Entity Detail — Knowledge Graph Node
This page aggregates everything SciDEX knows about SMPD1: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.
Sphingomyelin phosphodiesterase 1 (acid sphingomyelinase, ASM) hydrolyzes sphingomyelin to ceramide. Regulates membrane lipid composition, lysosomal function, and apoptosis. Implicated in Alzheimer disease through effects on amyloid processing and tau phosphorylation. Target for ceramide-modulating therapeutics.
| Gene Symbol | SMPD1 |
| Aliases | Acid sphingomyelinase, ASM, Page for SMPD1 Gene |
| Chromosome | 11p15.4 |
| Protein Type | Enzyme |
| Target Class | Enzyme |
| Function | The SMPD1 gene encodes acid sphingomyelinase (ASM), a lysosomal hydrolase enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. |
| Mechanism of Action | Small molecule inhibitor or modulator of sphingomyelinase activity |
| Primary Expression | neurons, astrocytes, microglia, and oligodendrocytes, with particular importance in white matter tracts |
| Druggability | Medium (0.47) |
| Clinical Stage | Approved |
| Molecular Weight | 75 kDa |
| Pathways | Sphingolipid metabolism, Lysosomal degradation, Ceramide signaling |
| UniProt ID | P17405 |
| NCBI Gene ID | 6609 |
| Ensembl ID | ENSG00000166311 |
| OMIM | 257200 |
| GeneCards | SMPD1 |
| Human Protein Atlas | SMPD1 |
| Associated Diseases | ALS, Aging, Alzheimer, Alzheimer's disease, CANCER |
| Known Drugs/Compounds | Olipudase alfa |
| Interactions | NLRP3, NPC1, GBA, CTSD, PROGRANULIN, GBM |
| SciDEX Target | View Target Profile (7 clinical trials) |
| SciDEX Hypotheses | Selective Acid Sphingomyelinase Modulation Therapy TREM2-ASM Crosstalk in Microglial Lysosomal Senesc Senescent Cell ASM-Complement Cascade Intervention |
| KG Connections | 511 knowledge graph edges |
| Databases | GeneCardsHPASTRING |
Knowledge base pages for this entity
graph TD
SMPD1["SMPD1/ASM Enzyme"] -->|"Hydrolyzes"| SM["Sphingomyelin"]
SM -->|"Produces"| Ceramide["Ceramide"]
Ceramide -->|"Regulates"| Apoptosis["Apoptosis"]
Ceramide -->|"Modulates"| Inflammation["Inflammation"]
SMPD1 -.Deficiency.-> NPD["Niemann-Pick Disease"]
SMPD1 -->|"In lysosomes"| Degradation["Lipid Degradation"]
Dysregulation -.Causes.-> Accumulation["Lipid Accumulation"]
Accumulation -.Associated with.-> ND["Neurodegeneration"]| Target | Relation | Type | Str |
|---|---|---|---|
| ds-83b31ef18d49 | provides_data_for | dataset | 1.00 |
| brain ischemia/reperfusion injury | aggravates | disease | 0.90 |
| NLRP3 inflammasome | activates | complex | 0.90 |
| ANGIOGENESIS | inhibits | process | 0.90 |
| frontotemporal dementia | implicated_in | disease | 0.90 |
| Acid Sphingomyelinase | encodes | protein | 0.90 |
| Alpha-Synuclein Neurotoxicity | modulates | phenotype | 0.85 |
| CNS disorders | implicated_in | disease | 0.80 |
| α-synuclein neurotoxicity | modulates | phenotype | 0.80 |
| Parkinson's disease | contributes_to | disease | 0.80 |
| oligodendrocytes | expressed_in | cell_type | 0.80 |
| GLIOBLASTOMA | biomarker_for | disease | 0.80 |
| Parkinson's disease | enhances | disease | 0.80 |
| DEPRESSION | implicated_in | disease | 0.80 |
| CANCER | implicated_in | disease | 0.80 |
| "middle temporal gyrus"_spiny_L3 | expressed_in | cell_type | 0.70 |
| "middle temporal gyrus"_aspiny_L3 | expressed_in | cell_type | 0.70 |
| "middle temporal gyrus"_spiny_L5 | expressed_in | cell_type | 0.70 |
| oligodendrocytes | associated_with | cell_type | 0.70 |
| oligodendrocytes | regulates | cell_type | 0.70 |
| Alzheimer's disease | implicated_in | disease | 0.70 |
| Parkinson's disease | accumulates_in | disease | 0.70 |
| oligodendrocytes | causes | cell_type | 0.70 |
| neurodegeneration | associated_with | disease | 0.69 |
| Retinal Degeneration | activates | disease | 0.65 |
| SNCA | co_discussed | gene | 0.65 |
| SQSTM1 | co_discussed | gene | 0.65 |
| pericyte | co_discussed | concept | 0.65 |
| SPHINGOMYELIN | encodes | phenotype | 0.65 |
| Parkinson | associated_with | disease | 0.65 |
| Als | associated_with | disease | 0.65 |
| Aging | associated_with | disease | 0.65 |
| Ms | associated_with | disease | 0.65 |
| Cancer | associated_with | disease | 0.65 |
| Ms | contributes_to | disease | 0.65 |
| Parkinson | contributes_to | disease | 0.65 |
| Obesity | activates | disease | 0.65 |
| Multiple Sclerosis | therapeutic_target | disease | 0.65 |
| Neurodegeneration | therapeutic_target | disease | 0.65 |
| Neuroinflammation | therapeutic_target | disease | 0.65 |
| Alzheimer | associated_with | disease | 0.65 |
| Ischemia | activates | disease | 0.65 |
| Cancer | therapeutic_target | disease | 0.65 |
| Glioblastoma | therapeutic_target | disease | 0.65 |
| Als | therapeutic_target | disease | 0.65 |
| Neurodegeneration | activates | disease | 0.65 |
| Als | activates | disease | 0.65 |
| Aging | activates | disease | 0.65 |
| Parkinson | activates | disease | 0.65 |
| Als | regulates | disease | 0.65 |
| Source | Relation | Type | Str |
|---|---|---|---|
| ds-83b31ef18d49 | data_in | dataset | 1.00 |
| PROGRANULIN | regulates | protein | 0.90 |
| h-de0d4364 | targets_gene | hypothesis | 0.90 |
| h-var-76afa28dfc | targets_gene | hypothesis | 0.90 |
| h-var-18aae53fe9 | targets_gene | hypothesis | 0.90 |
| h-de0d4364 | targets | hypothesis | 0.80 |
| APP | associated_with | gene | 0.65 |
| ABCA7 | co_discussed | gene | 0.65 |
| ATP13A2 | co_discussed | gene | 0.65 |
| MAPT | co_discussed | gene | 0.65 |
| OPTN | co_discussed | gene | 0.65 |
| NIEMANN-PICK DISEASE | encodes | disease | 0.65 |
| ALZHEIMER | associated_with | gene | 0.65 |
| AMYLOID | associated_with | gene | 0.65 |
| APOPTOSIS | associated_with | gene | 0.65 |
| AUTOPHAGY | associated_with | gene | 0.65 |
| PNPLA6 | associated_with | gene | 0.60 |
| BAX | associated_with | gene | 0.60 |
| BECN1 | associated_with | gene | 0.60 |
| RPS6 | associated_with | gene | 0.60 |
| PI3K | associated_with | gene | 0.60 |
| CTCF | associated_with | gene | 0.60 |
| SLC17A5 | associated_with | gene | 0.60 |
| ASAH1 | associated_with | gene | 0.60 |
| CTSB | associated_with | gene | 0.60 |
| SNCA | contributes_to | gene | 0.60 |
| PINK1 | associated_with | gene | 0.60 |
| PRKN | associated_with | gene | 0.60 |
| TMEM175 | associated_with | gene | 0.60 |
| PSAP | therapeutic_target | gene | 0.60 |
| EGFR | inhibits | gene | 0.60 |
| GBM | inhibits | gene | 0.60 |
| INPP5D | associated_with | gene | 0.60 |
| CTSD | associated_with | gene | 0.60 |
| SCARB2 | activates | gene | 0.60 |
| LIPA | activates | gene | 0.60 |
| SLC17A5 | activates | gene | 0.60 |
| GNPTAB | activates | gene | 0.60 |
| LRRN1 | regulates | gene | 0.60 |
| ERK1 | regulates | gene | 0.60 |
| PI3K | regulates | gene | 0.60 |
| VEGFA | associated_with | gene | 0.60 |
| CLU | associated_with | gene | 0.60 |
| CTSF | associated_with | gene | 0.60 |
| VEGFB | associated_with | gene | 0.60 |
| APOE | associated_with | gene | 0.60 |
| BIN1 | associated_with | gene | 0.60 |
| OVERVIEW | therapeutic_target | gene | 0.60 |
| NPC2 | causes | gene | 0.60 |
| GAIN | therapeutic_target | gene | 0.60 |
Hypotheses where this entity is a therapeutic target
| Hypothesis | Score | Disease | Analysis |
|---|---|---|---|
| Selective Acid Sphingomyelinase Modulation Therapy | 0.648 | neurodegeneration | Lipid raft composition changes in synapt |
| TREM2-ASM Crosstalk in Microglial Lysosomal Senescence | 0.612 | neurodegeneration | Gene expression changes in aging mouse b |
| Senescent Cell ASM-Complement Cascade Intervention | 0.552 | neurodegeneration | Lipid raft composition changes in synapt |
Scientific analyses that reference this entity
neurodegeneration | 2026-04-02 | 5 hypotheses Top: 0.519
neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.507
neurodegeneration | 2026-04-01 | 12 hypotheses Top: 0.648
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| Coenzyme Q10 Supplementation Modulates Hepatic Lipidomic Alterations and Attenua [PMID:41754105] | Go Y, Joung H, Han SY, Chung J | Nutrients | 2026 | 0 |
| SMPD1 as a Potential Prognostic Biomarker in Glioma Is Associated With an Immuno [PMID:41795144] | Xu Y, Liu X, Xu B, Li Q, Zhang L, Li C, | CNS neuroscience & therapeutic | 2026 | 0 |
| Endogenous Ceramide 24:1 Constrains Th17-Driven Neutrophilic Inflammation by Ant [PMID:41824764] | Liu H, Aili A, Kuang Z, Cao L, Li Z, Sha | Advanced science (Weinheim, Ba | 2026 | 0 |
| Suspected Niemann-Pick disease type B with sea-blue histiocytosis after splenect [PMID:41791926] | Liu W, Qin L, Wang G | Journal of clinical lipidology | 2026 | 0 |
| Olipudase alfa treatment for pediatric acid sphingomyelinase deficiency in Egypt [PMID:41716780] | Arafa NA, Mahfouz A, Anwar S, Marzouk I | Molecular genetics and metabol | 2026 | 0 |
| Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment s [PMID:39825014] | Chestnykh D, Mühle C, Schumacher F, Kali | Molecular psychiatry | 2025 | 0 |
| Reduction of sphingomyelinase activity associated with progranulin deficiency an [PMID:40633679] | Boyle NR, Fox SN, Tadepalli AS, Seyfried | Neurobiology of disease | 2025 | 0 |
| Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment s [PMID:39825014] | Chestnykh D, Mühle C, Schumacher F, Kali | Mol Psychiatry | 2025 | 0 |
| Large-scale Plasma Proteomic Profiling Unveils Novel Diagnostic Biomarkers and P [PMID:40166037] | Cruchaga C, Heo G, Thomas A, Wang E, Oh | Res Sq | 2025 | 0 |
| Reduction of sphingomyelinase activity associated with progranulin deficiency an [PMID:40633679] | Boyle NR, Fox SN, Tadepalli AS, Seyfried | Neurobiol Dis | 2025 | 0 |
| Acid sphingomyelinase as a pathological and therapeutic target in neurological d [PMID:38337058] | Choi BJ, Park MH, Jin HK, Bae JS | Experimental & molecular medic | 2024 | 0 |
| Optimal Control with RdCVFL for Degenerating Photoreceptors. [PMID:38345678] | ["Wifvat K", "Camacho E", "Kawski M", "L | Bulletin of mathematical biolo | 2024 | 0 |
| The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Dis [PMID:38397448] | Tirelli C, Rondinone O, Italia M, Mira S | Biomolecules | 2024 | 0 |
| Acid sphingomyelinase as a pathological and therapeutic target in neurological d [PMID:38337058] | Choi BJ, Park MH, Jin HK, Bae JS | Exp Mol Med | 2024 | 0 |
| EDIL3/Del-1 prevents aortic dissection through enhancing internalization and deg [PMID:38873925] | Yin Z, Zhang J, Zhao M, Liu J, Xu Y et a | Autophagy | 2024 | 0 |
| Consensus clinical management guidelines for acid sphingomyelinase deficiency (N [PMID:37069638] | Geberhiwot T, Wasserstein M, Wanninayake | Orphanet journal of rare disea | 2023 | 0 |
| Functional screening of lysosomal storage disorder genes identifies modifiers of [PMID:37200393] | Yu M, Ye H, De-Paula RB, Mangleburg CG, | PLoS genetics | 2023 | 0 |
| Case report: The spectrum of SMPD1 pathogenic variants in Hungary. [PMID:37347058] | ["Molnar M", "Szlepak T", "Cs\u00fcrke I | Frontiers in genetics | 2023 | 0 |
| The Niemann-Pick type diseases - A synopsis of inborn errors in sphingolipid and [PMID:37003582] | Pfrieger FW | Progress in lipid research | 2023 | 0 |
| The Niemann-Pick type diseases - A synopsis of inborn errors in sphingolipid and [PMID:37003582] | Pfrieger FW | Prog Lipid Res | 2023 | 0 |