CausalSentinel

Protein Dossier — TEPSIN (AP-4 complex accessory subunit Tepsin)

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
Non-cancer illness code self-reported: asthma -0.127 0.0416 0.00224 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression -0.167 0.0639 0.00881 Wald ratio 1 cis NA
Clear cell ovarian cancer 0.685 0.278 0.0136 Wald ratio 1 cis NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus 0.201 0.0951 0.0342 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.716 0.348 0.0395 Wald ratio 1 cis NA
Potassium in urine -0.0261 0.0132 0.0486 Wald ratio 1 cis NA
Birth weight -0.0381 0.0201 0.0577 Wald ratio 1 cis NA
Eczema -0.258 0.136 0.0587 Wald ratio 1 cis NA
Ovarian cancer 0.142 0.0783 0.0699 Wald ratio 1 cis NA
Eye problems or disorders: Cataract 0.115 0.0637 0.07 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0193 0.0107 0.0709 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.0922 0.053 0.0821 Wald ratio 1 cis NA
…and 49 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

5 association rows across 3 traits (2 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
AP-4 complex accessory subunit tepsin levels 6e-24 rs61745945 1 GCST90246531 no MR -> candidate analysis
AP-4 complex accessory subunit tepsin levels (ENTHD2.7947.19 6e-19 rs61745945 1 GCST90240305 no MR -> candidate analysis
Frontotemporal dementia 8e-7 rs906175; rs2659030; rs2725391; rs969413; rs1048775; rs9319617; rs2255166 3 GCST002960 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 31 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 disorder 0.086 common-variant locus no MR -> candidate analysis
response to xenobiotic stimulus 0.05 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.05 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 3 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=5.2e-18, LOEUF=1.31 — LoF-tolerant
GWAS Catalog 49 unique SNPs / 98 rows
ClinVar 45 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance