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 20... See more...

Aliases for SMPD4 Gene

Aliases for SMPD4 Gene

  • Sphingomyelin Phosphodiesterase 4 2 3 4 5
  • Sphingomyelin Phosphodiesterase 4, Neutral Membrane (Neutral Sphingomyelinase-3) 2 3
  • Neutral Sphingomyelinase III 3 4
  • Neutral Sphingomyelinase 3 3 4
  • NSMase-3 2 4
  • KIAA1418 2 4
  • NSMASE3 2 3
  • NET13 2 3
  • SKNY 3 4
  • Neutral Sphingomyelinase-3 2
  • EC 3.1.4.12 4
  • NSMASE-3 3
  • FLJ20297 2
  • FLJ20756 2
  • NEDMABA 3
  • NEDMEBA 3
  • NSMase3 4
  • SMPD4 5

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. Diseases associated with SMPD4 include Neurodevelopmental Disorder With Microcephaly, Arthrogryposis, And Structural Brain Anomalies and Microcephaly With Simplified Gyral Pattern. Among its related pathways are Sphingolipid metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include sphingomyelin phosphodiesterase activity and sphingomyelin phosphodiesterase D activity.

UniProtKB/Swiss-Prot Summary for SMPD4 Gene

  • Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide (PubMed:16517606, PubMed:25180167). It has a relevant role in the homeostasis of membrane sphingolipids, thereby influencing membrane integrity, and endoplasmic reticulum organization and function (PubMed:31495489). May sensitize cells to DNA damage-induced apoptosis (PubMed:18505924). In skeletal muscle, mediates TNF-stimulated oxidant production (By similarity).

Gene Wiki entry for SMPD4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SMPD4 Gene

Genomics for SMPD4 Gene

GeneHancer (GH) Regulatory Elements Pubs

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 CraniofacialAtlas dbSUPER 250.7 +0.4 350 5.2 SP1 ZNF207 NCOR1 MYC IKZF1 ZNF592 POLR2A BRCA1 NFIC ZIC2 MZT2B SMPD4 lnc-MZT2B-5 lnc-TUBA3E-1 TUBA3E NOC2LP1 RAB6C-AS1
GH02J130341 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 67 -159.8 -159750 4.2 BCLAF1 SP1 ZNF207 MYC ZNF600 IKZF1 SIX5 ZNF580 KLF9 POLR2A CCDC115 HSALNG0018800 IMP4 lnc-PTPN18-2 lnc-POTEI-3 piR-37496 SMPD4 PTPN18
GH02J130190 Promoter 0.4 EPDnew 250.4 -7.9 -7925 0.1 SCRT2 SMPD4 MZT2B TUBA3E lnc-MZT2B-5
GH02J130336 Promoter/Enhancer 1.5 ENCODE CraniofacialAtlas 31.7 -155.6 -155617 3.4 BCLAF1 ZNF207 IKZF1 ZNF600 SSRP1 JUND ZNF580 ZNF592 CEBPA ATF3 TRE-TTC1-1 SMPD4 PTPN18 RAB6C-AS1 CCDC115 IMP4 lnc-POTEI-3 TUBA3E
GH02J130369 Promoter/Enhancer 2 Ensembl ENCODE CraniofacialAtlas dbSUPER 15.4 -189.8 -189836 5.6 SP1 ZNF207 IKZF1 NCOR1 MYC JUND ZNF592 POLR2A NFIC ZIC2 HSALNG0018810 PTPN18 SMPD4 HSALNG0018811 HSALNG0018807-001 POTEI
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SMPD4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SMPD4

Top Transcription factor binding sites by QIAGEN in the SMPD4 gene promoter:
  • AREB6
  • Arnt
  • CUTL1
  • E47
  • FOXI1
  • HFH-3
  • RORalpha1
  • Sox5
  • Sp1
  • XBP-1

Genomic Locations for SMPD4 Gene

Latest Assembly
chr2:130,151,392-130,182,750
(GRCh38/hg38)
Size:
31,359 bases
Orientation:
Minus strand

Previous Assembly
chr2:130,908,965-130,939,330
(GRCh37/hg19 by Entrez Gene)
Size:
30,366 bases
Orientation:
Minus strand

chr2:130,908,981-130,940,323
(GRCh37/hg19 by Ensembl)
Size:
31,343 bases
Orientation:
Minus strand

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=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA91070.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA91368.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA91567.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA92656.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for SMPD4 Gene

neXtProt entry for SMPD4 Gene

Post-translational modifications for SMPD4 Gene

  • Ubiquitination at Lys145, Lys500, Lys568, Lys277, Lys580, Lys604, and Lys660
  • 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:

Suggested Antigen Peptide Sequences for SMPD4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59341, highly similar to Homo sapiens sphingomyelin phosphodiesterase 4, neutral membrane, transcript variant 1, mRNA (B4DM23_HUMAN)
  • cDNA FLJ53156, highly similar to Homo sapiens sphingomyelin phosphodiesterase 4, neutral membrane, transcript variant 2, mRNA (B4DQ31_HUMAN)
  • cDNA FLJ58546, highly similar to Homo sapiens sphingomyelin phosphodiesterase 4, neutral membrane, transcript variant 1, mRNA (B4DWK7_HUMAN)
  • cDNA FLJ53260, highly similar to Homo sapiens sphingomyelin phosphodiesterase 4, neutral membrane, transcript variant 2, mRNA (B4E0L6_HUMAN)
  • Neutral sphingomyelinase III (NSMA3_HUMAN)
genes like me logo Genes that share domains with SMPD4: view

No data available for Graphical View of Domain Structure and 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, PubMed:25180167). It has a relevant role in the homeostasis of membrane sphingolipids, thereby influencing membrane integrity, and endoplasmic reticulum organization and function (PubMed:31495489). May sensitize cells to DNA damage-induced apoptosis (PubMed:18505924). In skeletal muscle, mediates TNF-stimulated oxidant production (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=a sphingomyelin + H2O = an N-acylsphing-4-enine + H(+) + phosphocholine; Xref=Rhea:RHEA:19253, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639, ChEBI:CHEBI:295975; EC=3.1.4.12; Evidence={ECO:0000269|PubMed:16517606, ECO:0000269|PubMed:25180167};.
UniProtKB/Swiss-Prot Induction:
Expression is induced by DNA-damage and TNF.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
pH dependence: Optimum pH is 7.0. {ECO:0000269|PubMed:16517606};
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphatidylserine and tumor necrosis factor (TNF). Inhibited by scyphostatin.

Enzyme Numbers (IUBMB) for SMPD4 Gene

Phenotypes From GWAS Catalog for SMPD4 Gene

Gene Ontology (GO) - Molecular Function for SMPD4 Gene

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

Human Phenotype Ontology for SMPD4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SMPD4 Gene

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

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SMPD4

Clone products for research

No data available for 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. Nucleus envelope. Cell membrane, sarcolemma.

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
plasma membrane 5
nucleus 5
endoplasmic reticulum 5
golgi apparatus 4
mitochondrion 2
lysosome 2
extracellular 1
endosome 1
cytosol 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear membrane (2)
  • Cytosol (1)
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:0005634 nucleus IEA --
GO:0005635 nuclear envelope ISS --
GO:0005640 nuclear outer membrane IDA 31495489
GO:0005783 endoplasmic reticulum IEA,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 IBA,IDA 16517606
GO:0006687 glycosphingolipid metabolic process TAS --
GO:0007029 endoplasmic reticulum organization IMP 31495489
GO:0046475 glycerophospholipid catabolic process IDA 16517606
GO:0046513 ceramide biosynthetic process 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

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

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

(269) 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 (D18:1/12:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
852100-88-0
3-O-Sulfogalactosylceramide (d18:1/14:0)
  • 3-O-Sulphogalactosylceramide (D18:1/14:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
3-O-Sulfogalactosylceramide (d18:1/16:0)
  • 3-O-Sulphogalactosylceramide (D18:1/16:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
862509-48-6
3-O-Sulfogalactosylceramide (d18:1/18:0)
  • 3-O-Sulphogalactosylceramide (D18:1/18:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
244215-65-4
3-O-Sulfogalactosylceramide (d18:1/18:1(9Z))
  • 3-O-Sulphogalactosylceramide (D18:1/18:1(9Z))
  • 3'-O-Sulphogalactosylceramide
  • 3-O-SulfO-beta-D-galactosylceramide
  • 3-O-SulfO-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
genes like me logo Genes that share compounds with SMPD4: view

Transcripts for SMPD4 Gene

mRNA/cDNA for SMPD4 Gene

4 REFSEQ mRNAs :
22 NCBI additional mRNA sequence :
27 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SMPD4

Clone products for research

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

No ASD Table

Relevant External Links for SMPD4 Gene

GeneLoc Exon Structure for
SMPD4

Expression for SMPD4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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(4.5)
  • Liver(2.3)
  • Blood(2.3)
  • Muscle(2.3)
  • Skin(2.2)
  • Kidney(2.2)
  • Intestine(2.1)
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 29
  • 96.41 (n)
Dog
(Canis familiaris)
Mammalia SMPD4 29 30
  • 88.52 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Smpd4 29
  • 86.37 (n)
Mouse
(Mus musculus)
Mammalia Smpd4 29 16 30
  • 85.6 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SMPD4 29 30
  • 83.58 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SMPD4 30
  • 74 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 73 (a)
OneToMany
-- 30
  • 70 (a)
OneToMany
Chicken
(Gallus gallus)
Aves SMPD4 29 30
  • 70.63 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SMPD4 30
  • 61 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia smpd4 29
  • 66.12 (n)
Str.6070 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.4713 29
Zebrafish
(Danio rerio)
Actinopterygii smpd4 29 30
  • 64.59 (n)
OneToOne
wufb22d05 29
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4009 29
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000405 29
  • 48.41 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG6962 29 30
  • 43.27 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 32 (a)
OneToOne
Species where no ortholog for SMPD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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
Alliance of Genome Resources:
Additional Orthologs for SMPD4

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, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SMPD4 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
1030617 Likely Pathogenic: Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 130,153,700(-) A/G
NM_017951.5(SMPD4):c.1893+2T>C
SPLICE_DONOR
870336 Uncertain Significance: Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 130,153,730(-) G/A
NM_017951.4(SMPD4):c.1982C>T (p.Ala661Val)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
870337 Likely Pathogenic: Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 130,173,530(-) C/A
NM_017951.4(SMPD4):c.370G>T (p.Glu124Ter)
NONSENSE,NON_CODING_TRANSCRIPT_VARIANT,INTRON
870338 Likely Pathogenic: Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 130,172,433(-) A/G
NM_017951.4(SMPD4):c.692T>C (p.Leu231Pro)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
870339 Uncertain Significance: Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 130,152,875(-) G/A
NM_017951.4(SMPD4):c.2281C>T (p.Gln761Ter)
NONSENSE,NON_CODING_TRANSCRIPT

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SMPD4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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
Leiden Open Variation Database (LOVD)
SMPD4

SNP Genotyping and Copy Number Assays for research

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

Disorders for SMPD4 Gene

MalaCards: The human disease database

(7) MalaCards diseases for SMPD4 Gene - From: OMI, CVR, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search SMPD4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NSMA3_HUMAN
  • Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (NEDMABA) [MIM:618622]: An autosomal recessive disorder characterized by severe global developmental delay, severely impaired intellectual development with poor or absent speech, severe encephalopathy, microcephaly with simplified gyral pattern, hypomyelination, thin corpus callosum, mild cerebellar hypoplasia, brainstem hypoplasia, congenital arthrogryposis, dysmorphic features, and respiratory problems often leading to early demise. {ECO:0000269 PubMed:31495489}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for SMPD4

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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
  2. Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis. (PMID: 31495489) Magini P … Mancini GMS (American journal of human genetics 2019) 3 4 72
  3. Neutral sphingomyelinase-3 mediates TNF-stimulated oxidant activity in skeletal muscle. (PMID: 25180167) Moylan JS … Reid MB (Redox biology 2014) 3 4
  4. 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 40
  5. 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

Products for SMPD4 Gene

Sources for SMPD4 Gene