Protein Dossier — SMPDL3A (Cyclic GMP-AMP phosphodiesterase SMPDL3A)
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 |
0.00771 |
0.00286 |
0.00707 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
0.0143 |
0.00545 |
0.00852 |
Wald ratio |
1 |
cis |
NA |
| Neo-agreeableness |
0.248 |
0.0966 |
0.0101 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: prostate cancer |
-0.1 |
0.042 |
0.0168 |
Wald ratio |
1 |
cis |
NA |
| Diastolic blood pressure automated reading |
0.00762 |
0.00332 |
0.0216 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: pneumothorax |
0.278 |
0.122 |
0.0228 |
Wald ratio |
1 |
cis |
NA |
| Urinary albumin-to-creatinine ratio |
0.0288 |
0.013 |
0.0268 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis |
-0.0913 |
0.0413 |
0.0271 |
Wald ratio |
1 |
cis |
NA |
| Body mass index (BMI) |
0.00704 |
0.00324 |
0.0297 |
Wald ratio |
1 |
cis |
NA |
| Neo-neuroticism |
-0.319 |
0.147 |
0.0303 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K35 Acute appendicitis |
-0.112 |
0.0522 |
0.0314 |
Wald ratio |
1 |
cis |
NA |
| Intracranial volume |
5.6e+03 |
2.65e+03 |
0.0343 |
Wald ratio |
1 |
cis |
NA |
| …and 97 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4771_10_3 |
ASM3A |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
47 association rows across 28 traits (41 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 |
| SMPD1/SMPDL3A protein level ratio |
2e-3823 |
rs28385609 |
1 |
GCST90315854 |
no MR -> candidate analysis |
| CTSF/SMPDL3A protein level ratio |
7e-3346 |
rs28385609 |
1 |
GCST90314316 |
no MR -> candidate analysis |
| CREG1/SMPDL3A protein level ratio |
1e-3343 |
rs28385609 |
1 |
GCST90314252 |
no MR -> candidate analysis |
| PLA2G15/SMPDL3A protein level ratio |
1e-3109 |
rs28385609 |
1 |
GCST90315663 |
no MR -> candidate analysis |
| CTSZ/SMPDL3A protein level ratio |
3e-3028 |
rs28385609 |
1 |
GCST90314322 |
no MR -> candidate analysis |
| IDS/SMPDL3A protein level ratio |
2e-2825 |
rs28385609 |
1 |
GCST90315126 |
no MR -> candidate analysis |
| Acid sphingomyelinase-like phosphodiesterase 3a (analyte X47 |
2e-408 |
rs28385609 |
1 |
GCST90426104 |
no MR -> candidate analysis |
| Serum levels of protein SMPDL3A |
2e-283 |
rs28385609 |
2 |
GCST90087771 |
no MR -> candidate analysis |
| Acid sphingomyelinase-like phosphodiesterase 3a levels (SMPD |
2e-282 |
rs28385609 |
3 |
GCST90240172 |
no MR -> candidate analysis |
| SMPDL3A protein levels |
1e-242 |
rs184473777 |
13 |
GCST90470686 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein SMPDL3A levels |
5e-229 |
rs28385609 |
1 |
GCST90944584 |
no MR -> candidate analysis |
| Blood protein levels |
9e-161 |
rs13192569 |
1 |
GCST006585 |
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 95 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 |
0.483 |
— |
common-variant locus |
no MR -> candidate analysis |
| urolithiasis |
0.209 |
— |
common-variant locus |
no MR -> candidate analysis |
| idiopathic pulmonary fibrosis |
0.199 |
— |
common-variant locus |
no MR -> candidate analysis |
| temporomandibular joint disorder |
0.144 |
— |
common-variant locus |
no MR -> candidate analysis |
| breast disorder |
0.11 |
— |
common-variant locus |
no MR -> candidate analysis |
| ocular hypotension |
0.095 |
— |
common-variant locus |
no MR -> candidate analysis |
| placenta praevia |
0.072 |
— |
common-variant locus |
no MR -> candidate analysis |
| androgenetic alopecia |
0.059 |
— |
common-variant locus |
no MR -> candidate analysis |
| atrial fibrillation |
0.059 |
— |
common-variant locus |
no MR -> candidate analysis |
| benign neoplasm of adrenal gland |
0.041 |
— |
common-variant locus |
no MR -> candidate analysis |
| stroke disorder |
0.039 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 11 rows above, 11 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=5.3e-14, LOEUF=1.32 — LoF-tolerant |
| GWAS Catalog |
53 unique SNPs / 106 rows |
| ClinVar |
93 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 95 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘SMPDL3A’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 93 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 28 traits by best p-value, aggregated from 47 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/Q92484 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000172594/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/SMPDL3A — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SMPDL3A — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SMPDL3A%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SMPDL3A — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:09:48 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none