SMPD1 sphingomyelin phosphodiesterase 1 [Homo sapiens (human)] - Gene

Summary

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

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_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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?

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.
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.
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.
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.
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.
SMPD1 gene variants in patients with beta-Thalassemia major.
Title: SMPD1 gene variants in patients with β-Thalassemia major.
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.
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.
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.
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	Compare labs
Niemann-Pick disease, type B MedGen: C0268243 OMIM: 607616 GeneReviews: Acid Sphingomyelinase Deficiency	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH69187 (e-PCR)
- UniSTS:66320

GDB:197904 (e-PCR)
- UniSTS:155997

D11S4426 (e-PCR)
- UniSTS:21687

A002D29 (e-PCR)
- UniSTS:17869

SMPD1 (e-PCR)
- UniSTS:48627

STS-M81780 (e-PCR)
- UniSTS:12276

SMPD1_855 (e-PCR)
- UniSTS:277756

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 more info	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

EC 3.1.4.12

EC 3.1.4.3

NP_001007594.2

EC 3.1.4.12

EC 3.1.4.3

NP_001305016.1

EC 3.1.4.12

EC 3.1.4.3

NP_001305017.1

EC 3.1.4.12

EC 3.1.4.3

NP_001352064.1

EC 3.1.4.12

EC 3.1.4.3

XP_011518606.1

EC 3.1.4.12

EC 3.1.4.3

XP_054225711.1

EC 3.1.4.12

EC 3.1.4.3

XP_054225712.1

EC 3.1.4.12

EC 3.1.4.3

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

NG_011780.1 RefSeqGene

Range

5050..9572

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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

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
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

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

6390474..6394996

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_060935.1 Alternate T2T-CHM13v2.0

Range

6448931..6453455

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054369736.1 → XP_054225711.1 sphingomyelin phosphodiesterase isoform X1

UniProtKB/TrEMBL

E9LUE8
XM_054369737.1 → XP_054225712.1 sphingomyelin phosphodiesterase isoform X2