CausalSentinel

Protein Dossier — SIRPA (Tyrosine-protein phosphatase non-receptor type substrate 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
Sodium in urine -0.00648 0.00201 0.00129 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders -0.0967 0.0307 0.00162 Wald ratio 1 cis NA
Cough on most days -0.0333 0.0108 0.0021 Wald ratio 1 cis NA
Schizophrenia -0.0274 0.00925 0.00304 Wald ratio 1 cis NA
Diagnoses - main ICD10: I30 Acute pericarditis 0.261 0.0906 0.00399 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0302 0.0107 0.00455 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.0409 0.0149 0.00601 Wald ratio 1 cis NA
Weight -0.00482 0.00181 0.00769 Wald ratio 1 cis NA
Alcohol intake frequency -0.00781 0.00302 0.00985 Wald ratio 1 cis NA
Happiness 0.00619 0.00254 0.0148 Wald ratio 1 cis NA
Pulse rate -0.00853 0.00362 0.0183 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.00406 0.00177 0.0218 Wald ratio 1 cis NA
…and 64 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

229 association rows across 83 traits (213 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 SIRPA levels 1e-10333 rs6136377 6 GCST90859973 no MR -> candidate analysis
Tyrosine-protein phosphatase non-receptor type substrate 1 l 1e-5100 rs1569960 17 GCST90250037 no MR -> candidate analysis
Tyrosine-protein phosphatase non-receptor type substrate 1 l 8e-1361 rs6136377 2 GCST90243222 no MR -> candidate analysis
Blood protein levels 2e-1072 rs6075340 1 GCST006585 no MR -> candidate analysis
Cerebrospinal fluid protein SIRPA levels 1e-698 rs4813331 1 GCST90944895 no MR -> candidate analysis
Tyrosine-protein phosphatase non-receptor type substrate 1 ( 1e-310 rs6075339 1 GCST90426344 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 2e-304 rs4814779 6 GCST90468087 no MR -> candidate analysis
Mean platelet volume 2e-264 rs4814776 13 GCST90002346 no MR -> candidate analysis
Tyrosine-protein phosphatase non-receptor type substrate 1 l 2e-263 rs6075340 1 GCST90237933 no MR -> candidate analysis
Platelet crit (UKB data field 30090) 1e-250 rs11906768 4 GCST90468096 no MR -> candidate analysis
SIRPA protein levels 2e-237 rs77985164 32 GCST90470639 no MR -> candidate analysis
mean platelet volume (MPV, mean, inv-norm transformed) 3e-134 rs6136492 2 GCST90479708 no MR -> candidate analysis
…and 71 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 731 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
type 2 diabetes mellitus 0.692 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.561 common-variant locus no MR -> candidate analysis
thrombocytopenia 4 0.554 common-variant locus no MR -> candidate analysis
hemorrhagic disease 0.559 common-variant locus no MR -> candidate analysis
tooth disorder 0.545 common-variant locus no MR -> candidate analysis
alcohol drinking 0.404 common-variant locus no MR -> candidate analysis
urolithiasis 0.347 common-variant locus 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=1, LOEUF=0.312 — LoF-INTOLERANT
GWAS Catalog 140 unique SNPs / 327 rows
ClinVar 133 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance