CausalSentinel

Protein Dossier — PSD (PH and SEC7 domain-containing 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
Forced vital capacity (FVC) 0.0202 0.00633 0.00142 Wald ratio 1 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.13 0.0425 0.0022 Wald ratio 1 trans NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.075 0.0246 0.00232 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension -0.0402 0.0137 0.00334 Wald ratio 1 trans NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux -0.114 0.0417 0.00647 Wald ratio 1 trans NA
Thalamus volume 49.8 20 0.0127 Wald ratio 1 trans NA
Transferrin -0.0806 0.0325 0.013 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) 0.0164 0.00668 0.0143 Wald ratio 1 trans NA
Diastolic blood pressure automated reading -0.0166 0.00789 0.0353 Wald ratio 1 trans NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0431 0.0207 0.0374 Wald ratio 1 trans NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.111 0.0541 0.0407 Wald ratio 1 trans NA
Body mass index (BMI) -0.0156 0.00771 0.043 Wald ratio 1 trans NA
…and 96 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

8 association rows across 8 traits (8 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
Phospholipids to Total Lipids in Large HDL percentage 2e-16 rs79931565 1 GCST90501143 no MR -> candidate analysis
Alanine transaminase (ALT, mean, inv-norm transformed) 4e-12 rs148337160 1 GCST90479507 no MR -> candidate analysis
Chronic elevation of alanine aminotransferase (cALT) levels 3e-11 rs148337160 1 GCST90129601 no MR -> candidate analysis
Alanine transaminase (ALT, maximum, inv-norm transformed) 3e-11 rs148337160 1 GCST90479506 no MR -> candidate analysis
Apolipoprotein B levels 2e-10 rs79931565 1 GCST010243 no MR -> candidate analysis
Alzheimer’s disease or educational attainment (pleiotropy) 4e-10 rs55970842 1 GCST90095190 no MR -> candidate analysis
Phospholipids to total lipids in small HDL percentage (UKB d 4e-10 rs148337160 1 GCST90269741 no MR -> candidate analysis
Educational attainment (MTAG) 1e-8 rs3781291 1 GCST006571 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 114 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
mathematical ability 0.09 common-variant locus no MR -> candidate analysis
Abnormal nasolacrimal system morphology 0.077 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.064 common-variant locus no MR -> candidate analysis
cannabis dependence 0.062 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.051 common-variant locus no MR -> candidate analysis
autism spectrum disorder 0.051 common-variant locus no MR -> candidate analysis
intelligence 0.051 common-variant locus MR: beta=0.0594, p=0.152 (trans)
dislocation 0.036 common-variant locus no MR -> candidate analysis

Of the 8 rows above, 7 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 0 known modulators (PH and SEC7 domain-containing protein 1)
gnomAD constraint pLI=1, LOEUF=0.469 — LoF-INTOLERANT
GWAS Catalog 89 unique SNPs / 177 rows
ClinVar 178 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance