CausalSentinel

Protein Dossier — SERPINF1 (Pigment epithelium-derived factor)

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
Forced vital capacity (FVC) -0.0239 0.00466 3.08e-07 Wald ratio 1 cis 0.977
Forced expiratory volume in 1-second (FEV1) -0.0237 0.00492 1.39e-06 Wald ratio 1 cis NA
Weight -0.0197 0.00502 8.49e-05 Wald ratio 1 cis NA
Height -0.027 0.00719 1.77e-04 Wald ratio 1 cis NA
Fasting glucose -0.02 0.00764 0.00885 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.102 0.0391 0.00933 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.0962 0.0383 0.012 Wald ratio 1 cis NA
Age at menopause 0.112 0.045 0.0124 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis 0.126 0.0507 0.0128 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.0625 0.0258 0.0154 Wald ratio 1 cis NA
Hip osteoarthritis 0.163 0.0675 0.0157 Wald ratio 1 cis NA
Subjective well being 0.0157 0.00674 0.0196 Wald ratio 1 cis NA
…and 93 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

38 association rows across 20 traits (35 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
Pigment epithelium-derived factor levels 2e-174 rs62088172 5 GCST90248939 no MR -> candidate analysis
Height 8e-158 rs1136287 4 GCST90245848 MR: beta=-0.027, p=1.77e-04 (cis)
Serum levels of protein SERPINF1 1e-89 rs62088172 2 GCST90089792 no MR -> candidate analysis
Pigment epithelium-derived factor levels (SERPINF1.9211.19.3 2e-70 rs62088172 4 GCST90242263 no MR -> candidate analysis
SERPINF1 protein levels 4e-49 rs62088172 5 GCST90453230 no MR -> candidate analysis
Blood protein levels 5e-49 rs1136287 2 GCST006585 no MR -> candidate analysis
Cerebrospinal fluid protein SERPINF1 levels 1e-31 rs58697961 1 GCST90945130 no MR -> candidate analysis
Standing height (UKB data field 50) 4e-23 rs12450371 1 GCST90468178 no MR -> candidate analysis
Alzheimer’s disease or family history of Alzheimer’s disease 5e-23 rs1306536849 1 GCST90624094 no MR -> candidate analysis
Height (baseline) 2e-21 rs12450371 1 GCST90565843 no MR -> candidate analysis
Body size (confirmatory factor analysis Factor 21) 6e-19 rs201076030 1 GCST90309355 no MR -> candidate analysis
Physical function (baseline) 1e-18 rs62088172 1 GCST90565837 no MR -> candidate analysis
…and 8 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 748 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
osteogenesis imperfecta 0.934 established (curated) no MR -> candidate analysis
osteogenesis imperfecta type 3 0.588 established (curated) no MR -> candidate analysis
osteogenesis imperfecta type 4 0.608 established (curated) no MR -> candidate analysis
Abnormality of the skeletal system 0.438 established (curated) no MR -> candidate analysis
breast cancer 0.38 common-variant locus MR: beta=0.016, p=0.381 (cis)
Alzheimer disease 0.363 common-variant locus no MR -> candidate analysis
breast neoplasm 0.38 common-variant locus MR: beta=0.0448, p=0.292 (cis)
hereditary disease 0.317 established (curated) no MR -> candidate analysis
heart disorder 0.294 common-variant locus no MR -> candidate analysis
estrogen-receptor positive breast cancer 0.26 common-variant locus no MR -> candidate analysis
hypogonadism 0.248 common-variant locus no MR -> candidate analysis
osteoporosis 0.228 established (curated) MR: beta=-0.0934, p=0.0628 (cis)

Of the 12 rows above, 9 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 (Pigment epithelium-derived factor)
gnomAD constraint pLI=2e-08, LOEUF=1.06 — LoF-tolerant
GWAS Catalog 97 unique SNPs / 194 rows
ClinVar 529 records; 9 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance