Seroatlas · Human Serome Atlas

SMPD4

Sphingomyelin phosphodiesterase 4

Also known as: FLJ20297, FLJ20756, KIAA1418, NET13, NSMA3_HUMAN, nSMase-3, NSMASE3

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q9NXE4
Gene
SMPD4
Ensembl
ENSG00000136699
Chromosome
2
Canonical length
866 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location
Nuclear membrane,Cytosol

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

866 residues, UniProt reviewed canonical sequence.

>Q9NXE4|SMPD4
     1  MTTFGAVAEW RLPSLRRATL WIPQWFAKKA IFNSPLEAAM AFPHLQQPSF LLASLKADSI
    61  NKPFAQQCQD LVKVIEDFPA KELHTIFPWL VESIFGSLDG VLVGWNLRCL QGRVNPVEYS
   121  IVMEFLDPGG PMMKLVYKLQ AEDYKFDFPV SYLPGPVKAS IQECILPDSP LYHNKVQFTP
   181  TGGLGLNLAL NPFEYYIFFF ALSLITQKPL PVSLHVRTSD CAYFILVDRY LSWFLPTEGS
   241  VPPPLSSSPG GTSPSPPPRT PAIPFASYGL HHTSLLKRHI SHQTSVNADP ASHEIWRSET
   301  LLQVFVEMWL HHYSLEMYQK MQSPHAKLEV LHYRLSVSSA LYSPAQPSLQ ALHAYQESFT
   361  PTEEHVLVVR LLLKHLHAFA NSLKPEQASP SAHSHATSPL EEFKRAAVPR FVQQKLYLFL
   421  QHCFGHWPLD ASFRAVLEMW LSYLQPWRYA PDKQAPGSDS QPRCVSEKWA PFVQENLLMY
   481  TKLFVGFLNR ALRTDLVSPK HALMVFRVAK VFAQPNLAEM IQKGEQLFLE PELVIPHRQH
   541  RLFTAPTFTG SFLSPWPPAV TDASFKVKSH VYSLEGQDCK YTPMFGPEAR TLVLRLAQLI
   601  TQAKHTAKSI SDQCAESPAG HSFLSWLGFS SMDTNGSYTA NDLDEMGQDS VRKTDEYLEK
   661  ALEYLRQIFR LSEAQLRQFT LALGTTQDEN GKKQLPDCIV GEDGLILTPL GRYQIINGLR
   721  RFEIEYQGDP ELQPIRSYEI ASLVRTLFRL SSAINHRFAG QMAALCSRDD FLGSFCRYHL
   781  TEPGLASRHL LSPVGRRQVA GHTRGPRLSL RFLGSYRTLV SLLLAFFVAS LFCVGPLPCT
   841  LLLTLGYVLY ASAMTLLTER GKLHQP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMPD4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0.36
Highest tissue expression
25 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 25 nTPM
  • thymus: 19 nTPM
  • pituitary gland: 18 nTPM
  • endometrium: 18 nTPM
  • testis: 17 nTPM
  • blood vessel: 15 nTPM

Single-cell type

  • mesothelial cells: 50 nCPM
  • somatotrophs: 41 nCPM
  • plasma cells: 40 nCPM
  • distal convoluted tubule cells: 39 nCPM
  • podocytes: 39 nCPM
  • erythrocyte progenitors: 38 nCPM

Immune cell

  • eosinophil: 15 nTPM
  • MAIT T-cell: 14 nTPM
  • gdT-cell: 13 nTPM
  • NK-cell: 12 nTPM
  • memory CD8 T-cell: 12 nTPM
  • intermediate monocyte: 11 nTPM

Brain region

  • white matter: 37 nTPM
  • medulla oblongata: 34 nTPM
  • hypothalamus: 33 nTPM
  • cerebral cortex: 32 nTPM
  • pons: 32 nTPM
  • thalamus: 30 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SMPD4.

Disease | AllUniProt

Conditions SMPD4 is implicated in, by any mechanism.

  • Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (NEDMABA) MIM:618622

Disease | GeneticClinVar

30 pathogenic / likely-pathogenic of 255 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
1.02
gnomAD pLI
0
gnomAD missense Z
0.86
DepMap mean gene effect
-0.21
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

  • Sphingomyelin phosphodiesterase 4
  • Mitochondrial-associated sphingomyelin phosphodiesterase

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SMPD4 as an antibody target. Whether an autoantibody or antibody against SMPD4 could matter depends on whether native SMPD4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SMPD4 is annotated at the cell surface, where native SMPD4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label SMPD4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SMPD4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

© 2026 · Seroatlas, Discover Oregon LLC · Terms of use

Loading the interactive Seroatlas protein explorer...