CausalSentinel

Protein Dossier — SIRPB1 (Signal-regulatory protein beta-1 isoform 3)

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
Neo-neuroticism -0.46 0.139 9.27e-04 Wald ratio 1 cis NA
Endometrioid ovarian cancer -0.126 0.0428 0.00324 Wald ratio 1 cis NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate -0.14 0.0502 0.0053 Wald ratio 1 cis NA
Fractured bone site(s): Other bones -0.045 0.0161 0.00532 Wald ratio 1 cis NA
Sleep duration 0.00662 0.00277 0.0168 Wald ratio 1 cis NA
Serum cystatin C (eGFRcys) -0.0059 0.00268 0.0278 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years -0.0245 0.0113 0.0304 Wald ratio 1 cis NA
Cancer code self-reported: prostate cancer -0.097 0.0458 0.0342 Wald ratio 1 cis NA
Large vessel disease -0.102 0.0504 0.0441 Wald ratio 1 cis NA
Mean cell haemoglobin -0.0323 0.0162 0.0464 Wald ratio 1 cis NA
Low grade serous ovarian cancer 0.136 0.0699 0.0515 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression 0.0268 0.0142 0.0592 Wald ratio 1 cis NA
…and 91 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

75 association rows across 46 traits (73 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 4 GCST90860614 no MR -> candidate analysis
CD58/SIRPB1 protein level ratio 2e-2380 rs76958425 1 GCST90313855 no MR -> candidate analysis
Signal-regulatory protein beta-1 levels 1e-1037 rs12480515 4 GCST90249559 no MR -> candidate analysis
Circulating SIRPA levels 6e-299 rs2253427 1 GCST90859973 no MR -> candidate analysis
Serum levels of protein SIRPB1 2e-273 rs16995228 3 GCST90089319 no MR -> candidate analysis
Blood protein levels 5e-226 rs4814391 1 GCST006585 no MR -> candidate analysis
Cerebrospinal fluid protein SIRPB1 levels 4e-223 rs2318043 1 GCST90944578 no MR -> candidate analysis
Signal-regulatory protein beta-1 levels (SIRPB1.6247.9.3) 1e-213 rs3848788 5 GCST90242820 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 5e-191 rs11696739 1 GCST90468087 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 5e-174 rs6074894 2 GCST90838669 no MR -> candidate analysis
…and 34 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 309 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
alcohol drinking 0.463 common-variant locus no MR -> candidate analysis
type 1 diabetes mellitus 0.253 common-variant locus no MR -> candidate analysis
rheumatoid arthritis 0.153 common-variant locus no MR -> candidate analysis
tooth disorder 0.087 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 4 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=1.3e-08, LOEUF=1.12 — LoF-tolerant
GWAS Catalog 93 unique SNPs / 186 rows
ClinVar 126 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance