274	no MR -> candidate analysis
Kidney replaced by transpant (PheCode 587)	1e-36	rs73885319	2	GCST90480384	no MR -> candidate analysis
Renal dialysis (PheCode 585.31)	2e-35	rs73885319	2	GCST90480375	no MR -> candidate analysis
Apolipoprotein L1 (analyte X11510.51) levels	7e-34	rs10854688	1	GCST90421522	no MR -> candidate analysis
estimated glomerular filtration rate (eGFR, maximum, inv-nor	8e-32	rs9622362	2	GCST90475279	no MR -> candidate analysis
Disorders resulting from impaired renal function (PheCode 58	4e-31	rs9622362	2	GCST90476135	no MR -> candidate analysis
estimated glomerular filtration rate (eGFR, mean, inv-norm t	5e-31	rs73885319	1	GCST90479599	no MR -> candidate analysis
Secondary hyperparathyroidism (of renal origin) (PheCode 588	6e-31	rs73885319	1	GCST90480386	no MR -> candidate analysis
…and 41 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 478 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
focal segmental glomerulosclerosis	0.784	—	established (curated)	no MR -> candidate analysis
sporadic idiopathic steroid-resistant nephrotic syndrome	0.826	—	established (curated)	no MR -> candidate analysis
glomerulonephritis	0.72	—	established (curated)	no MR -> candidate analysis
chronic kidney disease	0.83	—	common-variant locus	no MR -> candidate analysis
kidney disorder	0.824	—	common-variant locus	no MR -> candidate analysis
Proteinuria	0.681	—	established (curated)	no MR -> candidate analysis
kidney failure	0.816	—	common-variant locus	no MR -> candidate analysis
phosphorus metabolism disease	0.776	—	common-variant locus	no MR -> candidate analysis
Nephrotic range proteinuria	0.745	—	established (curated)	no MR -> candidate analysis
secondary hyperparathyroidism of renal origin	0.713	—	common-variant locus	no MR -> candidate analysis
hypertensive heart disease	0.711	—	common-variant locus	no MR -> candidate analysis
mineral metabolism disease	0.707	—	common-variant locus	no MR -> candidate analysis
calcium metabolic disease	0.704	—	common-variant locus	no MR -> candidate analysis
renal dialysis	0.701	—	common-variant locus	no MR -> candidate analysis
anemia	0.674	—	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	0 known modulators (Apolipoprotein L1)
gnomAD constraint	pLI=3.4e-07, LOEUF=1.71 — LoF-tolerant
GWAS Catalog	71 unique SNPs / 142 rows
ClinVar	233 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 478 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 ‘APOL1’ and resolved to ‘Apolipoprotein L1’ — confirm this is the intended target.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 233 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 53 traits by best p-value, aggregated from 92 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/O14791 — 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 v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000100342/associations — Open Targets data release 26.06
• chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4680021/ — ChEMBL_37 (released 2026-05-01)
• gnomad: https://gnomad.broadinstitute.org/gene/APOL1 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/APOL1 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=APOL1%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/APOL1 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T01:08:53 · 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

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