Protein Dossier — APOB (Apolipoprotein B-100)
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 |
| LDL cholesterol |
-0.19 |
0.0122 |
1.84e-54 |
Wald ratio |
1 |
cis |
NA |
| Total cholesterol |
-0.154 |
0.0119 |
1.22e-38 |
Wald ratio |
1 |
cis |
NA |
| HDL cholesterol |
0.092 |
0.0112 |
2.29e-16 |
Wald ratio |
1 |
cis |
NA |
| Triglycerides |
-0.0841 |
0.0112 |
6.38e-14 |
Wald ratio |
1 |
cis |
NA |
| Neo-openness to experience |
0.747 |
0.235 |
0.0015 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux |
0.00391 |
0.00178 |
0.028 |
Inverse variance weighted |
3 |
trans |
NA |
| Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux |
0.00391 |
0.00178 |
0.028 |
Inverse variance weighted |
3 |
trans |
NA |
| Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux |
0.00391 |
0.00178 |
0.028 |
Inverse variance weighted |
3 |
cis |
NA |
| Subjective well being |
-0.0198 |
0.00948 |
0.0368 |
Inverse variance weighted |
2 |
trans |
NA |
| Subjective well being |
-0.0198 |
0.00948 |
0.0368 |
Inverse variance weighted |
2 |
cis |
NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.0701 |
0.0336 |
0.0368 |
Inverse variance weighted |
3 |
trans |
NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.0701 |
0.0336 |
0.0368 |
Inverse variance weighted |
3 |
trans |
NA |
| …and 237 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2797_56_2 |
Apo B |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
2667 association rows across 1083 traits (2576 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 |
| Low density lipoprotein cholesterol levels |
9e-971 |
rs934197 |
94 |
GCST90239655 |
no MR -> candidate analysis |
| Total cholesterol levels |
5e-796 |
rs934197 |
116 |
GCST90239673 |
no MR -> candidate analysis |
| Non-HDL cholesterol levels |
2e-670 |
rs934197 |
7 |
GCST90239667 |
no MR -> candidate analysis |
| Phospholipids to Total Lipids in IDL percentage |
2e-622 |
rs676210 |
2 |
GCST90501130 |
no MR -> candidate analysis |
| Triglycerides in small VLDL |
3e-506 |
rs676210 |
3 |
GCST90501268 |
no MR -> candidate analysis |
| Cholesteryl Esters to Total Lipids in IDL percentage |
6e-477 |
rs676210 |
2 |
GCST90501124 |
no MR -> candidate analysis |
| Free Cholesterol to Total Lipids in Large LDL percentage |
3e-442 |
rs676210 |
2 |
GCST90501151 |
no MR -> candidate analysis |
| Cholesterol to Total Lipids in IDL percentage |
1e-420 |
rs676210 |
2 |
GCST90501122 |
no MR -> candidate analysis |
| Cysteine-rich protein 1 levels |
1e-418 |
rs679899 |
1 |
GCST90247157 |
no MR -> candidate analysis |
| Concentration of small VLDL particles |
2e-401 |
rs676210 |
4 |
GCST90501265 |
no MR -> candidate analysis |
| Triglyceride levels |
4e-398 |
rs676210 |
47 |
GCST90239661 |
no MR -> candidate analysis |
| Triglyceride to phosphoglyceride ratio |
2e-389 |
rs676210 |
2 |
GCST90501273 |
no MR -> candidate analysis |
| …and 1071 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 1224 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 |
| hypercholesterolemia, autosomal dominant, type B |
0.909 |
— |
established (curated) |
no MR -> candidate analysis |
| Hypercholesterolemia |
0.916 |
0.955 |
established (curated) |
MR: beta=-0.19, p=1.84e-54 (cis) |
| familial hypobetalipoproteinemia 1 |
0.91 |
— |
established (curated) |
no MR -> candidate analysis |
| familial hypercholesterolemia |
0.85 |
0.783 |
established (curated) |
no MR -> candidate analysis |
| metabolic disease |
0.942 |
0.926 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| hypobetalipoproteinemia |
0.919 |
— |
established (curated) |
no MR -> candidate analysis |
| coronary artery disorder |
0.906 |
— |
common-variant locus |
no MR -> candidate analysis |
| Disorder of lipid metabolism |
0.838 |
0.84 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| cardiovascular disorder |
0.867 |
— |
common-variant locus |
no MR -> candidate analysis |
| hyperlipidemia |
0.938 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypercholesterolemia, familial, 1 |
0.931 |
— |
established (curated) |
no MR -> candidate analysis |
| metabolic syndrome |
0.884 |
— |
common-variant locus |
no MR -> candidate analysis |
| familial hyperlipidemia |
0.886 |
— |
common-variant locus |
no MR -> candidate analysis |
| homozygous familial hypercholesterolemia |
0.72 |
— |
established (curated) |
no MR -> candidate analysis |
| Abnormality of the cardiovascular system |
0.909 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 15 rows above, 14 have no MR estimate in this resource. Across all retrieved diseases for this gene: 2 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 (Apolipoprotein B-100) |
| gnomAD constraint |
pLI=1.8e-14, LOEUF=0.557 — LoF-tolerant |
| GWAS Catalog |
187 unique SNPs / 539 rows |
| ClinVar |
5193 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
5 clinical annotations across 3 drugs |
phenome — Top 30 of 1224 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 ‘APOB’ and resolved to ‘Apolipoprotein B-100’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 5193 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 1083 traits by best p-value, aggregated from 2667 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/P04114 — 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/ENSG00000084674/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4549/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/APOB — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/APOB — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=APOB%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=APOB — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/APOB — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:07:48 · 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