CausalSentinel

Protein Dossier — ENPP5 (Ectonucleotide pyrophosphatase/phosphodiesterase family member 5)

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
Autism -0.149 0.0378 7.74e-05 Wald ratio 1 cis NA
Mean cell haemoglobin -0.0523 0.0139 1.74e-04 Wald ratio 1 cis NA
Mean cell volume -0.124 0.036 5.45e-04 Wald ratio 1 cis NA
PGC cross-disorder traits -0.0485 0.016 0.00239 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.074 0.0246 0.00264 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.062 0.0207 0.00267 Wald ratio 1 cis NA
Schizophrenia -0.0408 0.0141 0.00373 Wald ratio 1 cis NA
Fasting proinsulin -0.0266 0.00925 0.00402 Wald ratio 1 cis NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis -0.139 0.0536 0.00943 Wald ratio 1 cis NA
Fasting glucose -0.0105 0.00406 0.00949 Wald ratio 1 cis NA
Paget’s disease -0.203 0.08 0.0112 Wald ratio 1 cis NA
Potassium in urine 0.00809 0.00322 0.0121 Wald ratio 1 cis NA
…and 109 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

26 association rows across 13 traits (22 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
Ectonucleotide pyrophosphatase/phosphodiesterase family memb 2e-1111 rs77991465 2 GCST90247463 no MR -> candidate analysis
Ectonucleotide pyrophosphatase/phosphodiesterase family memb 8e-299 rs1047153 1 GCST90241026 no MR -> candidate analysis
Serum levels of protein ENPP5 4e-240 rs1047153 1 GCST90089495 no MR -> candidate analysis
ENPP5 protein levels 5e-197 rs149796129 13 GCST90469116 no MR -> candidate analysis
Ectonucleotide pyrophosphatase/phosphodiesterase family memb 1e-27 rs1047153 1 GCST90238335 no MR -> candidate analysis
Skeletal muscle ENPP5 levels 3e-11 rs62400863 1 GCST90807121 no MR -> candidate analysis
Mean spheric corpuscular volume 6e-11 rs34269469 1 GCST90002397 no MR -> candidate analysis
Mean reticulocyte volume 7e-11 rs34269469 1 GCST90002396 no MR -> candidate analysis
Liver ENPP5 levels 1e-10 rs62400863 1 GCST90801405 no MR -> candidate analysis
Lymphocytic leukemia 7e-7 rs114961115 1 GCST90011814 no MR -> candidate analysis
Total cholesterol change in response to fenofibrate in stati 9e-7 rs9472719 1 GCST004765 no MR -> candidate analysis
General cognitive ability 1e-6 rs2223776 1 GCST006269 no MR -> candidate analysis
…and 1 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 102 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
ptosis 0.517 common-variant locus no MR -> candidate analysis
infectious disease 0.511 common-variant locus no MR -> candidate analysis
severe acute respiratory syndrome 0.347 common-variant locus no MR -> candidate analysis
COVID-19 0.347 common-variant locus no MR -> candidate analysis
color vision disorder 0.179 common-variant locus no MR -> candidate analysis
skin neoplasm 0.119 common-variant locus no MR -> candidate analysis
mental disorder 0.067 common-variant locus no MR -> candidate analysis
tooth disorder 0.066 common-variant locus no MR -> candidate analysis
temporomandibular joint disorder 0.065 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.056 common-variant locus MR: beta=-0.0497, p=0.0772 (cis)
skin aging 0.053 common-variant locus no MR -> candidate analysis
hair color 0.052 common-variant locus no MR -> candidate analysis
external ear disorder 0.046 common-variant locus no MR -> candidate analysis
osteoarthritis 0.046 common-variant locus MR: beta=-0.0497, p=0.0772 (cis)
total hip arthroplasty 0.041 common-variant locus no MR -> candidate analysis

Of the 15 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.

5. Downstream annotation (druggability & safety preview)

Layer Result
ChEMBL druggability not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=3.7e-08, LOEUF=1.11 — LoF-tolerant
GWAS Catalog 60 unique SNPs / 120 rows
ClinVar 81 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance