ICOSLG

Summary

ICOSLG (inducible T cell costimulator ligand, HGNC:17087) is a protein-coding gene on chromosome 21q22.3, encoding ICOS ligand (O75144). Ligand for the T-cell-specific cell surface receptor ICOS.

Enables identical protein binding activity and receptor ligand activity. Involved in T follicular helper cell differentiation. Located in extracellular exosome. Is active in plasma membrane. Implicated in immunodeficiency 119.

Source: NCBI Gene 23308 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): combined immunodeficiency (Moderate, ClinGen) — +1 more curated relationship
• GWAS associations: 21
• Clinical variants (ClinVar): 337 total — 4 likely-pathogenic (top 10% of genes corpus-wide)
• GTEx eGene: eQTL in 43 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 17
• Drug target: yes — 1 curated mechanism-of-action drug
• MANE Select transcript: NM_015259
• Notable: 337 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17087
Approved symbol	ICOSLG
Name	inducible T cell costimulator ligand
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0653, GL50, B7-H2, B7RP-1, B7H2, B7RP1, ICOS-L, CD275, B7h
Ensembl gene	ENSG00000160223
Ensembl biotype	protein_coding
OMIM	605717
Entrez	23308

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000407780

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1

ENST00000407780, ENST00000344330, ENST00000400377, ENST00000400379, ENST00000643466, ENST00000700350, ENST00000700351, ENST00000700352, ENST00000700353, ENST00000700354, ENST00000700355, ENST00000700356, ENST00000700357, ENST00000700358, ENST00000700359, ENST00000700360, ENST00000700361, ENST00000867614, ENST00000867615, ENST00001016063, ENST00001131522

RefSeq mRNA: 6 — MANE Select: NM_015259 NM_001283050, NM_001283051, NM_001283052, NM_001365759, NM_001395918, NM_015259

CCDS: CCDS42952, CCDS63377, CCDS63379, CCDS93102, CCDS93104

Canonical transcript exons

ENST00000407780 — 7 exons

Exon	Start	End
ENSE00001110032	44230054	44230089
ENSE00001881360	44222991	44229044
ENSE00003979594	44231280	44231444
ENSE00003979602	44240804	44240943
ENSE00003979611	44238448	44238488
ENSE00003979622	44236867	44237217
ENSE00003979624	44235272	44235562

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 81.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0028 / max 2.2146, expressed in 2 samples.

Highest expression (Bgee): cartilage tissue, upper arm skin, apex of heart, C1 segment of cervical spinal cord, spinal cord.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ICOSLG is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 43 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 43 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	9.1e-14	+0.47	21:44255944:A:G
Thyroid	eqtl	2.0e-13	+0.45	21:44263486:A:ACTG
Skin Not Sun Exposed Suprapubic	eqtl	1.3e-11	+0.43	21:44263486:A:ACTG
Whole Blood	eqtl	1.6e-11	+0.34	21:44263486:A:ACTG
Nerve Tibial	eqtl	4.1e-11	+0.46	21:44255944:A:G
Lung	eqtl	1.9e-10	+0.43	21:44263486:A:ACTG
Muscle Skeletal	eqtl	7.6e-10	+0.33	21:44263486:A:ACTG
Artery Tibial	eqtl	4.1e-09	+0.33	21:44263486:A:ACTG
Heart Left Ventricle	eqtl	1.5e-08	+0.45	21:44255944:A:G
Esophagus Mucosa	eqtl	2.8e-08	+0.42	21:44255944:A:G
Esophagus Muscularis	eqtl	3.2e-08	-0.50	21:44278186:A:T
Artery Aorta	eqtl	1.1e-07	+0.39	21:44263486:A:ACTG
Breast Mammary Tissue	eqtl	1.1e-07	+0.47	21:44255944:A:G
Adipose Visceral Omentum	eqtl	1.3e-07	+0.39	21:44263486:A:ACTG
Heart Atrial Appendage	eqtl	2.7e-07	+0.44	21:44255944:A:G
Adipose Subcutaneous	eqtl	3.1e-07	+0.34	21:44263486:A:ACTG
Brain Amygdala	eqtl	3.2e-06	+0.59	21:44255944:A:G
Esophagus Gastroesophageal Junction	eqtl	5.0e-06	+0.44	21:44263486:A:ACTG
Colon Transverse	eqtl	7.7e-06	+0.35	21:44263486:A:ACTG
Brain Putamen basal ganglia	eqtl	7.9e-06	+0.55	21:44255944:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
190735	0.0028	2

Top tissues by expression

showing 100 of 248 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	81.51	gold quality
upper arm skin	UBERON:0004263	81.09	gold quality
apex of heart	UBERON:0002098	80.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.47	gold quality
spinal cord	UBERON:0002240	78.62	gold quality
lower esophagus mucosa	UBERON:0035834	78.45	gold quality
corpus callosum	UBERON:0002336	75.81	gold quality
putamen	UBERON:0001874	75.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	75.38	gold quality
left ventricle myocardium	UBERON:0006566	75.02	gold quality
bone marrow cell	CL:0002092	74.98	gold quality
substantia nigra	UBERON:0002038	74.88	gold quality
skin of leg	UBERON:0001511	74.54	gold quality
skin of abdomen	UBERON:0001416	74.51	gold quality
prefrontal cortex	UBERON:0000451	73.83	gold quality
amygdala	UBERON:0001876	73.77	gold quality
lymph node	UBERON:0000029	73.58	gold quality
Ammon’s horn	UBERON:0001954	73.50	gold quality
zone of skin	UBERON:0000014	73.44	gold quality
midbrain	UBERON:0001891	73.40	gold quality
granulocyte	CL:0000094	73.13	gold quality
vermiform appendix	UBERON:0001154	72.95	gold quality
adult mammalian kidney	UBERON:0000082	72.91	gold quality
esophagus mucosa	UBERON:0002469	72.75	gold quality
metanephros cortex	UBERON:0010533	72.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.79	gold quality
gall bladder	UBERON:0002110	71.71	gold quality
caudate nucleus	UBERON:0001873	71.32	gold quality
hypothalamus	UBERON:0001898	71.22	gold quality
endocervix	UBERON:0000458	70.86	gold quality
myocardium	UBERON:0002349	70.83	gold quality
ectocervix	UBERON:0012249	70.65	gold quality
frontal cortex	UBERON:0001870	70.57	gold quality
heart right ventricle	UBERON:0002080	70.21	gold quality
leukocyte	CL:0000738	69.99	gold quality
right lung	UBERON:0002167	69.97	gold quality
cortex of kidney	UBERON:0001225	69.95	gold quality
body of stomach	UBERON:0001161	69.93	gold quality
bone marrow	UBERON:0002371	69.90	gold quality
caecum	UBERON:0001153	69.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	69.58	silver quality
kidney	UBERON:0002113	69.54	gold quality
monocyte	CL:0000576	69.53	gold quality
temporal lobe	UBERON:0001871	69.47	gold quality
mucosa of transverse colon	UBERON:0004991	69.40	gold quality
right frontal lobe	UBERON:0002810	69.36	gold quality
heart left ventricle	UBERON:0002084	69.16	gold quality
cardiac ventricle	UBERON:0002082	69.07	gold quality
uterine cervix	UBERON:0000002	69.04	gold quality
omental fat pad	UBERON:0010414	68.95	gold quality
peritoneum	UBERON:0002358	68.92	gold quality
upper lobe of left lung	UBERON:0008952	68.87	gold quality
spleen	UBERON:0002106	68.72	gold quality
neocortex	UBERON:0001950	68.67	gold quality
nucleus accumbens	UBERON:0001882	68.62	gold quality
islet of Langerhans	UBERON:0000006	68.59	gold quality
forebrain	UBERON:0001890	68.46	gold quality
metanephros	UBERON:0000081	68.42	gold quality
cerebral cortex	UBERON:0000956	68.40	gold quality
stomach	UBERON:0000945	68.37	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.28	gold quality
buccal mucosa cell	CL:0002336	68.18	gold quality
sural nerve	UBERON:0015488	68.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.05	gold quality
blood	UBERON:0000178	67.96	gold quality
cardiac atrium	UBERON:0002081	67.94	gold quality
stromal cell of endometrium	CL:0002255	67.93	gold quality
vagina	UBERON:0000996	67.87	gold quality
minor salivary gland	UBERON:0001830	67.86	gold quality
kidney epithelium	UBERON:0004819	67.79	gold quality
right atrium auricular region	UBERON:0006631	67.69	gold quality
tonsil	UBERON:0002372	67.63	gold quality
esophagus squamous epithelium	UBERON:0006920	67.63	gold quality
small intestine	UBERON:0002108	67.61	gold quality
cerebellar vermis	UBERON:0004720	67.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.56	gold quality
brain	UBERON:0000955	67.38	gold quality
saliva-secreting gland	UBERON:0001044	67.32	gold quality
mouth mucosa	UBERON:0003729	67.32	gold quality
heart	UBERON:0000948	67.20	gold quality
right lobe of liver	UBERON:0001114	67.09	gold quality
medial globus pallidus	UBERON:0002477	66.47	silver quality
upper lobe of lung	UBERON:0008948	66.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	66.36	silver quality
subcutaneous adipose tissue	UBERON:0002190	66.29	gold quality
globus pallidus	UBERON:0001875	66.21	silver quality
prostate gland	UBERON:0002367	66.16	gold quality
esophagus	UBERON:0001043	65.79	gold quality
superior frontal gyrus	UBERON:0002661	65.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	65.77	gold quality
duodenum	UBERON:0002114	65.70	gold quality
anterior cingulate cortex	UBERON:0009835	65.59	gold quality
tibial nerve	UBERON:0001323	65.54	gold quality
right coronary artery	UBERON:0001625	65.53	gold quality
adipose tissue	UBERON:0001013	64.96	gold quality
transverse colon	UBERON:0001157	64.89	gold quality
colonic epithelium	UBERON:0000397	64.84	silver quality
anatomical system	UBERON:0000467	64.81	gold quality
lateral nuclear group of thalamus	UBERON:0002736	64.73	silver quality
parotid gland	UBERON:0001831	64.71	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.16

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	36.5
Hippocampus	tissue	32.3	high
Locus coeruleus	tissue	30.7
Postcentral gyrus	tissue	21.2
Choroid plexus	tissue	19.7
Bone marrow	tissue	15.9	low
Spinal cord	tissue	12.4
Lymph node	tissue	11.1	high
Hypothalamus	tissue	10.2
Tonsil	tissue	9.8	high
Substantia nigra	tissue	9.3
Septum	tissue	8.8
Skin 1	tissue	8.7	medium
Stomach 1	tissue	8.1	high
Appendix	tissue	7.9	high
Periaqueductal gray	tissue	7.8
Medulla oblongata	tissue	7.6
Pons	tissue	7.4
Corpus callosum	tissue	7.4
Midbrain	tissue	7.2
Duodenum	tissue	7.0	medium
Thalamus	tissue	6.7
Superior colliculi	tissue	6.7
Spleen	tissue	6.7	high
Ventral forebrain	tissue	6.1
Hippocampal formation	tissue	5.9
Amygdala	tissue	5.8
Small intestine	tissue	5.8	high
Kidney	tissue	5.8	medium
Gallbladder	tissue	5.5	high
Urinary bladder	tissue	5.4	medium
Putamen	tissue	5.4
Heart muscle	tissue	5.2	medium
Basal ganglia	tissue	5.1	high
Esophagus	tissue	5.0	medium
Placenta	tissue	4.9	medium
Liver	tissue	4.9	medium
Cervix	tissue	4.6	medium
Fallopian tube	tissue	4.6	medium
Cerebral cortex	tissue	4.2	medium
Entorhinal cortex	tissue	4.2
Insular cortex	tissue	4.2
Colon	tissue	4.1	medium
Temporal cortex	tissue	4.1
Motor cortex	tissue	4.0
Adipose tissue	tissue	3.9	medium
Thymus	tissue	3.9
Breast	tissue	3.8	medium
Prefrontal cortex	tissue	3.8
Salivary gland	tissue	3.8	medium
Retrosplenial cortex	tissue	3.8
Vagina	tissue	3.7	low
Rectum	tissue	3.7	medium
Retrosplenial and cingulate cortex	tissue	3.7
Lung	tissue	3.3	high
Prostate	tissue	3.1	medium
Adrenal gland	tissue	3.1	high
Somatosensory cortex	tissue	3.1
Caudate putamen	tissue	3.0
Skeletal muscle	tissue	2.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Temporal white matter (95.3), Parieto-temporal junction (white matter) (89.5), Angular gyrus (white matter) (81.5), Corpus callosum, splenium (white matter) (75.9), Corpus callosum, genu (white matter) (71.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

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

showing 30 of 62 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-7113-3P	98.75	65.71	1120

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000400379 — one region, missense o/e 0.22.

Literature-anchored findings (GeneRIF, showing 40)

• ICOS-L is a ligand for ICOS and plays an important functional role in the activation of memory T cells by endothelial cells [review] (PMID:12456022)
• These results demonstrate that airway epithelial cells express the costimulatory molecule B7-H2, and suggest the possibility that B7-H2 may participate in antigen presentation by epithelial cells. (PMID:12707012)
• ICOS-B7H costimulatory pathway may be involved in the negative regulation of cell-mediated immune responses. (PMID:12800259)
• A critical role of the B7-like protein-ICOS costimulatory pathway is demonstrated in the pathogenesis of lupus nephritis. (PMID:12960306)
• ICOSL protein and mRNA was expressed in 7 of 12 glioma cell lines and expression is upregulated by the inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), whereas interferon-gamma (IFN-gamma) has no such effect (PMID:14603470)
• Expression of B7-H3 by nasal epithelial. Expands range of potential costimulatory signals through which these cells may interact with activated mucosal T lymphocytes. Extent of mucociliary differentiation of cultured cells may influence this capability. (PMID:15047568)
• B7h-ICOS protein costimulatory pathway may be important in intestinal epithelial cell(iec):T-cell interactions. IEC expressed B7h and B7-H1. (PMID:15131796)
• Results indicate the expression of functional B7-H2 molecule may facilitate progression of acute myeloid leukemia. (PMID:16115907)
• Interaction of tubular epithelial cells and kidney infiltrating T cells via ICOS-L and B7-H1 may change the balance of positive and negative signals to the T cells (PMID:16221208)
• ICOSL receptor binding site is mediated solely by the immunoglobulin (Ig) variable domain but requires the Ig constant domain for maintaining structural integrity of the protein. (PMID:16951355)
• ICOS-L 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)
• The generated a 3T3 cellular library retrovirally expressing mutants of the murine B7h gene. Screening of this unbiased cellular library identified residues of murine B7h. These residues are located on the same of human B7h by mutagenesis. (PMID:18294651)
• Genetic variation in this protein affects the outcome and failure of kidney tranplantation. (PMID:19202444)
• role of stimulus by B7 in myeloblastic leukemic (PMID:19347721)
• ICOSL:ICOS+ pathway costimulates effector T cells, shaping the Th2 response and regulating humoral immunity. (PMID:19395451)
• B7RP-1 is expressed on the membrane of HCAECs. (PMID:19726311)
• Oxidized low density lipoprotein up-regulates the expression of ICOSL in coronary artery endothelial cells. (PMID:19737469)
• Suppressed ICOSLG gene expression is associated with cigarette smoking. (PMID:20217071)
• Data show that ICOS-L expression by melanoma tumor cells may directly drive Treg activation and expansion in the tumor microenvironment as another mechanism of immune evasion. (PMID:21098714)
• Similar to B7-1 and B7-2, B7-H2 costimulation via CD28 induced survival factor Bcl-xL, downregulated cell cycle inhibitor p27(kip1), and triggered signaling cascade of ERK and AKT kinase-dependent pathways (PMID:21530327)
• A model of positive feedback conferred by ICOS-LICOS interaction between TGN1412-treated T cells and endothelial cells. (PMID:22577174)
• ICOS-ICOSL signaling plays a direct role in proliferation and differentiation of thyroid gland cells and may have important effects on the initiation, maintenance and exaggeration of autoimmune responses in local tissue. (PMID:22706735)
• ICOSL-expressing macrophages and mRNA levels of ICOSL were increased in the lesional skin of patients with early diffuse cutaneous systemic sclerosis. (PMID:23024058)
• Results highlight an important relationship between Treg and pDC in breast tumors, and show that ICOS/ICOS-L interaction is a central event in immunosuppression of tumor-associated memory CD4(+) T cells. (PMID:23026134)
• These data suggest that rs2294020 SNP of FOXP3 gene and rs378299 SNP of ICOSLG gene are associated with alopecia areata and with a reduced expression of the FOXP3 and ICOSLG genes in alopecia patients. (PMID:23196741)
• Findings suggest that the single nucleotide polymorphism (snp) rs4819388 in B7-H2 3’-UTR, through disrupting the regulatory role of miR-24 on B7-H2 expression, contributes to the occurrence of gastric cancer. (PMID:23688438)
• Our data show that mDCs from patients with AR display impaired expression of ICOSL, and this defect licenses mDCs to promote aberrant IL-13- and IL-5-producing Th2 cell responses. (PMID:24661627)
• the B7h-ICOS interaction may modulate the spread of cancer metastases (PMID:24729612)
• a critical role is described for the rs7282490 ICOSLG region polymorphism associated with immune-mediated diseases in amplifying pattern-recognition receptor initiated inflammatory signaling and cytokine secretion (PMID:24837102)
• Loss-of-function mutations in NIK cause impaired ICOSL expression. (PMID:25406581)
• ICOS-ICOS-L interaction promoted cytokine production and survival in type 2 innate lymphoid cells through STAT5 signaling in asthma. (PMID:25769613)
• The ICOS and ICOSL SNPs examined do not have an apparent effect on the disease susceptibility and prognosis of autoimmune thyroid diseases. (PMID:26560438)
• results showed that monocyte-derived osteoclast (OC)-like cells (MDOCs) express B7h during their differentiation, and that B7h triggering reversibly inhibits OC differentiation and function both in vitro and in vivo (PMID:27798154)
• ICOSL-ICOS signaling promoted Treg differentiation from CD4(+) T cells through activation of the phosphoinositide 3-kinase-Akt pathway. MSCs primed with Interleukin-1beta significantly induced Tregs through ICOSL upregulation. We demonstrated that the Treg-inducing activity of MSCs is proportionate to their basal ICOSL expression. (PMID:28290526)
• study confirms the importance of ICOSL shedding in ICOS/ICOSL function and expression and it identifies ADAM10 as the most important sheddase for controlling ICOSL levels (PMID:28814605)
• this study found that B7-H2 expression on CD8(+) T cells in colorectal cancer patients’ tumor tissues was significantly higher than in non-tumor tissues (PMID:29414642)
• The expression of ICOSL of patient acute myeloid leukemia (AML) cells and ICOS+ Tregs were found to be predictors for survival in patients with AML, with ICOS+ Treg cell subset being a stronger predictor than total Tregs. Results suggested that AML cells expressed ICOSL promote the expansion of ICOS+ Tregs in tumor environment, and ICOS+ Tregs further promote the proliferation of AML cells through secreting IL-10. (PMID:30319662)
• study identifies human ICOSLG deficiency as a novel cause of a combined immunodeficiency. (PMID:30498080)
• High glucose and advanced glycation end products cause T cell inflammatory response and vascular endothelial dysfunction by upregulating ICOS/ICOSL activity. (PMID:30575933)
• The ICOSL Expression Predicts Better Prognosis for Nasopharyngeal Carcinoma via Enhancing Oncoimmunity. (PMID:31998801)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Icosl	ENSMUSG00000000732
rattus_norvegicus	Icoslg	ENSRNOG00000023109

Paralogs (15): BTN3A1 (ENSG00000026950), CD276 (ENSG00000103855), BTN3A3 (ENSG00000111801), BTN2A1 (ENSG00000112763), BTNL8 (ENSG00000113303), HHLA2 (ENSG00000114455), BTN2A2 (ENSG00000124508), BTN1A1 (ENSG00000124557), VTCN1 (ENSG00000134258), ERMAP (ENSG00000164010), BTNL9 (ENSG00000165810), BTNL3 (ENSG00000168903), BTN3A2 (ENSG00000186470), BTNL2 (ENSG00000204290), MOG (ENSG00000204655)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1354701) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 26 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased IgG1 level	2
decreased IgG2a level	2
abnormal spleen morphology	1
small spleen	1
abnormal immune system physiology	1
abnormal humoral immune response	1
decreased IgG level	1
decreased IgM level	1
decreased IgA level	1
decreased inflammatory response	1
abnormal T cell differentiation	1
abnormal spleen germinal center morphology	1
abnormal immunoglobulin level	1
decreased IgE level	1
abnormal immune serum protein physiology	1
abnormal class switch recombination	1
abnormal T-helper 2 physiology	1
abnormal T-helper 2 cell differentiation	1
decreased spleen germinal center number	1
decreased spleen germinal center size	1
decreased IgG2b level	1
increased interferon-gamma secretion	1
abnormal interleukin secretion	1
decreased interleukin-10 secretion	1
decreased interleukin-4 secretion	1

+1 more (showing top 25).

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
DNMT3L-AS1	ncRNA	105372833
DNMT3L	protein-coding	29947
AIRE	protein-coding	326
PFKL	protein-coding	5211
LINC01678	ncRNA	105377138
CFAP410	protein-coding	755

Protein

Protein identifiers

ICOS ligand — O75144 (reviewed: O75144)

Alternative names: B7 homolog 2, B7-like protein Gl50, B7-related protein 1

All UniProt accessions (11): O75144, A0A096LPE5, A0A2R8Y5W7, A0A8V8TQ42, A0A8V8TQ73, A0A8V8TQV9, A0A8V8TQW2, A0A8V8TR62, A0N0L8, B7Z1W8, K4DIA0

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for the T-cell-specific cell surface receptor ICOS. Acts as a costimulatory signal for T-cell proliferation and cytokine secretion. Also induces B-cell proliferation and differentiation into plasma cells. Could play an important role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T-cell function. In endothelial cells, required for proper neutrophil transmigration in response to chemoattractants, such as CXCL8/IL8 or N-formyl-methionyl peptides (fMLP).

Subunit / interactions. Interacts with CTLA4 (in vitro).

Subcellular location. Cell membrane Cell membrane.

Tissue specificity. Expressed on peripheral blood B-cells and monocytes, as well as on monocyte-derived dendritic cells (at protein level). Widely expressed (brain, heart, kidney, liver, lung, pancreas, placenta, skeletal muscle, bone marrow, colon, ovary, prostate, testis, lymph nodes, leukocytes, spleen, thymus and tonsil). Detected only in lymph nodes, leukocytes and spleen. Expressed on activated monocytes and dendritic cells.

Disease relevance. Immunodeficiency 119 (IMD119) [MIM:620825] An autosomal recessive immunologic disorder characterized by childhood-onset of recurrent respiratory tract infections, susceptibility to chronic DNA-based viral infections, hypogammaglobulinemia, and panlymphopenia. The disease may be caused by variants affecting the gene represented in this entry.

Induction. Constitutive expression is up-regulated by treatment with TNF in peripheral blood B-cells and monocytes, while it is decreased in dendritic cells. In monocytes, up-regulated by CCL3/macrophage inflammatory protein 1-alpha and IFNG.

Similarity. Belongs to the immunoglobulin superfamily. BTN/MOG family.

Isoforms (3)

UniProt ID	Names	Canonical?
O75144-1	1	yes
O75144-2	2
O75144-3	3

RefSeq proteins (7): NP_001269979, NP_001269980, NP_001269981, NP_001350699, NP_001352688, NP_001382847, NP_056074* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050504	IgSF_BTN/MOG-like	Family
IPR053896	BTN3A2-like_Ig-C	Domain

Pfam: PF07686, PF22705

UniProt features (43 total): strand 15, glycosylation site 5, turn 5, helix 5, disulfide bond 2, splice variant 2, sequence variant 2, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
6X4T	Crystal structure of ICOS-L in complex with Prezalumab and VNAR domain	X-RAY DIFFRACTION	3.15
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-O75144-F1	82.99	0.63

Antibody-complex structures (SAbDab)

4 antibodies co-crystallized with this protein: 6X4G, 6X4T, PREZALUMAB, ROZIBAFUSP

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; vesicles

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	37–113, 158–216

Glycosylation sites (5)

Type	Positions
N-linked (glcnac…) asparagine	186, 225, 70, 137, 173

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9927354	Co-stimulation by ICOS	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-9938027	Affinity selection of immunoglobulins	electronic
R-HSA-168256	Immune System	—
R-HSA-388841	Regulation of T cell activation by CD28 family	—

MSigDB gene sets: 260 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, GOBP_HYPEROSMOTIC_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_CD4_POSITIVE_ALPHA_BETA_T_CELL_ACTIVATION

GO Biological Process (11): regulation of cytokine production (GO:0001817), adaptive immune response (GO:0002250), defense response (GO:0006952), hyperosmotic response (GO:0006972), signal transduction (GO:0007165), positive regulation of activated T cell proliferation (GO:0042104), T cell activation (GO:0042110), B cell activation (GO:0042113), T cell receptor signaling pathway (GO:0050852), T follicular helper cell differentiation (GO:0061470), immune system process (GO:0002376)

GO Molecular Function (4): signaling receptor binding (GO:0005102), identical protein binding (GO:0042802), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Regulation of T cell activation by CD28 family	1
Immunoglobulin maturation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

31 GO namespaces:

Category	Terms
lymphocyte activation	2
protein binding	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
immune response	1
response to stress	1
response to osmotic stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
positive regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
antigen receptor-mediated signaling pathway	1
T-helper cell differentiation	1
exhausted T cell differentiation	1
biological_process	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
T follicular helper cell differentiation	BP	direct assay
extracellular exosome	CC	high-throughput assay
plasma membrane	CC	direct assay
identical protein binding	MF	physical interaction
receptor ligand activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,212 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ICOSLG	ICOS	Q9Y6W8	952
ICOSLG	CD28	P10747	863
ICOSLG	CTLA4	P16410	847
ICOSLG	TNFSF4	P23510	835
ICOSLG	VTCN1	Q7Z7D3	831
ICOSLG	TNFSF9	P41273	815
ICOSLG	TNFSF18	Q9UNG2	774
ICOSLG	TNFRSF4	P43489	772
ICOSLG	IL10	P22301	747
ICOSLG	CD40	P25942	718
ICOSLG	CD40LG	P29965	716
ICOSLG	IL2	P01585	704
ICOSLG	CD4	P01730	702
ICOSLG	CXCR5	P32302	658
ICOSLG	CD8A	P01732	650

IntAct

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

6 partners by confidence:

Partner	Interaction type	MIscore	Records
ICOS	physical association	0.850	10
CD28	physical association	0.400	1
CTLA4	physical association	0.400	1
GTF2H3	association	0.350	1
TMEM131L	association	0.350	1
UPK3BL1	association	0.350	1

BioGRID (25 interactions; top human partners by supporting records): C2CD2L (Affinity Capture-MS; 2 records), ICOS (Affinity Capture-MS; 2 records), LGALS1 (Affinity Capture-MS; 2 records), PREB (Affinity Capture-MS; 2 records), PTPRD (Affinity Capture-MS; 2 records), UPK3BL (Affinity Capture-MS; 2 records), ALG11 (Affinity Capture-MS), AMFR (Affinity Capture-MS), AXL (Affinity Capture-MS), CLCN3 (Affinity Capture-MS), GET4 (Affinity Capture-MS), GTF2H3 (Affinity Capture-MS), KIAA0922 (Affinity Capture-MS), KIAA1429 (Affinity Capture-RNA), MAN1B1 (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
ICOSLG	“up-regulates activity”	ICOS	binding
PRKCB	“up-regulates activity”	ICOSLG	phosphorylation
PRKCA	“up-regulates activity”	ICOSLG	phosphorylation

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
ICOS	ligand

Disease & clinical

Genetic variants

Variant evidence for ICOSLG: 337 ClinVar records (4 pathogenic / likely pathogenic); 21 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	4
Uncertain significance	149
Likely benign	148
Benign	4

Top pathogenic / likely-pathogenic (4)

Showing all 4 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
522117	NM_015259.6(ICOSLG):c.55+1G>T	Likely pathogenic	criteria provided, single submitter	1
1339546	NM_015259.6(ICOSLG):c.499C>T (p.Pro167Ser)	Likely pathogenic	criteria provided, single submitter	1
4887815	NM_015259.6(ICOSLG):c.406+1G>T	Likely pathogenic	criteria provided, single submitter	1
816179	GRCh37/hg19 21q22.3(chr21:45490774-48097372)x1	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ICOSLG’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; 35 predictions of 760):

Position(s)	Effect	Δscore	Sites
21:44231445	acceptor_loss	1.0000	2
21:44235270–44235271	donor_loss	1.0000	5
21:44235563–44235564	acceptor_loss	1.0000	6
21:44235567	acceptor_gain	1.0000
21:44231278–44231279	donor_loss	0.9900	6
21:44231287	donor_gain	0.9900
21:44231446	acceptor_loss	0.9900	3
21:44231449	acceptor_gain	0.9900
21:44238446–44238447	donor_loss	0.9900	5
21:44240802–44240803	donor_loss	0.9900	5

AlphaMissense

433 missense substitutions predicted likely pathogenic (of 1,985 scored), across 119 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
D107	8	0.983	0.994
N219	8	0.953	0.996
F96	8	0.912	0.985
N225	8	0.794	0.880
C158	7	0.994	0.997
W54	7	0.986	0.999
W171	7	0.986	0.999
C215	7	0.986	0.997
C113	7	0.985	0.996
F138	7	0.979	0.995
F111	7	0.977	0.997
C37	7	0.959	0.982
S201	7	0.928	0.995
F156	7	0.849	0.970
D198	7	0.771	0.901
P165	6	0.991	0.996
G163	6	0.968	0.995
P167	6	0.954	0.997
P141	6	0.951	0.994
S139	6	0.927	0.964

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
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000363
Breast Invasive Carcinoma (TCGA)	unfavorable	0.000631

Disease associations

OMIM: gene MIM:605717 | disease phenotypes: MIM:620825

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
immunodeficiency 119	Moderate	Autosomal recessive	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
combined immunodeficiency	Moderate	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
COVID-19 research	green

Mondo (2): combined immunodeficiency (MONDO:0015131), immunodeficiency 119 (MONDO:0970993)

Orphanet (1): Combined T and B cell immunodeficiency (Orphanet:101972)

HPO phenotypes

17 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000403	Recurrent otitis media
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count
HP:0002090	Pneumonia
HP:0002837	Recurrent bronchitis
HP:0002863	Myelodysplasia
HP:0003453	Antineutrophil antibody positivity
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0005387	Combined immunodeficiency
HP:0011108	Recurrent sinusitis
HP:0011463	Childhood onset
HP:0030318	Angular cheilitis
HP:0030388	Decreased class-switched memory B cell proportion
HP:0031160	Myelokathexis
HP:0032301	Genital warts
HP:0410028	Recurrent oral herpes

GWAS associations

21 associations:

Study	Trait	p-value
GCST006585_2124	Blood protein levels	6e-194
GCST90002381_233	Eosinophil count	1e-28
GCST90002382_586	Eosinophil percentage of white cells	9e-28
GCST001725_107	Inflammatory bowel disease	2e-26
GCST000879_9	Crohn’s disease	2e-14
GCST000964_24	Ulcerative colitis	6e-11
GCST90013445_37	Type 1 diabetes	7e-11
GCST90013445_72	Type 1 diabetes	7e-11
GCST004606_3	Eosinophil count	5e-10
GCST000207_26	Crohn’s disease	1e-9
GCST000612_27	Celiac disease	2e-9
GCST004600_119	Eosinophil percentage of white cells	2e-9
GCST005529_25	Ankylosing spondylitis	6e-9
GCST004617_118	Eosinophil percentage of granulocytes	7e-9
GCST006959_4	Rheumatoid arthritis	8e-8
GCST005536_48	Type 1 diabetes	1e-7
GCST005523_38	Celiac disease	6e-7
GCST005529_13	Ankylosing spondylitis	1e-6
GCST006585_1786	Blood protein levels	2e-6
GCST006904_6	Cerebral amyloid deposition (PET imaging)	3e-6
GCST003630_2	Left ventricular QRS voltage	6e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0007741	R wave amplitude
EFO:0007742	QRS amplitude
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007707	cerebral amyloid deposition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3712949 (SINGLE PROTEIN), CHEMBL5482971 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ICOSLG 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.

1 curated-mechanism drugs:

Drug	Modality	Max phase
AMG-557	Unknown	2

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

5 potent at pChembl≥5 of 17 total, top 5 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
5.33	IC50	4680	nM	CHEMBL2171562
5.25	IC50	5650	nM	CHEMBL5429501

PubChem BioAssay actives

5 with measured affinity, of 26 total; 4 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
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

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	decreases expression, increases expression, affects cotreatment	2
Benzo(a)pyrene	increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Ozone	affects cotreatment, increases expression, increases oxidation	2
Tetrachlorodibenzodioxin	increases expression	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
bisphenol A	increases expression, affects cotreatment	1
dimethylselenide	increases expression, increases oxidation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
Aripiprazole	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Vehicle Emissions	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5329816	Binding	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	First-in-class small molecule inhibitors of ICOS/ICOSL interaction as a novel class of immunomodulators. — *RSC Med Chem*

Cellosaurus cell lines

8 cell lines: 4 cancer cell line, 4 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8HR	Abcam HCT 116 ICOSLG KO	Cancer cell line	Male
CVCL_B9K1	Abcam A-549 ICOSLG KO	Cancer cell line	Male
CVCL_D2FN	Abcam MCF-7 ICOSLG KO	Cancer cell line	Female
CVCL_D7BK	Abeomics CHO-K1 ICOSL	Spontaneously immortalized cell line	Female
CVCL_E2Z7	L929/CD275	Spontaneously immortalized cell line	Male
CVCL_E5IT	CHO-K1/B7-H2	Spontaneously immortalized cell line	Female
CVCL_E6QR	Genomeditech CHO-K1 H_ICOSLG(CD275)	Spontaneously immortalized cell line	Female
CVCL_RP37	JEM493	Cancer cell line	Male

Clinical trials (associated diseases)

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

4 trials:

NCT	Phase	Status	Title
NCT02737384	Phase 2	TERMINATED	Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID)
NCT02915406	Not specified	NO_LONGER_AVAILABLE	cliniMACs HUD for T Cell Depletion
NCT04902807	Not specified	COMPLETED	Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation
NCT06659588	Not specified	RECRUITING	Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency

Predicted chemistry — Sugi Predict

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