Niemann-Pick disease, type B: genes and variants

Genes linked to Niemann-Pick disease, type B

• SMPD1: Sphingomyelin phosphodiesterase

  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.

  113 disease-causing and 130 uncertain variants in SMPD1 are linked to Niemann-Pick disease, type B.

Known disease-causing variants in Niemann-Pick disease, type B

Showing 60 of 113.

Uncertain variants in Niemann-Pick disease, type B that look disease-causing

Which prediction tools work for Niemann-Pick disease, type B

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 97 out of 100
• PolyPhen-2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 96 out of 100
• phyloP: 94 out of 100

Same protein, different disease

• Sphingomyelin/cholesterol lipidosis is also caused by SMPD1 variants; they fall partly in the same places as the Niemann-Pick disease, type B variants (28 disease-causing).

Diseases related to Niemann-Pick disease, type B

• Niemann-Pick disease, type A, also linked to SMPD1
• Alzheimer disease, also linked to SMPD1
• Sphingomyelin/cholesterol lipidosis, also linked to SMPD1
• Parkinson disease, also linked to SMPD1

Frequently asked questions

Which genes are linked to Niemann-Pick disease, type B?

In CATVariant, Niemann-Pick disease, type B is linked to 1 analyzed protein: SMPD1 (Sphingomyelin phosphodiesterase).

How many genetic variants are linked to Niemann-Pick disease, type B?

278 variants: 113 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 130 are of uncertain significance or have conflicting reports.

Which uncertain variants in Niemann-Pick disease, type B look disease-causing?

10 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example SMPD1 H427L, SMPD1 R378S, SMPD1 P477Q, SMPD1 Y369C and SMPD1 R476Q. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Niemann-Pick disease, type B?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.97, based on 69 disease-causing and 14 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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