Protein Dossier — LRPAP1 (Alpha-2-macroglobulin receptor-associated protein)
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 |
| Depressive symptoms |
0.0498 |
0.0176 |
0.00461 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Wrist |
0.149 |
0.0606 |
0.0138 |
Wald ratio |
1 |
cis |
NA |
| Mean cell haemoglobin concentration |
-0.0345 |
0.0155 |
0.0266 |
Wald ratio |
1 |
cis |
NA |
| Neuroticism |
0.0381 |
0.0176 |
0.0303 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal |
-0.216 |
0.104 |
0.0379 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: prostate cancer |
-0.348 |
0.168 |
0.0388 |
Wald ratio |
1 |
cis |
NA |
| Endometrioid ovarian cancer |
0.257 |
0.125 |
0.0394 |
Wald ratio |
1 |
cis |
NA |
| Eczema |
-0.159 |
0.0813 |
0.0507 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Cataract |
-0.115 |
0.0597 |
0.0544 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
0.119 |
0.062 |
0.0552 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: C61 Malignant neoplasm of prostate |
-0.324 |
0.173 |
0.0604 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: uterine fibroids |
-0.174 |
0.0953 |
0.0684 |
Wald ratio |
1 |
cis |
NA |
| …and 88 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3640_14_3 |
RAP |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
27 association rows across 14 traits (26 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 |
| Circulating LRPAP1 levels |
8e-324 |
rs143486729 |
4 |
GCST90859675 |
no MR -> candidate analysis |
| LRPAP1 protein levels |
5e-298 |
rs143486729 |
2 |
GCST90469800 |
no MR -> candidate analysis |
| alpha-2-macroglobulin receptor-associated protein levels |
3e-98 |
rs1800493 |
4 |
GCST90249239 |
no MR -> candidate analysis |
| HGFAC protein levels |
4e-92 |
rs183895110 |
5 |
GCST90469448 |
no MR -> candidate analysis |
| Circulating LRP1 levels |
1e-41 |
rs143486729 |
1 |
GCST90860254 |
no MR -> candidate analysis |
| LRP1 protein levels |
2e-30 |
rs143486729 |
2 |
GCST90469797 |
no MR -> candidate analysis |
| FVC |
2e-15 |
rs10001975 |
1 |
GCST90270083 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein LRPAP1 levels |
1e-14 |
rs730748 |
1 |
GCST90944406 |
no MR -> candidate analysis |
| Nonsyndromic cleft palate |
5e-11 |
rs3468 |
1 |
GCST009356 |
no MR -> candidate analysis |
| Height (baseline) |
5e-11 |
rs13325 |
1 |
GCST90565843 |
no MR -> candidate analysis |
| Body fat percentage (adjusted for testosterone and SHBG) |
2e-9 |
rs112726576 |
2 |
GCST90432180 |
no MR -> candidate analysis |
| Forced expiratory volume (baseline) |
8e-9 |
rs13125213 |
1 |
GCST90565844 |
no MR -> candidate analysis |
| …and 2 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 455 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 |
| Rare isolated myopia |
0.765 |
— |
established (curated) |
no MR -> candidate analysis |
| Abnormality of limbs |
0.4 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.253 |
— |
common-variant locus |
no MR -> candidate analysis |
| cleft palate |
0.248 |
— |
common-variant locus |
no MR -> candidate analysis |
| bronchial disorder |
0.144 |
— |
common-variant locus |
no MR -> candidate analysis |
| congenital anomaly of cardiovascular system |
0.101 |
— |
common-variant locus |
no MR -> candidate analysis |
| spinal cord injury |
0.101 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 7 rows above, 7 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=7.5e-15, LOEUF=1.33 — LoF-tolerant |
| GWAS Catalog |
117 unique SNPs / 282 rows |
| ClinVar |
262 records; 13 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 455 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 ‘LRPAP1’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 262 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 14 of 14 traits by best p-value, aggregated from 27 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/P30533 — 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/ENSG00000163956/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/LRPAP1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/LRPAP1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=LRPAP1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/LRPAP1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:37:54 · 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