CausalSentinel

Protein Dossier — SPOCK3 (Testican-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
Pallidum volume -31 10.7 0.00383 Wald ratio 1 cis NA
Forearm bone mineral density 0.14 0.0649 0.0307 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.0188 0.0087 0.0309 Wald ratio 1 cis NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation 0.116 0.0565 0.0402 Wald ratio 1 cis NA
Eye problems or disorders: Injury or trauma resulting in loss of vision 0.195 0.0984 0.0474 Wald ratio 1 cis NA
Body mass index (BMI) -0.0176 0.00908 0.0531 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol 0.0417 0.0236 0.0769 Wald ratio 1 cis NA
Eye problems or disorders: Cataract -0.0952 0.0547 0.0819 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.1 0.0581 0.085 Wald ratio 1 cis NA
Weight -0.0134 0.00802 0.0939 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0193 0.0117 0.101 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate -0.147 0.0909 0.106 Wald ratio 1 cis NA
…and 54 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

61 association rows across 45 traits (32 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
Serum levels of protein SPOCK3 1e-186 rs62353586 4 GCST90090901 no MR -> candidate analysis
Testican-3 levels 1e-152 rs62353586 6 GCST90249873 no MR -> candidate analysis
Blood protein levels 5e-96 rs62353586 1 GCST006585 no MR -> candidate analysis
Testican-3 levels (SPOCK3.9906.21.3) 2e-28 rs17599599 2 GCST90242988 no MR -> candidate analysis
Testican-3 level in Chronic kidney disease with hypertension 4e-17 rs4385095 1 GCST90239534 no MR -> candidate analysis
GLIPR1 protein levels 4e-12 rs774502822 1 GCST90469357 no MR -> candidate analysis
Symptomatic extra- and intra-cranial atherosclerotic stenosi 1e-11 rs139225422 1 GCST90319540 no MR -> candidate analysis
Toxic multinodular goiter (PheCode 242.2) 1e-11 rs147778808 1 GCST90479864 no MR -> candidate analysis
DnaJ homolog subfamily B member 3 protein levels (SomaScan I 2e-11 rs35065151 1 GCST90439025 no MR -> candidate analysis
Adolescent idiopathic scoliosis 2e-11 rs6841675 1 GCST006287 no MR -> candidate analysis
Immune reponse to smallpox (secreted IL-10) 3e-11 rs13111850 1 GCST001534 no MR -> candidate analysis
Total PHF-tau (SNP x SNP interaction) 1e-9 rs17696409 x rs1419028 1 GCST010340 no MR -> candidate analysis
…and 33 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 164 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
Hypercholesterolemia 0.537 common-variant locus MR: beta=0.0417, p=0.0769 (cis)
medical procedure 0.523 common-variant locus no MR -> candidate analysis
complication 0.523 common-variant locus no MR -> candidate analysis
trauma complication 0.523 common-variant locus no MR -> candidate analysis
response to antihypertensive drug 0.519 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.506 common-variant locus no MR -> candidate analysis
liver disorder 0.49 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.479 common-variant locus no MR -> candidate analysis
alcohol drinking 0.469 common-variant locus no MR -> candidate analysis
response to vaccine 0.409 common-variant locus no MR -> candidate analysis
bone Paget disease 0.396 common-variant locus no MR -> candidate analysis
pericarditis 0.393 common-variant locus no MR -> candidate analysis
tooth disorder 0.388 common-variant locus no MR -> candidate analysis
alopecia areata 0.382 common-variant locus no MR -> candidate analysis
congenital anomaly of cardiovascular system 0.382 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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=0.0001, LOEUF=0.719 — LoF-tolerant
GWAS Catalog 66 unique SNPs / 119 rows
ClinVar 130 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance