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Aliases for SMPD4 Gene

Aliases for SMPD4 Gene

  • Sphingomyelin Phosphodiesterase 4 2 3 3 5
  • Sphingomyelin Phosphodiesterase 4, Neutral Membrane (Neutral Sphingomyelinase-3) 2 3
  • Neutral Sphingomyelinase III 3 4
  • Neutral Sphingomyelinase 3 3 4
  • SKNY 3 4
  • Neutral Sphingomyelinase-3 2
  • EC 3.1.4.12 4
  • NSMASE-3 3
  • KIAA1418 4
  • NSMase-3 4
  • NSMASE3 3
  • NSMase3 4
  • NET13 3

External Ids for SMPD4 Gene

Previous GeneCards Identifiers for SMPD4 Gene

  • GC02M130626
  • GC02M130908
  • GC02M123204

Summaries for SMPD4 Gene

Entrez Gene Summary for SMPD4 Gene

  • The protein encoded by this gene is a sphingomyelinase that catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide. This gene is activated by DNA damage, cellular stress, and tumor necrosis factor, but it is downregulated by wild-type p53. The encoded protein localizes to the endoplasmic reticulum and Golgi network. [provided by RefSeq, Mar 2017]

GeneCards Summary for SMPD4 Gene

SMPD4 (Sphingomyelin Phosphodiesterase 4) is a Protein Coding gene. Among its related pathways are Metabolism and Sphingolipid metabolism. Gene Ontology (GO) annotations related to this gene include sphingomyelin phosphodiesterase activity and sphingomyelin phosphodiesterase D activity.

UniProtKB/Swiss-Prot for SMPD4 Gene

  • Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide (PubMed:16517606). May sensitize cells to DNA damage-induced apoptosis (PubMed:18505924).

Gene Wiki entry for SMPD4 Gene

Additional gene information for SMPD4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SMPD4 Gene

Genomics for SMPD4 Gene

GeneHancer (GH) Regulatory Elements for SMPD4 Gene

Promoters and enhancers for SMPD4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J130180 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 650.7 +0.2 213 4.5 HDGF PKNOX1 MLX ZFP64 ARID4B SIN3A DMAP1 YY1 POLR2B E2F8 MZT2B SMPD4 TUBA3E NOC2LP1 RAB6C-AS1
GH02J130190 Promoter 0.6 EPDnew 650.4 -7.9 -7925 0.1 SCRT2 SMPD4 MZT2B TUBA3E
GH02J130341 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 39.1 -159.8 -159841 3 HDGF HNRNPUL1 PKNOX1 SMAD1 ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2 CCDC115 PIR60541 IMP4 GC02P130344 SMPD4 PTPN18
GH02J130336 Enhancer 1.3 Ensembl ENCODE 39.5 -155.6 -155557 3.5 HDGF PKNOX1 CLOCK ARNT ARID4B SIN3A ZNF2 IRF4 POLR2B ZNF766 TRE-TTC1-1 SMPD4 PTPN18 RAB6C-AS1 IMP4 CCDC115
GH02J130332 Enhancer 1.1 Ensembl ENCODE 32.8 -149.8 -149842 0.8 PKNOX1 ARID4B SIN3A YY1 ARID2 ZNF143 FOS REST KAT8 ZNF585B SMPD4 PTPN18 ENSG00000224352 TRE-TTC1-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SMPD4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SMPD4 gene promoter:

Genomic Locations for SMPD4 Gene

Genomic Locations for SMPD4 Gene
chr2:130,151,392-130,182,750
(GRCh38/hg38)
Size:
31,359 bases
Orientation:
Minus strand
chr2:130,908,965-130,940,323
(GRCh37/hg19)

Genomic View for SMPD4 Gene

Genes around SMPD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMPD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMPD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMPD4 Gene

Proteins for SMPD4 Gene

  • Protein details for SMPD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NXE4-NSMA3_HUMAN
    Recommended name:
    Sphingomyelin phosphodiesterase 4
    Protein Accession:
    Q9NXE4
    Secondary Accessions:
    • B1PBA3
    • B4DM23
    • B4DQ31
    • B4DRB8
    • B4DWK7
    • B4E0L6
    • E7ESA2
    • E9PCE6
    • Q6FI76
    • Q6P1P7
    • Q6ZT43
    • Q9H0M2
    • Q9NW20
    • Q9NWL2
    • Q9P2C9

    Protein attributes for SMPD4 Gene

    Size:
    866 amino acids
    Molecular mass:
    97810 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAY14883.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA91070.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA91368.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA91567.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA92656.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for SMPD4 Gene

neXtProt entry for SMPD4 Gene

Post-translational modifications for SMPD4 Gene

  • Ubiquitination at isoforms=10, 2, 3, 4, 5, 6, 7, 8, 9621, isoforms=10, 2, 3, 4, 5, 6, 7, 8, 9565, posLast=541541, posLast=529529, isoforms=10, 2, 3, 4, 6, 7, 8, 9461, isoforms=2, 3, 4, 6238, and posLast=106106
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SMPD4 Gene

Domains & Families for SMPD4 Gene

Gene Families for SMPD4 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for SMPD4 Gene

InterPro:
ProtoNet:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with SMPD4: view

No data available for UniProtKB/Swiss-Prot for SMPD4 Gene

Function for SMPD4 Gene

Molecular function for SMPD4 Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide (PubMed:16517606). May sensitize cells to DNA damage-induced apoptosis (PubMed:18505924).
UniProtKB/Swiss-Prot CatalyticActivity:
Sphingomyelin + H(2)O = N-acylsphingosine + phosphocholine.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphatidylserine and tumor necrosis factor (TNF). Inhibited by scyphostatin.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
pH dependence: Optimum pH is 7.0. {ECO:0000269 PubMed:16517606};
UniProtKB/Swiss-Prot Induction:
Expression is induced by DNA-damage and TNF.

Enzyme Numbers (IUBMB) for SMPD4 Gene

Gene Ontology (GO) - Molecular Function for SMPD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004767 sphingomyelin phosphodiesterase activity TAS --
GO:0016787 hydrolase activity IEA --
GO:0046872 metal ion binding IEA --
GO:0050290 sphingomyelin phosphodiesterase D activity IDA 16517606
genes like me logo Genes that share ontologies with SMPD4: view
genes like me logo Genes that share phenotypes with SMPD4: view

Animal Models for SMPD4 Gene

MGI Knock Outs for SMPD4:
  • Smpd4 Smpd4<tm2b(KOMP)Wtsi>

Animal Model Products

miRNA for SMPD4 Gene

miRTarBase miRNAs that target SMPD4

Clone Products

No data available for Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SMPD4 Gene

Localization for SMPD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMPD4 Gene

Endoplasmic reticulum membrane; Single-pass membrane protein. Golgi apparatus membrane; Single-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SMPD4 gene
Compartment Confidence
endoplasmic reticulum 5
golgi apparatus 4
plasma membrane 3
mitochondrion 1
peroxisome 1
nucleus 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nuclear membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SMPD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005783 endoplasmic reticulum IDA 16517606
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0005794 Golgi apparatus IDA 16517606
GO:0005802 trans-Golgi network IDA 16517606
genes like me logo Genes that share ontologies with SMPD4: view

Pathways & Interactions for SMPD4 Gene

genes like me logo Genes that share pathways with SMPD4: view

Pathways by source for SMPD4 Gene

Gene Ontology (GO) - Biological Process for SMPD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006685 sphingomyelin catabolic process IDA 16517606
GO:0006687 glycosphingolipid metabolic process TAS --
GO:0046475 glycerophospholipid catabolic process IDA 16517606
GO:0046513 ceramide biosynthetic process IDA 16517606
GO:0071356 cellular response to tumor necrosis factor IDA 16517606
genes like me logo Genes that share ontologies with SMPD4: view

No data available for SIGNOR curated interactions for SMPD4 Gene

Drugs & Compounds for SMPD4 Gene

(4) Drugs for SMPD4 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphatidyl serine Approved, Investigational Nutra Target 0
Water Approved Pharma 0
Magnesium Approved Nutra 0
PHOSPHATIDYLSERINE Pharma 0

(274) Additional Compounds for SMPD4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
3-O-Sulfogalactosylceramide (d18:1/12:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
852100-88-0
3-O-Sulfogalactosylceramide (d18:1/14:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
3-O-Sulfogalactosylceramide (d18:1/16:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
862509-48-6
3-O-Sulfogalactosylceramide (d18:1/18:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
244215-65-4
3-O-Sulfogalactosylceramide (d18:1/18:1(9Z))
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
genes like me logo Genes that share compounds with SMPD4: view

Transcripts for SMPD4 Gene

Unigene Clusters for SMPD4 Gene

Sphingomyelin phosphodiesterase 4, neutral membrane (neutral sphingomyelinase-3):
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SMPD4 Gene

No ASD Table

Relevant External Links for SMPD4 Gene

GeneLoc Exon Structure for
SMPD4
ECgene alternative splicing isoforms for
SMPD4

Expression for SMPD4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SMPD4 Gene

Protein differential expression in normal tissues from HIPED for SMPD4 Gene

This gene is overexpressed in Bone (8.8) and Peripheral blood mononuclear cells (6.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SMPD4 Gene



Protein tissue co-expression partners for SMPD4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of SMPD4 Gene:

SMPD4

SOURCE GeneReport for Unigene cluster for SMPD4 Gene:

Hs.516450

mRNA Expression by UniProt/SwissProt for SMPD4 Gene:

Q9NXE4-NSMA3_HUMAN
Tissue specificity: Widely expressed, with highest levels in heart and skeletal muscle.

