ICOS (inducible T cell costimulator)

Gene

• Entrez ID: 29851
• Gene name: Inducible T cell costimulator
• Gene symbol: ICOS
• Synonyms: AILIM, CD278, CVID1
• Chromosome: 2
• Chromosome location: 2q33.2
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs76778263	G>A,C	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs201031378	C>G,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, missense variant
rs375299065	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1559035937	T>C	Likely-pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1058877	hsa-miR-1207-3p	CLIP-seq
MIRT1058878	hsa-miR-153	CLIP-seq
MIRT1058879	hsa-miR-320a	CLIP-seq
MIRT1058880	hsa-miR-320b	CLIP-seq
MIRT1058881	hsa-miR-320c	CLIP-seq
MIRT1058882	hsa-miR-320d	CLIP-seq
MIRT1058883	hsa-miR-320e	CLIP-seq
MIRT1058884	hsa-miR-323b-5p	CLIP-seq
MIRT1058885	hsa-miR-338-3p	CLIP-seq
MIRT1058886	hsa-miR-3691-3p	CLIP-seq
MIRT1058887	hsa-miR-3924	CLIP-seq
MIRT1058888	hsa-miR-3941	CLIP-seq
MIRT1058889	hsa-miR-4310	CLIP-seq
MIRT1058890	hsa-miR-4429	CLIP-seq
MIRT1058891	hsa-miR-4530	CLIP-seq
MIRT1058892	hsa-miR-4643	CLIP-seq
MIRT1058893	hsa-miR-466	CLIP-seq
MIRT1058894	hsa-miR-4672	CLIP-seq
MIRT1058895	hsa-miR-4684-3p	CLIP-seq
MIRT1058896	hsa-miR-4696	CLIP-seq
MIRT1058897	hsa-miR-4789-3p	CLIP-seq
MIRT1058898	hsa-miR-515-5p	CLIP-seq
MIRT1058899	hsa-miR-586	CLIP-seq
MIRT2013695	hsa-miR-27a	CLIP-seq
MIRT2013696	hsa-miR-27b	CLIP-seq
MIRT2013697	hsa-miR-513a-5p	CLIP-seq
MIRT2245786	hsa-miR-1266	CLIP-seq
MIRT2245787	hsa-miR-23a	CLIP-seq
MIRT2245788	hsa-miR-23b	CLIP-seq
MIRT2245789	hsa-miR-23c	CLIP-seq
MIRT2245790	hsa-miR-3133	CLIP-seq
MIRT2245791	hsa-miR-3170	CLIP-seq
MIRT2245792	hsa-miR-4270	CLIP-seq
MIRT2245793	hsa-miR-4291	CLIP-seq
MIRT2245794	hsa-miR-4441	CLIP-seq
MIRT2245795	hsa-miR-4518	CLIP-seq
MIRT2245796	hsa-miR-510	CLIP-seq
MIRT2245797	hsa-miR-522	CLIP-seq
MIRT2245798	hsa-miR-545	CLIP-seq
MIRT2245799	hsa-miR-582-5p	CLIP-seq
MIRT2682552	hsa-miR-1972	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002517	Process	T cell tolerance induction	IBA	21873635
GO:0005515	Function	Protein binding	IPI	11956294, 16951355, 18641334, 27135603
GO:0005576	Component	Extracellular region	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006955	Process	Immune response	NAS	9930702
GO:0016021	Component	Integral component of membrane	IEA
GO:0031295	Process	T cell costimulation	IBA	21873635
GO:0031295	Process	T cell costimulation	TAS
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0098609	Process	Cell-cell adhesion	IBA	21873635

Other IDs

• MIM: 604558
• HGNC: 5351
• e!Ensembl: ENSG00000163600

Protein

• UniProt ID: Q9Y6W8
• Protein name: Inducible T-cell costimulator (Activation-inducible lymphocyte immunomediatory molecule) (CD antigen CD278)
• Protein function: Stimulatory receptor expressed in activated or antigen-experienced T-cells that plays an important role in the immune response (PubMed:9930702). Upon binding to its ligand ICOSL expressed on antigen presenting cells (APCs), delivers costimulator
• PDB: 6X4G, 7JOO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF15910	V-set_2	23 → 134	ICOS V-set domain	Domain

• Sequence:

  MKSGLWYFFLFCLRIKVLTGEINGSANYEMFIFHNGGVQILCKYPDIVQQFKMQLLKGGQ
  ILCDLTKTKGSGNTVSIKSLKFCHSQLSNNSVSFFLYNLDHSHANYYFCNLSIFDPPPFK
  VTLTGGYLHIYESQLCCQLKFWLPIGCAAFVVVCILGCILICWLTKKKYSSSVHDPNGEY
  MFMRAVNTAKKSRLTDVTL

• Sequence length: 199

Pathways

KEGG:

Cell adhesion molecules
T cell receptor signaling pathway
Intestinal immune network for IgA production
Primary immunodeficiency

Reactome:

PIP3 activates AKT signaling
Constitutive Signaling by Aberrant PI3K in Cancer
Costimulation by the CD28 family
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia, Hemolytic	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Asthma	Asthma	rs324981, rs121912630, rs150116809, rs4950928, rs708494, rs1581842283	21150878
Autoimmune diseases	Autoimmune Diseases	rs41285370, rs869025224	21383967
Bronchiectasis	Bronchiectasis	rs121908758, rs121908811, rs76649725, rs267606722, rs121909008, rs387906360, rs387906361, rs80034486, rs74767530, rs121908776, rs121909012, rs77646904, rs121908754, rs121909015, rs121909016, rs387906365, rs80055610, rs75528968, rs121908748, rs77932196, rs121909026, rs121908751, rs121908750, rs746418935, rs79282516, rs77409459, rs121909031, rs76554633, rs75115087, rs79633941, rs387906375, rs75389940, rs121909043, rs387906379, rs121908784, rs121909047, rs137852709, rs1596894031, rs137852710, rs61759860, rs121908805, rs193922501, rs193922503, rs193922504, rs1554389296, rs121908812, rs74467662, rs193922510, rs193922514, rs121908797, rs193922515, rs76151804, rs78984783, rs77035409, rs193922532, rs121908767, rs77188391, rs121908789, rs121908779, rs36210737, rs121908763, rs121908794, rs121908796, rs121908772, rs79031340, rs397508137, rs397508139, rs121908774, rs397508150, rs397508152, rs397508158, rs397508165, rs397508168, rs397508173, rs397508192, rs397508196, rs397508200, rs397508205, rs397508208, rs397508211, rs397508222, rs397508225, rs397508231, rs397508243, rs397508251, rs397508261, rs397508272, rs397508273, rs397508276, rs397508295, rs397508296, rs397508298, rs397508300, rs77284892, rs397508310, rs201978662, rs201124247, rs121908780, rs397508331, rs397508333, rs397508339, rs397508341, rs121908760, rs397508350, rs397508353, rs121908810, rs397508360, rs374946172, rs145449046, rs397508377, rs397508379, rs397508380, rs397508386, rs397508387, rs397508393, rs397508399, rs397508400, rs397508412, rs397508413, rs121909034, rs149790377, rs121908792, rs397508426, rs397508431, rs397508441, rs397508451, rs397508461, rs397508479, rs397508482, rs397508496, rs397508498, rs397508506, rs397508510, rs142394380, rs121909036, rs139304906, rs121908798, rs397508532, rs397508535, rs146521846, rs139729994, rs397508570, rs397508572, rs77834169, rs78655421, rs121908765, rs397508595, rs397508596, rs397508600, rs397508604, rs397508609, rs397508616, rs397508620, rs397508624, rs121908808, rs397508635, rs397508636, rs397508637, rs397508658, rs397508673, rs397508680, rs397508686, rs76371115, rs397508702, rs397508706, rs397508712, rs397508715, rs397508721, rs397508732, rs397508734, rs397508740, rs121908771, rs397508761, rs78440224, rs121908793, rs397508767, rs121908803, rs397508777, rs397508784, rs397508791, rs397508796, rs397508799, rs397508805, rs397508808, rs397508809, rs397508824, rs786204693, rs755416052, rs397508263, rs1057516619, rs397508176, rs1057516415, rs1057516970, rs754392413, rs1057516457, rs397508709, rs1060503164, rs775663783, rs397508294, rs1554380497, rs397508163, rs121908785, rs1235397597, rs397508405, rs1554392800, rs375661578, rs397508693, rs766063304, rs141482808, rs1290078234, rs756219310, rs1554390958, rs1555112332, rs750559671, rs533959068, rs1554389062, rs1554389486, rs1330431481, rs193922730, rs779177972, rs1562928997, rs1562908997, rs1562876459, rs1584785196, rs1584786454, rs1299250440, rs1584837090, rs1584764596, rs1584812425
Common variable immunodeficiency	Common Variable Immunodeficiency, Acquired Hypogammaglobulinemia, IMMUNODEFICIENCY, COMMON VARIABLE, 1	rs72553883, rs121908379, rs104894650, rs587776775, rs398122863, rs398122864, rs397514332, rs397514331, rs727502786, rs727502787, rs72553882, rs869320688, rs869320689, rs869320754, rs773694113, rs1553319504, rs201017642, rs1555550717, rs1558192723, rs1030733127, rs749636258, rs185689791, rs1559035937, rs1565214594, rs1560679469, rs1560711146, rs1569376229, rs1578790573, rs939459600, rs1572952530, rs1572950925, rs772481080, rs369363360, rs72553885, rs72553879, rs1265262160, rs1303637368, rs757598952, rs1016142312, rs1578771120, rs1578771197, rs1578793298, rs1578793312, rs1578809101, rs1578811073, rs1590715754, rs144718007, rs759649059, rs1723945421, rs2061279365	12577056, 19380800, 11343122, 29226301
Gastrointestinal stromal tumor	Gastrointestinal Stromal Tumors	rs587776653, rs74315368, rs74315369, rs587776793, rs587776794, rs587776795, rs606231209, rs121908589, rs121913685, rs121913680, rs794726675, rs587776804, rs121913517, rs121913234, rs121913512, rs267607032, rs387906780, rs201286421, rs587778661, rs587781270, rs587782243, rs74315370, rs587782703, rs786203457, rs764575966, rs786203251, rs587782604, rs200245469, rs397516836, rs786202732, rs786201161, rs786201063, rs751000085, rs869025568, rs876660642, rs876658713, rs151170408, rs878854632, rs752360961, rs121913235, rs121913521, rs121913513, rs1057519708, rs1057519710, rs121913514, rs1057519713, rs778582853, rs1060503757, rs1060502521, rs1060502543, rs898854295, rs981049067, rs916516745, rs1553887262, rs1057520032, rs1553887960, rs775143272, rs1560395607, rs1560418178, rs751904543, rs1560420761, rs1560417385, rs1560417396, rs1560417427, rs1560417438, rs1560417535, rs1560417642, rs1560417666, rs1560417673, rs1577992594, rs1577995761, rs1578003055, rs1301704156, rs1734957331
Lymphoma	Lymphoma	rs11540652, rs1592119138, rs1592123162, rs1599367044
Multiple sclerosis	Multiple Sclerosis	rs104895219, rs483353022, rs483353023, rs483353028, rs483353029, rs483353024, rs483353030, rs3207617, rs483353031, rs483353032, rs483353033, rs483353034, rs483353035, rs483353036, rs483353039, rs483353038, rs61731956, rs568165874, rs767480544	22190364
Severe combined immunodeficiency disease	Combined immunodeficiency	rs886037607, rs118203993, rs121908714, rs121908739, rs121908740, rs121908735, rs121908721, rs121908722, rs121908156, rs1564414523, rs1564418254, rs1564446526, rs786205074, rs121908157, rs121908159, rs786200884, rs397515357, rs104894562, rs137852624, rs137852625, rs137852626, rs137852627, rs137852507, rs137852509, rs111033619, rs111033620, rs1569480018, rs111033621, rs137852510, rs587776729, rs111033622, rs111033617, rs111033618, rs121917894, rs121917896, rs2133313409, rs121917897, rs28933392, rs104894282, rs104894283, rs104894285, rs121918570, rs121918572, rs730880318, rs104893674, rs730880319, rs104894453, rs104894454, rs104894451, rs137853206, rs777503956, rs267606645, rs267606648, rs397515390, rs193922346, rs193922347, rs193922348, rs193922349, rs193922350, rs137852508, rs193922640, rs193922641, rs193922643, rs193922645, rs193922361, rs193922364, rs193922464, rs148508754, rs193922574, rs113994174, rs606231246, rs397514671, rs397514686, rs397514755, rs199474679, rs199474685, rs199474686, rs199474681, rs150739647, rs267605358, rs886041036, rs587777335, rs587778405, rs145092287, rs587777562, rs606231256, rs200296680, rs786205456, rs786205517, rs774202259, rs786205615, rs878853261, rs786205890, rs782753385, rs746052951, rs869025224, rs869312857, rs869320660, rs869320659, rs869320658, rs879253742, rs886037924, rs886037925, rs750610248, rs886039394, rs761242509, rs886039387, rs886041043, rs886041044, rs886042051, rs886041333, rs749481781, rs1057517747, rs1057519506, rs1057523762, rs1057521062, rs1057520644, rs761583890, rs751635016, rs55729925, rs1064793248, rs1064793347, rs1064794027, rs781410769, rs1555524788, rs1486760100, rs769633203, rs1556330713, rs1555322558, rs1556330234, rs1556330755, rs1556329779, rs1556330552, rs1556329822, rs1556330286, rs1556331272, rs2146178281, rs376610445, rs757797994, rs775704953, rs1555743321, rs1564995660, rs1564995662, rs1556330249, rs144104577, rs886041796, rs1026474882, rs570768621, rs1556330562, rs1556330568, rs780014431, rs778343059, rs1555844617, rs1567629968, rs1567628757, rs1567629943, rs1567632864, rs1567632829, rs1567626023, rs1559328006, rs1561423197, rs1452483770, rs1568400897, rs1569479913, rs1568404443, rs1569480047, rs1563340753, rs368303189, rs1568431262, rs1568431102, rs1561424886, rs1602289943, rs1241698978, rs1569479994, rs1569480082, rs1602289649, rs1573261820, rs770985198, rs1589050343, rs1340132582, rs1589064324, rs1589070600, rs1213680890, rs149316157, rs1599873591, rs755706305, rs1602288051, rs1602289411, rs1602289183, rs1583513256, rs1589136659, rs1380154594, rs1011307501, rs1599876167, rs1569967422, rs1602289631, rs1573262398, rs760191638, rs1592117677, rs1640406042, rs372597855, rs1839558393, rs1839622622, rs1839957089, rs777008519, rs1233957241, rs2092261618, rs1839255008, rs1677695565, rs936493226, rs1162344514, rs991089005	29226301
Vasculitis	Vasculitis	rs376785840, rs587777240, rs200930463, rs587777241, rs77563738, rs202134424, rs148936893, rs587777242, rs775440641, rs770689762, rs45511697, rs139750129, rs756881285, rs747774101, rs1568966771, rs766602945, rs1601419986, rs1489114116, rs754904956, rs755007390, rs368615054

Unknown
Disease name	Disease term	dbSNP ID	References
Brachycephaly	Brachycephaly
Bronchitis	Recurrent bronchitis
Celiac disease	Celiac Disease	rs2305764, rs35218876	20190752
Conjunctivitis	Conjunctivitis
Hypogammaglobulinemia	Hypogammaglobulinemia		29226301
Immune system diseases	Immune System Diseases		21383967
Immune thrombocytopenic purpura	Immune thrombocytopenic purpura
Immunoglobulin deficiency	Immunoglobulin Deficiency, Late-Onset
Immunologic deficiency syndromes	Immunologic Deficiency Syndromes
Imperforate anus	Anus, Imperforate
Lymphopenia	Lymphopenia
Neoplasms	Neoplasms
Otitis media	Chronic otitis media, Recurrent otitis media	rs601338, rs1047781, rs1800028
Sinusitis	Recurrent sinusitis
T-cell lymphoma/leukemia	Adult T-Cell Lymphoma/Leukemia		26437031