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The protein encoded by this gene plays a crucial role in B-cell development. Mutations in this gene cause X-linked agammaglobulinemia type 1, which is an immunodeficiency characterized by the failure to produce mature B lymphocytes, and associated with a failure of Ig heavy chain rearrangement. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]
BTK (Bruton Tyrosine Kinase) is a Protein Coding gene. Diseases associated with BTK include Agammaglobulinemia, X-Linked and Isolated Growth Hormone Deficiency, Type Iii, With Agammaglobulinemia. Among its related pathways are Antigen processing-Cross presentation and B cell receptor signaling pathway (KEGG). Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is TEC.
Bruton's Tyrosine Kinase (BTK) is member of the Tec family that is critically important for the growth, differentiation and activation of myeloid-, mast- and B-cells. BTK is initially activated by membrane localization which is stimulated by the generation of PIP3.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IEA,TAS | 11913944 |
GO:0004715 | non-membrane spanning protein tyrosine kinase activity | IEA,TAS | 19290921 |
GO:0005515 | protein binding | IEA,IPI | 8892607 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | TAS | 19290921 |
GO:0005737 | cytoplasm | TAS | 15046600 |
GO:0005829 | cytosol | IDA,TAS | 19290921 |
GO:0005886 | plasma membrane | IDA,TAS | 19290921 |
GO:0016020 | membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | PEDF Induced Signaling |
MIF Mediated Glucocorticoid Regulation
.94
MIF Regulation of Innate Immune Cells
.94
PEDF Induced Signaling
.73
all-trans-Retinoic Acid Signaling in Brain
.71
RAR-Gamma-RXR-Alpha Degradation
.62
IL-6 Pathway
.61
|
NFAT Signaling and Lymphocyte Interactions
.57
PGC1Alpha Pathway
.51
STAT3 Pathway
.47
Endothelin-1 Signaling Pathway
.46
Glucocorticoid Receptor Signaling
.43
|
2 | Activated TLR4 signalling | ||
3 | TGF-Beta Pathway |
MAPK Family Pathway
.60
TGF-Beta Pathway
.60
JAK-STAT Pathway
.57
|
JNK Pathway
.51
Regulation of eIF4 and p70S6K
.43
SOCS Pathway
.41
|
4 | Immune response Fc epsilon RI pathway |
Immune response BCR pathway
.44
Immune response Fc epsilon RI pathway
.44
|
|
5 | Diseases associated with the TLR signaling cascade |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001805 | positive regulation of type III hypersensitivity | IEA | -- |
GO:0001812 | positive regulation of type I hypersensitivity | IEA | -- |
GO:0001818 | negative regulation of cytokine production | IEA | -- |
GO:0002250 | adaptive immune response | TAS | 19290921 |
GO:0002344 | B cell affinity maturation | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
ibrutinib | Approved | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
Zanubrutinib | Approved, Investigational | Pharma | Target, inhibitor | 33 | ||
Vincristine | Approved, Investigational | Pharma | Microtubule disrupter,antitumor agent | 1073 | ||
Tyrosine | Approved, Investigational | Nutra | 1044 | |||
Acalabrutinib | Approved, Investigational | Pharma | Target, inhibitor | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 | |||
(-)-Terreic acid |
|
121-40-4 |
|
|
||
PCI 29732 |
|
330786-25-9 |
|
|
Compound | Action | Cas Number |
---|---|---|
(-)-Terreic acid | Selective inhibitor of BTK | 121-40-4 |
LFM-A13 | Potent, selective BTK inhibitor | 62004-35-7 |
PCI 29732 | Potent BTK inhibitor | 330786-25-9 |
Compound | Action | Cas Number |
---|---|---|
AVL-292 | Btk inhibitor | 1202757-89-8 |
Btk inhibitor 1 R enantiomer | 1022150-12-4 | |
CGI-1746 | Btk inhibitor | 910232-84-7 |
CNX-774 | BTK inhibitor, orally active, irreversible and selective | 1202759-32-7 |
LFM-A13 | BTK-specific tyrosine kinase inhibitor | 244240-24-2 |
ONO-4059 | Highly potent and selective oral Btk inhibitor | 1351635-67-0 |
PCI-32765 (Ibrutinib) | Bruton's tyrosine kinase (BTK) inhibitor | 936563-96-1 |
PCI-32765 Racemate | BTK inhibitor | 936563-87-0 |
RN486 | Btk inhibitor,potent and selective | 1242156-23-5 |
ExUns: | 1a | · | 1b | · | 1c | ^ | 2 | ^ | 3 | ^ | 4a | · | 4b | ^ | 5a | · | 5b | · | 5c | ^ | 6 | ^ | 7 | ^ | 8a | · | 8b | ^ | 9 | ^ | 10a | · | 10b | ^ | 11 | ^ | 12a | · | 12b | ^ | 13 | ^ | 14a | · | 14b | · | 14c | ^ | 15 | ^ | 16 | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP3: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP8: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP9: | - | - | - | - | - | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||
SP10: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP11: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP12: |
ExUns: | 17 | ^ | 18 | ^ | 19a | · | 19b | · | 19c | ^ | 20a | · | 20b | ^ | 21a | · | 21b | · | 21c | · | 21d | · | 21e |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||
SP3: | - | - | |||||||||||||||||||||
SP4: | - | - | |||||||||||||||||||||
SP5: | |||||||||||||||||||||||
SP6: | - | - | - | ||||||||||||||||||||
SP7: | |||||||||||||||||||||||
SP8: | - | - | |||||||||||||||||||||
SP9: | |||||||||||||||||||||||
SP10: | |||||||||||||||||||||||
SP11: | |||||||||||||||||||||||
SP12: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | BTK 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | BTK 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | BTK 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | BTK 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | BTK 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Btk 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Btk 30 |
|
||
Chicken (Gallus gallus) |
Aves | BTK 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | BTK 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | btk 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | btk 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | Btk29A 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | spe-8 32 |
|
|
|
F09G2.1 32 |
|
|
|||
kin-24 32 |
|
|
|||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 0X pos | Variation | AA Info | Type |
---|---|---|---|---|---|
632728 | Pathogenic: X-linked agammaglobulinemia; X-linked agammaglobulinemia with growth hormone deficiency | 101,374,594(-) | ATCT/A | INFRAME_DELETION | |
636441 | Likely Pathogenic: not provided | 101,356,780(-) | T/A | INTRON_VARIANT | |
636572 | Likely Pathogenic: not provided | 101,353,919(-) | T/G | MISSENSE_VARIANT | |
636806 | Uncertain Significance: X-linked agammaglobulinemia with growth hormone deficiency; not provided | 101,353,259(-) | G/A | MISSENSE_VARIANT | |
636945 | Likely Pathogenic: not provided | 101,374,839(-) | T/C | INTRON_VARIANT |