Evidence on tissue expression from TISSUES for SMPD4 Gene

  • Nervous system(4.9)
  • Lung(4.3)
genes like me logo Genes that share expression patterns with SMPD4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SMPD4 Gene

Orthologs for SMPD4 Gene

This gene was present in the common ancestor of animals.

Orthologs for SMPD4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SMPD4 33
  • 96.41 (n)
dog
(Canis familiaris)
Mammalia SMPD4 34 33
  • 88.52 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Smpd4 33
  • 86.37 (n)
mouse
(Mus musculus)
Mammalia Smpd4 16 34 33
  • 85.6 (n)
cow
(Bos Taurus)
Mammalia SMPD4 34 33
  • 83.58 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SMPD4 34
  • 74 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 73 (a)
OneToMany
-- 34
  • 70 (a)
OneToMany
chicken
(Gallus gallus)
Aves SMPD4 34 33
  • 70.63 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SMPD4 34
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia smpd4 33
  • 66.12 (n)
Str.6070 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.4713 33
zebrafish
(Danio rerio)
Actinopterygii smpd4 34 33
  • 64.59 (n)
OneToOne
wufb22d05 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4009 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000405 33
  • 48.41 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG6962 34 33
  • 43.27 (n)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 32 (a)
OneToOne
Species where no ortholog for SMPD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SMPD4 Gene

ENSEMBL:
Gene Tree for SMPD4 (if available)
TreeFam:
Gene Tree for SMPD4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SMPD4: view image

Paralogs for SMPD4 Gene

genes like me logo Genes that share paralogs with SMPD4: view

No data available for Paralogs for SMPD4 Gene

Variants for SMPD4 Gene

Sequence variations from dbSNP and Humsavar for SMPD4 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs879255412 uncertain-significance, not specified 130,154,461(-) G/A coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs1000136066 -- 130,180,891(-) G/T intron_variant
rs1000285877 -- 130,154,163(-) G/T intron_variant
rs1000387399 -- 130,154,602(-) C/T intron_variant
rs1000536099 -- 130,182,056(-) G/A/C genic_upstream_transcript_variant, non_coding_transcript_variant, upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for SMPD4 Gene

Variant ID Type Subtype PubMed ID
dgv2032n106 OTHER inversion 24896259
dgv4072n100 CNV loss 25217958
dgv4073n100 CNV gain 25217958
dgv7079n54 CNV loss 21841781
esv2751826 CNV gain 17911159
esv2759092 CNV gain+loss 17122850
esv2760631 CNV gain+loss 21179565
esv2763387 CNV loss 21179565
esv3584065 CNV loss 25503493
esv3592440 CNV loss 21293372
esv3592441 CNV gain 21293372
esv3893326 CNV gain 25118596
nsv1001337 CNV loss 25217958
nsv1004301 CNV loss 25217958
nsv1005664 CNV loss 25217958
nsv1008911 CNV gain 25217958
nsv1008970 CNV loss 25217958
nsv1011360 CNV loss 25217958
nsv428403 CNV loss 18775914
nsv459274 CNV loss 19166990
nsv482053 CNV gain 20164927
nsv520559 CNV gain+loss 19592680
nsv583046 CNV loss 21841781
nsv583113 CNV gain 21841781
nsv7327 OTHER inversion 18451855
nsv821629 CNV loss 15273396
nsv834375 CNV loss 17160897
nsv961882 CNV duplication 23825009
nsv998333 CNV gain+loss 25217958

Variation tolerance for SMPD4 Gene

Residual Variation Intolerance Score: 40.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.24; 52.56% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SMPD4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMPD4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMPD4 Gene

Disorders for SMPD4 Gene

Additional Disease Information for SMPD4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for SMPD4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for SMPD4 Gene

Publications for SMPD4 Gene

  1. Novel tumor necrosis factor-responsive mammalian neutral sphingomyelinase-3 is a C-tail-anchored protein. (PMID: 16517606) Krut O … Krönke M (The Journal of biological chemistry 2006) 2 3 4 25 58
  2. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 44 58
  3. Neutral sphingomyelinase-3 is a DNA damage and nongenotoxic stress-regulated gene that is deregulated in human malignancies. (PMID: 18505924) Corcoran CA … Sheikh MS (Molecular cancer research : MCR 2008) 3 4 58
  4. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier LW … Wilson RK (Nature 2005) 3 4 58
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58

Products for SMPD4 Gene

Sources for SMPD4 Gene

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