CausalSentinel

Protein Dossier — TYMP (Thymidine phosphorylase)

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
Mean cell volume 1.37 0.169 6.26e-16 Wald ratio 1 cis NA
Mean cell haemoglobin 0.473 0.0672 1.97e-12 Wald ratio 1 cis NA
Inflammatory bowel disease -0.283 0.0594 1.84e-06 Wald ratio 1 cis NA
Ulcerative colitis -0.336 0.0744 6.28e-06 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0867 0.0229 1.52e-04 Wald ratio 1 cis NA
Weight 0.0458 0.0128 3.38e-04 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0378 0.0119 0.00143 Wald ratio 1 cis NA
Multiple sclerosis -0.304 0.0976 0.00183 Wald ratio 1 cis NA
Crohn’s disease -0.223 0.072 0.00192 Wald ratio 1 cis NA
Age at menopause -0.441 0.147 0.0027 Wald ratio 1 cis NA
Red blood cell count -0.0402 0.0147 0.00627 Wald ratio 1 cis NA
HbA1C -0.0647 0.024 0.00706 Wald ratio 1 cis NA
…and 99 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

15 association rows across 9 traits (14 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
Mean corpuscular volume 7e-68 rs131801 4 GCST90018746 no MR -> candidate analysis
Mean corpuscular hemoglobin 5e-45 rs470119 3 GCST90002323 no MR -> candidate analysis
ARSA protein levels 2e-41 rs184299570 1 GCST90468368 no MR -> candidate analysis
5-methyluridine (ribothymidine) levels 5e-26 rs470119 1 GCST90102853 no MR -> candidate analysis
2’-deoxyuridine levels 2e-25 rs74624637 1 GCST90200413 no MR -> candidate analysis
Red cell distribution width 3e-19 rs131801 1 GCST004621 no MR -> candidate analysis
Red blood cell count 2e-16 rs131801 2 GCST90662878 MR: beta=-0.0402, p=0.00627 (cis)
Mean spheric corpuscular volume 3e-9 rs131804 1 GCST90002397 no MR -> candidate analysis
Mean reticulocyte volume 6e-9 rs131804 1 GCST90002396 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 479 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
mitochondrial DNA depletion syndrome 1 0.937 established (curated) no MR -> candidate analysis
mitochondrial neurogastrointestinal encephalomyopathy 0.819 established (curated) no MR -> candidate analysis
hereditary disease 0.774 established (curated) no MR -> candidate analysis
renal carcinoma 0.576 common-variant locus no MR -> candidate analysis
intestinal pseudo-obstruction 0.438 established (curated) no MR -> candidate analysis
multiple sclerosis 0.388 common-variant locus MR: beta=-0.304, p=0.00183 (cis)
B-cell chronic lymphocytic leukemia 0.322 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 6 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 1 known modulators (Thymidine phosphorylase)
gnomAD constraint pLI=2.1e-17, LOEUF=1.39 — LoF-tolerant
GWAS Catalog 115 unique SNPs / 276 rows
ClinVar 1288 records; 17 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 2 drugs

Caveats declared by the tools

Sources

Provenance