CausalSentinel

Protein Dossier — PTPN4 (Tyrosine-protein phosphatase non-receptor type 4)

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
Body mass index (BMI) 0.0444 0.0137 0.00116 Wald ratio 1 trans NA
Heel bone mineral density (BMD) T-score automated -0.0507 0.0177 0.00417 Wald ratio 1 trans NA
Creatinine (enzymatic) in urine 0.0361 0.0131 0.00582 Wald ratio 1 trans NA
Weight 0.0317 0.0121 0.00852 Wald ratio 1 trans NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.119 0.0458 0.00937 Wald ratio 1 trans NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.3 0.116 0.00997 Wald ratio 1 trans NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0954 0.0383 0.0128 Wald ratio 1 trans NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.207 0.0852 0.0153 Wald ratio 1 trans NA
Serum cystatin C (eGFRcys) -0.024 0.0109 0.0273 Wald ratio 1 trans NA
Fractured bone site(s): Other bones -0.14 0.0688 0.0419 Wald ratio 1 trans NA
Depressive symptoms -0.0376 0.0188 0.0455 Wald ratio 1 trans NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis -0.223 0.112 0.0469 Wald ratio 1 trans NA
…and 87 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

27 association rows across 19 traits (21 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
Hematological traits (multi-trait analysis) 4e-38 rs72836805 3 GCST90838669 no MR -> candidate analysis
Height 7e-36 rs3111728 3 GCST90245848 MR: beta=0.0255, p=0.131 (trans)
Lymphocyte count 2e-18 rs77713896 4 GCST90002316 no MR -> candidate analysis
C1QL2 protein levels 3e-14 rs143843154 1 GCST90468487 no MR -> candidate analysis
Lymphocyte count (UKB data field 30120) 1e-12 rs77713896 1 GCST90468082 no MR -> candidate analysis
Bone mineral density mean 1e-11 rs147401949 1 GCST90321120 no MR -> candidate analysis
Smoking initiation 1e-10 rs78986663 1 GCST90243968 no MR -> candidate analysis
Educational attainment 1e-10 rs6542543 1 GCST90105038 no MR -> candidate analysis
Dupuytren’s disease 2e-10 rs10174596 2 GCST90301252 no MR -> candidate analysis
Brain morphology (MOSTest) 1e-9 rs1995916 1 GCST90239729 no MR -> candidate analysis
Lymphocyte percentage of white cells 1e-9 rs17661862 1 GCST90002389 no MR -> candidate analysis
Severe COVID-19 infection 2e-9 rs13000543 1 GCST90255357 no MR -> candidate analysis
…and 7 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 352 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
hereditary disease 0.816 established (curated) no MR -> candidate analysis
Intellectual disability 0.426 established (curated) no MR -> candidate analysis
neurodevelopmental disorder 0.69 established (curated) no MR -> candidate analysis
Dupuytren Contracture 0.612 common-variant locus no MR -> candidate analysis
placenta praevia 0.548 common-variant locus no MR -> candidate analysis
smoking initiation 0.42 common-variant locus no MR -> candidate analysis
palmar fibromatosis 0.394 common-variant locus no MR -> candidate analysis
fasciitis 0.387 common-variant locus no MR -> candidate analysis
scoliosis 0.357 common-variant locus no MR -> candidate analysis
severe acute respiratory syndrome 0.331 common-variant locus no MR -> candidate analysis
COVID-19 0.331 common-variant locus no MR -> candidate analysis

Of the 11 rows above, 11 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 (Tyrosine-protein phosphatase non-receptor type 4)
gnomAD constraint pLI=1, LOEUF=0.459 — LoF-INTOLERANT
GWAS Catalog 32 unique SNPs / 64 rows
ClinVar 222 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance