Seroatlas · Human Serome Atlas

SIGLEC12

Sialic acid-binding Ig-like lectin 12

Also known as: S2V, SIG12_HUMAN, Siglec-12, Siglec-L1, Siglec-XII, SIGLECL1, SLG

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

Protein identityUniProt · HPA

UniProt accession
Q96PQ1
Gene
SIGLEC12
Ensembl
ENSG00000254521
Chromosome
19
Canonical length
595 aa
Protein class
Predicted membrane proteins

OverviewNCBI Gene

Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are a family of cell surface proteins belonging to the immunoglobulin superfamily. They mediate protein-carbohydrate interactions by selectively binding to different sialic acid moieties present on glycolipids and glycoproteins. This gene encodes a member of the SIGLEC3-like subfamily of SIGLECs. Members of this subfamily are characterized by an extracellular V-set immunoglobulin-like domain followed by two C2-set immunoglobulin-like domains, and the cytoplasmic tyrosine-based motifs ITIM and SLAM-like. The encoded protein, upon tyrosine phosphorylation, has been shown to recruit the Src homology 2 domain-containing protein-tyrosine phosphatases SHP1 and SHP2. It has been suggested that the protein is involved in the negative regulation of macrophage signaling by functioning as an inhibitory receptor. This gene is located in a cluster with other SIGLEC3-like genes on 19q13.4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Canonical amino-acid sequenceUniProt

595 residues, UniProt reviewed canonical sequence.

>Q96PQ1|SIGLEC12
     1  MLLLLLLLPP LLCGRVGAKE QKDYLLTMQK SVTVQEGLCV SVLCSFSYPQ NGWTASDPVH
    61  GYWFRAGDHV SRNIPVATNN PARAVQEETR DRFHLLGDPQ NKDCTLSIRD TRESDAGTYV
   121  FCVERGNMKW NYKYDQLSVN VTASQDLLSR YRLEVPESVT VQEGLCVSVP CSVLYPHYNW
   181  TASSPVYGSW FKEGADIPWD IPVATNTPSG KVQEDTHGRF LLLGDPQTNN CSLSIRDARK
   241  GDSGKYYFQV ERGSRKWNYI YDKLSVHVTA LTHMPTFSIP GTLESGHPRN LTCSVPWACE
   301  QGTPPTITWM GASVSSLDPT ITRSSMLSLI PQPQDHGTSL TCQVTLPGAG VTMTRAVRLN
   361  ISYPPQNLTM TVFQGDGTAS TTLRNGSALS VLEGQSLHLV CAVDSNPPAR LSWTWGSLTL
   421  SPSQSSNLGV LELPRVHVKD EGEFTCRAQN PLGSQHISLS LSLQNEYTGK MRPISGVTLG
   481  AFGGAGATAL VFLYFCIIFV VVRSCRKKSA RPAVGVGDTG MEDANAVRGS ASQGPLIESP
   541  ADDSPPHHAP PALATPSPEE GEIQYASLSF HKARPQYPQE QEAIGYEYSE INIPK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SIGLEC12 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)
0.4
Highest tissue expression
16 nTPM

Expression across tissuesHPA

Tissue

  • spleen: 16 nTPM
  • appendix: 4.4 nTPM
  • duodenum: 4.3 nTPM
  • small intestine: 3.7 nTPM
  • lymph node: 2.6 nTPM
  • smooth muscle: 2.4 nTPM

Single-cell type

  • macrophages: 11 nCPM
  • monocytes: 9.3 nCPM
  • kupffer cells: 6.1 nCPM
  • hofbauer cells: 4.8 nCPM
  • mast cells: 3.6 nCPM
  • monocyte progenitors: 3.2 nCPM

Immune cell

  • eosinophil: 0.7 nTPM
  • classical monocyte: 0.4 nTPM
  • intermediate monocyte: 0.2 nTPM
  • memory B-cell: 0.2 nTPM
  • myeloid DC: 0.2 nTPM
  • total PBMC: 0.2 nTPM

Brain region

  • choroid plexus: 0.4 nTPM
  • hypothalamus: 0.2 nTPM
  • medulla oblongata: 0.2 nTPM
  • thalamus: 0.2 nTPM
  • amygdala: 0.1 nTPM
  • basal ganglia: 0.1 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)
1.23
gnomAD pLI
0
gnomAD missense Z
-0.67
DepMap mean gene effect
0.13
DepMap dependency class
none

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 SIGLEC12 as an antibody target. Whether an autoantibody or antibody against SIGLEC12 could matter depends on whether native SIGLEC12 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SIGLEC12 is annotated at the cell surface, where native SIGLEC12 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 SIGLEC12 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SIGLEC12. 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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