BTK (Bruton agammaglobulinemia tyrosine kinase)

Identity

Other names	AGMX1
	AT
	ATK
	BPK
	IMD1
	MGC126261
	MGC126262
	PSCTK1
	XLA
HGNC	BTK
Location	Xq22.1
Location_base_pair	Starts at 100491098 and ends at 100527838 bp from pter (hg18-Mar_2006).

Note	BTK (Bruton's tyrosine kinase) is a cytoplasmic non-receptor protein tyrosine kinase that is essential for B cell maturation in humans and mice.

DNA/RNA

Description	The gene spans over 36 kb and is composed of 19 exons, both in human and mouse.
Transcription	The transcript is about 2,573 bps in human and about 2,477 bps mice and has UTR regions in exons 1, 2 and 19.

Protein

	Table 1: BTK dependent receptor signaling cascades.
Description	The BTK protein is a 77 kDa protein of 659 amino acids. Translation of the BTK transcript starts at the ATG site that is located in exon 2 and ends in exon 19. The BTK protein is composed of an N-terminal Pleckstrin homology (PH) domain followed three protein interacting domains: Tec homology (TH) region, Src homology 3 (SH3) domain and SH2 domain. A tyrosine-kinase catalytic domain is located at the C-terminal end. Two tyrosine phosphorylation sites are located at the positions Y223 and Y551, which are located in the SH3 and kinase domain, respectively. Both phosphorylation sites play a pivotal role in the activation of BTK. Y551 is transphosphorylated by Syk (or Lyn) kinases which promotes the catalytic activity of BTK, with subsequent autophosphorylation at position Y223.
Expression	BTK is expressed in all cell lineages of the hematopoietic system, except for T cells. Therefore BTK expression is found in B lymphocytes, platelets, erythroid and myeloid cells (monocytes, macrophages, granulocytes and dendritic cells). Within the B cell lineage, BTK is already expressed in the earliest detectable B cell precursors, and expression is downregulated in plasma cells.
Localisation	The protein is predominantly localized in the cytoplasm. BTK activation upon receptor signaling results in translocation of BTK protein from the cytoplasm to the membrane. The membrane association of BTK is dependent on the interaction of its PH domain with PIP3 (phosphatidylinositol (3,4,5)-trisphosphate), which is a second messenger that is synthesized from PIP2 by PI3K (phosphoinositide-3 kinase). The translocation to the membrane brings the BTK protein in close proximity to the Lyn en Syk kinases that transphosphorylate BTK at tyrosine Y551. The E41K gain-of-function BTK mutant, in which the E41 residue is mutated in to a lysine residue, manifests increased membrane localization in quiescent cells, independent of PI3K activity, probably resulting from increased affinity for PIP2. Transforming activity is kinase-domain dependent and is potentiated by introduction of a second mutation at position Y223.
Function	BTK is a signaling mediator downstream of a variety of receptors in several different cell types (listed in Table 1), including the B cell receptor (BCR).
Homology	BTK belongs to the TEC family of cytoplasmic tyrosine kinases. This family is composed of TEC, BTK, TXK/RLK, ITK/EMT, and BMX. Btk is highly conserved between mouse and human.

Implicated in

Entity	Pre-B cell tumors
Note	Truncated BTK forms in human BCR-ABL1 + leukemia BTK is constitutively phosphorylated by the oncogenic BCR- ABL1 fusion product. Inhibition of BTK activity specifically induces apoptosis in BCR-ABL1+ leukemia cells to a similar extent as inhibition of BCR-ABL1 kinase activity itself. BCR-ABL1 cannot directly bind to full-length BTK, but induces the expression of a truncated BTK splice variant that acts as a linker between the two kinases. Thus, truncated BTK enables BCR-ABL1-dependent activation of full-length BTK, which initiates downstream survival signals and mimics pre-B cell receptor signaling. Defective expression of BTK in acute lymphoblastic leukemia (ALL) In an analysis of BTK protein and mRNA expression in infant B-lineage leukemia cells variable but often reduced levels of BTK expression was found. RT-PCR revealed the presence of aberrant transcripts which would encode BTK proteins with either a deleted or a truncated kinase domain. In infant pre-B MLL-AF4+ leukemia cells full-length BTK was detectable in only half of the cases, whereas in ALL cells harboring other fusion genes (including BCR-ABL1, E2A- PBX1 and TEL- AML1) full-length BTK was typically co-expressed with kinase-deficient variants. Thus, lack of BTK or expression of dominant-negative BTK splice variants in B cell precursor leukemia cells can inhibit differentiation beyond the pre-B cell stage and protect from radiation-induced apoptosis. Btk as a tumor suppressor in pre-B cell leukemia in mice Expression of the pre-B cell receptor (pre-BCR) leads to activation of the adaptor molecule Slp65 (also termed Bash or Blnk) and Btk. Spontaneous pre-B cell leukemia development in Slp65-deficient mice demonstrate that Slp65 acts as a tumor suppressor. Slp65 and Btk have a synergistic role in the developmental progression of large cycling into small resting pre-B cells. Btk/Slp65 double mutant mice have a dramatically increased pre-B cell tumor incidence (approximately 75%, 16 wk of age), as compared with Slp65 single deficient mice (<10%). Therefore, Btk cooperates with Slp65 as a tumor suppressor in pre-B cells. Moreover, transgenic expression of a constitutive active form of Btk, the E41K-Y223F mutant, prevented tumor formation in Btk/Slp65 double mutant mice, indicating that constitutive active Btk can substitute for Slp65 as a tumor suppressor. Using a kinase-inactive K430R-Btk mutant, it was shown that Btk exerts its tumor suppressor function in pre-B cells as an adaptor protein, independent of its catalytic activity. Furthermore, loss of Btk and Tec increases the tumor frequency in Eµ-myc transgenic mice, expressing the c-myc oncogenic transcription factor that promotes both proliferation and differentiation.
Entity	X-linked agammaglobulinemia (XLA).
Note	In 1993 BTK was identified as the gene defective in the human immunodeficiency disease X-linked agammaglobulinemia (XLA). The XLA disease, which was first described by Dr. O.C. Bruton in 1952, is characterized by protracted and recurrent bacterial infections. Clinical manifestations of XLA XLA Patients have less than 1% of the normal number of peripheral B cells. Serum levels of all Ig classes are very low due to the lack of plasma cells in the secondary lymphoid organs. In XLA patients, B cell development is almost completely arrested at the pre-B cell stage: the pre-B cell fraction mainly consists of small cells, suggesting that Btk is necessary for their proliferative expansion. Heterozygous female XLA carriers do not have clinical or immunological symptoms, but manifest a unilateral X chromosome inactivation in the peripheral blood B lymphocyte population, because of a selective disadvantage of cells that have the defective Btk gene on the active X chromosome. In contrast to XLA, Btk-deficiency in the mouse, termed X-linked immunodeficiency (xid), is associated with a very mild early B cell developmental block, but with impaired maturation and poor survival of peripheral B cells. XLA is a heterogeneous disease, even within single families and no correlation has been observed between the position of the mutation and phenotypic variables, such as age at time of diagnosis or severity of the clinical or immunological symptoms. Therefore, this heterogeneity might be related to other genetic or environmental factors. Mutations in BTK gene that cause XLA The BTK mutations that have been identified in XLA patients compromise BTK function either through gross structural changes (such as deletions or altered protein folding) or through specific loss of functionally relevant residues. Strikingly, none of the found unique missense mutations found in XLA patients is located in the SH3 domain of BTK, which harbors the Y223 tyrosine residue. An international registry for XLA (http://bioinf.uta.fi/BTKbase/) shows that mutations in all domains of the BTK gene cause the disease. Approximately 80-90% of the patients that have agammaglobulinemia patients have a deficiency of the BTK protein. The other about 15% of the agammaglobulinemia cases are caused by defects in autosomal genes such as the constant region of immunoglobulin (Ig) heavy chain, λ5, (IGLL), Igα (CD79a), Igβ (CD79b), or SLP65 (BLNK) resemble the clinical manifestation of XLA.

External links

	Nomenclature
HGNC	BTK   1133
Entrez_Gene	BTK  695  Bruton agammaglobulinemia tyrosine kinase
	Cards
Atlas	BTKID851chXq22
GeneCards	BTK
Ensembl	BTK [Search_View]   ENSG00000010671 [Gene_View]
Genatlas	BTK
GeneLynx	BTK
eGenome	BTK
euGene	695
	Genomic and cartography
GoldenPath	BTK  -  Xq22.1   chrX:100491098-100527838 -  Xq21.33-q22   [Description]    (hg18-Mar_2006)
Ensembl	BTK - Xq21.33-q22 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	BTK
	Gene and transcription
Genbank	AF153364 [ ENTREZ ]
Genbank	AF153755 [ ENTREZ ]
Genbank	AF153756 [ ENTREZ ]
Genbank	AF153757 [ ENTREZ ]
Genbank	AF153758 [ ENTREZ ]
RefSeq	NM_000061 [ SRS ]    NM_000061 [ ENTREZ ]
RefSeq	AC_000066 [ SRS ]    AC_000066 [ ENTREZ ]
RefSeq	AC_000155 [ SRS ]    AC_000155 [ ENTREZ ]
RefSeq	NC_000023 [ SRS ]    NC_000023 [ ENTREZ ]
RefSeq	NT_011651 [ SRS ]    NT_011651 [ ENTREZ ]
RefSeq	NW_001842387 [ SRS ]    NW_001842387 [ ENTREZ ]
RefSeq	NW_927715 [ SRS ]    NW_927715 [ ENTREZ ]
AceView	BTK AceView - NCBI
Unigene	Hs.159494 [ SRS ]    Hs.159494 [ NCBI ]     HS159494 [ spliceNest ]
Fast-db	12393 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q06187 [ SRS]    Q06187 [ EXPASY ]     Q06187 [ INTERPRO ]     Q06187 [ UNIPROT ]
Prosite	PS50003 PH_DOMAIN [ SRS ]    PS50003 PH_DOMAIN [ Expasy ]
Prosite	PS00107 PROTEIN_KINASE_ATP [ SRS ]    PS00107 PROTEIN_KINASE_ATP [ Expasy ]
Prosite	PS50011 PROTEIN_KINASE_DOM [ SRS ]    PS50011 PROTEIN_KINASE_DOM [ Expasy ]
Prosite	PS00109 PROTEIN_KINASE_TYR [ SRS ]    PS00109 PROTEIN_KINASE_TYR [ Expasy ]
Prosite	PS50001 SH2 [ SRS ]    PS50001 SH2 [ Expasy ]
Prosite	PS50002 SH3 [ SRS ]    PS50002 SH3 [ Expasy ]
Prosite	PS51113 ZF_BTK [ SRS ]    PS51113 ZF_BTK [ Expasy ]
Interpro	IPR001562 BTK [ SRS ]    IPR001562 BTK [ EBI ]
Interpro	IPR001849 PH [ SRS ]    IPR001849 PH [ EBI ]
Interpro	IPR011993 PH_type [ SRS ]    IPR011993 PH_type [ EBI ]
Interpro	IPR000719 Prot_kinase_core [ SRS ]    IPR000719 Prot_kinase_core [ EBI ]
Interpro	IPR017441 Protein_kinase_ATP_bd_CS [ SRS ]    IPR017441 Protein_kinase_ATP_bd_CS [ EBI ]
Interpro	IPR000980 SH2 [ SRS ]    IPR000980 SH2 [ EBI ]
Interpro	IPR001452 SH3 [ SRS ]    IPR001452 SH3 [ EBI ]
Interpro	IPR001245 Tyr_pkinase [ SRS ]    IPR001245 Tyr_pkinase [ EBI ]
Interpro	IPR008266 Tyr_pkinase_AS [ SRS ]    IPR008266 Tyr_pkinase_AS [ EBI ]
CluSTr	Q06187
Pfam	PF00779 BTK [ SRS ]    PF00779 BTK [ Sanger ]    pfam00779 [ NCBI-CDD ]
Pfam	PF00169 PH [ SRS ]    PF00169 PH [ Sanger ]    pfam00169 [ NCBI-CDD ]
Pfam	PF07714 Pkinase_Tyr [ SRS ]    PF07714 Pkinase_Tyr [ Sanger ]    pfam07714 [ NCBI-CDD ]
Pfam	PF00017 SH2 [ SRS ]    PF00017 SH2 [ Sanger ]    pfam00017 [ NCBI-CDD ]
Pfam	PF00018 SH3_1 [ SRS ]    PF00018 SH3_1 [ Sanger ]    pfam00018 [ NCBI-CDD ]
Smart	SM00107 BTK [EMBL]
Smart	SM00233 PH [EMBL]
Smart	SM00252 SH2 [EMBL]
Smart	SM00326 SH3 [EMBL]
Smart	SM00219 TyrKc [EMBL]
Prodom	PD000001 Prot_kinase[INRA-Toulouse]
Prodom	Q06187 BTK_HUMAN [ Domain structure ]   Q06187 BTK_HUMAN  [ sequences sharing at least 1 domain ]
Prodom	PD000001[INRA-Toulouse]
Prodom	Q06187 BTK_HUMAN [ Domain structure ]   Q06187 BTK_HUMAN  [ sequences sharing at least 1 domain ]
Prodom	PD000001[INRA-Toulouse]
Prodom	Q06187 BTK_HUMAN [ Domain structure ]   Q06187 BTK_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	Q06187
PDB	1AWW [ SRS ]    1AWW [ PdbSum ],   1AWW [ IMB ]   1AWW [ RSDB ]
PDB	1AWX [ SRS ]    1AWX [ PdbSum ],   1AWX [ IMB ]   1AWX [ RSDB ]
PDB	1B55 [ SRS ]    1B55 [ PdbSum ],   1B55 [ IMB ]   1B55 [ RSDB ]
PDB	1BTK [ SRS ]    1BTK [ PdbSum ],   1BTK [ IMB ]   1BTK [ RSDB ]
PDB	1BWN [ SRS ]    1BWN [ PdbSum ],   1BWN [ IMB ]   1BWN [ RSDB ]
PDB	1K2P [ SRS ]    1K2P [ PdbSum ],   1K2P [ IMB ]   1K2P [ RSDB ]
PDB	1QLY [ SRS ]    1QLY [ PdbSum ],   1QLY [ IMB ]   1QLY [ RSDB ]
PDB	2GE9 [ SRS ]    2GE9 [ PdbSum ],   2GE9 [ IMB ]   2GE9 [ RSDB ]
PDB	2Z0P [ SRS ]    2Z0P [ PdbSum ],   2Z0P [ IMB ]   2Z0P [ RSDB ]
HPRD	02248
	Protein Interaction databases
DIP	Q06187
IntAct	Q06187
	Polymorphism : SNP, mutations, diseases
OMIM	300300;307200    [ map ]
GENECLINICS	300300;307200
SNP	BTK [dbSNP-NCBI]
SNP	NM_000061 [SNP-NCI]
SNP	BTK [GeneSNPs - Utah]  BTK] [HGBASE - SRS]
HAPMAP	BTK [HAPMAP]
COSMIC	BTK [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	BTK
	General knowledge
Family Browser	BTK [UCSC Family Browser]
SOURCE	NM_000061
SMD	Hs.159494
SAGE	Hs.159494
Enzyme	2.7.10.2 [ Enzyme-Expasy ]   2.7.10.2 [ Enzyme-SRS ]   2.7.10.2 [ IntEnz-EBI ]   2.7.10.2 [ BRENDA ]   2.7.10.2 [ KEGG ]   2.7.10.2 [ WIT ]
GO	nucleotide binding [Amigo]  nucleotide binding
GO	protein tyrosine kinase activity [Amigo]  protein tyrosine kinase activity
GO	non-membrane spanning protein tyrosine kinase activity [Amigo]  non-membrane spanning protein tyrosine kinase activity
GO	protein binding [Amigo]  protein binding
GO	ATP binding [Amigo]  ATP binding
GO	ATP binding [Amigo]  ATP binding
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	protein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GO	protein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GO	intracellular signaling cascade [Amigo]  intracellular signaling cascade
GO	intracellular signaling cascade [Amigo]  intracellular signaling cascade
GO	mesoderm development [Amigo]  mesoderm development
GO	zinc ion binding [Amigo]  zinc ion binding
GO	induction of apoptosis by extracellular signals [Amigo]  induction of apoptosis by extracellular signals
GO	membrane [Amigo]  membrane
GO	kinase activity [Amigo]  kinase activity
GO	transferase activity [Amigo]  transferase activity
GO	calcium-mediated signaling [Amigo]  calcium-mediated signaling
GO	identical protein binding [Amigo]  identical protein binding
GO	membrane raft [Amigo]  membrane raft
GO	metal ion binding [Amigo]  metal ion binding
BIOCARTA	BCR Signaling Pathway    [Genes]
BIOCARTA	Fc Epsilon Receptor I Signaling in Mast Cells    [Genes]
BIOCARTA	Phosphoinositides and their downstream targets.    [Genes]
KEGG	B cell receptor signaling pathway
KEGG	Fc epsilon RI signaling pathway
PubGene	BTK
TreeFam	BTK
CTD	695 [Comparative ToxicoGenomics Database]
	Other databases
Other database	http://bioinf.uta.fi/BTKbase/
	Probes
Probe	BTK Related clones (RZPD - Berlin)
	PubMed
PubMed	145 Pubmed reference(s) in Entrez

Bibliography

Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia.

Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, Sparkes RS, Kubagawa H, Mohandas T, Quan S, et al.

Cell. 1993 Jan 29;72(2):279-90.

PMID 8425221

The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases.

Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, Hammarstrom L, Kinnon C, Levinsky R, Bobrow M, et al.

Nature. 1993 Jan 21;361(6409):226-33.

PMID 8380905

Defective B cell development and function in Btk-deficient mice.

Khan WN, Alt FW, Gerstein RM, Malynn BA, Larsson I, Rathbun G, Davidson L, Muller S, Kantor AB, Herzenberg LA, et al.

Immunity. 1995 Sep;3(3):283-99.

Activation of Bruton's tyrosine kinase (BTK) by a point mutation in its pleckstrin homology (PH) domain.

Li T, Tsukada S, Satterthwaite A, Havlik MH, Park H, Takatsu K, Witte ON.

Immunity. 1995 May;2(5):451-60.

PMID 7538439

Inactivation of Btk by insertion of lacZ reveals defects in B cell development only past the pre-B cell stage.

Hendriks RW, de Bruijn MF, Maas A, Dingjan GM, Karis A, Grosveld F.

EMBO J. 1996 Sep 16;15(18):4862-72.

PMID 8890160

Regulation of Btk function by a major autophosphorylation site within the SH3 domain.

Park H, Wahl MI, Afar DE, Turck CW, Rawlings DJ, Tam C, Scharenberg AM, Kinet JP, Witte ON.

Immunity. 1996 May;4(5):515-25.

PMID 8630736

BTK as a mediator of radiation-induced apoptosis in DT-40 lymphoma B cells.

Uckun FM, Waddick KG, Mahajan S, Jun X, Takata M, Bolen J, Kurosaki T.

Science. 1996 Aug 23;273(5278):1096-100.

PMID 8688094

Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide].

Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, Uckun FM.

J Biol Chem. 1999 Apr 2;274(14):9587-99.

PMID 10092645

Genetic defect in human X-linked agammaglobulinemia impedes a maturational evolution of pro-B cells into a later stage of pre-B cells in the B-cell differentiation pathway.

Nomura K, Kanegane H, Karasuyama H, Tsukada S, Agematsu K, Murakami G, Sakazume S, Sako M, Tanaka R, Kuniya Y, Komeno T, Ishihara S, Hayashi K, Kishimoto T, Miyawaki T.

Blood. 2000 Jul 15;96(2):610-7.

PMID 10887125

Impaired precursor B cell differentiation in Bruton's tyrosine kinase-deficient mice.

Middendorp S, Dingjan GM, Hendriks RW.

J Immunol. 2002 Mar 15;168(6):2695-703.

PMID 11884435

Defective expression of Bruton's tyrosine kinase in acute lymphoblastic leukemia.

Goodman PA, Wood CM, Vassilev AO, Mao C, Uckun FM.

Leuk Lymphoma. 2003 Jun;44(6):1011-8.

PMID 12854903

Bruton's tyrosine kinase cooperates with the B cell linker protein SLP-65 as a tumor suppressor in Pre-B cells.

Kersseboom R, Middendorp S, Dingjan GM, Dahlenborg K, Reth M, Jumaa H, Hendriks RW.

J Exp Med. 2003 Jul 7;198(1):91-8.

PMID 12835482

The pre-BCR checkpoint as a cell-autonomous proliferation switch.

Hendriks RW, Middendorp S.

Trends Immunol. 2004 May;25(5):249-56.

PMID 15099565

Mimicry of a constitutively active pre-B cell receptor in acute lymphoblastic leukemia cells.

Feldhahn N, Klein F, Mooster JL, Hadweh P, Sprangers M, Wartenberg M, Bekhite MM, Hofmann WK, Herzog S, Jumaa H, Rowley JD, Muschen M.

J Exp Med. 2005 Jun 6;201(11):1837-52.

PMID 15939795

Deficiency of Bruton's tyrosine kinase in B cell precursor leukemia cells.

Feldhahn N, Río P, Soh BN, Liedtke S, Sprangers M, Klein F, Wernet P, Jumaa H, Hofmann WK, Hanenberg H, Rowley JD, Müschen M.

Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13266-71.

PMID 16141323

B cell signaling and tumorigenesis.

Jumaa H, Hendriks RW, Reth M.

Annu Rev Immunol. 2005;23:415-45.

PMID 15771577

Tumor suppressor function of Bruton tyrosine kinase is independent of its catalytic activity.

Middendorp S, Zijlstra AJ, Kersseboom R, Dingjan GM, Jumaa H, Hendriks RW.

Blood. 2005 Jan 1;105(1):259-65.

PMID 15331445

Involvement of SLP-65 and Btk in tumor suppression and malignant transformation of pre-B cells.

Hendriks RW, Kersseboom R.

Semin Immunol. 2006 Feb;18(1):67-76.

PMID 16300960

BTKbase: the mutation database for X-linked agammaglobulinemia.

Valiaho J, Smith CI, Vihinen M.

Hum Mutat. 2006 Dec;27(12):1209-17.

PMID 16969761

Myc stimulates B lymphocyte differentiation and amplifies calcium signaling.

Habib T, Park H, Tsang M, de Alboran IM, Nicks A, Wilson L, Knoepfler PS, Andrews S, Rawlings DJ, Eisenman RN, Iritani BM.

J Cell Biol. 2007 Nov 19;179(4):717-31.

PMID 17998397

The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib.

Hantschel O, Rix U, Schmidt U, Bürckstummer T, Kneidinger M, Schutze G, Colinge J, Bennett KL, Ellmeier W, Valent P, Superti-Furga G

Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13283-8.

PMID 17684099

Bruton's tyrosine kinase prevents activation of the anti-apoptotic transcription factor STAT3 and promotes apoptosis in neoplastic B-cells and B-cell precursors exposed to oxidative stress.

Uckun F, Ozer Z, Vassilev A.

Br J Haematol. 2007 Feb;136(4):574-89.

PMID 17367410

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Contributor(s)

Written	03-2008	Rudi W Hendriks, Pieter Fokko van Loo
		Department of Pulmonary Medicine, Room Ee2251a, Erasmus MC Rotterdam, PO Box 2040

Citation

This paper should be referenced as such :

Hendriks RW, van Loo PF . BTK (Bruton agammaglobulinemia tyrosine kinase). Atlas Genet Cytogenet Oncol Haematol. March 2008 . URL : http://AtlasGeneticsOncology.org/Genes/BTKID851chXq22.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Oct 11 12:49:10 2008