gene

SMPD1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

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.

532Connections

5Hypotheses

5Analyses

50Outgoing

50Incoming

1Experiments

10Debates

Summary

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.

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🧬 Gene Info

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	Aging, Als, Alzheimer, Alzheimer's disease
Known Drugs/Compounds	Olipudase alfa
Interactions	AGING, ALPHA-SYNUCLEIN, ALS, App, asah1, ASAH1
SciDEX Target	View Target Profile (7 clinical trials)
SciDEX Hypotheses	Senescent Cell ASM-Complement Cascade Intervention Selective Acid Sphingomyelinase Modulation Therapy SMPD1 (Acid Sphingomyelinase) Inhibition for Ceram (+2 more)
KG Connections	532 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure Comparison — SMPD1 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

5I73 — X-ray / Cryo-EM

🔮 AI Predicted Structure

P17405 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

SMPD1 Gene - Acid Sphingomyelinase

gene · 720 words

→

Pathway Diagram

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"]

Outgoing (298)

Target	Relation	Type	Str
benchmark_ot_ad_answer_key:SMPD1	data_in	dataset_row	0.00
ds-83b31ef18d49	provides_data_for	dataset	1.00
NLRP3 inflammasome	activates	complex	0.90
frontotemporal dementia	associated_with	disease	0.90
ANGIOGENESIS	inhibits	process	0.90
brain ischemia/reperfusion injury	aggravates	disease	0.90
Alpha-Synuclein Neurotoxicity	modulates	phenotype	0.85
Parkinson's disease	enhances	disease	0.80
CNS disorders	implicated_in	disease	0.80
Parkinson's disease	associated_with	disease	0.80
DEPRESSION	implicated_in	disease	0.80
α-synuclein neurotoxicity	modulates	phenotype	0.80
GLIOBLASTOMA	biomarker_for	disease	0.80
oligodendrocytes	expressed_in	cell_type	0.80
CANCER	associated_with	disease	0.80
STING	expresses	gene	0.70
middle_temporal_gyrus_spiny_L3	expressed_in	cell_type	0.70
middle_temporal_gyrus_spiny_L5	expressed_in	cell_type	0.70
middle_temporal_gyrus_aspiny_L3	expressed_in	cell_type	0.70
AD-risk variants	risk_factor_for	phenotype	0.70
oligodendrocytes	causes	cell_type	0.70
ceramide	regulates	metabolite	0.70
sphingolipid metabolism	regulates	pathway	0.70
ceramide_production	activates	pathway	0.70
oligodendrocytes	regulates	cell_type	0.70
Parkinson's disease	accumulates_in	disease	0.70
Alzheimer's disease	associated_with	disease	0.70
oligodendrocytes	associated_with	cell_type	0.70
ceramide_metabolism	regulates	pathway	0.70
neurodegeneration	associated_with	disease	0.69
Tumor	activates	disease	0.65
ALS	associated_with	disease	0.65
Cancer	activates	disease	0.65
Neuroinflammation	contributes_to	disease	0.65
Multiple Sclerosis	protects_against	disease	0.65
Inflammation	contributes_to	disease	0.65
ALS	activates	disease	0.65
Stroke	activates	disease	0.65
Inflammation	activates	disease	0.65
Dementia	inhibits	disease	0.65
Als	regulates	disease	0.65
Depression	therapeutic_target	disease	0.65
Neurodegeneration	contributes_to	disease	0.65
Glioblastoma	activates	disease	0.65
Glioblastoma	therapeutic_target	disease	0.65
Cancer	therapeutic_target	disease	0.65
Als	therapeutic_target	disease	0.65
Parkinson	activates	disease	0.65
Cancer	regulates	disease	0.65
Alzheimer	associated_with	disease	0.65

Incoming (234)

Source	Relation	Type	Str
benchmark_ot_ad_answer_key:SMPD1	data_in	dataset_row	0.00
ds-83b31ef18d49	data_in	dataset	1.00
h-var-18aae53fe9	targets_gene	hypothesis	0.90
h-var-76afa28dfc	targets_gene	hypothesis	0.90
h-de0d4364	targets	hypothesis	0.90
PROGRANULIN	regulates	protein	0.90
RAGE	causes	gene	0.70
MICROGLIA	activates	cell_type	0.70
IBA1	interacts_with	gene	0.70
LRP1	associated_with	gene	0.70
MACROPHAGE	regulates	cell_type	0.70
MACROPHAGE	expresses	cell_type	0.70
MULTIPLE SCLEROSIS	protects_against	disease	0.70
ENDOTHELIAL	regulates	cell_type	0.70
APOPTOSIS	associated_with	gene	0.65
APP	associated_with	gene	0.65
OPTN	co_discussed	gene	0.65
ATP13A2	co_discussed	gene	0.65
AUTOPHAGY	associated_with	gene	0.65
MAPT	co_discussed	gene	0.65
ABCA7	co_discussed	gene	0.65
NIEMANN-PICK DISEASE	encodes	disease	0.65
AMYLOID	associated_with	gene	0.65
ALZHEIMER	associated_with	gene	0.65
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
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
CTSF	associated_with	gene	0.60
VEGFB	associated_with	gene	0.60
OVERVIEW	therapeutic_target	gene	0.60
NPC2	causes	gene	0.60
GAIN	therapeutic_target	gene	0.60
PARKINSON	associated_with	gene	0.60
CTSB	associated_with	gene	0.60
SNCA	contributes_to	gene	0.60
BIN1	associated_with	gene	0.60
CLU	associated_with	gene	0.60
SLC17A5	associated_with	gene	0.60

Targeting Hypotheses (5)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Senescent Cell ASM-Complement Cascade Intervention	0.852	neurodegeneration	Lipid raft composition changes in synapt
Selective Acid Sphingomyelinase Modulation Therapy	0.782	neurodegeneration	Lipid raft composition changes in synapt
SMPD1 (Acid Sphingomyelinase) Inhibition for Ceramide Reduct	0.732	neurodegeneration	How do sphingomyelin/ceramide ratios spe
TREM2-ASM Crosstalk in Microglial Lysosomal Senescence	0.713	neurodegeneration	Gene expression changes in aging mouse b
Sphingolipid Metabolism Rebalancing	0.455	neurodegeneration	Which specific metabolic pathways in APO

Mentioning Analyses (5)

Scientific analyses that reference this entity

Experiments (1)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Mobile App-Based Intervention for BPSD in Community-Dwelling Dementia	clinical	dementia with behavioral and p	0.950	0.00	human patients	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Pathogenic Variants and Olipudase Alfa Treatment of Patients With Acid Sphingomy [PMID:41692468]	["Hsu-Heng Lin", "Hui-An Chen", "Shyh-Je	Molecular genetics & genom	2026
Multi-omics analysis identifies SMPD1 as a key contributor in sphingolipid pathw [PMID:41428198]	["Aron Park", "Baeki E Kang", "Eun-Ju Ji	Genes & genomics	2026
Coenzyme Q10 Supplementation Modulates Hepatic Lipidomic Alterations and Attenua [PMID:41754105]	Go Y, Joung H, Han SY, Chung J	Nutrients	2026
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
A multi-dimensional bioinformatic dissection of the molecular mechanisms in high [PMID:41191606]	Yu X MD, Lei J MSc, Du X MSc, He Y MSc,	Int J Surg	2026
Plasma metabolites may inhibit childhood obesity by regulating ferroptosis throu [PMID:41249848]	Wang JG, Pan XH, Li Y	Int J Obes (Lond)	2026
Multi-omics analysis identifies SMPD1 as a key contributor in sphingolipid pathw [PMID:41428198]	Park A, Kang BE, Jin EJ, Kim HJ, Lee CW	Genes Genomics	2026
AXL Promotes Ischemic Myelin Repair Through Alleviating Myelin Debris Deposition [PMID:41524160]	Jia J, Gan Y, Li J, Li L, Meng H et al.	Adv Sci (Weinh)	2026
Pathogenic Variants and Olipudase Alfa Treatment of Patients With Acid Sphingomy [PMID:41692468]	Lin HH, Chen HA, Lin SJ, Hsu RH, Lee NC	Mol Genet Genomic Med	2026
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
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
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
AXL Promotes Ischemic Myelin Repair Through Alleviating Myelin Debris Deposition [PMID:41524160]	Jia J, Gan Y, Li J, Li L, Meng H, Sun M,	Advanced science (Weinheim, Ba	2026
A multi-dimensional bioinformatic dissection of the molecular mechanisms in high [PMID:41191606]	Yu X, Lei J, Du X, He Y, Peng W, Yang R,	International journal of surge	2026
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025
Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment s [PMID:39825014]	Chestnykh D, Mühle C, Schumacher F, Kali	Mol Psychiatry	2025
Reduction of sphingomyelinase activity associated with progranulin deficiency an [PMID:40633679]	Boyle NR, Fox SN, Tadepalli AS, Seyfried	Neurobiol Dis	2025
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025
Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment s [PMID:39825014]	Chestnykh D, Mühle C, Schumacher F, Kali	Molecular psychiatry	2025
Reduction of sphingomyelinase activity associated with progranulin deficiency an [PMID:40633679]	Boyle NR, Fox SN, Tadepalli AS, Seyfried	Neurobiology of disease	2025

Debates (10)

Multi-agent debates referencing this entity

Related Research

Hypotheses and analyses mentioning SMPD1 in their description or question text

No additional research found

SMPD1

Understanding Entity Pages

Summary

Wiki Pages (1)

SMPD1 Gene - Acid Sphingomyelinase

Pathway Diagram

Outgoing (298)

Incoming (234)

Targeting Hypotheses (5)

Mentioning Analyses (5)

Which specific metabolic pathways in APOE4+ microglia are most therapeutically t

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

4R-tau strain-specific spreading patterns in PSP vs CBD

Lipid raft composition changes in synaptic neurodegeneration

Experiments (1)

Related Papers (20)

Debates (10)

Extended debate: CYP46A1 Overexpression Gene Therapy

Hypothesis debate: Membrane Cholesterol Gradient Modulators

Hypothesis debate: Selective Acid Sphingomyelinase Modulation Therapy

Hypothesis debate: CYP46A1 Overexpression Gene Therapy

How do metabolomic alterations in glucose metabolism, mitochondrial function, an

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

Investigate how lipid raft composition (cholesterol metabolism, sphingolipids) c

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

While APOE4 disrupts microglial metabolism broadly, the debate didn't identify w

Cell-type specific expression patterns of neurodegeneration genes in SEA-AD

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