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 |
|---|---|---|---|---|---|---|---|
| Weight | -0.0175 | 0.00218 | 1.11e-15 | Wald ratio | 1 | cis | 0.991 |
| Fasting proinsulin | -0.0528 | 0.00711 | 1.04e-13 | Wald ratio | 1 | cis | 0.992 |
| Height | -0.0191 | 0.00301 | 1.97e-10 | Wald ratio | 1 | cis | 0.932 |
| Body mass index (BMI) | -0.0125 | 0.00247 | 3.77e-07 | Wald ratio | 1 | cis | NA |
| Fasting glucose | 0.0137 | 0.00319 | 1.82e-05 | Wald ratio | 1 | cis | NA |
| Forced vital capacity (FVC) | -0.00688 | 0.00203 | 6.91e-04 | Wald ratio | 1 | cis | NA |
| Forced expiratory volume in 1-second (FEV1) | -0.00583 | 0.00214 | 0.0064 | Wald ratio | 1 | cis | NA |
| Glioma | -0.112 | 0.0437 | 0.0102 | Wald ratio | 1 | cis | NA |
| Amygdala volume | -5.85 | 2.37 | 0.0134 | Wald ratio | 1 | cis | NA |
| Age at menarche | 0.0137 | 0.00578 | 0.018 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis | -0.0888 | 0.0396 | 0.0248 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: G47 Sleep disorders | -0.0764 | 0.0348 | 0.0281 | Wald ratio | 1 | cis | NA |
| …and 78 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
43 association rows across 25 traits (42 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 |
|---|---|---|---|---|---|
| Neuroendocrine convertase 1 levels | 1e-2086 | rs13169290 | 2 | GCST90248629 | no MR -> candidate analysis |
| Neuroendocrine convertase 1 levels (PCSK1.13388.57.3) | 1e-599 | rs6234 | 2 | GCST90242073 | no MR -> candidate analysis |
| Fasting blood glucose | 2e-54 | rs2882298 | 1 | GCST90662896 | no MR -> candidate analysis |
| Neuroendocrine convertase 1 level in Chronic kidney disease | 2e-49 | rs6234 | 1 | GCST90233854 | no MR -> candidate analysis |
| Insulin-related traits (multivariate analysis) | 8e-32 | rs13169290 | 1 | GCST009863 | no MR -> candidate analysis |
| Mitochondrial ubiquitin ligase activator of NFKB 1:Mitochind | 4e-30 | rs6234 | 1 | GCST90437114 | no MR -> candidate analysis |
| Height | 1e-28 | rs5869716 | 5 | GCST90662911 | MR: beta=-0.0191, p=1.97e-10 (cis) |
| Proinsulin levels | 1e-26 | rs6235 | 1 | GCST001212 | no MR -> candidate analysis |
| Body mass index | 2e-25 | rs6234 | 8 | GCST90255621 | MR: beta=-0.0125, p=3.77e-07 (cis) |
| Fasting glucose | 9e-24 | rs6235 | 2 | GCST90256408 | MR: beta=0.0137, p=1.82e-05 (cis) |
| Height (baseline) | 2e-20 | rs6234 | 1 | GCST90565843 | no MR -> candidate analysis |
| ICD10 O24.4: Diabetes mellitus arising in pregnancy | 6e-19 | rs17085675 | 1 | GCST90454236 | no MR -> candidate analysis |
| …and 13 more traits (see JSON) |
Top diseases by Open Targets association (of 864 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 |
|---|---|---|---|---|
| obesity due to prohormone convertase I deficiency | 0.859 | — | established (curated) | no MR -> candidate analysis |
| Abnormality of the skeletal system | 0.862 | — | common-variant locus | no MR -> candidate analysis |
| obesity disorder | 0.722 | — | common-variant locus | no MR -> candidate analysis |
| gestational diabetes | 0.759 | — | common-variant locus | no MR -> candidate analysis |
| osteoarthritis, knee | 0.736 | — | common-variant locus | no MR -> candidate analysis |
| aneurysm | 0.716 | — | common-variant locus | no MR -> candidate analysis |
| aortic aneurysm | 0.716 | — | common-variant locus | no MR -> candidate analysis |
| smoking initiation | 0.701 | — | common-variant locus | no MR -> candidate analysis |
| obesity due to melanocortin 4 receptor deficiency | 0.617 | — | established (curated) | no MR -> candidate analysis |
| osteoarthritis, hip | 0.613 | — | common-variant locus | no MR -> candidate analysis |
| type 2 diabetes mellitus | 0.576 | — | common-variant locus | no MR -> candidate analysis |
| frozen shoulder | 0.523 | — | common-variant locus | no MR -> candidate analysis |
| thoracic aortic aneurysm | 0.515 | — | common-variant locus | no MR -> candidate analysis |
| pregnancy disorder | 0.499 | — | common-variant locus | no MR -> candidate analysis |
| total joint arthroplasty | 0.499 | — | 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.
| Layer | Result |
|---|---|
| ChEMBL druggability | 0 known modulators (Neuroendocrine convertase 1) |
| gnomAD constraint | pLI=3.2e-11, LOEUF=0.772 — LoF-tolerant |
| GWAS Catalog | 158 unique SNPs / 266 rows |
| ClinVar | 492 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 864 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 ‘PCSK1’ and resolved to ‘Neuroendocrine convertase 1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 492 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 25 traits by best p-value, aggregated from 43 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/P29120 — 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/ENSG00000175426/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3182/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PCSK1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PCSK1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PCSK1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PCSK1 — GWAS Catalog search API (live; release not exposed)