SMPD1 (Sphingomyelin phosphodiesterase) variants and mutations

SMPD1 (also known as Sphingomyelin phosphodiesterase) is a human protein-coding gene encoding a sphingomyelin phosphodiesterase protein. It hydrolyzes sphingomyelin to ceramide in lysosomes and participates in membrane-lipid turnover and stress signaling. Biallelic loss-of-function variants cause acid sphingomyelinase deficiency, including Niemann-Pick disease types A and B. This analysis covers 1,242 SMPD1 variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes Niemann-Pick disease type A, Niemann-Pick disease type B, and Niemann-Pick disease. Example SMPD1 variants include P2L, P2R, and P2S.

Variant analysis overview

Gene: SMPD1
Protein: Sphingomyelin phosphodiesterase
UniProt accession: P17405
Organism: Homo sapiens
Variants analyzed: 1242
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 978 unspecified-consequence records; 96 missense variants; 91 synonymous variants; 47 frameshift variants; 3 stop-gained variants; 10 in-frame deletions; 9 in-frame insertions; 2 splice-region variants; 5 substitution
Prediction scores: 951 variants have prediction scores (77% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Niemann-Pick disease type A, Niemann-Pick disease type B, Niemann-Pick disease, acid sphingomyelinase deficiency, lysosomal storage disease, Parkinson disease, Alzheimer disease, neurodegenerative disease, multiple sclerosis, hereditary disease, Niemann-Pick disease, type C1, Intellectual disability.

Protein structure and variant hotspots

Protein features: 1 domains; 8 binding sites; 7 post-translational modification sites.
Structural context: 210 variants have structural context.
PTM context: 12 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable SMPD1 variants

Examples include P2L, P2R, P2S, P2T, P2P, R3C, R3H, R3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

SMPD1 analysis run — SMPD1 (1,242 variants) — completed 2026-08-19