Sphingomyelin/cholesterol lipidosis: genes and variants
Sphingomyelin/cholesterol lipidosis is linked to 2 analyzed proteins (SMPD1 and NPC1). 29 DNA variants are known to cause it; 12 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Sphingomyelin/cholesterol lipidosis
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.
28 disease-causing and 12 uncertain variants in SMPD1 are linked to Sphingomyelin/cholesterol lipidosis.
NPC1: NPC intracellular cholesterol transporter 1
It moves cholesterol and other lipids out of late endosomes and lysosomes so they can be redistributed throughout the cell. Biallelic loss-of-function variants cause Niemann-Pick disease type C with progressive neurologic and visceral lipid-storage disease.
1 disease-causing and 0 uncertain variants in NPC1 are linked to Sphingomyelin/cholesterol lipidosis.
Known disease-causing variants in Sphingomyelin/cholesterol lipidosis
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| NPC1 P691Q | 691 | SSD | Disease-causing (★★) |
| SMPD1 G168R | 168 | Saposin B-type | Disease-causing (★★) |
| SMPD1 L227P | 227 | Disease-causing (★★) | |
| SMPD1 N385S | 385 | Disease-causing (★★) | |
| SMPD1 H423R | 423 | Disease-causing (★★) | |
| SMPD1 F465S | 465 | Disease-causing (★★) | |
| SMPD1 R498H | 498 | Disease-causing (★★) | |
| SMPD1 N383S | 383 | Disease-causing (★★) | |
| SMPD1 H427R | 427 | Disease-causing (★★) | |
| SMPD1 L105P | 105 | Saposin B-type | Disease-causing (★★) |
| SMPD1 C228R | 228 | Disease-causing (★★) | |
| SMPD1 W342C | 342 | Disease-causing (★★) | |
| SMPD1 L382F | 382 | Disease-causing (★★) | |
| SMPD1 M384I | 384 | Disease-causing (★★) | |
| SMPD1 S486R | 486 | Disease-causing (★★) | |
| SMPD1 Y469C | 469 | Disease-causing (★★) | |
| SMPD1 Y500H | 500 | Disease-causing (★★) | |
| SMPD1 L558P | 558 | Disease-causing (★★) | |
| SMPD1 G579S | 579 | Disease-causing (★★) | |
| SMPD1 R602C | 602 | Disease-causing (★★) | |
| SMPD1 L121P | 121 | Saposin B-type | Disease-causing (★★) |
| SMPD1 W211R | 211 | Disease-causing (★★) | |
| SMPD1 C223S | 223 | Disease-causing (★★) | |
| SMPD1 W246C | 246 | Disease-causing (★★) | |
| SMPD1 G247D | 247 | Disease-causing (★★) | |
| SMPD1 D253E | 253 | Disease-causing (★★) | |
| SMPD1 F572L | 572 | Disease-causing (★★) | |
| SMPD1 L595V | 595 | Disease-causing (★★) | |
| SMPD1 T488A | 488 | Disease-causing (★) |
Which prediction tools work for Sphingomyelin/cholesterol lipidosis
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 97 out of 100
- SIFT: 94 out of 100
- phyloP: 83 out of 100
Same protein, different disease
- Niemann-Pick disease, type A is also caused by SMPD1 variants; they fall partly in the same places as the Sphingomyelin/cholesterol lipidosis variants (129 disease-causing).
- Niemann-Pick disease, type B is also caused by SMPD1 variants; they fall partly in the same places as the Sphingomyelin/cholesterol lipidosis variants (113 disease-causing).
- Niemann-Pick disease, type C1 is also caused by NPC1 variants; they fall mostly in different places as the Sphingomyelin/cholesterol lipidosis variants (175 disease-causing).
- Niemann-Pick disease, type C is also caused by NPC1 variants; they fall mostly in different places as the Sphingomyelin/cholesterol lipidosis variants (60 disease-causing).
Diseases related to Sphingomyelin/cholesterol lipidosis
- Niemann-Pick disease, type A, also linked to NPC1 and SMPD1
- Niemann-Pick disease, type C1, also linked to NPC1
- Alzheimer disease, also linked to SMPD1
- Niemann-Pick disease, type B, also linked to SMPD1
- Niemann-Pick disease, type C, also linked to NPC1
- Dystonic disorder, also linked to NPC1
- Parkinson disease, also linked to SMPD1
Frequently asked questions
Which genes are linked to Sphingomyelin/cholesterol lipidosis?
In CATVariant, Sphingomyelin/cholesterol lipidosis is linked to 2 analyzed proteins: SMPD1 (Sphingomyelin phosphodiesterase) and NPC1 (NPC intracellular cholesterol transporter 1).
How many genetic variants are linked to Sphingomyelin/cholesterol lipidosis?
42 variants: 29 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 12 are of uncertain significance or have conflicting reports.
Which uncertain variants in Sphingomyelin/cholesterol lipidosis look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Sphingomyelin/cholesterol lipidosis?
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 16 disease-causing and 30 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center