SMPD1

Chr 11AR

sphingomyelin phosphodiesterase 1

Also known as: ASM, ASMASE, NPD

The protein encoded by this gene is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide. The encoded protein also has phospholipase C activity. Defects in this gene are a cause of Niemann-Pick disease type A (NPA) and Niemann-Pick disease type B (NPB). Multiple transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Niemann-Pick disease, type AMIM #257200
AR
Niemann-Pick disease, type BMIM #607616
AR

Clinical highlights

Gene-disease validity (ClinGen)
acid sphingomyelinase deficiency · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the established mechanism, though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
74
Pubs (1 yr)
P/LP submissions
P/LP missense
1.08
LOEUF
LOF
Mechanism· annotated
📖
GeneReview available — SMPD1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.08LOEUF
pLI 0.000
Z-score 1.23
OE 0.73 (0.511.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.10Z-score
OE missense 1.01 (0.931.10)
382 obs / 376.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.73 (0.511.08)
00.351.4
Missense OE?1.01 (0.931.10)
00.61.4
Synonymous OE?1.10
01.21.6
LoF obs/exp: 18 / 24.6Missense obs/exp: 382 / 376.7Syn Z: -1.00

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SMPD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.