ITGA2B (integrin subunit alpha 2b)

Gene

• Entrez ID: 3674
• Gene name: Integrin subunit alpha 2b
• Gene symbol: ITGA2B
• Synonyms: BDPLT16, BDPLT2, CD41, CD41B, FMAIT2, GP2B, GPIIb, GT, GT1, GTA, HPA3, PPP1R93
• Chromosome: 17
• Chromosome location: 17q21.31
• Summary: This gene encodes a member of the integrin alpha chain family of proteins. The encoded preproprotein is proteolytically processed to generate light and heavy chains that associate through disulfide linkages to form a subunit of the alpha-IIb/beta-3 integr

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74475415	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs76066357	G>C	Pathogenic, benign	Missense variant, coding sequence variant
rs76811038	A>G,T	Pathogenic	Missense variant, coding sequence variant
rs78657866	C>T	Likely-pathogenic	Intron variant, missense variant, coding sequence variant
rs80002943	G>A	Pathogenic	Intron variant, missense variant, coding sequence variant
rs80277041	C>G	Pathogenic	Missense variant, coding sequence variant
rs137852906	G>A,T	Pathogenic	Coding sequence variant, synonymous variant, stop gained
rs137852907	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852908	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852910	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852911	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs746091910	C>T	Likely-pathogenic	Splice donor variant
rs759664025	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant
rs763330792	G>A,C,T	Pathogenic	Intron variant
rs766503255	G>A,T	Pathogenic	Coding sequence variant, synonymous variant, missense variant
rs778608263	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs780017389	TCTACG>-	Pathogenic	Inframe deletion, coding sequence variant
rs879255508	GGCGCAGGCCTGG>-	Pathogenic	Coding sequence variant, splice acceptor variant, intron variant
rs879255509	C>T	Pathogenic	Splice donor variant
rs879255514	C>T	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs1131692013	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant, stop gained
rs1214448436	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1393747638	C>T	Pathogenic	Splice acceptor variant
rs1469711487	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555613692	A>G	Pathogenic	Splice donor variant
rs1598375578	A>-	Pathogenic	Frameshift variant, coding sequence variant, intron variant
rs1598375779	G>-	Pathogenic	Frameshift variant, coding sequence variant, intron variant
rs1598377051	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1598377980	->C	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1598378490	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1598379928	C>T	Pathogenic	Splice acceptor variant
rs1598380253	C>T	Pathogenic	Missense variant, coding sequence variant
rs1598380380	C>G	Likely-pathogenic	Splice acceptor variant
rs1598381654	AGCAGATCA>-	Likely-pathogenic	Coding sequence variant, inframe indel
rs1598381778	C>G	Likely-pathogenic	Splice donor variant
rs1598383011	C>T	Likely-pathogenic	Intron variant

Transcription factors

Transcription factor	Regulation	Reference
FLI1	Unknown	15466856
GATA1	Unknown	8408012
RUNX1	Activation	12576332;17725493;18316480
SPI1	Unknown	9305885
STAT6	Unknown	20652946

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002576	Process	Platelet degranulation	TAS
GO:0002687	Process	Positive regulation of leukocyte migration	IEA
GO:0005515	Function	Protein binding	IPI	14681217, 15379538, 19279667, 22779914
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	TAS
GO:0005925	Component	Focal adhesion	IEA
GO:0007160	Process	Cell-matrix adhesion	IEA
GO:0007229	Process	Integrin-mediated signaling pathway	HDA	23382103
GO:0008305	Component	Integrin complex	IEA
GO:0009897	Component	External side of plasma membrane	IEA
GO:0009986	Component	Cell surface	HDA	23382103
GO:0030198	Process	Extracellular matrix organization	TAS
GO:0031092	Component	Platelet alpha granule membrane	TAS
GO:0042802	Function	Identical protein binding	IPI	11606749, 14681217, 15067009
GO:0045652	Process	Regulation of megakaryocyte differentiation	TAS
GO:0046872	Function	Metal ion binding	IEA
GO:0050840	Function	Extracellular matrix binding	IEA
GO:0070051	Function	Fibrinogen binding	IEA
GO:0070062	Component	Extracellular exosome	IDA	15908444
GO:0070527	Process	Platelet aggregation	IEA
GO:0072562	Component	Blood microparticle	HDA	22516433

Other IDs

• MIM: 607759
• HGNC: 6138
• e!Ensembl: ENSG00000005961

Protein

• UniProt ID: P08514
• Protein name: Integrin alpha-IIb (GPalpha IIb) (GPIIb) (Platelet membrane glycoprotein IIb) (CD antigen CD41) [Cleaved into: Integrin alpha-IIb heavy chain; Integrin alpha-IIb light chain, form 1; Integrin alpha-IIb light chain, form 2]
• Protein function: Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in f
• PDB: 1DPK, 1DPQ, 1KUP, 1KUZ, 1M8O, 1S4W, 1TYE, 2K1A, 2K9J, 2KNC, 2MTP, 2N9Y, 2VC2, 2VDK, 2VDL, 2VDM, 2VDN, 2VDO, 2VDP, 2VDQ, 2VDR, 3FCS, 3FCU, 3NID, 3NIF, 3NIG, 3T3M, 3T3P, 3ZDX, 3ZDY, 3ZDZ, 3ZE0, 3ZE1, 3ZE2, 4CAK, 4Z7N, 4Z7O, 4Z7Q, 5HDB, 6V4P, 7KN0, 7L8P, 7LA4, 7SC4, 7SFT, 7TCT, 7TD8, 7THO, 7TMZ, 7TPD, 7U60
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01839	FG-GAP	320 → 362	FG-GAP repeat	Repeat
  PF01839	FG-GAP	387 → 423	FG-GAP repeat	Repeat
  PF08441	Integrin_alpha2	481 → 921	Integrin alpha	Family
  PF00357	Integrin_alpha	1020 → 1034	Integrin alpha cytoplasmic region	Family

• Sequence:

  MARALCPLQALWLLEWVLLLLGPCAAPPAWALNLDPVQLTFYAGPNGSQFGFSLDFHKDS
  HGRVAIVVGAPRTLGPSQEETGGVFLCPWRAEGGQCPSLLFDLRDETRNVGSQTLQTFKA
  RQGLGASVVSWSDVIVACAPWQHWNVLEKTEEAEKTPVGSCFLAQPESGRRAEYSPCRGN
  TLSRIYVENDFSWDKRYCEAGFSSVVTQAGELVLGAPGGYYFLGLLAQAPVADIFSSYRP
  GILLWHVSSQSLSFDSSNPEYFDGYWGYSVAVGEFDGDLNTTEYVVGAPTWSWTLGAVEI
  LDSYYQRLHRLRGEQMASYFGHSVAVTDVNGDGRHDLLVGAPLYMESRADRKLAEVGRVY
  LFLQPRGPHALGAPSLLLTGTQLYGRFGSAIAPLGDLDRDGYNDIAVAAPYGGPSGRGQV
  LVFLGQSEGLRSRPSQVLDSPFPTGSAFGFSLRGAVDIDDNGYPDLIVGAYGANQVAVYR
  AQPVVKASVQLLVQDSLNPAVKSCVLPQTKTPVSCFNIQMCVGATGHNIPQKLSLNAELQ
  LDRQKPRQGRRVLLLGSQQAGTTLNLDLGGKHSPICHTTMAFLRDEADFRDKLSPIVLSL
  NVSLPPTEAGMAPAVVLHGDTHVQEQTRIVLDCGEDDVCVPQLQLTASVTGSPLLVGADN
  VLELQMDAANEGEGAYEAELAVHLPQGAHYMRALSNVEGFERLICNQKKENETRVVLCEL
  GNPMKKNAQIGIAMLVSVGNLEEAGESVSFQLQIRSKNSQNPNSKIVLLDVPVRAEAQVE
  LRGNSFPASLVVAAEEGEREQNSLDSWGPKVEHTYELHNNGPGTVNGLHLSIHLPGQSQP
  SDLLYILDIQPQGGLQCFPQPPVNPLKVDWGLPIPSPSPIHPAHHKRDRRQIFLPEPEQP
  SRLQDPVLVSCDSAPCTVVQCDLQEMARGQRAMVTVLAFLWLPSLYQRPLDQFVLQSHAW
  FNVSSLPYAVPPLSLPRGEAQVWTQLLRALEERAIPIWWVLVGVLGGLLLLTILVLAMWK
  VGFFKRNRPPLEEDDEEGE

• Sequence length: 1039

Pathways

KEGG:

Rap1 signaling pathway
PI3K-Akt signaling pathway
Focal adhesion
ECM-receptor interaction
Platelet activation
Neutrophil extracellular trap formation
Hematopoietic cell lineage
Regulation of actin cytoskeleton
Cytoskeleton in muscle cells
Human papillomavirus infection
Pathways in cancer
Small cell lung cancer
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Dilated cardiomyopathy
Fluid shear stress and atherosclerosis

Reactome:

Platelet degranulation
Integrin cell surface interactions
ECM proteoglycans
Integrin signaling
GRB2:SOS provides linkage to MAPK signaling for Integrins
p130Cas linkage to MAPK signaling for integrins
Signal transduction by L1
MAP2K and MAPK activation
Signaling by moderate kinase activity BRAF mutants
Signaling by high-kinase activity BRAF mutants
Signaling by BRAF and RAF fusions
Paradoxical activation of RAF signaling by kinase inactive BRAF
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
Signaling downstream of RAS mutants

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Alloimmune thrombocytopenia	Fetal and neonatal alloimmune thrombocytopenia, Neonatal Alloimmune Thrombocytopenia	rs1555572829
Anemia	Anemia	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
Arthritis	Juvenile arthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470	19565504
Cerebral palsy	Cerebral Palsy	rs121918149, rs75184679, rs730880264, rs587777428, rs797045067, rs767399782, rs564185858, rs886039513
Developmental delay	Global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Glanzmann thrombasthenia	Glanzmann Thrombasthenia, Autosomal Dominant, Glanzmann Thrombasthenia, Type A, Glanzmann thrombasthenia	rs879255508, rs137852906, rs763330792, rs137852907, rs879255509, rs137852908, rs780017389, rs137852910, rs76811038, rs137852911, rs80277041, rs121918444, rs121918445, rs121918446, rs2143068731, rs121918449, rs121918450, rs121918451, rs121918452, rs483352692, rs74475415, rs1057518838, rs1057518837, rs78657866, rs780786843, rs1555613692, rs746091910, rs1567764064, rs1598375779, rs1598377051, rs1598377980, rs1598378490, rs778608263, rs1214448436, rs1469711487, rs1302506624, rs1598690979, rs1386425657, rs74664206, rs1598380380, rs992856733, rs1393747638, rs151179377, rs199866795, rs1567764299, rs1598380253, rs1598690937, rs958609406, rs1598381778, rs2048642260, rs745766760	21454453, 9834222, 24498605
Leukemia	Leukemia, Myelocytic, Acute	rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297, rs11978267, rs4132601	27903959
Macrothrombocytopenia	Macrothrombocytopenia, Autosomal dominant macrothrombocytopenia	rs121908063, rs5030764, rs121918037, rs80338835, rs80338834, rs80338829, rs121913655, rs80338831, rs121913656, rs80338826, rs80338828, rs587776808, rs80338827, rs121913657, rs876661302, rs2146392848, rs121909750, rs121909751, rs121909752, rs80338830, rs387907345, rs387907348, rs387907350, rs797044804, rs1057517996, rs1321659356, rs1184544985, rs1603484047, rs1603484048, rs1297298519, rs1594756590, rs747559032, rs1598377980, rs1597638300, rs1597638379, rs1597638745, rs1601239696, rs1601248210, rs1601248859, rs1360071443, rs1254692009, rs1598700249, rs1601238563, rs1601247763, rs1601248245, rs1601248530, rs770554119	21454453

Unknown
Disease name	Disease term	dbSNP ID	References
Carotid artery thrombosis	Carotid Artery Thrombosis		1605806
Common carotid artery thrombosis	Common Carotid Artery Thrombosis		1605806
External carotid artery thrombosis	External Carotid Artery Thrombosis		1605806
Fetal and neonatal alloimmune thrombocytopenia	FNAITP
Hematomas	Spontaneous hematomas
Internal carotid artery thrombosis	Internal Carotid Artery Thrombosis		1605806
Juvenile arthritis	Juvenile psoriatic arthritis		19565504
Seronegative polyarthritis	Polyarthritis, Juvenile, Rheumatoid Factor Negative		19565504
Polyarthritis, rheumatoid factor positive	Polyarthritis, Juvenile, Rheumatoid Factor Positive		19565504
Sensorineural hearing loss	Sensorineural hearing loss, bilateral
Still disease	Juvenile-Onset Still Disease		19565504
Stroke	Cerebrovascular accident, Acute Cerebrovascular Accidents		9445356
Subarachnoid hemorrhage	Subarachnoid Hemorrhage
Thrombasthenia	Thrombasthenia		7508443, 15219201, 12181054, 20020534, 11798398, 9920835, 7706461, 9834222, 8704171, 16103235, 21917754, 12083483, 9734640, 22190468, 9473221, 9215749, 12424194, 10607701, 17018384, 15099289, 24498605, 9763559, 1702098, 6213621, 9722314, 12506038, 6460044, 8282784