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] See more...

Aliases for ICOS Gene

Aliases for ICOS Gene

  • Inducible T Cell Costimulator 2 3 5
  • Activation-Inducible Lymphocyte Immunomediatory Molecule 2 3 4
  • Inducible T-Cell Costimulator 2 3 4
  • AILIM 2 3 4
  • CD278 2 3
  • Inducible T-Cell Co-Stimulator 3
  • Inducible Costimulator 3
  • CD278 Antigen 4
  • CVID1 3
  • ICOS 5

External Ids for ICOS Gene

Previous GeneCards Identifiers for ICOS Gene

  • GC02P203018
  • GC02P203526
  • GC02P204765
  • GC02P205004
  • GC02P204626
  • GC02P204509
  • GC02P196648

Summaries for ICOS Gene

Entrez Gene Summary for ICOS 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]

GeneCards Summary for ICOS Gene

ICOS (Inducible T Cell Costimulator) is a Protein Coding gene. Diseases associated with ICOS include Immunodeficiency, Common Variable, 1 and Common Variable Immunodeficiency. Among its related pathways are RET signaling and Signaling by GPCR.

UniProtKB/Swiss-Prot Summary for ICOS Gene

  • Enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes (By similarity).

Gene Wiki entry for ICOS Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ICOS Gene

Genomics for ICOS Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ICOS Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J203936 Promoter/Enhancer 1.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 275.8 +1.5 1538 6.2 ZMYM3 POLR2A MLLT1 ICOS CD28 CTLA4 LOC101927840 HSALNG0021706-001 HSALNG0021706-002 PARD3B
GH02J203704 Promoter/Enhancer 1.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 38.6 -228.6 -228585 8 BCLAF1 SP1 CEBPA BCL11A IRF4 EBF1 BHLHE40 BATF HNF4A STAT5A CD28 ICOS CTLA4 RNU6-474P KRT18P39 NBEAL1 ENSG00000228513 CARF HSALNG0021688
GH02J203717 Enhancer 1.1 FANTOM5 ENCODE dbSUPER 12.4 -216.5 -216526 6.2 CEBPA THAP11 FOXA2 RXRA RARA TAL1 FOXP1 BCL6 SOX5 MYC HSALNG0021688 CD28 ICOS RAPH1 RNU6-474P KRT18P39 CTLA4 CARF CYP20A1
GH02J203737 Enhancer 0.8 FANTOM5 ENCODE dbSUPER 14.4 -195.3 -195347 7.2 CEBPB ZSCAN4 SOX6 EP300 HSALNG0021689 CD28 KRT18P39 ICOS RNU6-474P RAPH1 CTLA4 HSALNG0021690
GH02J203949 Enhancer 0.7 FANTOM5 dbSUPER 13.9 +12.7 12654 0.3 FOXA1 NR2F1 IKZF2 ARNT ICOS CD28 CTLA4 HSALNG0021706-001 HSALNG0021706-002 piR-53029-065 PARD3B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ICOS on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ICOS

Top Transcription factor binding sites by QIAGEN in the ICOS gene promoter:
  • AML1a
  • AP-1
  • ATF-2
  • c-Jun
  • Chx10
  • HOXA3
  • IRF-7A
  • LCR-F1
  • Pax-4a
  • Sp1

Genomic Locations for ICOS Gene

Latest Assembly
chr2:203,936,763-203,961,577
(GRCh38/hg38)
Size:
24,815 bases
Orientation:
Plus strand

Previous Assembly
chr2:204,801,486-204,826,300
(GRCh37/hg19 by Entrez Gene)
Size:
24,815 bases
Orientation:
Plus strand

chr2:204,801,471-204,826,300
(GRCh37/hg19 by Ensembl)
Size:
24,830 bases
Orientation:
Plus strand

Genomic View for ICOS Gene

Genes around ICOS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ICOS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ICOS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ICOS Gene

Proteins for ICOS Gene

  • Protein details for ICOS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6W8-ICOS_HUMAN
    Recommended name:
    Inducible T-cell costimulator
    Protein Accession:
    Q9Y6W8
    Secondary Accessions:
    • Q8N6W8

    Protein attributes for ICOS Gene

    Size:
    199 amino acids
    Molecular mass:
    22625 Da
    Quaternary structure:
    • Homodimer; disulfide-linked.

    Three dimensional structures from OCA and Proteopedia for ICOS Gene

    Alternative splice isoforms for ICOS Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ICOS Gene

Post-translational modifications for ICOS Gene

Other Protein References for ICOS Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for ICOS

No data available for DME Specific Peptides for ICOS Gene

Domains & Families for ICOS Gene

Gene Families for ICOS Gene

HGNC:
Human Protein Atlas (HPA):
  • CD markers
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for ICOS Gene

Suggested Antigen Peptide Sequences for ICOS Gene

GenScript: Design optimal peptide antigens:
  • Activation-inducible lymphocyte immunomediatory molecule (ICOS_HUMAN)
  • cDNA, FLJ95906, Homo sapiens inducible T-cell co-stimulator (ICOS), mRNA (Q53QY6_HUMAN)
genes like me logo Genes that share domains with ICOS: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ICOS Gene

Function for ICOS Gene

Molecular function for ICOS Gene

UniProtKB/Swiss-Prot Function:
Enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes (By similarity).
UniProtKB/Swiss-Prot Induction:
By phorbol myristate acetate (PMA) and ionomycin. Up-regulated early on T-cells and continues to be expressed into the later phases of T-cell activation.

Phenotypes From GWAS Catalog for ICOS Gene

Gene Ontology (GO) - Molecular Function for ICOS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 11956294
genes like me logo Genes that share ontologies with ICOS: view
genes like me logo Genes that share phenotypes with ICOS: view

Human Phenotype Ontology for ICOS Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ICOS Gene

MGI Knock Outs for ICOS:
  • Icos Icos<tm1Flv>
  • Icos Icos<tm1Shr>
  • Icos Icos<tm1Tkan>
  • Icos Icos<tm1Dgry>
  • Icos Icos<tm1Mak>
  • Icos Icos<tm2b(EUCOMM)Wtsi>

Animal Models for research

  • Taconic Biosciences Mouse Models for ICOS

miRNA for ICOS Gene

miRTarBase miRNAs that target ICOS

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ICOS

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ICOS Gene

Localization for ICOS Gene

Subcellular locations from UniProtKB/Swiss-Prot for ICOS Gene

[Isoform 1]: Cell membrane. Single-pass type I membrane protein.
[Isoform 2]: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ICOS gene
Compartment Confidence
plasma membrane 5
extracellular 4
nucleus 2
cytosol 2
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (2)
  • Actin filaments (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ICOS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with ICOS: view

Pathways & Interactions for ICOS Gene

genes like me logo Genes that share pathways with ICOS: view

Pathways by source for ICOS Gene

1 Qiagen pathway for ICOS Gene
  • ICos-ICosL Pathway in T-Helper Cell
1 Cell Signaling Technology pathway for ICOS Gene

Gene Ontology (GO) - Biological Process for ICOS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002517 T cell tolerance induction IBA 21873635
GO:0006955 immune response NAS 9930702
GO:0031295 T cell costimulation TAS --
GO:0051897 positive regulation of protein kinase B signaling TAS --
GO:0098609 cell-cell adhesion IBA 21873635
genes like me logo Genes that share ontologies with ICOS: view

No data available for SIGNOR curated interactions for ICOS Gene

Drugs & Compounds for ICOS Gene

(9) Drugs for ICOS Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ipilimumab Approved Pharma Therapeutic Antibodies, Immunotherapies, Immunomodulatory agents 731
nivolumab Approved Pharma Therapeutic Antibodies, Immunotherapies 1298
Pembrolizumab Approved Pharma 1463
Antibodies Pharma 8474
Antibodies, Monoclonal Pharma 4203
genes like me logo Genes that share compounds with ICOS: view

Transcripts for ICOS Gene

mRNA/cDNA for ICOS Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ICOS

Alternative Splicing Database (ASD) splice patterns (SP) for ICOS Gene

ExUns: 1 ^ 2 ^ 3 ^ 4
SP1:
SP2: -

Relevant External Links for ICOS Gene

GeneLoc Exon Structure for
ICOS

Expression for ICOS Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ICOS Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ICOS Gene

This gene is overexpressed in Whole Blood (x15.2), Small Intestine - Terminal Ileum (x7.1), Spleen (x6.0), and Lung (x4.2).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ICOS

SOURCE GeneReport for Unigene cluster for ICOS Gene:

Hs.56247

mRNA Expression by UniProt/SwissProt for ICOS Gene:

Q9Y6W8-ICOS_HUMAN
Tissue specificity: Activated T-cells. Highly expressed on tonsillar T-cells, which are closely associated with B-cells in the apical light zone of germinal centers, the site of terminal B-cell maturation. Expressed at lower levels in thymus, lung, lymph node and peripheral blood leukocytes. Expressed in the medulla of fetal and newborn thymus.

Evidence on tissue expression from TISSUES for ICOS Gene

  • Blood(4.5)
  • Lymph node(2.7)
  • Bone marrow(2.4)
  • Spleen(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ICOS Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • head
  • hypothalamus
  • meninges
  • middle ear
  • neck
  • pituitary gland
  • sinus
  • skull
  • thyroid
Thorax:
  • bronchus
  • heart
  • lung
Abdomen:
  • adrenal gland
  • intestine
  • large intestine
  • liver
  • small intestine
  • spleen
  • stomach
Pelvis:
  • anus
  • rectum
  • uterus
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • lymph node
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with ICOS: view

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for ICOS Gene

Orthologs for ICOS Gene

This gene was present in the common ancestor of chordates.

Orthologs for ICOS Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ICOS 29 30
  • 99.16 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ICOS 29 30
  • 84.26 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ICOS 29 30
  • 83.67 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Icos 29
  • 77.54 (n)
Mouse
(Mus musculus)
Mammalia Icos 29 16 30
  • 77.44 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ICOS 30
  • 43 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ICOS 30
  • 42 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ICOS 30
  • 29 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ICOS 30
  • 22 (a)
OneToOne
Species where no ortholog for ICOS was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for ICOS Gene

ENSEMBL:
Gene Tree for ICOS (if available)
TreeFam:
Gene Tree for ICOS (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ICOS: view image
Alliance of Genome Resources:
Additional Orthologs for ICOS

Paralogs for ICOS Gene

No data available for Paralogs for ICOS Gene

Variants for ICOS Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ICOS Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
1002484 Uncertain Significance: Common variable immunodeficiency 1 203,956,730(+) T/G
NM_012092.4(ICOS):c.466T>G (p.Leu156Val)
MISSENSE
1031176 Uncertain Significance: Common variable immunodeficiency 1 203,955,706(+) A/T
NM_012092.4(ICOS):c.129A>T (p.Lys43Asn)
MISSENSE
1035995 Uncertain Significance: Common variable immunodeficiency 1 203,957,877(+) C/A
NM_012092.4(ICOS):c.580C>A (p.Leu194Ile)
MISSENSE
835162 Uncertain Significance: Common variable immunodeficiency 1 203,957,886(+) A/G
NM_012092.4(ICOS):c.586+3A>G
INTRON
841396 Uncertain Significance: Common variable immunodeficiency 1 203,955,654(+) C/A
NM_012092.4(ICOS):c.77C>A (p.Ala26Asp)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ICOS Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for ICOS Gene

Variant ID Type Subtype PubMed ID
nsv1001799 CNV gain 25217958

Variation tolerance for ICOS Gene

Residual Variation Intolerance Score: 55.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.51; 29.40% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ICOS Gene

Human Gene Mutation Database (HGMD)
ICOS
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ICOS
Leiden Open Variation Database (LOVD)
ICOS

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ICOS Gene

Disorders for ICOS Gene

MalaCards: The human disease database

(9) MalaCards diseases for ICOS Gene - From: OMI, CVR, GTR, ORP, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search ICOS in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ICOS_HUMAN
  • Immunodeficiency, common variable, 1 (CVID1) [MIM:607594]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. {ECO:0000269 PubMed:12577056}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for ICOS

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with ICOS: view

No data available for Genatlas for ICOS Gene

Publications for ICOS Gene

  1. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. (PMID: 12577056) Grimbacher B … Peter HH (Nature immunology 2003) 3 4 22 72
  2. Association of the CD28/CTLA4/ICOS polymorphisms with susceptibility to rheumatoid arthritis. (PMID: 20113255) Kim YO … Hong SJ (Clinical chemistry and laboratory medicine 2010) 3 22 40
  3. Association of genetic variation in inducible costimulator gene with outcome of kidney transplantation. (PMID: 19202444) Haimila K … Partanen J (Transplantation 2009) 3 22 40
  4. Functional polymorphism of CTLA-4 and ICOS genes in allogeneic hematopoietic stem cell transplantation. (PMID: 19332044) Wu J … Yang YC (Clinica chimica acta; international journal of clinical chemistry 2009) 3 22 40
  5. Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus. (PMID: 18174230) Miyagawa H … Horiuchi T (Rheumatology (Oxford, England) 2008) 3 22 40

Products for ICOS Gene

Sources for ICOS Gene