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    SMPD1 sphingomyelin phosphodiesterase 1 [ Homo sapiens (human) ]

    Gene ID: 6609, updated on 28-Oct-2024

    Summary

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    Official Symbol
    SMPD1provided by HGNC
    Official Full Name
    sphingomyelin phosphodiesterase 1provided by HGNC
    Primary source
    HGNC:HGNC:11120
    See related
    Ensembl:ENSG00000166311 MIM:607608; AllianceGenome:HGNC:11120
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ASM; NPD; ASMASE
    Summary
    The protein encoded by this gene is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide. The encoded protein also has phospholipase C activity. Defects in this gene are a cause of Niemann-Pick disease type A (NPA) and Niemann-Pick disease type B (NPB). Multiple transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]
    Expression
    Ubiquitous expression in kidney (RPKM 23.5), thyroid (RPKM 14.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SMPD1 in Genome Data Viewer
    Location:
    11p15.4
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (6390474..6394996)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (6448931..6453455)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (6411704..6416226)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902623 Neighboring gene Sharpr-MPRA regulatory region 11421 Neighboring gene uncharacterized LOC124902624 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3099 Neighboring gene amyloid beta precursor protein binding family B member 1 Neighboring gene Sharpr-MPRA regulatory region 8482 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3100 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3101 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4340 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3102 Neighboring gene hemopexin

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Increased acid sphingomyelinase activity in peripheral blood cells of acutely intoxicated patients with alcohol dependence. Reichel M, et al. Alcohol Clin Exp Res, 2010 Jan. PMID 19860808
    2. Functional implications of novel human acid sphingomyelinase splice variants. Rhein C, et al. PLoS One, 2012. PMID 22558155, Free PMC Article
    3. Two siblings with Niemann-Pick disease (NPD) type B: clinical findings and novel mutations of the acid sphingomyelinase gene. Gucev Z, et al. Indian J Pediatr, 2013 Feb. PMID 22367733
    4. Acid sphingomyelinase contributes to evodiamine-induced apoptosis in human gastric cancer SGC-7901 cells. Huang H, et al. DNA Cell Biol, 2011 Jun. PMID 21294641
    5. A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing. Jenkins RW, et al. J Biol Chem, 2011 Feb 4. PMID 21098024, Free PMC Article

    See all (191) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ASM variants in the spotlight: A structure-based atlas for unraveling pathogenic mechanisms in lysosomal acid sphingomyelinase.
      Title: ASM variants in the spotlight: A structure-based atlas for unraveling pathogenic mechanisms in lysosomal acid sphingomyelinase.
    2. Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.
      Title: Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.
    3. Effect of acid sphingomyelinase deficiency in type A Niemann-Pick disease on the transport of therapeutic nanocarriers across the blood-brain barrier.
      Title: Effect of acid sphingomyelinase deficiency in type A Niemann-Pick disease on the transport of therapeutic nanocarriers across the blood-brain barrier.
    4. Acid sphingomyelinase expression is associated with survival in resectable pancreatic ductal adenocarcinoma.
      Title: Acid sphingomyelinase expression is associated with survival in resectable pancreatic ductal adenocarcinoma.
    5. Acid sphingomyelinase deficiency (ASMD): addressing knowledge gaps in unmet needs and patient journey in Italy-a Delphi consensus.
      Title: Acid sphingomyelinase deficiency (ASMD): addressing knowledge gaps in unmet needs and patient journey in Italy-a Delphi consensus.
    6. SMPD1 gene variants in patients with beta-Thalassemia major.
      Title: SMPD1 gene variants in patients with β-Thalassemia major.
    7. SMPD1 expression profile and mutation landscape help decipher genotype-phenotype association and precision diagnosis for acid sphingomyelinase deficiency.
      Title: SMPD1 expression profile and mutation landscape help decipher genotype-phenotype association and precision diagnosis for acid sphingomyelinase deficiency.
    8. Functional characterization of novel variants in SMPD1 in Indian patients with acid sphingomyelinase deficiency.
      Title: Functional characterization of novel variants in SMPD1 in Indian patients with acid sphingomyelinase deficiency.
    9. Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.
      Title: Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.
    10. Analysis of the HEXA, HEXB, ARSA, and SMPD1 Genes in 68 Iranian Patients.
      Title: Analysis of the HEXA, HEXB, ARSA, and SMPD1 Genes in 68 Iranian Patients.
    Submit: New GeneRIF Correction See all GeneRIFs (136)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Treatment of cells with sphingomyelinase inhibits viral fusion after the engagement of HIV-1 gp120 with CD4 and sphingomyelinase restricts CD4 mobility. This inhibition is dependent on CD4 expression levels PubMed
    env In human primary neurons, HIV-1 gp120 induces the activation of sphingomyelinases (primarily neutral sphingomyelinase); antisense knockdown of neutral sphingomyelinase markedly inhibits gp120-mediated apoptosis and cell death of primary neurons PubMed
    Nef nef HIV-1 Nef inhibits sphingomyelinase activity in human podocyte PubMed
    nef HIV-1 Nef expression in human glial cells modulates the sphingomyelinase signaling pathway triggered by TNF-alpha PubMed
    Tat tat HIV-1 Tat upregulates sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1) expression in Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables acid sphingomyelin phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables acid sphingomyelin phosphodiesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables hydrolase activity, acting on glycosyl bonds IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phosphatidylcholine phospholipase C activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sphingomyelin phosphodiesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables sphingomyelin phosphodiesterase activity TAS
    Traceable Author Statement
    more info
    		  
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular response to UV IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to calcium ion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ceramide biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ceramide biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ceramide biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cholesterol metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glycosphingolipid catabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in negative regulation of MAP kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in nervous system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in plasma membrane repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of endocytosis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of viral entry into host cell IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to cocaine IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to interleukin-1 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to ionizing radiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to tumor necrosis factor IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to type I interferon IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to virus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to xenobiotic stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in sphingomyelin catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sphingomyelin catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sphingomyelin metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    acts_upstream_of symbiont entry into host cell IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_positive_effect symbiont entry into host cell IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in symbiont entry into host cell IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in termination of signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in wound healing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in endolysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lamellar body IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in lipid droplet IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in lysosomal lumen TAS
    Traceable Author Statement
    more info
    		  
    is_active_in lysosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    sphingomyelin phosphodiesterase
    Names
    Niemann-Pick type A/B
    acid sphingomyelinase
    sphingomyelin phosphodiesterase 1, acid lysosomal
    NP_000534.3
    NP_001007594.2
    NP_001305016.1
    NP_001305017.1
    NP_001352064.1
    XP_011518606.1
    XP_054225711.1
    XP_054225712.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011780.1 RefSeqGene

      Range
      5050..9572
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000543.5 → NP_000534.3  sphingomyelin phosphodiesterase isoform 1 precursor

      See identical proteins and their annotated locations for NP_000534.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AA746054, AB209775, M59916
      Consensus CDS
      CCDS44531.1
      UniProtKB/Swiss-Prot
      A8K8M3, E9PKS3, P17405, P17406, Q13811, Q16837, Q16841
      UniProtKB/TrEMBL
      E9LUE6
      Related
      ENSP00000340409.4, ENST00000342245.9
      Conserved Domains (2) summary
      smart00741
      Location:89 → 162
      SapB; Saposin (B) Domains
      cd00842
      Location:203 → 498
      MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain

    2. NM_001007593.3 → NP_001007594.2  sphingomyelin phosphodiesterase isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. The encoded protein (isoform 2) is one amino acid shorter than isoform 1.
      Source sequence(s)
      AA746054, AB209775, M59916
      Consensus CDS
      CCDS31409.2
      UniProtKB/TrEMBL
      E9LUE6
      Related
      ENSP00000435350.1, ENST00000527275.5
      Conserved Domains (3) summary
      smart00741
      Location:89 → 161
      SapB; Saposin (B) Domains
      cd00842
      Location:202 → 497
      MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain
      pfam00149
      Location:255 → 462
      Metallophos; Calcineurin-like phosphoesterase

    3. NM_001318087.2 → NP_001305016.1  sphingomyelin phosphodiesterase isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in its 3' exon resulting in a frameshift and an early stop codon compared to variant 1. The encoded isoform (3) has a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      BC041164, BI599208, HQ132747, M59916
      UniProtKB/TrEMBL
      E9LUE8
      Conserved Domains (3) summary
      smart00741
      Location:89 → 162
      SapB; Saposin (B) Domains
      cd00842
      Location:203 → 495
      MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain
      pfam00149
      Location:256 → 463
      Metallophos; Calcineurin-like phosphoesterase

    4. NM_001318088.2 → NP_001305017.1  sphingomyelin phosphodiesterase isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate translation start site compared to variant 1. The encoded isoform (4) has a shorter and distinct N-terminus, and lacks a predicted signal peptide compared to isoform 1.
      Source sequence(s)
      AB209775, BI599208, BM977655, HQ132748, M59916
      UniProtKB/Swiss-Prot
      P17405
      UniProtKB/TrEMBL
      E9LUE9, Q59EN6
      Conserved Domains (2) summary
      COG1409
      Location:95 → 214
      CpdA; 3',5'-cyclic AMP phosphodiesterase CpdA [Signal transduction mechanisms]
      cd00842
      Location:47 → 191
      MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain

    5. NM_001365135.2 → NP_001352064.1  sphingomyelin phosphodiesterase isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC068733
      UniProtKB/TrEMBL
      E9LUE7
      Conserved Domains (2) summary
      smart00741
      Location:89 → 162
      SapB; Saposin (B) Domains
      cd00842
      Location:203 → 454
      MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain

    RNA

    1. NR_027400.3 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (ASM-3) lacks an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC041164, HY095805
      Related
      ENST00000533123.5

    2. NR_134502.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AY649987, BI599208, BM977655, M59916
      Related
      ENST00000531303.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      6390474..6394996
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011520304.3 → XP_011518606.1  sphingomyelin phosphodiesterase isoform X1

      UniProtKB/TrEMBL
      E9LUE8
      Conserved Domains (3) summary
      smart00741
      Location:89 → 162
      SapB; Saposin (B) Domains
      cd00842
      Location:203 → 451
      MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain
      pfam00149
      Location:256 → 419
      Metallophos; Calcineurin-like phosphoesterase

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      6448931..6453455
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369736.1 → XP_054225711.1  sphingomyelin phosphodiesterase isoform X1

    2. XM_054369737.1 → XP_054225712.1  sphingomyelin phosphodiesterase isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P17405.5 GenPept UniProtKB/Swiss-Prot:P17405

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