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Updated November 2019

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Nomenclature

Short Name:
SYK
Full Name:
Tyrosine-protein kinase SYK
Alias:
  • DKFZp313N1010
  • EC 2.7.10.2
  • Spleen tyrosine kinase
  • SYK
  • FLJ25043
  • FLJ37489
  • Kinase Syk
  • KSYK

Classification

Type:
Protein-tyrosine kinase
Group:
TK
Family:
Syk
SubFamily:
NA
 
 

Specific Links

BioCarta Entry: bcr pathway
Entrez-Gene Entry: 6850
Entrez-Protein Entry: NP_003168
GeneCards Entry: SYK
KinBASE Entry: SYK
OMIM Entry: 600085
Pfam Entry: P43405
PhosphoNET Entry: P43405
Phosphosite Plus Entry: 662
Protein Data Bank Entry: 1A81
ScanSite Entry: P43405
Source Entry: SYK
UCSD-Nature Entry: A000040
UniProt Entry: P43405
Kinexus Products: SYK
Spleen protein-tyrosine kinase Y323 phosphosite-specific antibody AB-PK821
Spleen protein-tyrosine kinase Y525+Y526 phosphosite-specific antibody AB-PK823
SykSubtide - Syk protein kinase substrate peptide - Powder PE-01BJM85
Spleen protein-tyrosine kinase (F320-E326, human) pY323 phosphopeptide - Powder PE-04ALE99
Spleen protein-tyrosine kinase (E349-P355, human) pY352 phosphopeptide - Powder PE-04APT99
Spleen protein-tyrosine kinase (D522-Q529, human) pY525+pY526 phosphopeptide - Powder PE-04APU95
Spleen protein-tyrosine kinase (D522-K533, human) pY525+pY526+pT530 phosphopeptide - Powder PE-04AXF95

General Links

ClustalW2
GPS-Cuckoo
Human Protein Atlas
Kinase.com
Kinase Research
Kinasource
Kinomer
Netphorest
NetworKIN
Phosida
PhosphoElm
Protein Blast
ScanSite
String

Structure

Mol. Mass (Da):
72,066
# Amino Acids:
635
# mRNA Isoforms:
2
mRNA Isoforms:
72,066 Da (635 AA; P43405); 69,510 Da (612 AA; P43405-2)
4D Structure:
Interacts with RHOH, GAB2 and with NFAM1 (phosphorylated form). Interacts (via its SH2 domains) with CD79A (via its phosphorylated ITAM domain); the interaction stimulates SYK autophosphorylation and activation By similarity. Interacts (phosphorylated form) with SLA; the interaction may link it to CBL, leading to its destruction. Interacts with Epstein-Barr virus LMP2A. Interacts with FCRL3. Interacts (via the second SH2 domain) with USP25 (via C-terminus).
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
4FL1

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
15 107 SH2
168 259 SH2
371 628 TyrKc
371 631 Pkinase
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ Spleen protein-tyrosine kinase Y323 phosphosite-specific antibody AB-PK821
○ Spleen protein-tyrosine kinase Y525+Y526 phosphosite-specific antibody AB-PK823
○ SykSubtide - Syk protein kinase substrate peptide - Powder PE-01BJM85
○ Spleen protein-tyrosine kinase (F320-E326, human) pY323 phosphopeptide - Powder PE-04ALE99
○ Spleen protein-tyrosine kinase (E349-P355, human) pY352 phosphopeptide - Powder PE-04APT99
○ Spleen protein-tyrosine kinase (D522-Q529, human) pY525+pY526 phosphopeptide - Powder PE-04APU95
○ Spleen protein-tyrosine kinase (D522-K533, human) pY525+pY526+pT530 phosphopeptide - Powder PE-04AXF95
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K105, K116, K394, K402, K571.
Serine phosphorylated:

S178, S202, S295, S297, S316, S319, S350, S579.
Threonine phosphorylated:

T73-, T161, T345, T504, T530.
Tyrosine phosphorylated:

Y28, Y47, Y74, Y91, Y131-, Y203, Y244, Y296, Y323+, Y348+, Y352+, Y431, Y507, Y525+, Y526+, Y539, Y546, Y568, Y629, Y630, Y631.
Ubiquitinated:
K60, K509, K517.
 

