CausalSentinel

Protein Dossier — TMED10 (Transmembrane emp24 domain-containing protein 10)

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
Serum cystatin C (eGFRcys) -0.108 0.00362 9.81e-198 Wald ratio 1 trans 0.904
Eye problems or disorders: Diabetes related eye disease 0.196 0.0495 7.76e-05 Wald ratio 1 trans NA
Autism -0.187 0.057 0.00102 Wald ratio 1 trans NA
Alcohol intake frequency -0.0188 0.00695 0.00685 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoporosis -0.109 0.0422 0.00944 Wald ratio 1 trans NA
PGC cross-disorder traits -0.0582 0.024 0.0153 Wald ratio 1 trans NA
Height 0.0136 0.00575 0.0177 Wald ratio 1 trans NA
Heel bone mineral density (BMD) T-score automated 0.0141 0.00609 0.0208 Wald ratio 1 trans NA
Birth weight 0.0159 0.00707 0.0241 Wald ratio 1 trans NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.0685 0.0311 0.0279 Wald ratio 1 trans NA
Eye problems or disorders: Injury or trauma resulting in loss of vision -0.158 0.0722 0.0283 Wald ratio 1 trans NA
Non-cancer illness code self-reported: asthma 0.0277 0.0128 0.0309 Wald ratio 1 trans 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

16 association rows across 14 traits (13 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
Height 3e-75 rs876402 3 GCST90245848 MR: beta=0.0136, p=0.0177 (trans)
TMPRSS5 protein levels 2e-21 rs546034924 1 GCST90470893 no MR -> candidate analysis
Circulating TMPRSS5 levels 8e-20 rs10149880 1 GCST90859695 no MR -> candidate analysis
PGF protein levels 7e-18 rs190193666 1 GCST90470218 no MR -> candidate analysis
IGF 1 (UKB data field 30770) 1e-17 rs12433944 1 GCST90468078 no MR -> candidate analysis
Diseases of sebaceous glands (PheCode 706) 3e-15 rs4903293 1 GCST90480484 no MR -> candidate analysis
Heel bone mineral density 4e-15 rs876403 1 GCST006433 MR: beta=0.0141, p=0.0208 (trans)
Alzheimer’s disease (PheCode 290.11) 3e-11 rs568436451 1 GCST90480731 no MR -> candidate analysis
Body size or adipose distribution (multivariate analysis) 5e-10 rs175426 1 GCST90624105 no MR -> candidate analysis
Hypothyroidism 7e-9 rs7156476 1 GCST90627750 no MR -> candidate analysis
Gut microbial network clusters (Salmon (at 1 year) x Any Bre 1e-8 rs56201181 1 GCST90569461 no MR -> candidate analysis
Coronary artery disease 4e-8 rs2098297 1 GCST010479 MR: beta=0.0192, p=0.286 (trans)
…and 2 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 130 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
Alzheimer disease 0.267 common-variant locus no MR -> candidate analysis
Pilonidal abscess 0.265 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.241 common-variant locus no MR -> candidate analysis
hypothyroidism 0.218 common-variant locus no MR -> candidate analysis
Epidermal Inclusion Cyst 0.202 common-variant locus no MR -> candidate analysis
sebaceous gland disorder 0.158 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.067 common-variant locus no MR -> candidate analysis
skin infection 0.065 common-variant locus no MR -> candidate analysis
subcutaneous tissue infection 0.065 common-variant locus no MR -> candidate analysis
abdominal aortic aneurysm 0.058 common-variant locus no MR -> candidate analysis

Of the 10 rows above, 10 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 (Transmembrane emp24 domain-containing protein 10)
gnomAD constraint pLI=0.91, LOEUF=0.57 — LoF-INTOLERANT
GWAS Catalog 45 unique SNPs / 90 rows
ClinVar 50 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance