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SMPD1 sphingomyelin phosphodiesterase 1 [ Homo sapiens (human) ]

Gene ID: 6609, updated on 14-Nov-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
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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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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

Associated conditions

Description Tests
Niemann-Pick disease, type A
MedGen: C0268242 OMIM: 257200 GeneReviews: Acid Sphingomyelinase Deficiency
not available
Niemann-Pick disease, type B
MedGen: C0268243 OMIM: 607616 GeneReviews: Acid Sphingomyelinase Deficiency
not available

Variation

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See Variation Viewer (GRCh37.p13)

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 MAPK cascade 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

Gene LinkOut

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