Distribution

Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
  • adipose
    100

    1393

    41

    1286

  • adrenal
    1.1

    15

    19

    11

  • bladder
    23

    320

    14

    308

  • brain
    21

    286

    154

    1008

  • breast
    56

    777

    43

    547

  • cervix
    4

    49

    94

    48

  • colon
    25

    346

    59

    536

  • heart
    92

    1287

    51

    3097

  • intestine
    47

    648

    17

    543

  • kidney
    10

    133

    162

    161

  • liver
    6

    87

    38

    160

  • lung
    41

    576

    235

    628

  • lymphnode
    31

    430

    36

    688

  • ovary
    0.5

    7

    11

    7

  • pancreas
    9

    127

    37

    173

  • pituitary
    2

    28

    26

    23

  • prostate
    10

    140

    360

    1684

  • salivarygland
    19

    268

    25

    354

  • skeletalmuscle"
    3

    41

    137

    57

  • skin
    45

    627

    165

    552

  • spinalcord
    16

    218

    33

    339

  • spleen
    33

    465

    39

    620

  • stomach
    20

    278

    24

    374

  • testis
    17

    234

    26

    665

  • thymus
    35

    487

    35

    641

  • thyroid
    67

    928

    100

    852

  • tonsil
    35

    489

    38

    680

  • trachea
    15

    207

    26

    306

  • uterus
    10

    141

    25

    200

  • reticulocytes"
    7

    100

    56

    93

  • t-lymphocytes
    26

    363

    24

    369

  • b-lymphocytes
    49

    687

    46

    658

  • neutrophils
    22

    312

    96

    331

  • macrophages
    90

    1249

    109

    901

  • sperm
    11

    148

    61

    203

 

Evolution

Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
  • tableheader
    100

    100

    100
  • tableheader
    85.5

    85.7

    95
  • tableheader
    99.1

    99.5

    99
  • tableheader
    -

    -

    93
  • tableheader
    -

    -

    92
  • tableheader
    91.2

    94.4

    93
  • tableheader
    -

    -

    -
  • tableheader
    92.1

    94.5

    93
  • tableheader
    91

    93.7

    92
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    77.5

    87.4

    81
  • tableheader
    67.7

    79.1

    -
  • tableheader
    66

    77.5

    72
  • tableheader
    -

    -

    -
  • tableheader
    25.6

    39.9

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    26.5

    40.7

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Binding Proteins

Examples of known interacting proteins
hiddentext
No. Name – UniProt ID
1 CBL - P22681
2 VAV1 - P15498
3 FCGR2A - P12318
4 PTPN6 - P29350
5 CBLB - Q13191
6 CD79B - P40259
7 BLNK - Q8WV28
8 POU2AF1 - Q16633
9 CD22 - P20273
10 HCLS1 - P14317
11 DBNL - Q9UJU6
12 SLC4A1 - P02730
13 CSF2RB - P32927
14 TUBA4A - P68366
15 MS4A2 - Q01362
 

Regulation

Activation:
Phosphorylation of Tyr-348 and Tyr-352 enhances the binding, phosphorylation and activation of phospholipase C-gamma and the early phase of Ca(2+) mobilization via a phosphoinositide 3-kinase-independent pathway. Phosphorylation of Tyr-525 and Tyr-526 increases phosphotransferase activity.
Inhibition:
Phosphorylation of Tyr-131 inhibits interaction with Bcr. Phosphorylation of Tyr-323 negatively regulates B cell Ag receptor signaling and strongly dampens the Ca(2+) signal.
Synthesis:
NA
Degradation:
NA
 

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.
Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name UniProt ID (Human) Phosphosite Location Phosphosite Sequence Effect of Phosphorylation
SYK P43405 Y131 KENLIREYVKQTWNL -
SYK P43405 Y323 STVSFNPYEPELAPW +
LCK P06239 Y323 STVSFNPYEPELAPW +
LYN P07948 Y323 STVSFNPYEPELAPW +
SYK P43405 Y348 LPMDTEVYESPYADP +
LCK P06239 Y348 LPMDTEVYESPYADP +
LYN P07948 Y348 LPMDTEVYESPYADP +
SYK P43405 Y352 TEVYESPYADPEEIR +
LCK P06239 Y352 TEVYESPYADPEEIR +
LYN P07948 Y352 TEVYESPYADPEEIR +
SYK P43405 Y525 ALRADENYYKAQTHG +
SYK P43405 Y526 LRADENYYKAQTHGK +
 

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.
Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name UniProt ID (Human) Phosphosite Location Phosphosite Sequence Effect of Phosphorylation
BLNK Q8WV28 Y178 LLEDEADYVVPVEDN +
BLNK Q8WV28 Y189 VEDNDENYIHPTESS +
BLNK Q8WV28 Y72 SDDFDSDYENPDEHS +
BLNK Q8WV28 Y84 EHSDSEMYVMPAEEN +
BLNK Q8WV28 Y96 EENADDSYEPPPVEQ +
Btk Q06187 Y551 RYVLDDEYTSSVGSK +
Cbl P22681 Y700 EGEEDTEYMTPSSRP
Cbl P22681 Y731 QQIDSCTYEAMYNIQ
Cbl P22681 Y774 SENEDDGYDVPKPPV
DUSP3 (VHR) P51452 Y138 SPTLVIAYLMMRQKM +
DUSP3 (VHR) P51452 Y38 NEVTPRIYVGNASVA
FcGR2A P12318 Y281 LEETNNDYETADGGY
FcGR2A P12318 Y304 TDDDKNIYLTLPPND
FcGR2C P31995 Y287 PEETNNDYETADGGY
FcGR2C P31995 Y310 TDDDKNIYLTLPPND
GCET2 Q8N6F7 Y107 GNSAEEYYENVPCKA
GCET2 Q8N6F7 Y128 LGGTETEYSLLHMPS
HCA59 (C9orf78) Q9NZ63 Y147 KNAEDCLYELPENIR
HPK1 (MAP4K1) Q92918 Y381 SESSDDDYDDVDIPT +
HS1 P14317 Y378 EPEPENDYEDVEEMD
HS1 P14317 Y397 EDEPEGDYEEVLEPE +
ICLN (CLNS1A) P54105 Y214 TEDSIRDYEDGMEVD
IL15R alpha Q13261 Y227 AVSLLACYLKSRQTP
ITGB3 P05106 Y773 DTANNPLYKEATSTF
ITGB3 P05106 Y785 STFTNITYRGI____
LAB Q9GZY6 Y136 EDDDANSYENVLICK
LAB Q9GZY6 Y193 EDEESEDYQNSASIH
LAB Q9GZY6 Y233 EEDGEPDYVNGEVAA
LAT O43561 Y200 SMESIDDYVNVPESG
LAT O43561 Y220 SLDGSREYVNVSQEL
LCP2 Q13094 Y113 SSFEEDDYESPNDDQ +
LCP2 Q13094 Y128 DGEDDGDYESPNEEE +
LCP2 Q13094 Y145 PVEDDADYEPPPSND +
MAPRE1 Q15691 Y124 ANYDGKDYDPVAARQ
NEK9 Q8TD19 Y520 GLDSEEDYYTPQKVD
NUCKS1 Q9H1E3 Y26 SDDADEDYGRDSGPP
PIK3AP1 (BCAP) Q6ZUJ8 Y195 CGAETTVYVIVRCKL
PIK3AP1 (BCAP) Q6ZUJ8 Y419 GEEADAVYESMAHLS
PIK3AP1 (BCAP) Q6ZUJ8 Y444 PGCDEDLYESMAAFV
PIK3AP1 (BCAP) Q6ZUJ8 Y459 PAATEDLYVEMLQAS
PKCa (PRKCA) P17252 Y657 SDFEGFSYVNPQFVH
PKCb (PRKCB) P05771 Y662 NEFAGFSYTNPEFVI
PLCG1 P19174 Y771 IGTAEPDYGALYEGR
PLCG1 P19174 Y783 EGRNPGFYVEANPMP +
PLCG2 P16885 Y759 LYDVSRMYVDPSEIN +
POU2AF1 (BOB1) Q16633 Y245 EEEDSDAYALNHTLS
RHBG Q9H310-6 Y429 SPPDSQHYEDQVHWQ
SH3BP2 (3BP2) P78314 S225 SDMPRAHSFTSKGPG
SH3BP2 (3BP2) P78314 S278 PATPRRMSDPPLSTM
SH3BP2 (3BP2) P78314 Y174 YPTDNEDYEHDDEDD
SH3BP2 (3BP2) P78314 Y183 HDDEDDSYLEPDSPE +
SH3BP2 (3BP2) P78314 Y448 GDDSDEDYEKVPLPN +
SLC4A1 P02730 Y21 ENLEQEEYEDPDIPE
SLC4A1 P02730 Y359 AKPDSSFYKGLDLNG
SLC4A1 P02730 Y8 MEELQDDYEDMMEEN
SLC4A1 P02730 Y904 EEEGRDEYDEVAMPV
SNCA P37840 Y125 VDPDNEAYEMPSEEG
SNCA P37840 Y133 EMPSEEGYQDYEPEA
SNCA P37840 Y136 SEEGYQDYEPEA___
STAT5A P42229 Y964 LAKAVDGYVKPQIKQ
Syk P43405 Y131 KENLIREYVKQTWNL -
Syk P43405 Y323 STVSFNPYEPELAPW +
Syk P43405 Y348 LPMDTEVYESPYADP +
Syk P43405 Y352 TEVYESPYADPEEIR +
Syk P43405 Y525 ALRADENYYKAQTHG +
Syk P43405 Y526 LRADENYYKAQTHGK +
Tau P10636 Y17 MEDHAGTYGLGDRKD
TUBA1A Q71U36 Y432 MAALEKDYEEVGVDS
 

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Kinections GIF
Matrix Type:
Experimentally derived from alignment of 64 known protein substrate phosphosites and 41 peptides phosphorylated by recombinant Syk in vitro tested in-house by Kinexus.
Domain #:
1
 

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's
Based on in vitro and/or in vivo phosphorylation data
Compound Name KD, Ki or IC50 (nM) PubChem ID ChEMBL ID PubMed ID
Staurosporine IC50 = 100 pM 5279 19397322
CHEMBL1684800 IC50 = 1 nM 52938983 1684800 21353571
TTT-3002 IC50 < 6 nM
Lestaurtinib Kd = 9.5 nM 126565 22037378
AC1NS4N8 IC50 = 14 nM 5353854 101797 18077363
Syk Inhibitor IC50 = 14 nM 6419747 104279 12941345
CHEMBL249097 IC50 = 26 nM 25138012 249097 17600705
Staurosporine aglycone IC50 < 40 nM 3035817 281948
Syk Inhibitor II IC50 = 41 nM 16760670 15990316
K-252a; Nocardiopsis sp. IC50 > 50 nM 3813 281948 22037377
Bosutinib IC50 = 52 nM 5328940 288441 19039322
CHEMBL1240703 Kd = 64 nM 52945601 1240703 19654408
2hiw EC50 = 71 nM 10062694 18077425
N-Benzoylstaurosporine Kd = 88 nM 56603681 608533 18183025
Amgen TBK 1 inhibitor (Compound II) IC50 = 100 nM
AT9283 IC50 > 100 nM 24905142 19143567
R406 IC50 = 100 nM 11984591
Cdk1/2 Inhibitor III IC50 > 150 nM 5330812 261720 22037377
Gö6976 IC50 > 150 nM 3501 302449 22037377
SB218078 IC50 > 150 nM 447446 289422 22037377
SureCN373973 Kd < 150 nM 9818573 30678 19035792
SureCN5235694 IC50 = 200 nM 11785878 410295 18278858
Syk Inhibitor IV IC50 = 200 nM 10200390
IDR E804 IC50 > 250 nM 6419764 1802727 22037377
TWS119 IC50 > 250 nM 9549289 405759 22037377
Foretinib Kd = 280 nM 42642645 1230609 22037378
GSK-3 Inhibitor IX IC50 < 400 nM 5287844 409450
PD173955 Kd = 410 nM 447077 386051 22037378
Aloisine A IC50 = 500 nM 5326843 75680 22037377
Aloisine; RP106 IC50 = 500 nM 44350092 126343 22037377
Alsterpaullone IC50 = 500 nM 5005498 50894 22037377
TG101209 IC50 = 500 nM 16722832 17541402
AST-487 Kd = 600 nM 11409972 574738 18183025
K00596a IC50 < 600 nM 9549298 200027
KW2449 Kd = 670 nM 11427553 1908397 22037378
Momelotinib IC50 < 750 nM 25062766 19295546
BX795 IC50 < 800 nM 10077147 577784
CHEMBL307152 IC50 < 800 nM 11655119 307152 12824014
SureCN3470757 IC50 < 800 nM 11588244 375236
CHEMBL383899 IC50 = 887 nM 9549303 383899 18077363
BX517 IC50 > 900 nM 11161844 228654
Alsterpaullone; 2-Cyanoethyl IC50 > 1 µM 16760286 260138 22037377
ALX-270-403-M001 IC50 > 1 µM 22037377
Dasatinib IC50 > 1 µM 11153014 1421 22037377
Dovitinib IC50 > 1 µM 57336746 22037377
Gö6983 IC50 > 1 µM 3499 261491 22037377
GSK-3 Inhibitor XIII IC50 > 1 µM 6419766 359482 22037377
GSK-3b Inhibitor XI IC50 > 1 µM 10020713 272629 22037377
IKK-2 Inhibitor IV IC50 > 1 µM 9903786 257167 22037377
Indirubin-3′-monoxime IC50 > 1 µM 5326739 22037377
IPA-3 IC50 < 1 µM 521106 472940
MK5108 IC50 > 1 µM 24748204 20053775
NU6140 IC50 > 1 µM 10202471 1802728 22037377
Ponatinib IC50 > 1 µM 24826799 20513156
Silmitasertib IC50 > 1 µM 24748573 21174434
SNS314 IC50 > 1 µM 16047143 514582 18678489
SU11652 IC50 > 1 µM 24906267 13485 22037377
Wyeth PDK1 Inhibitor Compound 1 IC50 = 1 µM
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
Pelitinib Kd = 1.2 µM 6445562 607707 15711537
Hesperadin Kd < 1.25 µM 10142586 514409 19035792
JNJ-7706621 Kd = 1.3 µM 5330790 191003 18183025
NVP-TAE684 Kd = 1.3 µM 16038120 509032 22037378
Tozasertib Kd = 1.8 µM 5494449 572878 18183025
Crizotinib Kd = 2.5 µM 11626560 601719 22037378
Pyrrolo-pyrimidone; 17 IC50 = 2.5 µM 16119021 461140 18945615
SureCN5302803 Kd > 2.5 µM 24788740 19035792
Syk Inhibitor III IC50 = 2.5 µM 672296 596380 16837624
TG101348 Kd = 2.7 µM 16722836 1287853 22037378
Doramapimod IC50 > 3 µM 156422 103667
KIN 112 IC50 > 3 µM
Ruboxistaurin IC50 > 3 µM 153999 91829
SureCN4875304 IC50 > 3.5 µM 46871765 20472445
CHEMBL493169 Ki > 4 µM 44219632 493169 19414255
CHEMBL494221 Ki > 4 µM 5328125 494221 19414255
GSK650394A IC50 < 4 µM 25022668 558642
JNJ-28871063 IC50 > 4 µM 17747413 17975007
Pyrimidylpyrrole, 11e Ki > 4 µM 11634725 583042 19827834
BMS-690514 IC50 = 4.3 µM 11349170 21531814
RAF265 Kd = 4.4 µM 11656518 558752 22037378
(5Z)-7-Oxozeaenol IC50 > 4.5 µM 1077979
GSK429286 IC50 > 4.5 µM 11373846 375312
GW441756 hydrochloride IC50 > 4.5 µM 16219400
JNKIN7 IC50 > 4.5 µM 57340685
Purvalanol B IC50 > 4.5 µM 448991 23254
BI2536 Kd = 4.7 µM 11364421 513909 22037378
Pazopanib Kd = 4.7 µM 10113978 477772 22037378
 

Disease Linkage

General Disease Association:

Bone disorder and infectious disorder
Specific Diseases (Non-cancerous):

Cherubism (CRBM); Mycobacterium Abscessus
Comments:
Syk is a protein-tyrosine kinase that is widely expressed in hematopoietic cells, and is involved in coupling activated immunoreceptors that mediate diverse cellular responses.
 
Comments:
SYK appears to be an oncoprotein (OP) and a tumour suppressor protein (TSP). Syk is an oncoprotein in retinoblastoma, which is upregulated and is required for tumour cell survival. It is a potential tumour suppressor in human breast cancer. SYK is also an important regulator in acute myeloid leukemia.
 
Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Breast epithelial carcinomas (%CFC= -69, p<0.0009); Classical Hodgkin lymphomas (%CFC= -74, p<0.001); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +419, p<0.003); and Ovary adenocarcinomas (%CFC= +93, p<0.021) The COSMIC website notes an up-regulated expression score for SYK in diverse human cancers of 294, which is 0.6-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 52 for this protein kinase in human cancers was 0.9-fold of the average score of 60 for the human protein kinases.
Mutagenesis Experiments:

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis.
Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.09 % in 25821 diverse cancer specimens. This rate is only 20 % higher than the average rate of 0.075 % calculated for human protein kinases in general.
Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.57 % in 805 skin cancers tested; 0.44 % in 1152 large intestine cancers tested; 0.29 % in 589 stomach cancers tested; 0.16 % in 1270 liver cancers tested; 0.13 % in 1941 lung cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: A330T (8).
Comments:
Only 2 deletions, 4 insertions, and no complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
SYK
OMIM Entry:
600085
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