CausalSentinel

Protein Dossier — SCG3 (Secretogranin-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
Weight -0.0242 0.00512 2.15e-06 Wald ratio 1 cis NA
Body mass index (BMI) -0.0257 0.00579 8.97e-06 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0599 0.0181 9.44e-04 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0492 0.0152 0.00124 Wald ratio 1 cis NA
Birth length -0.0636 0.0251 0.0113 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0185 0.00751 0.0138 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypopituitarism 0.479 0.205 0.0193 Wald ratio 1 cis NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.254 0.114 0.0261 Wald ratio 1 cis NA
Body fat -0.029 0.0132 0.0276 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.0714 0.033 0.0305 Wald ratio 1 cis NA
Cancer code self-reported: malignant melanoma 0.124 0.0583 0.0338 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0105 0.00502 0.0362 Wald ratio 1 cis NA
…and 98 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

40 association rows across 28 traits (37 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
Secretogranin-3 levels 1e-315 rs1456295 2 GCST90249447 no MR -> candidate analysis
SCG3 protein levels 8e-248 rs2305710 5 GCST90470539 no MR -> candidate analysis
Serum levels of protein SCG3 2e-111 rs1456297 1 GCST90089949 no MR -> candidate analysis
Neutrophil collagenase (analyte X2954.56) levels 2e-74 rs2606139 1 GCST90425543 no MR -> candidate analysis
Secretogranin-3 levels (SCG3.7957.2.3) 1e-68 rs1378892 2 GCST90242735 no MR -> candidate analysis
Blood protein levels 4e-58 rs1456297 1 GCST006585 no MR -> candidate analysis
Cerebrospinal fluid protein SCG3 levels 3e-25 rs9672605 1 GCST90944552 no MR -> candidate analysis
Body mass index 9e-19 rs7170980 2 GCST90255621 MR: beta=-0.0257, p=8.97e-06 (cis)
Whole body fat mass (UKB data field 23100) 1e-13 rs7167760 2 GCST90428121 no MR -> candidate analysis
Educational attainment 2e-13 rs1378893 2 GCST90105038 no MR -> candidate analysis
Adiposity (multivariate analysis) 3e-13 rs979259 1 GCST90624107 no MR -> candidate analysis
Gliomedin level in Chronic kidney disease with hypertension 2e-12 rs2607117 1 GCST90235491 no MR -> candidate analysis
…and 16 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 174 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
intelligence 0.507 common-variant locus no MR -> candidate analysis
placental abruption 0.455 common-variant locus no MR -> candidate analysis
aortic atherosclerosis 0.379 common-variant locus no MR -> candidate analysis
osteoarthritis, knee 0.221 common-variant locus MR: beta=0.0807, p=0.11 (cis)
obesity disorder 0.196 common-variant locus no MR -> candidate analysis
developmental and epileptic encephalopathy, 13 0.195 established (curated) no MR -> candidate analysis
osteoarthritis, hip 0.189 common-variant locus MR: beta=0.0807, p=0.11 (cis)
schizophrenia 0.182 established (curated) no MR -> candidate analysis
type 2 diabetes mellitus 0.156 common-variant locus no MR -> candidate analysis
insomnia 0.126 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.085 common-variant locus no MR -> candidate analysis
autism spectrum disorder 0.085 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 10 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=4.3e-09, LOEUF=0.887 — LoF-tolerant
GWAS Catalog 74 unique SNPs / 124 rows
ClinVar 90 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance