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.

534Connections

4Hypotheses

4Analyses

50Outgoing

50Incoming

1Experiments

5Debates

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.

View on Wiki →

No AI portrait yet

🧬 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, AND, App, asah1
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 (+1 more)
KG Connections	534 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 (299)

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

Incoming (235)

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-76afa28dfc	targets_gene	hypothesis	0.90
h-de0d4364	targets	hypothesis	0.90
h-var-18aae53fe9	targets_gene	hypothesis	0.90
PROGRANULIN	regulates	protein	0.90
ENDOTHELIAL	regulates	cell_type	0.70
IBA1	interacts_with	gene	0.70
MICROGLIA	activates	cell_type	0.70
MULTIPLE SCLEROSIS	protects_against	disease	0.70
MACROPHAGE	expresses	cell_type	0.70
MACROPHAGE	regulates	cell_type	0.70
LRP1	associated_with	gene	0.70
RAGE	causes	gene	0.70
OPTN	co_discussed	gene	0.65
MAPT	co_discussed	gene	0.65
ATP13A2	co_discussed	gene	0.65
ABCA7	co_discussed	gene	0.65
ALZHEIMER	associated_with	gene	0.65
AUTOPHAGY	associated_with	gene	0.65
APOPTOSIS	associated_with	gene	0.65
AMYLOID	associated_with	gene	0.65
NIEMANN-PICK DISEASE	encodes	disease	0.65
APP	associated_with	gene	0.65
DEPRESSION	associated_with	gene	0.60
PSP	associated_with	gene	0.60
PSP	interacts_with	gene	0.60
GFP	associated_with	gene	0.60
DMSO	associated_with	gene	0.60
MAP1LC3	associated_with	gene	0.60
MYELIN	therapeutic_target	gene	0.60
MTORC1	therapeutic_target	gene	0.60
PARKINSON	activates	gene	0.60
NEURON	activates	gene	0.60
ASTROCYTES	activates	gene	0.60
ACHE	associated_with	gene	0.60
DEPRESSION	therapeutic_target	gene	0.60
STROKE	activates	gene	0.60
OLIGODENDROCYTE	associated_with	gene	0.60
GLIOBLASTOMA	associated_with	gene	0.60
ALPHA-SYNUCLEIN	associated_with	gene	0.60
ASAH1	interacts_with	gene	0.60
CTSD	interacts_with	gene	0.60
GBA	interacts_with	gene	0.60
SLC17A5	interacts_with	gene	0.60
BIN1	causes	gene	0.60
C5	causes	gene	0.60
CFB	causes	gene	0.60
CLU	causes	gene	0.60
CTSF	causes	gene	0.60

Targeting Hypotheses (4)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Selective Acid Sphingomyelinase Modulation Therapy	0.920	neurodegeneration	Lipid raft composition changes in synapt
TREM2-ASM Crosstalk in Microglial Lysosomal Senescence	0.910	neurodegeneration	Gene expression changes in aging mouse b
Senescent Cell ASM-Complement Cascade Intervention	0.852	neurodegeneration	Lipid raft composition changes in synapt
SMPD1 (Acid Sphingomyelinase) Inhibition for Ceramide Reduct	0.732	neurodegeneration	How do sphingomyelin/ceramide ratios spe

Mentioning Analyses (4)

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
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
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
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
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

Debates (5)

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 (299)

Incoming (235)

Targeting Hypotheses (4)

Mentioning Analyses (4)

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

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 (5)

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

Related Research