ZAP70 (zeta chain of T cell receptor associated protein kinase 70)

Gene

• Entrez ID: 7535
• Gene name: Zeta chain of T cell receptor associated protein kinase 70
• Gene symbol: ZAP70
• Synonyms: ADMIO2, IMD48, SRK, STCD, STD, TZK, ZAP-70
• Chromosome: 2
• Chromosome location: 2q11.2
• Summary: This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, fun

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104893674	C>A	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs113994172	C>A	Pathogenic	Non coding transcript variant, genic upstream transcript variant, coding sequence variant, missense variant
rs113994173	G>A	Pathogenic	Intron variant, 5 prime UTR variant
rs113994174	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs113994175	A>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs137853201	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs199840952	C>T	Pathogenic	Non coding transcript variant, upstream transcript variant, missense variant, coding sequence variant, genic upstream transcript variant
rs200126170	C>G	Likely-pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, stop gained
rs730880318	G>A	Pathogenic	Intron variant
rs730880319	AAGTGGTACGCAC>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs869025224	G>C	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs897972295	C>A,T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained, genic upstream transcript variant, synonymous variant
rs1017182331	G>A	Likely-pathogenic	Non coding transcript variant, missense variant, intron variant, genic downstream transcript variant, coding sequence variant
rs1064793298	G>A	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1064793340	T>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1559328006	->T	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1573262398	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, genic upstream transcript variant, missense variant
rs1573280624	C>G	Likely-pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005760	hsa-miR-34a-5p	Immunoblot, Luciferase reporter assay	21205967
MIRT005760	hsa-miR-34a-5p	Immunoblot, Luciferase reporter assay	21205967
MIRT005760	hsa-miR-34a-5p	Immunoblot, Luciferase reporter assay	21205967
MIRT005761	hsa-miR-34b-3p	Immunoblot, Luciferase reporter assay	21205967
MIRT005761	hsa-miR-34b-3p	Immunoblot, Luciferase reporter assay	21205967
MIRT005761	hsa-miR-34b-3p	Immunoblot, Luciferase reporter assay	21205967
MIRT005762	hsa-miR-34c-5p	Immunoblot, Luciferase reporter assay	21205967
MIRT005762	hsa-miR-34c-5p	Immunoblot, Luciferase reporter assay	21205967
MIRT005762	hsa-miR-34c-5p	Immunoblot, Luciferase reporter assay	21205967
MIRT005760	hsa-miR-34a-5p	Proteomics	21566225
MIRT005760	hsa-miR-34a-5p	Proteomics	21566225
MIRT732317	hsa-miR-631	Luciferase reporter assay, qRT-PCR, Western blot	26620225
MIRT732317	hsa-miR-631	Luciferase reporter assay, qRT-PCR, Western blot	26620225
MIRT736059	hsa-miR-370-3p	Microarray, qRT-PCR	31432183

Transcription factors

Transcription factor	Regulation	Reference
CREM	Unknown	16237091

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001772	Component	Immunological synapse	IEA
GO:0001784	Function	Phosphotyrosine residue binding	IMP	12051764
GO:0001784	Function	Phosphotyrosine residue binding	IPI	12051764
GO:0002250	Process	Adaptive immune response	TAS	20135127
GO:0004713	Function	Protein tyrosine kinase activity	IBA	21873635
GO:0004713	Function	Protein tyrosine kinase activity	NAS	1423621, 8613493
GO:0004713	Function	Protein tyrosine kinase activity	TAS
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IBA	21873635
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IDA	12447358
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	TAS	20135127
GO:0005102	Function	Signaling receptor binding	IBA	21873635
GO:0005515	Function	Protein binding	IPI	7509083, 7528772, 7761456, 8648092, 8901551, 9185620, 10318843, 10704231, 10752619, 11855827, 11891219, 12359715, 12646565, 15832366, 16273093, 16461343, 19843936, 21957439, 22266821, 23460737, 24658140, 24728074, 26783323, 31980649
GO:0005524	Function	ATP binding	NAS	1423621
GO:0005737	Component	Cytoplasm	TAS	12359715
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	12150984
GO:0005886	Component	Plasma membrane	TAS	20135127
GO:0005911	Component	Cell-cell junction	IEA
GO:0006468	Process	Protein phosphorylation	IDA	12447358
GO:0006468	Process	Protein phosphorylation	NAS	1423621
GO:0006955	Process	Immune response	IDA	1423621
GO:0007169	Process	Transmembrane receptor protein tyrosine kinase signaling pathway	IBA	21873635
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IDA	22732588
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IMP	23620790
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030217	Process	T cell differentiation	NAS	8613493
GO:0031234	Component	Extrinsic component of cytoplasmic side of plasma membrane	IBA	21873635
GO:0035556	Process	Intracellular signal transduction	NAS	1423621
GO:0042101	Component	T cell receptor complex	IDA	8176201
GO:0042110	Process	T cell activation	TAS	20135127
GO:0042113	Process	B cell activation	TAS	20135127
GO:0043366	Process	Beta selection	IEA
GO:0045059	Process	Positive thymic T cell selection	IDA	7630421
GO:0045060	Process	Negative thymic T cell selection	IEA
GO:0045087	Process	Innate immune response	IBA	21873635
GO:0045121	Component	Membrane raft	IDA	12150984
GO:0045582	Process	Positive regulation of T cell differentiation	IDA	7630421
GO:0046638	Process	Positive regulation of alpha-beta T cell differentiation	IEA
GO:0046641	Process	Positive regulation of alpha-beta T cell proliferation	IEA
GO:0050850	Process	Positive regulation of calcium-mediated signaling	IEA
GO:0050852	Process	T cell receptor signaling pathway	TAS	20135127
GO:0070489	Process	T cell aggregation	TAS	20135127
GO:0072678	Process	T cell migration	TAS	20135127

Other IDs

• MIM: 176947
• HGNC: 12858
• e!Ensembl: ENSG00000115085

Protein

• UniProt ID: P43403
• Protein name: Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase)
• Protein function: Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Also contributes to the development and activat
• PDB: 1FBV, 1M61, 1U59, 2CBL, 2OQ1, 2OZO, 2Y1N, 3ZNI, 4A4B, 4A4C, 4K2R, 4XZ0, 4XZ1, 5O76, 7SIY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00017	SH2	10 → 87	SH2 domain	Domain
  PF00017	SH2	163 → 239	SH2 domain	Domain
  PF07714	PK_Tyr_Ser-Thr	338 → 593	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MPDPAAHLPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFP
  IERQLNGTYAIAGGKAHCGPAELCEFYSRDPDGLPCNLRKPCNRPSGLEPQPGVFDCLRD
  AMVRDYVRQTWKLEGEALEQAIISQAPQVEKLIATTAHERMPWYHSSLTREEAERKLYSG
  AQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYLK
  LKADGLIYCLKEACPNSSASNASGAAAPTLPAHPSTLTHPQRRIDTLNSDGYTPEPARIT
  SPDKPRPMPMDTSVYESPYSDPEELKDKKLFLKRDNLLIADIELGCGNFGSVRQGVYRMR
  KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGG
  PLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDF
  GLSKALGADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPY
  KKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRACYYSL
  ASKVEGPPGSTQKAEAACA

• Sequence length: 619

Pathways

KEGG:

Ras signaling pathway
NF-kappa B signaling pathway
Natural killer cell mediated cytotoxicity
Th1 and Th2 cell differentiation
Th17 cell differentiation
T cell receptor signaling pathway
Yersinia infection
PD-L1 expression and PD-1 checkpoint pathway in cancer
Primary immunodeficiency

Reactome:

Translocation of ZAP-70 to Immunological synapse
Generation of second messenger molecules

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Alzheimer disease	Alzheimer`s Disease	rs63750215, rs28936379, rs63749851, rs63749884, rs28936380, rs63750048, rs63750579, rs63750264, rs63749964, rs63750671, rs281865161, rs63750066, rs63750399, rs63750734, rs63751039, rs63750973, rs63749810, rs63750643, rs193922916, rs63750306, rs63750590, rs63750526, rs63751235, rs661, rs63751037, rs63749885, rs63750231, rs63751229, rs63751272, rs63751223, rs63750391, rs63751163, rs281875357, rs63751141, rs63750082, rs121917807, rs63751399, rs63750265, rs63751144, rs63750886, rs63751068, rs121917808, rs63749891, rs63750083, rs63749824, rs63750577, rs267606983, rs63750218, rs63751287, rs63750900, rs145518263, rs63751475, rs63750450, rs63749805, rs63751278, rs63751106, rs63750004, rs63749806, rs63751024, rs63750248, rs63750779, rs63751139, rs63750219, rs63750298, rs63750687, rs63750851, rs1553268799, rs1561901881, rs1561905293, rs866101707, rs1566638673, rs63750009, rs1566656702, rs1566657804, rs1567885728, rs1568339995, rs1566630791, rs1555358260, rs63750964, rs1594998354, rs63751316	26993346
Autoimmune diseases	AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 2	rs41285370, rs869025224	26783323, 27288531
Hemophilia	Hemophilia, NOS	rs1178811105, rs2147483647, rs137852241, rs137852243, rs1927322453, rs1927322926, rs1166164399
Leukemia	Leukemia, Myelocytic, Acute	rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297, rs11978267, rs4132601	27903959
Lymphoma	Lymphoma	rs11540652, rs1592119138, rs1592123162, rs1599367044
Lymphoproliferative disorder	Lymphoproliferative Disorders	rs121908191, rs398122933, rs397514667, rs397514260, rs397514261, rs748418658, rs781593353
Nephrotic syndrome	Nephrotic Syndrome	rs876657369, rs121912601, rs121912602, rs876657370, rs121912603, rs121912604, rs121912605, rs121907900, rs121907901, rs28941778, rs587776576, rs28942089, rs587776577, rs28941777, rs121907910, rs1568296260, rs119473033, rs74315342, rs74315343, rs74315345, rs74315346, rs74315347, rs74315348, rs121434394, rs267606919, rs121912488, rs267606953, rs267606954, rs267606955, rs104886210, rs1591732280, rs1591750243, rs140511594, rs140781106, rs147972030, rs587776969, rs386833863, rs386833880, rs386833882, rs386833892, rs386833895, rs386833909, rs386833911, rs386833920, rs386833935, rs386833947, rs1555763603, rs398122978, rs398122979, rs398122980, rs369573693, rs398122981, rs398122982, rs398122983, rs200482683, rs730882194, rs180177201, rs587777552, rs587777553, rs775170915, rs749740335, rs12568913, rs530318579, rs786204583, rs786204708, rs786204632, rs138656762, rs797044992, rs797044994, rs797044995, rs864321632, rs864321687, rs864321688, rs864321633, rs869025495, rs869025541, rs869312747, rs145473779, rs757674160, rs869320695, rs138909849, rs869312984, rs1057516900, rs763818901, rs199506378, rs1057517164, rs1057516523, rs1057516414, rs778055996, rs1057516395, rs1057516747, rs1057516880, rs1057516680, rs778217926, rs1057519347, rs764587648, rs1060499703, rs121907903, rs769259446, rs1131692252, rs1131692253, rs1131692254, rs1131692255, rs1131692256, rs746887949, rs1131692235, rs1135402911, rs1135402912, rs1135402913, rs1554946480, rs1555331969, rs773173317, rs1555816634, rs775006954, rs1320543506, rs534522842, rs1272948499, rs1191455921, rs1291398331, rs1554939785, rs776016942, rs1031744496, rs748812981, rs755972674, rs1553312833, rs967339926, rs1462028977, rs1212702104, rs1167223941, rs762631237, rs1553316575, rs1553315173, rs1553316648, rs1553316611, rs780761368, rs368572297, rs1568070817, rs1321552081, rs1558108130, rs1558091788, rs1565707103, rs1558355124, rs1564622701, rs1351580598, rs1589475328, rs1589413498, rs1572255744, rs1572262824, rs761410195, rs1602413491, rs1590326226, rs375998390, rs570583897, rs369363545, rs201488687, rs1334894971, rs763782471, rs138047529, rs895782232, rs1572255047, rs1589433172, rs1589509476, rs1572277600, rs1572282458, rs1584675898, rs759043857, rs1853443391
Severe combined immunodeficiency disease	Severe Combined Immunodeficiency, Combined immunodeficiency, Severe combined immunodeficiency, atypical, Combined immunodeficiency due to ZAP70 deficiency	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	27288531, 8202713

Unknown
Disease name	Disease term	dbSNP ID	References
Antibody deficiency syndrome	Antibody Deficiency Syndrome		17767948
Autoimmune hemolytic anemia	Autoimmune hemolytic anemia
Bare lymphocyte syndrome	Bare Lymphocyte Syndrome		8202713
Bullous pemphigoid	Bullous pemphigoid
Colitis	Colitis
Eczema	Eczema
Eosinophilia	Eosinophilia
Immune thrombocytopenic purpura	Immune thrombocytopenic purpura
Immunologic deficiency syndromes	Immunologic Deficiency Syndromes		17767948
Lymphadenitis	Lymphadenitis
Lymphocytosis	Lymphocytosis
Omenn syndrome	Omenn Syndrome		8202713
Posterior cortical atrophy	Posterior cortical atrophy syndrome		26993346
T-cell immunodeficiency disorders	T cell immunodeficiency primary		8124727
Stomatitis	Stomatitis
Stroke	Cerebrovascular accident
Zap70 deficiency	ZAP70 deficiency		11412303, 8124727, 18509675, 8202713, 11123350