Human Gene ICOS (ENST00000316386.11) from GENCODE V44
  Description: Homo sapiens inducible T cell costimulator (ICOS), mRNA. (from RefSeq NM_012092)
RefSeq Summary (NM_012092): 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].
Gencode Transcript: ENST00000316386.11
Gencode Gene: ENSG00000163600.13
Transcript (Including UTRs)
   Position: hg38 chr2:203,936,763-203,961,577 Size: 24,815 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg38 chr2:203,936,815-203,959,599 Size: 22,785 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:203,936,763-203,961,577)mRNA (may differ from genome)Protein (199 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ICOS_HUMAN
DESCRIPTION: RecName: Full=Inducible T-cell costimulator; AltName: Full=Activation-inducible lymphocyte immunomediatory molecule; AltName: CD_antigen=CD278; Flags: Precursor;
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).
SUBUNIT: Homodimer; disulfide-linked.
SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein (Potential).
SUBCELLULAR LOCATION: Isoform 2: Secreted (Potential).
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.
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.
PTM: N-glycosylated.
DISEASE: Defects in ICOS are the cause of immunodeficiency common variable type 1 (CVID1) [MIM:607594]. CVID1 is 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 lo.
SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like) domain.
WEB RESOURCE: Name=ICOSbase; Note=ICOS mutation db; URL="http://bioinf.uta.fi/ICOSbase/";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ICOS";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: ICOS
Diseases sorted by gene-association score: immunodeficiency, common variable, 1* (930), icos-related common variable immune deficiency* (500), common variable immunodeficiency* (221), good syndrome (7), diffuse cutaneous systemic sclerosis (7)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1.76 RPKM in Spleen
Total median expression: 7.70 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -9.3052-0.179 Picture PostScript Text
3' UTR -546.901978-0.276 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013783 - Ig-like_fold

ModBase Predicted Comparative 3D Structure on Q9Y6W8
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process:
GO:0002517 T cell tolerance induction
GO:0006955 immune response
GO:0031295 T cell costimulation
GO:0046854 phosphatidylinositol phosphorylation
GO:0051897 positive regulation of protein kinase B signaling
GO:0098609 cell-cell adhesion

Cellular Component:
GO:0005576 extracellular region
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009897 external side of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  AK314985 - Homo sapiens cDNA, FLJ95906, Homo sapiens inducible T-cell co-stimulator (ICOS), mRNA.
AJ277832 - Homo sapiens mRNA for inducible T-cell co-stimulator (ICOS gene).
LP896182 - Sequence 1046 from Patent EP3253886.
BC028006 - Homo sapiens inducible T-cell co-stimulator, mRNA (cDNA clone MGC:39850 IMAGE:5212706), complete cds.
BC028210 - Homo sapiens inducible T-cell co-stimulator, mRNA (cDNA clone MGC:40066 IMAGE:5215237), complete cds.
AB023135 - Homo sapiens mRNA for activation-inducible lymphocyte immunomediatory molecule AILIM, complete cds.
CU688368 - Synthetic construct Homo sapiens gateway clone IMAGE:100017953 5' read ICOS mRNA.
KJ902514 - Synthetic construct Homo sapiens clone ccsbBroadEn_11908 ICOS gene, encodes complete protein.
AF218312 - Synthetic construct inducible costimulator precursor (ICOS) mRNA, complete cds.
CU688430 - Synthetic construct Homo sapiens gateway clone IMAGE:100023234 5' read ICOS mRNA.
HQ448206 - Synthetic construct Homo sapiens clone IMAGE:100071604; CCSB009464_01 inducible T-cell co-stimulator (ICOS) gene, encodes complete protein.
KJ893702 - Synthetic construct Homo sapiens clone ccsbBroadEn_03096 ICOS gene, encodes complete protein.
JD468264 - Sequence 449288 from Patent EP1572962.
JD158519 - Sequence 139543 from Patent EP1572962.
JD057581 - Sequence 38605 from Patent EP1572962.
JD058838 - Sequence 39862 from Patent EP1572962.
JD526370 - Sequence 507394 from Patent EP1572962.
JD160578 - Sequence 141602 from Patent EP1572962.
JD431409 - Sequence 412433 from Patent EP1572962.
JD425165 - Sequence 406189 from Patent EP1572962.
JD510191 - Sequence 491215 from Patent EP1572962.
JD296637 - Sequence 277661 from Patent EP1572962.
JD553722 - Sequence 534746 from Patent EP1572962.
JD418133 - Sequence 399157 from Patent EP1572962.
JD510497 - Sequence 491521 from Patent EP1572962.
JD277983 - Sequence 259007 from Patent EP1572962.
JD248143 - Sequence 229167 from Patent EP1572962.
JD318516 - Sequence 299540 from Patent EP1572962.
JD400528 - Sequence 381552 from Patent EP1572962.
JD157938 - Sequence 138962 from Patent EP1572962.
JD220404 - Sequence 201428 from Patent EP1572962.
JD189662 - Sequence 170686 from Patent EP1572962.
JD271613 - Sequence 252637 from Patent EP1572962.
JD228038 - Sequence 209062 from Patent EP1572962.
JD283124 - Sequence 264148 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04514 - Cell adhesion molecules (CAMs)
hsa04660 - T cell receptor signaling pathway
hsa04672 - Intestinal immune network for IgA production
hsa05340 - Primary immunodeficiency

BioCarta from NCI Cancer Genome Anatomy Project
h_ctla4Pathway - The Co-Stimulatory Signal During T-cell Activation

Reactome (by CSHL, EBI, and GO)

Protein Q9Y6W8 (Reactome details) participates in the following event(s):

R-HSA-388817 ICOS binds ICOSL/B7-H2
R-HSA-388830 PI3K binds ICOS
R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity
R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3
R-HSA-388841 Costimulation by the CD28 family
R-HSA-1280218 Adaptive Immune System
R-HSA-168256 Immune System
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-199418 Negative regulation of the PI3K/AKT network
R-HSA-5663202 Diseases of signal transduction
R-HSA-162582 Signal Transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: AILIM, ENST00000316386.1, ENST00000316386.10, ENST00000316386.2, ENST00000316386.3, ENST00000316386.4, ENST00000316386.5, ENST00000316386.6, ENST00000316386.7, ENST00000316386.8, ENST00000316386.9, ICOS_HUMAN, NM_012092, Q8N6W8, Q9Y6W8, uc002vam.1, uc002vam.2, uc002vam.3, uc002vam.4, uc002vam.5
UCSC ID: ENST00000316386.11
RefSeq Accession: NM_012092
Protein: Q9Y6W8 (aka ICOS_HUMAN)
CCDS: CCDS2363.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.