Seroatlas · Human Serome Atlas

ICOS

Inducible T-cell costimulator

Also known as: AILIM, CD278, ICOS_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q9Y6W8
Gene
ICOS
Ensembl
ENSG00000163600
Chromosome
2
Canonical length
199 aa
Protein class
CD markers, Disease related genes, Human disease related genes, Predicted membrane proteins
Subcellular location
Plasma membrane,Actin filaments
Secretome location
Intracellular and membrane
Quaternary structure
Homodimer

OverviewNCBI Gene

The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses, and regulation of cell proliferation. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

199 residues, UniProt reviewed canonical sequence.

>Q9Y6W8|ICOS
     1  MKSGLWYFFL FCLRIKVLTG EINGSANYEM FIFHNGGVQI LCKYPDIVQQ FKMQLLKGGQ
    61  ILCDLTKTKG SGNTVSIKSL KFCHSQLSNN SVSFFLYNLD HSHANYYFCN LSIFDPPPFK
   121  VTLTGGYLHI YESQLCCQLK FWLPIGCAAF VVVCILGCIL ICWLTKKKYS SSVHDPNGEY
   181  MFMRAVNTAK KSRLTDVTL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ICOS 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)
0.46
Highest tissue expression
19 nTPM

Expression across tissuesHPA

Tissue

  • thymus: 19 nTPM
  • bone marrow: 16 nTPM
  • tonsil: 15 nTPM
  • lymph node: 13 nTPM
  • appendix: 7.2 nTPM
  • spleen: 3.1 nTPM

Single-cell type

  • t-cells: 300 nCPM
  • innate lymphoid cells: 148 nCPM
  • thymocytes: 31 nCPM
  • nk-cells: 23 nCPM
  • gastric chief cells: 13 nCPM
  • lacrimal acinar cells: 8.2 nCPM

Immune cell

  • T-reg: 29 nTPM
  • naive CD4 T-cell: 16 nTPM
  • memory CD4 T-cell: 15 nTPM
  • naive CD8 T-cell: 7.2 nTPM
  • memory CD8 T-cell: 6.8 nTPM
  • total PBMC: 4.3 nTPM

Brain region

  • medulla oblongata: 0.3 nTPM
  • hypothalamus: 0.1 nTPM
  • pons: 0.1 nTPM
  • spinal cord: 0.1 nTPM
  • white matter: 0.1 nTPM
  • amygdala: 0 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ICOS.

Disease | AllUniProt

Conditions ICOS is implicated in, by any mechanism.

  • Immunodeficiency, common variable, 1 (CVID1) MIM:607594

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 197 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

ReferencesPubMed · IEDB

Publications for ICOS from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

5 publications

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)
0.91
gnomAD pLI
0.03
gnomAD missense Z
1.21
DepMap mean gene effect
0.1
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

InteractionsUniProt · HPA

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

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

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