BTK Bruton tyrosine kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: BTKprovided by HGNC
Official Full Name: Bruton tyrosine kinaseprovided by HGNC
Primary source: HGNC:HGNC:1133
See related: Ensembl:ENSG00000010671 MIM:300300
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AT; ATK; BPK; XLA; IMD1; AGMX1; IGHD3; PSCTK1
Summary: 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]
Expression: Biased expression in lymph node (RPKM 25.2), spleen (RPKM 18.4) and 13 other tissues See more
Orthologs: mouse all

Genomic context

Location:: Xq22.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	X	NC_000023.11 (101349447..101390796, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (100604435..100641212, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ROR1/CD19 complex effectively substitutes for BCR-BTK signaling to promote activation and growth of mantle cell lymphoma cells
Title: Cutting Edge: ROR1/CD19 Receptor Complex Promotes Growth of Mantle Cell Lymphoma Cells Independently of the B Cell Receptor-BTK Signaling Pathway.
In the resting state, the BTK PH domain binds to the activation loop face of the kinase domain and allosterically alters key sites within the kinase domain.
Title: Lipid-targeting pleckstrin homology domain turns its autoinhibitory face toward the TEC kinases.
PIP3-mediated dimerization of Btk at the cell membrane is a critical step in Btk activation.
Title: Structural mechanism for Bruton's tyrosine kinase activation at the cell membrane.
A novel Bruton tyrosine kinase gene variation was found in an adult with X-linked agammaglobulinemia during blood cross-matching prior to surgical operation.
Title: A novel Bruton tyrosine kinase gene variation was found in an adult with X-linked agammaglobulinemia during blood cross-matching prior to surgical operation.
Re-expression of SHP1 in GCB DBLCL cells reduces SYK, BLNK, and GSK3 phosphorylation.
Title: Inhibition of SYK or BTK augments venetoclax sensitivity in SHP1-negative/BCL-2-positive diffuse large B-cell lymphoma.
BTK inhibition abrogated CSF1 and IL-10 production in MCL cells.
Title: CSF1R and BTK inhibitions as novel strategies to disrupt the dialog between mantle cell lymphoma and macrophages.
The pleiotropic roles of BTK in cancer have been proposed.
Title: BTK: a two-faced effector in cancer and tumour suppression.
Allele-Specific BTK Expression in B Cells and Monocytes.
Title: Damaging BTK Variant Demonstrated by Carrier, Allele-Specific BTK Expression in B Cells and Monocytes.
REVIEW: Role of Bruton's Tyrosine Kinase in Immune Cell Signaling and Systemic Autoimmunity
Title: The Role of Bruton's Tyrosine Kinase in Immune Cell Signaling and Systemic Autoimmunity.
Our findings show that the BTK(Cys481Ser) mutation drives ibrutinib resistance in MYD88-mutated WM and ABC DLBCL cells through reactivation of ERK1/2 and can confer a protective effect on BTK(WT) cells through a paracrine mechanism.
Title: BTK<sup>Cys481Ser</sup> drives ibrutinib resistance via ERK1/2 and protects BTK<sup>wild-type</sup> MYD88-mutated cells by a paracrine mechanism.

Submit: New GeneRIF Correction See all GeneRIFs (153)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
X-linked agammaglobulinemia MedGen: C0221026 OMIM: 300755 GeneReviews: X-Linked Agammaglobulinemia	Compare labs
X-linked agammaglobulinemia with growth hormone deficiency MedGen: C0472813 OMIM: 307200 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2012-05-17) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2012-05-17) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	A cell-based bimolecular fluorescence complementation assay demonstrates that HIV-1 Nef interacts with the Tec family members Bmx, Btk, and Itk, but not with Tec or Txk in 293T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH35738 (e-PCR)
- UniSTS:49927

GDB:607597 (e-PCR)
- UniSTS:158239

RH70566 (e-PCR)
- UniSTS:76605

RH93533 (e-PCR)
- UniSTS:84045

BTK_4321 (e-PCR)
- UniSTS:464467

RH70553 (e-PCR)
- UniSTS:7531

Btk (e-PCR), detects polymorphism
- UniSTS:141197

DXS178 (e-PCR)
- UniSTS:147598

G44349 (e-PCR)
- UniSTS:95136

GDB:376892 (e-PCR)
- UniSTS:98978

RH80171 (e-PCR)
- UniSTS:85182

DXS7424 (e-PCR)
- UniSTS:99310

GDB:555566 (e-PCR)
- UniSTS:157683

GDB:555569 (e-PCR)
- UniSTS:157684

Homology

Homologs of the BTK gene: The BTK gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 323 organisms have orthologs with human gene BTK
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	TAS Traceable Author Statement more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
non-membrane spanning protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed
phosphatidylinositol-3,4,5-trisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein tyrosine kinase activity	EXP Inferred from Experiment more info	PubMed
protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
B cell activation	TAS Traceable Author Statement more info	PubMed
B cell affinity maturation	IEA Inferred from Electronic Annotation more info
B cell receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
Fc-epsilon receptor signaling pathway	TAS Traceable Author Statement more info
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
I-kappaB kinase/NF-kappaB signaling	IEA Inferred from Electronic Annotation more info
MyD88-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
adaptive immune response	TAS Traceable Author Statement more info	PubMed
apoptotic signaling pathway	TAS Traceable Author Statement more info	PubMed
calcium-mediated signaling	TAS Traceable Author Statement more info	PubMed
cell maturation	IEA Inferred from Electronic Annotation more info
cellular response to interleukin-7	IEA Inferred from Electronic Annotation more info
cellular response to molecule of fungal origin	IEA Inferred from Electronic Annotation more info
cellular response to reactive oxygen species	IEA Inferred from Electronic Annotation more info
histamine secretion by mast cell	IEA Inferred from Electronic Annotation more info
innate immune response	TAS Traceable Author Statement more info	PubMed
intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
mesoderm development	TAS Traceable Author Statement more info	PubMed
negative regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of cytokine production	IEA Inferred from Electronic Annotation more info
peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of B cell differentiation	TAS Traceable Author Statement more info	PubMed
positive regulation of NF-kappaB transcription factor activity	TAS Traceable Author Statement more info	PubMed
positive regulation of type I hypersensitivity	IEA Inferred from Electronic Annotation more info
positive regulation of type III hypersensitivity	IEA Inferred from Electronic Annotation more info
protein autophosphorylation	IEA Inferred from Electronic Annotation more info
protein phosphorylation	TAS Traceable Author Statement more info	PubMed
regulation of B cell apoptotic process	TAS Traceable Author Statement more info	PubMed
regulation of B cell cytokine production	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	TAS Traceable Author Statement more info	PubMed
cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
cytosol	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info	PubMed
mast cell granule	IEA Inferred from Electronic Annotation more info
membrane raft	IDA Inferred from Direct Assay more info	PubMed
nucleus	TAS Traceable Author Statement more info	PubMed
perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: tyrosine-protein kinase BTK

Names: B-cell progenitor kinase; Bruton agammaglobulinemia tyrosine kinase; Bruton's tyrosine kinase; agammaglobulinaemia tyrosine kinase; dominant-negative kinase-deficient Brutons tyrosine kinase; truncated Bruton agammaglobulinemia tyrosine kinase; tyrosine-protein kinase BTK isoform (lacking exon 13 to 17); tyrosine-protein kinase BTK isoform (lacking exon 14)

NP_000052.1

EC 2.7.10.2

NP_001274273.1

EC 2.7.10.2

NP_001274274.1

EC 2.7.10.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009616.1 RefSeqGene

Range

429..41778

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_128

mRNA and Protein(s)

NM_000061.3 → NP_000052.1 tyrosine-protein kinase BTK isoform 1

See identical proteins and their annotated locations for NP_000052.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AK057105, BC109079, DA619542, DB636737

Consensus CDS

CCDS14482.1

UniProtKB/Swiss-Prot

Q06187

UniProtKB/TrEMBL

Q5JY90

Related

ENSP00000308176.7, ENST00000308731.7

Conserved Domains (4) summary

cd05113
Location:397 → 652

PTKc_Btk_Bmx; Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome

cd10397
Location:274 → 379

SH2_Tec_Btk; Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk)

cd11906
Location:217 → 271

SH3_BTK; Src Homology 3 domain of Bruton's tyrosine kinase

cd01238
Location:6 → 166

PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain
NM_001287344.1 → NP_001274273.1 tyrosine-protein kinase BTK isoform 3

See identical proteins and their annotated locations for NP_001274273.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and CDS, and represents the use of an alternate promoter, compared to variant 1. The resulting protein (isoform 3) has a longer N-terminus, compared to isoform 1.

Source sequence(s)

AK309851, AV733045, DB331677, DB636737

Consensus CDS

CCDS76003.1

UniProtKB/Swiss-Prot

Q06187

Related

ENSP00000483570.1, ENST00000621635.4

Conserved Domains (6) summary

cd05113
Location:431 → 686

PTKc_Btk_Bmx; Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome

cd10397
Location:308 → 413

SH2_Tec_Btk; Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk)

cd11906
Location:251 → 305

SH3_BTK; Src Homology 3 domain of Bruton's tyrosine kinase

cd01238
Location:40 → 200

PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain

pfam00169
Location:38 → 167

PH; PH domain

pfam07714
Location:436 → 685

Pkinase_Tyr; Protein tyrosine kinase
NM_001287345.1 → NP_001274274.1 tyrosine-protein kinase BTK isoform 2

See identical proteins and their annotated locations for NP_001274274.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate exon in the 5' UTR and lacks several exons in the 3' CDS compared to variant 1. The resulting protein (isoform 2) is shorter compared to isoform 1.

Source sequence(s)

AK057105, AL035422, AU107296, BC109079, DA619542

Consensus CDS

CCDS76002.1

UniProtKB/Swiss-Prot

Q06187

UniProtKB/TrEMBL

Q5JY90

Related

ENSP00000361971.1, ENST00000372880.5

Conserved Domains (6) summary

cd11906
Location:217 → 271

SH3_BTK; Src Homology 3 domain of Bruton's tyrosine kinase

cd01238
Location:6 → 166

PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain

pfam00169
Location:4 → 133

PH; PH domain

pfam07714
Location:346 → 475

Pkinase_Tyr; Protein tyrosine kinase

cl15255
Location:274 → 350

SH2; Src homology 2 (SH2) domain

cl21453
Location:346 → 476

PKc_like; Protein Kinases, catalytic domain