ICOS

Summary

ICOS (inducible T cell costimulator, HGNC:5351) is a protein-coding gene on chromosome 2q33.2, encoding Inducible T-cell costimulator (Q9Y6W8). Stimulatory receptor expressed in activated or antigen-experienced T-cells that plays an important role in the immune response.

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.

Source: NCBI Gene 29851 — RefSeq curated summary.

At a glance

• Gene–disease (curated): common variable immunodeficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 17
• Clinical variants (ClinVar): 208 total — 9 pathogenic, 5 likely-pathogenic
• GTEx eGene: eQTL in 3 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 32
• Drug target: yes — 4 curated mechanism-of-action drugs
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.27 (unconstrained)
• MANE Select transcript: NM_012092
• Interaction hub: 2,132 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5351
Approved symbol	ICOS
Name	inducible T cell costimulator
Location	2q33.2
Locus type	gene with protein product
Status	Approved
Aliases	AILIM, CD278
Ensembl gene	ENSG00000163600
Ensembl biotype	protein_coding
OMIM	604558
Entrez	29851

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

MANE Select: ENST00000316386

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000316386, ENST00000435193, ENST00000897354, ENST00001138099

RefSeq mRNA: 1 — MANE Select: NM_012092 NM_012092

CCDS: CCDS2363

Canonical transcript exons

ENST00000316386 — 5 exons

Exon	Start	End
ENSE00001076433	203957799	203957883
ENSE00001076434	203936763	203936872
ENSE00001076436	203955636	203955971
ENSE00001076437	203956659	203956765
ENSE00003507544	203959586	203961577

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 79.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.1984 / max 718.3986, expressed in 181 samples.

Highest expression (Bgee): lymph node, vermiform appendix, thymus, granulocyte, epithelium of nasopharynx.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ICOS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 3 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

3 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	3.9e-03	-0.38	2:203633118:C:G
Artery Aorta	eqtl	3.0e-02	-0.36	2:204197738:A:G
Skin Sun Exposed Lower leg	eqtl	3.9e-02	+0.31	2:203761998:T:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
24785	6.5113	177
24786	0.4788	69
24784	0.2082	65

Top tissues by expression

showing 100 of 266 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	79.37	gold quality
vermiform appendix	UBERON:0001154	76.97	gold quality
thymus	UBERON:0002370	75.66	silver quality
granulocyte	CL:0000094	75.36	gold quality
epithelium of nasopharynx	UBERON:0001951	73.47	gold quality
blood	UBERON:0000178	72.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.18	gold quality
caecum	UBERON:0001153	70.66	gold quality
superficial temporal artery	UBERON:0001614	67.54	gold quality
bone marrow	UBERON:0002371	66.27	gold quality
tonsil	UBERON:0002372	65.23	gold quality
spleen	UBERON:0002106	65.17	gold quality
gall bladder	UBERON:0002110	64.88	gold quality
palpebral conjunctiva	UBERON:0001812	63.07	gold quality
rectum	UBERON:0001052	62.64	gold quality
colonic epithelium	UBERON:0000397	60.97	silver quality
right lung	UBERON:0002167	60.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	59.07	gold quality
upper lobe of left lung	UBERON:0008952	59.06	gold quality
upper lobe of lung	UBERON:0008948	58.63	gold quality
bone marrow cell	CL:0002092	58.40	silver quality
small intestine	UBERON:0002108	57.34	gold quality
epithelial cell of pancreas	CL:0000083	57.33	gold quality
gluteal muscle	UBERON:0002000	57.26	gold quality
lung	UBERON:0002048	56.92	gold quality
tendon of biceps brachii	UBERON:0008188	56.68	gold quality
visceral pleura	UBERON:0002401	56.57	silver quality
oral cavity	UBERON:0000167	56.41	silver quality
triceps brachii	UBERON:0001509	56.16	gold quality
esophagus squamous epithelium	UBERON:0006920	54.95	silver quality
duodenum	UBERON:0002114	54.60	gold quality
myocardium	UBERON:0002349	54.25	gold quality
lower lobe of lung	UBERON:0008949	53.05	silver quality
nasal cavity mucosa	UBERON:0001826	52.98	gold quality
smooth muscle tissue	UBERON:0001135	52.96	gold quality
mucosa of transverse colon	UBERON:0004991	52.94	gold quality
omental fat pad	UBERON:0010414	52.89	gold quality
peritoneum	UBERON:0002358	52.85	gold quality
adipose tissue of abdominal region	UBERON:0007808	52.21	gold quality
mucosa of sigmoid colon	UBERON:0004993	52.00	gold quality
left uterine tube	UBERON:0001303	51.71	gold quality
cervix squamous epithelium	UBERON:0006922	50.96	gold quality
mucosa of urinary bladder	UBERON:0001259	50.75	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	50.67	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
male germ cell	CL:0000015	50.33	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
right coronary artery	UBERON:0001625	50.15	gold quality
sperm	CL:0000019	50.00	gold quality
quadriceps femoris	UBERON:0001377	49.98	gold quality
cardia of stomach	UBERON:0001162	49.95	gold quality
urinary bladder	UBERON:0001255	49.62	gold quality
vastus lateralis	UBERON:0001379	49.61	gold quality
buccal mucosa cell	CL:0002336	49.49	gold quality
cervix epithelium	UBERON:0004801	49.34	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
oviduct epithelium	UBERON:0004804	48.88	gold quality
penis	UBERON:0000989	48.85	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
nasal cavity epithelium	UBERON:0005384	48.45	gold quality
layer of synovial tissue	UBERON:0007616	48.43	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
intestine	UBERON:0000160	48.16	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
renal glomerulus	UBERON:0000074	47.60	gold quality
cranial nerve II	UBERON:0000941	47.57	silver quality
fallopian tube	UBERON:0003889	47.51	gold quality
superior surface of tongue	UBERON:0007371	47.48	gold quality
transverse colon	UBERON:0001157	47.46	gold quality
kidney epithelium	UBERON:0004819	47.32	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
amniotic fluid	UBERON:0000173	46.78	silver quality
deltoid	UBERON:0001476	46.38	gold quality
muscle tissue	UBERON:0002385	46.31	gold quality
esophagus mucosa	UBERON:0002469	46.12	gold quality
body of stomach	UBERON:0001161	46.09	gold quality
liver	UBERON:0002107	45.93	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	45.46	silver quality
metanephros	UBERON:0000081	45.42	gold quality
stomach	UBERON:0000945	45.40	gold quality
pylorus	UBERON:0001166	45.35	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
large intestine	UBERON:0000059	45.33	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
endometrium	UBERON:0001295	45.12	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	1677.44
E-CURD-122	yes	40.30
E-CURD-88	yes	36.73
E-CURD-46	yes	16.04
E-ANND-3	yes	7.92

HPA expression

RNA tissue specificity: Group enriched

50 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	18.8
Bone marrow	tissue	15.6	not detected
Tonsil	tissue	15.2	medium
Lymph node	tissue	13.4	medium
Appendix	tissue	7.2	low
Spleen	tissue	3.1	not detected
Urinary bladder	tissue	2.5	not detected
Lung	tissue	2.5	not detected
Gallbladder	tissue	1.3	not detected
Stomach 1	tissue	1.2	not detected
Rectum	tissue	1.2	not detected
Small intestine	tissue	1.0	not detected
Colon	tissue	0.7	not detected
Duodenum	tissue	0.7	not detected
Esophagus	tissue	0.5	not detected
Spinal cord	tissue	0.5
Prostate	tissue	0.5	not detected
Adipose tissue	tissue	0.4	not detected
Salivary gland	tissue	0.4	not detected
Liver	tissue	0.4	not detected
Breast	tissue	0.3	not detected
Smooth muscle	tissue	0.3	not detected
Cervix	tissue	0.2	not detected
Skin 1	tissue	0.2	not detected
Testis	tissue	0.2	not detected
Vagina	tissue	0.2	not detected
Endometrium 1	tissue	0.2	not detected
Thalamus	tissue	0.2
Superior colliculi	tissue	0.2
Substantia nigra	tissue	0.2
Thyroid gland	tissue	0.2	not detected
Heart muscle	tissue	0.1	not detected
Pons	tissue	0.1
Epididymis	tissue	0.1	not detected
Basal ganglia	tissue	0.1	not detected
Putamen	tissue	0.1
Amygdala	tissue	0.1
Medulla oblongata	tissue	0.1
Hypothalamus	tissue	0.1
Placenta	tissue	0.1	not detected
Kidney	tissue	0.1	not detected
Corpus callosum	tissue	0.1
Adrenal gland	tissue	0.1	not detected
Hippocampal formation	tissue	0.1
Entorhinal cortex	tissue	0.1
Periaqueductal gray	tissue	0.1
Olfactory bulb	tissue	0.1
Fallopian tube	tissue	0.1	not detected
Septum	tissue	0.1
Caudate putamen	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 27; highest nTPM — Ventral spinal cord (0.5), Dorsal spinal cord (0.3), Motor hypoglossal nucleus (0.3), Nucleus gracilis (0.3), Nucleus tractus solitarii (0.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, GATA3, HAND1, NFATC2, STAT3, STAT6, TBX21

miRNA regulators (miRDB)

Targeting ICOS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 117 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-548AR-3P	99.85	71.26	3889

Functional genomics

gnomAD constraint: pLI 0.00324, LOEUF 1.27, missense Z 0.851 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000316386 — one region, missense o/e 0.86.

Literature-anchored findings (GeneRIF, showing 40)

• its polymorphism may contributes to the pathogenesis of spondyloarthropathy (PMID:11771526)
• Genetic polymorphism of the human ICOS gene. (PMID:11904679)
• role of ligation in modulating TCR-induced transcriptional profiles (PMID:12195015)
• ICOS reversely regulates IL-10 on re-activation of human effector T cells with mature dendritic cells. Interaction of ICOS with ICOS-L strongly promoted IL-10 secretion. (PMID:12207353)
• ICOS provides co-stimulation to memory t-cells [review] (PMID:12456021)
• Analysis of the upstream region of ICOS revealed an additional eight single nucleotide polymorphism (PMID:12753665)
• local immune responses may be modulated by H4/ICOS expressed on T cells in the joints of patients with rheumatoid arthritis, and thus it may be involved in the pathogenetic mechanism of rheumatoid arthritis. (PMID:12784384)
• ICOS is upregulated on human T cells after stimulation and can modulate both Th1 and Th2 cytokine production in the absence and presence of B7-1 (CD80) and B7-2 (CD86)costimulation. (PMID:12864987)
• Targeting of specific chemokine and chemokine receptor pathways and/or ICOS may have clinical application in the prevention and treatment of chronic allograft nephropathy. (PMID:12919091)
• AILIM has a role in regulating the signaling cascades for T-cell proliferation and IL-10 production (PMID:14550257)
• ICOS does not belong to the group of genes that, if mutated, present clinically as the hyper-IgM syndrome. (PMID:14610488)
• Highly expressed ICOS in activated CD4(+) lamina propria T cells of inflammatory bowel (IBD) contributes to dysregulated immune responses. Hyperexpression limited to inflammatory sites in IBD. Feasible therapeutic target for treatment of IBD. (PMID:14988837)
• A subtype of regulatory T cells in human blood can be identified by expression of ICOS after activation; these ICOS-expressing cells block the capacity of reciprocal ICOS-negative cells to proliferate and to produce cytokines. (PMID:15100277)
• ICOS expression on activated Th cells may provide a powerful means to amplify effector T cell responses in peripheral tissues, independently of the polarized state of the Th cells (PMID:15265908)
• AILIM/ICOS-B7h interactions play an important role in the endothelium in controlling the entry of memory/effector T-cells into inflamed tissues in the periphery. (PMID:15339883)
• The incidence of ICOS deficiency among patients with Common variable immunodeficiency is less than 5% (PMID:15507387)
• invariant NKT cell activation is regulated by CD28 and IOCS independently (PMID:15629449)
• A predominant effect of ICOS-mediated costimulation on T helper type 2 (Th2) cell differentiation in transgenic ICOS-deficient mice may be achieved by the enhancement of IL-4 receptor-mediated signaling. (PMID:15699127)
• ICOS is an influential costimulatory pathway in atherosclerosis & may play a protective role. It localizes with T cells in human aortic plaque. (PMID:15941568)
• This study could not confirm association with the CD28/CTLA4/ICOS gene region in multiple sclerosis. (PMID:16005527)
• Two variants in the ICOS promoter region are significantly associated with allergic sensitization and production of type 2 T helper (Th2) cell cytokines (PMID:16081771)
• ICOS is involved in abnormal T cell activation in systsemic lupus erythematosus (SLE) and blockade of the interaction between ICOS and its receptor may have therapeutic value in the treatment of this intractable disease. (PMID:16563187)
• There are no major effects of the CD28/CTLA4/ICOS gene region on susceptibility to primary sclerosing cholangitis but minor contributions cannot be excluded. (PMID:16638702)
• ICOS activation is associated with T helper type 1 (Th1) cell responses in human intracellular tuberculosis infection and may contribute to the amplification of those responses. (PMID:16670305)
• This review summarizes the evidence that ICOS expression regulates T-cell-dependent B cell responses and proposes a model for the role of ICOS in diseases characterized by dysregulated humoral immunity. (PMID:16790364)
• genetic variation in ICOS gene regulates the expression of both CTLA4 and ICOS and not only the splicing of sCTLA4 as suggested earlier. (PMID:16996590)
• Both the PI3-kinase/Akt and Rho family cascades operate coordinately to induce the forward migration of activated T cells by AILIM/ICOS signaling. (PMID:17077177)
• With multiethnic DNA panels that represent a wide spectrum of ethnic groups, we demonstrate long-range linkage disequilibrium among CD28, CTLA4, and ICOS costimulatory genes. (PMID:17197413)
• ICOS may be relevant in inducing an acute immune response and may be critically involved in perpetuating inflammation in chronically immune-mediated disorders of the peripheral nervous system. (PMID:17242332)
• These results define elevated populations of memory T-lymphocytes expressing B7 molecules in rheumatoid arthritis (RA) synovial fluid that either stimulate T cells through ICOS, or down-regulate RA synovial tissue T-lymphocytes through B7H1 and B7H2. (PMID:17323353)
• The whole blood gene expression quantities of costimulatory molecules CD154 and ICOS reasonably robustly differentiated rejection patients from control patients. (PMID:17414714)
• ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis. (PMID:17481737)
• Of 9 CVID patients…No mutations of SAP, ICOS, TACI, BAFFR, and CD19 were identified (PMID:18051214)
• definition of a newly discovered pathway that prevents autoimmunity by limiting the levels on T lymphocytes of aco-stimulatory receptor, the inducible T-cell co-stimulator(ICOS) (PMID:18172933)
• Modulation of immune responses by ICOS-expressing naturally occurring T regulatory cells present in melanoma tissue depends upon costimulatory signals delivered to the CD4-positive CD25-negative responder cells and the cytokine milieu. (PMID:18292519)
• p50alpha is likely a determining factor in ICOS-mediated PI3K activity in T cells (PMID:18641334)
• Children with type 1 diabetes show decreased inducrion of ICOS in T cells. (PMID:18973208)
• The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. (PMID:19020530)
• ICOS-induced T cell spreading and filopodia/microspike formation may promote antigen recognition by enhancing a T cell’s scanning potential of an adherent APC surface. (PMID:19095735)
• ICOS variants do not play a major role in the development of atopy in European children. (PMID:19175887)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Icos	ENSMUSG00000026009
rattus_norvegicus	Icos	ENSRNOG00000046196

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1858745) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 53 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased IgG1 level	4
abnormal immune system physiology	3
decreased IgG level	3
decreased IgE level	3
abnormal spleen morphology	2
abnormal Peyer’s patch germinal center morphology	2
abnormal T cell physiology	2
abnormal B cell physiology	2
abnormal immunoglobulin level	2
abnormal class switch recombination	2
abnormal CD4-positive, alpha-beta T cell physiology	2
small Peyer’s patches	2
decreased spleen germinal center number	2
decreased interleukin-4 secretion	2
abnormal interleukin level	2
abnormal leukocyte cell number	1
abnormal small intestine morphology	1
decreased IgA level	1
abnormal T cell differentiation	1
small lymph nodes	1
abnormal spleen germinal center morphology	1
abnormal B cell number	1
short tibia	1
decreased anti-insulin autoantibody level	1
abnormal cytokine secretion	1

+28 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q58DF9	73.4%	Diamond
Canis lupus familiaris	Q7YR73	72.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CTLA4	protein-coding	1493

Protein

Protein identifiers

Inducible T-cell costimulator — Q9Y6W8 (reviewed: Q9Y6W8)

Alternative names: Activation-inducible lymphocyte immunomediatory molecule

All UniProt accessions (2): Q9Y6W8, Q53QY6

UniProt curated annotations — full annotation on UniProt →

Function. Stimulatory receptor expressed in activated or antigen-experienced T-cells that plays an important role in the immune response. Upon binding to its ligand ICOSL expressed on antigen presenting cells (APCs), delivers costimulatory signals that enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines including IL10, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Also acts as a costimulatory receptor critical for the differentiation of T follicular regulatory cells upon immune challenges such as viral infection. Mechanistically, potentiates TCR-induced calcium flux by augmenting PLCG1 activation and actin remodeling. In addition, activates PI3K signaling pathways independently of calcium flux. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with ICOSLG. Interacts with PIK3R1. Interacts with TBK1; this interaction is critical for the maturation of T follicular regulatory cells.

Subcellular location. Cell membrane Secreted.

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.

Post-translational modifications. N-glycosylated.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6W8-1	1	yes
Q9Y6W8-2	2

RefSeq proteins (1): NP_036224* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR039943	ICOS	Family

Pfam: PF15910

UniProt features (22 total): strand 9, topological domain 2, glycosylation site 2, disulfide bond 2, signal peptide 1, chain 1, splice variant 1, mutagenesis site 1, helix 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7JOO	Crystal structure of ICOS in complex with antibody STIM003 and anti-kappa VHH domain	X-RAY DIFFRACTION	2.4
6X4G	Crystal structure of ICOS in complex with ICOS-L and an anti ICOS-L VNAR domain	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6W8-F1	74.24	0.22

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 6X4G, 7JOO, ALOMFILIMAB

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Disease related genes, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; actin filaments

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2)

Type	Positions
Disulfide bond	42–109, 63–83

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	89, 110

Mutagenesis-validated functional residues (1)

Position	Phenotype
110	about 4.3-fold improvement in binding affinity to icoslg.

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 10; 6 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

10 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer ⚕	curated
R-HSA-9927354	Co-stimulation by ICOS	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-9938027	Affinity selection of immunoglobulins	electronic

MSigDB gene sets: 385 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_TOLERANCE_INDUCTION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_CELL_CELL_ADHESION, GOBP_CD4_POSITIVE_ALPHA_BETA_T_CELL_ACTIVATION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_T_CELL_DIFFERENTIATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS

GO Biological Process (5): T cell tolerance induction (GO:0002517), immune response (GO:0006955), T cell costimulation (GO:0031295), T follicular helper cell differentiation (GO:0061470), cell-cell adhesion (GO:0098609)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Signaling by ALK fusions and activated point mutants	1
Immunoglobulin maturation	1
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Negative regulation of the PI3K/AKT network	1
Regulation of T cell activation by CD28 family	1
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Signaling by ALK in cancer	1

GO top-level categories

16 GO namespaces:

Category	Terms
tolerance induction	1
immune system process	1
response to stimulus	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
T-helper cell differentiation	1
exhausted T cell differentiation	1
cell adhesion	1
molecular transducer activity	1
binding	1
cellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
T follicular helper cell differentiation	BP	direct assay
plasma membrane	CC	direct assay
signaling receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,132 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ICOS	ICOSLG	O75144	952
ICOS	CTLA4	P16410	952
ICOS	A0A087X1L8	A0A087X1L8	944
ICOS	CXCR5	P32302	936
ICOS	CD4	P01730	919
ICOS	PDCD1	Q15116	892
ICOS	CD274	Q9NZQ7	884
ICOS	CD80	P33681	882
ICOS	CD8A	P01732	866
ICOS	CD40LG	P29965	862
ICOS	FOXP3	Q9BZS1	859
ICOS	TNFRSF4	P43489	857
ICOS	IL2	P01585	849
ICOS	PDCD1LG2	Q9BQ51	841
ICOS	CD86	P42081	836

IntAct

Human interaction partners of ICOS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
ICOSLG	physical association	0.850	10
PIK3R1	association	0.620	6
TBK1	physical association	0.500	3
WIF1	physical association	0.370	1
GAK	association	0.350	1
TNF	association	0.350	1
TNFSF9	association	0.350	1

BioGRID (20 interactions; top human partners by supporting records): ACY1 (Affinity Capture-MS; 2 records), ICOSLG (Affinity Capture-MS; 2 records), TNF (Affinity Capture-MS; 2 records), CDC20B (Affinity Capture-MS), ITFG3 (Affinity Capture-MS), MFI2 (Affinity Capture-MS), NUFIP2 (Protein-RNA), PCDH1 (Affinity Capture-MS), PGK1 (Cross-Linking-MS (XL-MS)), PIK3R1 (Affinity Capture-Western), RC3H1 (Protein-RNA), TBK1 (Affinity Capture-Western), TNFSF9 (Affinity Capture-MS), TRHDE (Affinity Capture-MS), WIF1 (Two-hybrid)

SIGNOR signaling

4 signaling interactions:

A	Effect	B	Mechanism
ICOSLG	“up-regulates activity”	ICOS	binding
ICOS	“up-regulates activity”	PIK3R1	binding
hsa-mir-146a-5p	“down-regulates quantity by repression”	ICOS	“post transcriptional regulation”
hsa-mir-27a-3p	“down-regulates quantity by repression”	ICOS	“post transcriptional regulation”

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ICOSLG	receptor

Disease & clinical

Genetic variants

Variant evidence for ICOS: 208 ClinVar records (14 pathogenic / likely pathogenic); 17 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

208 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	5
Uncertain significance	84
Likely benign	66
Benign	24

Top pathogenic / likely-pathogenic (14)

Showing all 14 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
663980	NM_012092.4(ICOS):c.58+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
940397	NM_012092.4(ICOS):c.181del (p.Ile61fs)	Pathogenic	criteria provided, single submitter	1
1359008	NM_012092.4(ICOS):c.61G>T (p.Glu21Ter)	Pathogenic	criteria provided, single submitter	1
1449576	NM_012092.4(ICOS):c.318T>G (p.Tyr106Ter)	Pathogenic	criteria provided, single submitter	1
2002817	NM_012092.4(ICOS):c.17G>A (p.Trp6Ter)	Pathogenic	criteria provided, single submitter	1
2003841	NM_012092.4(ICOS):c.357del (p.Phe119fs)	Pathogenic	criteria provided, single submitter	1
2993769	NM_012092.4(ICOS):c.291C>A (p.Tyr97Ter)	Pathogenic	criteria provided, single submitter	1
4728975	NM_012092.4(ICOS):c.272dup (p.Ser91fs)	Pathogenic	criteria provided, single submitter	1
573877	NM_012092.4(ICOS):c.394+2T>C	Likely pathogenic	criteria provided, single submitter	1
2585218	NM_012092.4(ICOS):c.136_139del (p.Asp46fs)	Likely pathogenic	criteria provided, single submitter	1
4871840	NM_012092.4(ICOS):c.285del (p.Leu96fs)	Likely pathogenic	criteria provided, single submitter	1
4959479	NM_012092.4(ICOS):c.501+2T>A	Likely pathogenic	criteria provided, single submitter	1
871366	GRCh37/hg19 2q33.2(chr2:204820359-204821488)x0	Pathogenic	criteria provided, single submitter	1
5501	NM_012092.4(ICOS):c.59-594_501+93del	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ICOS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 285):

Position(s)	Effect	Δscore	Sites
2:203942270	donor_gain	1.0000
2:203955631	acceptor_gain	0.9900
2:203955786	donor_gain	0.9900
2:203956657–203956658	acceptor_loss	0.9900	6
2:203956766–203956767	donor_loss	0.9900	5
2:203957884–203957885	donor_loss	0.9900	5
2:203936873–203936874	donor_loss	0.9800	3
2:203955634–203955635	acceptor_loss	0.9800	6
2:203955836	donor_gain	0.9800
2:203955972–203955973	donor_loss	0.9800	5

AlphaMissense

123 missense substitutions predicted likely pathogenic (of 1,313 scored), across 43 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C109	7	0.851	0.908
C42	7	0.814	0.901
C63	7	0.721	0.810
C83	7	0.696	0.767
F94	5	0.792	0.845
F31	5	0.786	0.857
F51	5	0.781	0.879
Y107	5	0.655	0.780
P116	5	0.653	0.731
F119	4	0.833	0.899
F114	4	0.776	0.817
W142	4	0.670	0.756
F95	3	0.816	0.816
F33	3	0.794	0.794
I40	3	0.785	0.877
M53	3	0.762	0.832
G146	3	0.689	0.696
G157	3	0.666	0.692
L96	3	0.656	0.702
F182	3	0.648	0.648

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	0.00046
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	0.000645

Disease associations

OMIM: gene MIM:604558 | disease phenotypes: MIM:607594

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
immunodeficiency, common variable, 1	Strong	Autosomal recessive	4

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
common variable immunodeficiency	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
COVID-19 research	green
Gastrointestinal epithelial barrier disorders	green
Infantile enterocolitis & monogenic inflammatory bowel disease	green
Intestinal failure or congenital diarrhoea	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (1): immunodeficiency, common variable, 1 (MONDO:0011864)

Orphanet (2): OBSOLETE: Common variable immunodeficiency (Orphanet:1572), Late-onset combined immunodeficiency due to ICOS deficiency (Orphanet:695183)

HPO phenotypes

32 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000403	Recurrent otitis media
HP:0000509	Conjunctivitis
HP:0001287	Meningitis
HP:0001744	Splenomegaly
HP:0001904	Autoimmune neutropenia
HP:0002014	Diarrhea
HP:0002090	Pneumonia
HP:0002110	Bronchiectasis
HP:0002240	Hepatomegaly
HP:0002664	Neoplasm
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002718	Recurrent bacterial infections
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002729	Follicular hyperplasia
HP:0002837	Recurrent bronchitis
HP:0002850	Decreased circulating IgM concentration
HP:0002960	Autoimmunity
HP:0004315	Decreased circulating IgG concentration
HP:0005387	Combined immunodeficiency
HP:0006532	Recurrent pneumonia
HP:0010976	Decreased total B cell count
HP:0011108	Recurrent sinusitis
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0011839	Abnormal total T cell number
HP:0011840	Abnormal T cell physiology
HP:0030388	Decreased class-switched memory B cell proportion
HP:0410301	Partial absence of specific antibody response to unconjugated pneumococcus polysaccharide

GWAS associations

17 associations:

Study	Trait	p-value
GCST004866_12	Alopecia areata	2e-20
GCST003988_11	Hypothyroidism	1e-15
GCST004302_16	Primary biliary cholangitis	1e-13
GCST000719_1	Alopecia areata	4e-13
GCST006627_46	Diastolic blood pressure	3e-12
GCST000612_31	Celiac disease	6e-9
GCST004904_18	Body mass index	4e-8
GCST005568_31	Rheumatoid arthritis (ACPA-positive)	4e-8
GCST003045_68	Ulcerative colitis	1e-7
GCST002931_2	Aluminium levels	3e-7
GCST003043_157	Inflammatory bowel disease	5e-7
GCST005569_4	Rheumatoid arthritis	5e-7
GCST001762_612	Obesity-related traits	1e-6
GCST005588_17	Idiopathic dilated cardiomyopathy	5e-6
GCST009391_779	Metabolite levels	5e-6
GCST009391_806	Metabolite levels	5e-6
GCST009391_736	Metabolite levels	7e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0004340	body mass index
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0006336	diastolic blood pressure
EFO:0010391	sphingomyelin 16:0 measurement
EFO:0010396	sphingomyelin 22:1 measurement
EFO:0010394	sphingomyelin 18:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3712953 (SINGLE PROTEIN), CHEMBL5482971 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ICOS protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

4 curated-mechanism drugs:

Drug	Modality	Max phase
FELADILIMAB	Antibody	3
ROZIBAFUSP ALFA	Protein	2
VOPRATELIMAB	Antibody	2
MEDI-570	Unknown	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — CD molecules

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
feladilimab	Binding	8.87	pKd

ChEMBL bioactivities

6 potent at pChembl≥5 of 19 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.73	IC50	1870	nM	CHEMBL5591374
5.43	IC50	3680	nM	CHEMBL5592269
5.35	IC50	4480	nM	CHEMBL5591374
5.35	Kd	4470	nM	CHEMBL5590462
5.33	IC50	4680	nM	CHEMBL2171562
5.25	IC50	5650	nM	CHEMBL5429501

PubChem BioAssay actives

6 with measured affinity, of 28 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(3S,9S,12S,18S,21S,27S,30R,35R,38S,41S,44S,47S)-30-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-41,44-dibenzyl-9,27-bis[(4-hydroxyphenyl)methyl]-38-(2-methylpropyl)-2,8,11,17,20,26,29,37,40,43,46-undecaoxo-18-propan-2-yl-32,33-dithia-1,7,10,16,19,25,28,36,39,42,45-undecazapentacyclo[45.3.0.03,7.012,16.021,25]pentacontane-35-carbonyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoic acid	2115250: Inhibition of ICOS/ICOSL (unknown origin) interaction by ELISA method	ic50	1.8700	uM
(1R,4S,10S,13S,19S,22S,28S,34S,37S,40S,43S,46R,49S,55S,58S,61S)-37,40,58-tribenzyl-4,22,61-tris[(4-hydroxyphenyl)methyl]-43,49-bis(2-methylpropyl)-13-propan-2-yl-65,66-dithia-3,6,12,15,21,24,30,36,39,42,45,48,51,57,60,63-hexadecazaheptacyclo[44.17.4.06,10.015,19.024,28.030,34.051,55]heptahexacontane-2,5,11,14,20,23,29,35,38,41,44,47,50,56,59,62-hexadecone	2115249: Inhibition of ICOS/ICOSL (unknown origin) interaction by TR-FRET assay	ic50	3.6800	uM
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-40-benzyl-19-[(2S)-butan-2-yl]-22-(hydroxymethyl)-25,28-bis[(4-hydroxyphenyl)methyl]-4,49-bis(2-methylpropyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-34-yl]propyl]guanidine	2115251: Binding affinity to ICOS (unknown origin) assessed as dissociation constant	kd	4.4700	uM
N-[3-(benzylamino)-6-chloro-9H-pyrido[3,4-b]indol-8-yl]pyridine-3-carboxamide	1977233: Inhibition of C-terminal IgG1 Fc region fused human ICOS extracellular domain (1 to 141 residues)/C-terminal polyhistidine tagged human ICOSL extracellular domain (1 to 258 residues) interaction incubated for 1 hr by TR-FRET assay	ic50	4.6800	uM
N-(6-chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-4-methylpyrimidine-5-carboxamide	1977233: Inhibition of C-terminal IgG1 Fc region fused human ICOS extracellular domain (1 to 141 residues)/C-terminal polyhistidine tagged human ICOSL extracellular domain (1 to 258 residues) interaction incubated for 1 hr by TR-FRET assay	ic50	5.6500	uM

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants, Occupational	affects expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Nickel	increases expression	2
(+)-JQ1 compound	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Dieldrin	increases expression	1
Ozone	increases abundance, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5580017	Binding	Binding affinity to ICOS (unknown origin) assessed as dissociation constant	Design of cyclic peptides as novel inhibitors of ICOS/ICOSL interaction. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7ZZ	Raji-hICOS	Cancer cell line	Male
CVCL_B8HQ	Abcam HCT 116 ICOS KO	Cancer cell line	Male
CVCL_B8WZ	Abcam MCF-7 ICOS KO	Cancer cell line	Female
CVCL_B9K0	Abcam A-549 ICOS KO	Cancer cell line	Male
CVCL_D7BJ	Abeomics CHO-K1 ICOS	Spontaneously immortalized cell line	Female
CVCL_E5IS	CHO-K1/ICOS	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ICOS across ~30M SureChEMBL compounds — explore on Sugi Predict.