Seroatlas · Human Serome Atlas

TLR9

Toll-like receptor 9

Also known as: CD289, TLR9_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q9NR96
Gene
TLR9
Ensembl
ENSG00000239732
Chromosome
3
Canonical length
1032 aa
Protein class
CD markers, FDA approved drug targets, Human disease related genes, Predicted membrane proteins
Quaternary structure
Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. Studies in mice and human indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

1032 residues, UniProt reviewed canonical sequence.

>Q9NR96|TLR9
     1  MGFCRSALHP LSLLVQAIML AMTLALGTLP AFLPCELQPH GLVNCNWLFL KSVPHFSMAA
    61  PRGNVTSLSL SSNRIHHLHD SDFAHLPSLR HLNLKWNCPP VGLSPMHFPC HMTIEPSTFL
   121  AVPTLEELNL SYNNIMTVPA LPKSLISLSL SHTNILMLDS ASLAGLHALR FLFMDGNCYY
   181  KNPCRQALEV APGALLGLGN LTHLSLKYNN LTVVPRNLPS SLEYLLLSYN RIVKLAPEDL
   241  ANLTALRVLD VGGNCRRCDH APNPCMECPR HFPQLHPDTF SHLSRLEGLV LKDSSLSWLN
   301  ASWFRGLGNL RVLDLSENFL YKCITKTKAF QGLTQLRKLN LSFNYQKRVS FAHLSLAPSF
   361  GSLVALKELD MHGIFFRSLD ETTLRPLARL PMLQTLRLQM NFINQAQLGI FRAFPGLRYV
   421  DLSDNRISGA SELTATMGEA DGGEKVWLQP GDLAPAPVDT PSSEDFRPNC STLNFTLDLS
   481  RNNLVTVQPE MFAQLSHLQC LRLSHNCISQ AVNGSQFLPL TGLQVLDLSH NKLDLYHEHS
   541  FTELPRLEAL DLSYNSQPFG MQGVGHNFSF VAHLRTLRHL SLAHNNIHSQ VSQQLCSTSL
   601  RALDFSGNAL GHMWAEGDLY LHFFQGLSGL IWLDLSQNRL HTLLPQTLRN LPKSLQVLRL
   661  RDNYLAFFKW WSLHFLPKLE VLDLAGNQLK ALTNGSLPAG TRLRRLDVSC NSISFVAPGF
   721  FSKAKELREL NLSANALKTV DHSWFGPLAS ALQILDVSAN PLHCACGAAF MDFLLEVQAA
   781  VPGLPSRVKC GSPGQLQGLS IFAQDLRLCL DEALSWDCFA LSLLAVALGL GVPMLHHLCG
   841  WDLWYCFHLC LAWLPWRGRQ SGRDEDALPY DAFVVFDKTQ SAVADWVYNE LRGQLEECRG
   901  RWALRLCLEE RDWLPGKTLF ENLWASVYGS RKTLFVLAHT DRVSGLLRAS FLLAQQRLLE
   961  DRKDVVVLVI LSPDGRRSRY VRLRQRLCRQ SVLLWPHQPS GQRSFWAQLG MALTRDNHHF
  1021  YNRNFCQGPT AE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TLR9 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
Other membrane
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0.28
Highest tissue expression
5.6 nTPM

Expression across tissuesHPA

Tissue

  • lymph node: 5.6 nTPM
  • spleen: 4.8 nTPM
  • tonsil: 3.8 nTPM
  • small intestine: 3.1 nTPM
  • cerebellum: 3 nTPM
  • appendix: 2.4 nTPM

Single-cell type

  • tuft cells: 23 nCPM
  • pdcs: 3.8 nCPM
  • bergmann glia: 1.1 nCPM
  • microglia: 1 nCPM
  • b-cells: 0.6 nCPM
  • astrocytes: 0.4 nCPM

Immune cell

  • plasmacytoid DC: 167 nTPM
  • memory B-cell: 24 nTPM
  • naive B-cell: 13 nTPM
  • MAIT T-cell: 2.7 nTPM
  • T-reg: 2.5 nTPM
  • total PBMC: 1.8 nTPM

Brain region

  • cerebral cortex: 10 nTPM
  • cerebellum: 3.8 nTPM
  • pons: 2.5 nTPM
  • medulla oblongata: 1.7 nTPM
  • white matter: 1.7 nTPM
  • basal ganglia: 1.4 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TLR9.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 139 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)
0.63
gnomAD pLI
0
gnomAD missense Z
2.29
DepMap mean gene effect
-0.04
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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

InteractionsUniProt · HPA

Protein binding partners of TLR9 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads TLR9 as an antibody target. Whether an autoantibody or antibody against TLR9 could matter depends on whether native TLR9 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TLR9 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label TLR9 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/TLR9. 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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