CausalSentinel

Protein Dossier — SMOC1 (SPARC-related modular calcium-binding protein 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
Mean cell volume 0.427 0.0951 6.98e-06 Wald ratio 1 cis NA
Mean cell haemoglobin 0.137 0.0372 2.28e-04 Wald ratio 1 cis NA
Eye problems or disorders: Cataract -0.227 0.0615 2.30e-04 Wald ratio 1 cis NA
Iron 0.134 0.0367 2.46e-04 Wald ratio 1 cis NA
Transferrin Saturation 0.121 0.0367 9.77e-04 Wald ratio 1 cis NA
Percent emphysema 0.0906 0.0327 0.00557 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.163 0.0638 0.0107 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0295 0.0116 0.0112 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia 0.152 0.0618 0.0138 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.219 0.0986 0.0265 Wald ratio 1 cis NA
Neo-conscientiousness 0.594 0.272 0.0289 Wald ratio 1 cis NA
Haemoglobin concentration 0.0462 0.0212 0.0296 Wald ratio 1 cis 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

166 association rows across 85 traits (149 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 SMOC1 levels 5e-376 rs55796722 4 GCST90860685 no MR -> candidate analysis
SMOC1 protein levels 1e-211 rs227419 3 GCST90470682 no MR -> candidate analysis
Height 7e-203 rs1547088 16 GCST90245848 no MR -> candidate analysis
SPARC-related modular calcium-binding protein 1 levels 1e-116 rs1958078 9 GCST90249582 no MR -> candidate analysis
Appendicular lean mass 4e-40 rs35230100 3 GCST90000025 no MR -> candidate analysis
Standing height (UKB data field 50) 1e-34 rs1547088 1 GCST90468178 no MR -> candidate analysis
mean corpuscular hemoglobin (MCH, maximum, inv-norm transfor 6e-34 rs1958078 2 GCST90475442 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 9e-34 rs1958078 2 GCST90838669 no MR -> candidate analysis
mean corpuscular hemoglobin (MCH, mean, inv-norm transformed 7e-33 rs1958078 2 GCST90475446 no MR -> candidate analysis
Mean corpuscular hemoglobin 1e-32 rs1958078 6 GCST90002322 no MR -> candidate analysis
SPARC-related modular calcium-binding protein 1 levels (SMOC 2e-30 rs1958078 2 GCST90242872 no MR -> candidate analysis
Mean corpuscular haemoglobin (UKB data field 30050) 2e-30 rs55796722 1 GCST90468084 no MR -> candidate analysis
…and 73 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 4360 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
microphthalmia with limb anomalies 0.84 established (curated) no MR -> candidate analysis
atherosclerosis 0.808 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.8 common-variant locus no MR -> candidate analysis
peripheral vascular disease 0.794 common-variant locus no MR -> candidate analysis
Intrahepatic cholestasis of pregnancy 0.739 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.682 common-variant locus no MR -> candidate analysis
hereditary disease 0.682 established (curated) no MR -> candidate analysis
hypertensive disorder 0.55 common-variant locus no MR -> candidate analysis
essential hypertension 0.55 common-variant locus no MR -> candidate analysis
self-injurious ideation 0.527 common-variant locus no MR -> candidate analysis
chronic obstructive pulmonary disease 0.464 common-variant locus no MR -> candidate analysis
tuberculosis 0.457 common-variant locus no MR -> candidate analysis
benign neoplasm 0.461 common-variant locus no MR -> candidate analysis
corneal edema 0.43 common-variant locus no MR -> candidate analysis
urolithiasis 0.424 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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=0.61, LOEUF=0.558 — LoF-tolerant
GWAS Catalog 107 unique SNPs / 224 rows
ClinVar 202 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance