MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Non-cancer illness code self-reported: vitiligo | 0.797 | 0.268 | 0.00296 | Wald ratio | 1 | cis | NA |
| Cancer code self-reported: basal cell carcinoma | 0.186 | 0.0788 | 0.018 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: K57 Diverticular disease of intestine | -0.18 | 0.0766 | 0.0187 | Wald ratio | 1 | cis | NA |
| Heel bone mineral density (BMD) T-score automated | 0.0271 | 0.0117 | 0.0204 | Wald ratio | 1 | cis | NA |
| Thyroid cancer | 0.738 | 0.348 | 0.0339 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: C50 Malignant neoplasm of breast | -0.169 | 0.0843 | 0.0444 | Wald ratio | 1 | cis | NA |
| Sodium in urine | -0.0176 | 0.00888 | 0.047 | Wald ratio | 1 | cis | NA |
| Putamen volume | 49.9 | 26.3 | 0.0579 | Wald ratio | 1 | cis | NA |
| Forced expiratory volume in 1-second (FEV1) | -0.0144 | 0.00781 | 0.0654 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: arthritis (nos) | 0.164 | 0.089 | 0.0655 | Wald ratio | 1 | cis | NA |
| Cough on most days | -0.0922 | 0.0509 | 0.07 | Wald ratio | 1 | cis | NA |
| Systolic blood pressure automated reading | -0.0164 | 0.00924 | 0.0752 | Wald ratio | 1 | cis | NA |
| …and 67 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
33 association rows across 17 traits (29 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 |
|---|---|---|---|---|---|
| PLA2G15/SMPD1 protein level ratio | 2e-971 | rs1050239 | 1 | GCST90315662 | no MR -> candidate analysis |
| CTSZ/SMPD1 protein level ratio | 7e-897 | rs1050239 | 1 | GCST90314321 | no MR -> candidate analysis |
| CTSF/SMPD1 protein level ratio | 1e-848 | rs1050239 | 1 | GCST90314315 | no MR -> candidate analysis |
| Circulating SMPD1 levels | 1e-631 | rs1050228 | 7 | GCST90859673 | no MR -> candidate analysis |
| HYAL1/SMPD1 protein level ratio | 5e-260 | rs2101469 | 1 | GCST90315100 | no MR -> candidate analysis |
| Sphingomyelin phosphodiesterase levels | 2e-141 | rs1050239 | 4 | GCST90246600 | no MR -> candidate analysis |
| Serum levels of protein SMPD1 | 8e-71 | rs1050239 | 1 | GCST90086460 | no MR -> candidate analysis |
| SMPD1 protein levels | 9e-70 | rs142787001 | 6 | GCST90470684 | no MR -> candidate analysis |
| Blood protein levels | 2e-31 | rs1050239 | 1 | GCST006585 | no MR -> candidate analysis |
| Cerebrospinal fluid protein SMPD1 levels | 4e-16 | rs1050239 | 1 | GCST90944583 | no MR -> candidate analysis |
| Restless legs syndrome | 4e-16 | rs10839553 | 1 | GCST90432061 | no MR -> candidate analysis |
| Neurological blood protein biomarker levels | 4e-13 | rs1050239 | 1 | GCST008478 | no MR -> candidate analysis |
| …and 5 more traits (see JSON) |
Top diseases by Open Targets association (of 1997 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 |
|---|---|---|---|---|
| Niemann-Pick disease type A | 0.949 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease type B | 0.951 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease | 0.939 | — | established (curated) | no MR -> candidate analysis |
| acid sphingomyelinase deficiency | 0.85 | — | established (curated) | no MR -> candidate analysis |
| lysosomal storage disease | 0.438 | — | established (curated) | no MR -> candidate analysis |
| hereditary disease | 0.773 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease, type C1 | 0.699 | — | established (curated) | no MR -> candidate analysis |
| Intellectual disability | 0.63 | — | established (curated) | no MR -> candidate analysis |
| ceroid lipofuscinosis, neuronal, 6A | 0.547 | — | established (curated) | no MR -> candidate analysis |
| Abnormality of metabolism/homeostasis | 0.438 | — | established (curated) | no MR -> candidate analysis |
| Gaucher disease | 0.182 | — | established (curated) | no MR -> candidate analysis |
| nephrotic syndrome | 0.115 | — | common-variant locus | no MR -> candidate analysis |
| male reproductive organ cancer | 0.115 | — | common-variant locus | no MR -> candidate analysis |
Of the 13 rows above, 13 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.
| Layer | Result |
|---|---|
| ChEMBL druggability | 0 known modulators (Sphingomyelin phosphodiesterase) |
| gnomAD constraint | pLI=1.1e-15, LOEUF=1.21 — LoF-tolerant |
| GWAS Catalog | 66 unique SNPs / 132 rows |
| ClinVar | 1224 records; 15 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 1997 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘SMPD1’ and resolved to ‘Sphingomyelin phosphodiesterase’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 1224 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 17 of 17 traits by best p-value, aggregated from 33 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/P17405 — 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/ENSG00000166311/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2760/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SMPD1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SMPD1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SMPD1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SMPD1 — GWAS Catalog search API (live; release not exposed)