CausalSentinel

Protein Dossier — SIRPG (Signal-regulatory protein gamma)

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
Diagnoses - main ICD10: R55 Syncope and collapse 0.279 0.0775 3.21e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: anxiety or panic attacks 0.232 0.0658 4.25e-04 Wald ratio 1 cis NA
Ulcerative colitis -0.128 0.0521 0.0138 Wald ratio 1 cis NA
Low grade serous ovarian cancer 0.476 0.194 0.0142 Wald ratio 1 cis NA
Diagnoses - main ICD10: R35 Polyuria 0.284 0.117 0.0155 Wald ratio 1 cis NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.14 0.0582 0.0162 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypopituitarism 0.676 0.293 0.0209 Wald ratio 1 cis NA
Schizophrenia -0.0989 0.043 0.0214 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.231 0.104 0.0269 Wald ratio 1 cis NA
Fasting insulin -0.0282 0.0129 0.0295 Wald ratio 1 cis NA
Ferritin -0.0814 0.0377 0.0306 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast -0.183 0.0909 0.0439 Wald ratio 1 cis NA
…and 94 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

45 association rows across 35 traits (40 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
LTBR/SIRPB1 protein level ratio 2e-2930 rs76958425 1 GCST90315339 no MR -> candidate analysis
OSCAR/SIRPB1 protein level ratio 6e-2733 rs76958425 1 GCST90315587 no MR -> candidate analysis
Circulating SIRPB1 levels 3e-2444 rs75649571 1 GCST90860614 no MR -> candidate analysis
CD58/SIRPB1 protein level ratio 2e-2380 rs76958425 1 GCST90313855 no MR -> candidate analysis
Blood protein levels 5e-226 rs4814391 2 GCST006585 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 5e-191 rs11696739 1 GCST90468087 no MR -> candidate analysis
SIRPB1 protein levels 1e-190 rs62186952 4 GCST90470640 no MR -> candidate analysis
Signal-regulatory protein beta-1 levels (SIRPB1.6247.9.3) 3e-161 rs76357893 1 GCST90242820 no MR -> candidate analysis
Signal-regulatory protein gamma levels 4e-132 rs6043409 1 GCST90249560 no MR -> candidate analysis
Signal-regulatory protein beta-1 levels 2e-105 rs2277760 1 GCST90249559 no MR -> candidate analysis
Mean platelet volume 3e-100 rs11696739 2 GCST90002395 no MR -> candidate analysis
Immature platelet count 1e-37 rs56078965 1 GCST90281199 no MR -> candidate analysis
…and 23 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 311 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 1 diabetes mellitus 0.842 common-variant locus no MR -> candidate analysis
rheumatoid arthritis 0.522 common-variant locus MR: beta=0.116, p=0.0536 (cis)
alcohol drinking 0.519 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.287 common-variant locus no MR -> candidate analysis
tooth disorder 0.254 common-variant locus no MR -> candidate analysis
placental retention 0.249 common-variant locus no MR -> candidate analysis
placenta praevia 0.243 common-variant locus no MR -> candidate analysis
placental abruption 0.243 common-variant locus no MR -> candidate analysis
narcolepsy-cataplexy syndrome 0.239 common-variant locus no MR -> candidate analysis
spermatogenic failure 0.206 common-variant locus no MR -> candidate analysis

Of the 10 rows above, 9 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=3.1e-14, LOEUF=1.4 — LoF-tolerant
GWAS Catalog 95 unique SNPs / 184 rows
ClinVar 123 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance