Seroatlas · Human Serome Atlas

SMPD3

Sphingomyelin phosphodiesterase 3

Also known as: NSMA2_HUMAN, NSMASE2

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

Protein identityUniProt · HPA

UniProt accession
Q9NY59
Gene
SMPD3
Ensembl
ENSG00000103056
Chromosome
16
Canonical length
655 aa
Protein class
Enzymes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location
Endoplasmic reticulum

OverviewNCBI Gene

Enables sphingomyelin phosphodiesterase activity. Involved in sphingomyelin catabolic process. Predicted to be located in plasma membrane. Predicted to be active in cytoplasm. Biomarker of pulmonary emphysema. [provided by Alliance of Genome Resources, Jul 2025]

Canonical amino-acid sequenceUniProt

655 residues, UniProt reviewed canonical sequence.

>Q9NY59|SMPD3
     1  MVLYTTPFPN SCLSALHCVS WALIFPCYWL VDRLAASFIP TTYEKRQRAD DPCCLQLLCT
    61  ALFTPIYLAL LVASLPFAFL GFLFWSPLQS ARRPYIYSRL EDKGLAGGAA LLSEWKGTGP
   121  GKSFCFATAN VCLLPDSLAR VNNLFNTQAR AKEIGQRIRN GAARPQIKIY IDSPTNTSIS
   181  AASFSSLVSP QGGDGVARAV PGSIKRTASV EYKGDGGRHP GDEAANGPAS GDPVDSSSPE
   241  DACIVRIGGE EGGRPPEADD PVPGGQARNG AGGGPRGQTP NHNQQDGDSG SLGSPSASRE
   301  SLVKGRAGPD TSASGEPGAN SKLLYKASVV KKAAARRRRH PDEAFDHEVS AFFPANLDFL
   361  CLQEVFDKRA ATKLKEQLHG YFEYILYDVG VYGCQGCCSF KCLNSGLLFA SRYPIMDVAY
   421  HCYPNKCNDD ALASKGALFL KVQVGSTPQD QRIVGYIACT HLHAPQEDSA IRCGQLDLLQ
   481  DWLADFRKST SSSSAANPEE LVAFDVVCGD FNFDNCSSDD KLEQQHSLFT HYRDPCRLGP
   541  GEEKPWAIGT LLDTNGLYDE DVCTPDNLQK VLESEEGRRE YLAFPTSKSS GQKGRKELLK
   601  GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSS GEEEA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMPD3 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
0
Mean surface accessibility (rSASA)
0.38
Highest tissue expression
58 nTPM

Expression across tissuesHPA

Tissue

  • duodenum: 58 nTPM
  • small intestine: 54 nTPM
  • thymus: 48 nTPM
  • stomach: 22 nTPM
  • basal ganglia: 17 nTPM
  • pituitary gland: 15 nTPM

Single-cell type

  • retinal horizontal cells: 515 nCPM
  • pdcs: 218 nCPM
  • enterocytes: 154 nCPM
  • epicardial cells: 152 nCPM
  • retinal bipolar cells: 144 nCPM
  • mesothelial cells: 91 nCPM

Immune cell

  • plasmacytoid DC: 139 nTPM
  • eosinophil: 21 nTPM
  • basophil: 4.4 nTPM
  • gdT-cell: 2.2 nTPM
  • T-reg: 1.9 nTPM
  • memory B-cell: 1.7 nTPM

Brain region

  • basal ganglia: 80 nTPM
  • hippocampal formation: 72 nTPM
  • cerebral cortex: 71 nTPM
  • amygdala: 35 nTPM
  • thalamus: 26 nTPM
  • white matter: 23 nTPM

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)
0.43
gnomAD pLI
0.59
gnomAD missense Z
1.11
DepMap mean gene effect
-0.1
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SMPD3 as an antibody target. Whether an autoantibody or antibody against SMPD3 could matter depends on whether native SMPD3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SMPD3 is annotated at the cell surface, where native SMPD3 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 SMPD3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SMPD3. 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).

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