MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Diagnoses - main ICD10: H25 Senile cataract | -0.00256 | 0.000839 | 0.00229 | Inverse variance weighted | 2 | trans | NA |
| Diagnoses - main ICD10: H25 Senile cataract | -0.00256 | 0.000839 | 0.00229 | Inverse variance weighted | 2 | trans | NA |
| Diagnoses - main ICD10: I48 Atrial fibrillation and flutter | -0.0029 | 0.00103 | 0.00506 | Inverse variance weighted | 2 | trans | NA |
| Diagnoses - main ICD10: I48 Atrial fibrillation and flutter | -0.0029 | 0.00103 | 0.00506 | Inverse variance weighted | 2 | trans | NA |
| Transferrin | 0.164 | 0.0591 | 0.00555 | Wald ratio | 1 | trans | NA |
| HOMA-B | -0.0348 | 0.0126 | 0.00583 | Inverse variance weighted | 2 | trans | NA |
| HOMA-B | -0.0348 | 0.0126 | 0.00583 | Inverse variance weighted | 2 | trans | NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) | -0.124 | 0.0469 | 0.00802 | Inverse variance weighted | 2 | trans | NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) | -0.124 | 0.0469 | 0.00802 | Inverse variance weighted | 2 | trans | NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting | 0.0015 | 0.000603 | 0.0128 | Inverse variance weighted | 2 | trans | NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting | 0.0015 | 0.000603 | 0.0128 | Inverse variance weighted | 2 | trans | NA |
| Age at menarche | -0.0551 | 0.0228 | 0.0155 | Inverse variance weighted | 2 | trans | NA |
| …and 195 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
9 association rows across 9 traits (8 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 PILRB levels | 2e-302 | rs11766098 | 1 | GCST90860357 | no MR -> candidate analysis |
| Circulating PILRA levels | 3e-231 | rs11766098 | 1 | GCST90860604 | no MR -> candidate analysis |
| CNPY4 protein levels | 7e-23 | rs999885 | 1 | GCST90468800 | no MR -> candidate analysis |
| PILRB protein levels | 2e-16 | rs140843407 | 1 | GCST90470237 | no MR -> candidate analysis |
| PILRA protein levels | 2e-15 | rs140843407 | 1 | GCST90470236 | no MR -> candidate analysis |
| Mean corpuscular hemoglobin | 1e-12 | rs117460458 | 1 | GCST007068 | no MR -> candidate analysis |
| Hematological traits (multi-trait analysis) | 1e-12 | rs1534310 | 1 | GCST90838663 | no MR -> candidate analysis |
| Menarche (age at onset) | 2e-8 | rs999885 | 1 | GCST007078 | no MR -> candidate analysis |
| Alzheimer’s disease or family history of Alzheimer’s disease | 5e-8 | rs2293479 | 1 | GCST005922 | no MR -> candidate analysis |
Top diseases by Open Targets association (of 141 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 |
|---|---|---|---|---|
| Severe intellectual disability and progressive spastic paraplegia | 0.872 | — | established (curated) | no MR -> candidate analysis |
| Spastic paraplegia | 0.94 | — | established (curated) | no MR -> candidate analysis |
| Intellectual disability | 0.804 | — | established (curated) | no MR -> candidate analysis |
| hereditary disease | 0.744 | — | established (curated) | no MR -> candidate analysis |
| AP-4 deficiency syndrome | 0.52 | — | established (curated) | no MR -> candidate analysis |
| hereditary spastic paraplegia | 0.676 | — | established (curated) | no MR -> candidate analysis |
| Abnormality of the nervous system | 0.559 | — | established (curated) | no MR -> candidate analysis |
| microcephaly | 0.426 | — | established (curated) | no MR -> candidate analysis |
| Global developmental delay | 0.426 | — | established (curated) | no MR -> candidate analysis |
| Brain atrophy | 0.426 | — | established (curated) | no MR -> candidate analysis |
| CNS hypomyelination | 0.426 | — | established (curated) | no MR -> candidate analysis |
| Hypoplasia of the corpus callosum | 0.426 | — | established (curated) | no MR -> candidate analysis |
| Alazami-Yuan syndrome | 0.295 | — | established (curated) | no MR -> candidate analysis |
Of the 13 rows above, 13 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.
| Layer | Result |
|---|---|
| ChEMBL druggability | not available — no ChEMBL target (undrugged) |
| gnomAD constraint | pLI=8.2e-19, LOEUF=1.16 — LoF-tolerant |
| GWAS Catalog | 98 unique SNPs / 196 rows |
| ClinVar | 627 records; 10 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 141 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 ‘AP4M1’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 627 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 9 of 9 traits by best p-value, aggregated from 9 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/O00189 — 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/ENSG00000221838/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/AP4M1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/AP4M1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=AP4M1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/AP4M1 — GWAS Catalog search API (live; release not exposed)