CausalSentinel

Protein Dossier — PROK2 (Prokineticin-2)

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
Diagnoses - main ICD10: I30 Acute pericarditis 0.356 0.129 0.00593 Wald ratio 1 cis NA
HOMA-B 0.00999 0.0041 0.0147 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.00784 0.00325 0.016 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis 0.0574 0.0241 0.017 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0076 0.00325 0.0195 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.0197 0.00872 0.0236 Wald ratio 1 cis NA
Packed cell volume 0.0514 0.0232 0.0264 Wald ratio 1 cis NA
Non-cancer illness code self-reported: iron deficiency anaemia 0.0885 0.0399 0.0265 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee 0.0451 0.0204 0.0271 Wald ratio 1 cis NA
Lung adenocarcinoma 0.0833 0.039 0.0326 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.0535 0.0252 0.0336 Wald ratio 1 cis NA
Pulse rate 0.0115 0.00562 0.0415 Wald ratio 1 cis NA
…and 97 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

22 association rows across 19 traits (19 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
Prokineticin-2 levels 6e-1260 rs7644362 2 GCST90249111 no MR -> candidate analysis
Blood protein levels 3e-289 rs7644362 1 GCST006585 no MR -> candidate analysis
Serum levels of protein PROK2 2e-97 rs6777956 1 GCST90086438 no MR -> candidate analysis
Prokineticin-2 level in Chronic kidney disease with hyperten 6e-46 rs7644362 1 GCST90232979 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 9e-25 rs7644362 1 GCST90838669 no MR -> candidate analysis
Smoking initiation 3e-13 rs116516927 2 GCST90243985 no MR -> candidate analysis
Monocyte percentage of white cells 6e-12 rs7634474 1 GCST90002394 no MR -> candidate analysis
Albumin levels 2e-11 rs2654439 1 GCST90501097 no MR -> candidate analysis
Monocyte count 5e-11 rs3796224 2 GCST90002344 no MR -> candidate analysis
Frailty (General Factor) 7e-11 rs116310555 1 GCST90624046 no MR -> candidate analysis
Depression 9e-9 rs116310555 1 GCST90319327 MR: beta=0.0469, p=0.431 (cis)
Neuroticism conditioned on self-rated math ability (multi-tr 1e-8 rs116310555 1 GCST90027244 no MR -> candidate analysis
…and 7 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 299 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
hypogonadotropic hypogonadism 0.807 established (curated) no MR -> candidate analysis
hypogonadotropic hypogonadism 4 with or without anosmia 0.875 established (curated) no MR -> candidate analysis
Kallmann syndrome 0.608 established (curated) no MR -> candidate analysis
hereditary disease 0.736 established (curated) no MR -> candidate analysis
male infertility with azoospermia or oligozoospermia due to single gene mutation 0.559 established (curated) no MR -> candidate analysis
Male infertility with spermatogenesis disorder 0.547 established (curated) no MR -> candidate analysis
Alzheimer disease 0.449 common-variant locus no MR -> candidate analysis
smoking initiation 0.443 common-variant locus no MR -> candidate analysis
malignant renal pelvis neoplasm 0.364 common-variant locus no MR -> candidate analysis
dermatophytosis 0.35 common-variant locus no MR -> candidate analysis
vertebral joint disorder 0.347 common-variant locus no MR -> candidate analysis
anaphylaxis 0.336 common-variant locus no MR -> candidate analysis
scoliosis 0.336 common-variant locus no MR -> candidate analysis
placenta praevia 0.329 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.306 common-variant locus MR: beta=0.0238, p=0.418 (cis)

Of the 15 rows above, 14 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 (Prokineticin-2)
gnomAD constraint pLI=0.03, LOEUF=1.02 — LoF-tolerant
GWAS Catalog 31 unique SNPs / 62 rows
ClinVar 114 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance