CausalSentinel

Protein Dossier — TFRC (Transferrin receptor protein 1)

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
Transferrin Saturation -0.951 0.05 1.17e-80 Wald ratio 1 trans NA
Iron -0.925 0.05 2.26e-76 Wald ratio 1 trans NA
Mean cell haemoglobin -0.955 0.0555 2.07e-66 Wald ratio 1 trans NA
Mean cell volume -2.11 0.142 4.15e-50 Wald ratio 1 trans NA
Haemoglobin concentration -0.392 0.0312 3.71e-36 Wald ratio 1 trans NA
Packed cell volume -0.767 0.0921 8.22e-17 Wald ratio 1 trans NA
HbA1C 0.134 0.0178 5.16e-14 Wald ratio 1 trans 1
Ferritin -0.254 0.0471 6.66e-08 Wald ratio 1 trans NA
Diagnoses - main ICD10: R07 Pain in throat and chest 0.187 0.0446 2.66e-05 Wald ratio 1 trans NA
Transferrin 0.196 0.051 1.26e-04 Wald ratio 1 trans NA
Mean cell haemoglobin concentration -0.0614 0.0183 8.04e-04 Wald ratio 1 trans NA
LDL cholesterol 0.0515 0.0188 0.0062 Wald ratio 1 trans NA
…and 110 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

221 association rows across 98 traits (199 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
Circulating TFRC levels 3e-1757 rs3817672 3 GCST90859941 no MR -> candidate analysis
Mean corpuscular hemoglobin 1e-319 rs3804139 19 GCST90002326 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 1e-300 rs11718657 3 GCST90838671 no MR -> candidate analysis
Mean corpuscular haemoglobin (UKB data field 30050) 8e-263 rs9877493 5 GCST90468084 no MR -> candidate analysis
Mean corpuscular volume 2e-257 rs3804139 14 GCST90002338 no MR -> candidate analysis
Red cell distribution width 4e-220 rs41300435 12 GCST90002369 no MR -> candidate analysis
Mean corpuscular volume (UKB data field 30040) 4e-217 rs9877493 4 GCST90468086 no MR -> candidate analysis
Red blood cell erythrocyte distribution width (UKB data fiel 2e-175 rs41300435 3 GCST90468099 no MR -> candidate analysis
mean corpuscular hemoglobin (MCH, mean, inv-norm transformed 1e-104 rs493661 2 GCST90479673 no MR -> candidate analysis
mean corpuscular hemoglobin (MCH, maximum, inv-norm transfor 3e-104 rs454516 2 GCST90479672 no MR -> candidate analysis
Red blood cell count 2e-94 rs9877493 8 GCST90002363 MR: beta=0.0213, p=0.0732 (trans)
mean corpuscular hemoglobin (MCH, minimum, inv-norm transfor 8e-90 rs493661 2 GCST90479674 no MR -> candidate analysis
…and 86 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 1129 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
TFRC-related combined immunodeficiency 0.694 established (curated) no MR -> candidate analysis
type 2 diabetes mellitus 0.79 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.729 common-variant locus no MR -> candidate analysis
combined immunodeficiency 0.547 established (curated) no MR -> candidate analysis
Combined T and B cell immunodeficiency 0.547 established (curated) no MR -> candidate analysis
diabetic retinopathy 0.542 common-variant locus no MR -> candidate analysis
hereditary disease 0.317 established (curated) no MR -> candidate analysis

Of the 7 rows above, 7 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 (Transferrin receptor protein 1)
gnomAD constraint pLI=0.31, LOEUF=0.541 — LoF-tolerant
GWAS Catalog 124 unique SNPs / 270 rows
ClinVar 840 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance