CausalSentinel

Protein Dossier — TREML2 (Trem-like transcript 2 protein)

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
Weight -0.0149 0.00449 9.08e-04 Wald ratio 1 cis NA
Body mass index (BMI) -0.0145 0.00508 0.00437 Wald ratio 1 cis NA
Cancer code self-reported: malignant melanoma -0.189 0.0701 0.00694 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.0866 0.0326 0.00793 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.07 0.0264 0.00804 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.156 0.0594 0.00867 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bladder problem (not cancer) 0.145 0.0579 0.0126 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt -0.164 0.0668 0.0141 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.0118 0.00487 0.0156 Wald ratio 1 cis NA
Potassium in urine 0.0123 0.00516 0.0168 Wald ratio 1 cis NA
Clear cell ovarian cancer -0.204 0.0894 0.0223 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0326 0.0144 0.0238 Wald ratio 1 cis NA
…and 62 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

59 association rows across 37 traits (46 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
Trem-like transcript 2 protein levels 4e-897 rs62396356 3 GCST90249975 no MR -> candidate analysis
Circulating TREML2 levels 6e-566 rs11759347 4 GCST90859936 no MR -> candidate analysis
PEAR1/TREML2 protein level ratio 9e-403 rs62396356 1 GCST90315645 no MR -> candidate analysis
CD244/TREML2 protein level ratio 6e-402 rs41273772 1 GCST90313767 no MR -> candidate analysis
SEMA4D/TREML2 protein level ratio 5e-391 rs62396356 1 GCST90315823 no MR -> candidate analysis
CD84/TREML2 protein level ratio 3e-352 rs62396356 1 GCST90313919 no MR -> candidate analysis
Blood protein levels 2e-233 rs13207171 1 GCST006585 no MR -> candidate analysis
Trem-like transcript 2 protein levels (TREML2.5736.1.3) 5e-86 rs61998254 1 GCST90243113 no MR -> candidate analysis
TREML2 protein levels 7e-46 rs62621763 4 GCST90470962 no MR -> candidate analysis
TREM2 protein levels 3e-39 rs9462674 1 GCST90470960 no MR -> candidate analysis
HBEGF/PDGFA protein level ratio 3e-37 rs62396356 1 GCST90315033 no MR -> candidate analysis
CCN2/HBEGF protein level ratio 7e-31 rs62396356 1 GCST90313713 no MR -> candidate analysis
…and 25 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 78 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 0.47 common-variant locus no MR -> candidate analysis
Lewy body dementia 0.49 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.436 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=2.2e-08, LOEUF=1.3 — LoF-tolerant
GWAS Catalog 77 unique SNPs / 154 rows
ClinVar 66 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance