SMPD1

Chr 11AR

sphingomyelin phosphodiesterase 1

The protein is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide and has phospholipase C activity. Mutations cause Niemann-Pick disease types A and B through an autosomal recessive inheritance pattern. The pathogenic mechanism involves loss of function, leading to sphingomyelin accumulation in lysosomes.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.082 OMIM phenotypes
Clinical SummarySMPD1
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Gene-Disease Validity (ClinGen)
acid sphingomyelinase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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 OE0.73 (0.511.08)
00.351.4
Missense OE1.01 (0.931.10)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 18 / 24.6Missense obs/exp: 382 / 376.7Syn Z: -1.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSMPD1-related Niemann-Pick diseaseLOFAR
Mechanism Note (expert annotation)
LOF

Acid sphingomyelinase. Biallelic LOF causes Niemann-Pick disease type A (severe, neuronopathic) or type B (milder, non-neuronopathic). GOF prediction is incorrect for this classic lysosomal storage disease.

References:PMID:2023319

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5575th %ile
GOF
0.6736th %ile
LOF
0.3355th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

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.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
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