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
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Genomic context

Location:: Xq22.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
109.20211119	current	GRCh38.p13 (GCF_000001405.39)	X	NC_000023.11 (101349450..101390796, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (100604438..100645784, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Clinicopathologic and Prognostic Significance of Bruton's Tyrosine Kinase Expression in Diffuse Large B-Cell Lymphoma.
Title: Clinicopathologic and Prognostic Significance of Bruton's Tyrosine Kinase Expression in Diffuse Large B-Cell Lymphoma.
[Genetic study of an X-linked agammaglobulinemia pedigree caused by an BTK mutation].
Title: [Genetic study of an X-linked agammaglobulinemia pedigree caused by an BTK mutation].
Bruton's agammaglobulinemia tyrosine kinase (Btk) regulates TPAinduced breast cancer cell invasion via PLCgamma2/PKCbeta/NFkappaB/AP1dependent matrix metalloproteinase9 activation.
Title: Bruton's agammaglobulinemia tyrosine kinase (Btk) regulates TPA‑induced breast cancer cell invasion via PLCγ2/PKCβ/NF‑κB/AP‑1‑dependent matrix metalloproteinase‑9 activation.
Identification of 22 novel BTK gene variants in B cell deficiency with hypogammaglobulinemia.
Title: Identification of 22 novel BTK gene variants in B cell deficiency with hypogammaglobulinemia.
Aberrantly expressed Bruton's tyrosine kinase preferentially drives metastatic and stem cell-like phenotypes in neuroblastoma cells.
Title: Aberrantly expressed Bruton's tyrosine kinase preferentially drives metastatic and stem cell-like phenotypes in neuroblastoma cells.
Novel mutations in hyper-IgM syndrome type 2 and X-linked agammaglobulinemia detected in three patients with primary immunodeficiency disease.
Title: Novel mutations in hyper-IgM syndrome type 2 and X-linked agammaglobulinemia detected in three patients with primary immunodeficiency disease.
Bruton's tyrosine kinase in systemic lupus erythematosus.
Title: Bruton's tyrosine kinase in systemic lupus erythematosus.
BTK gatekeeper residue variation combined with cysteine 481 substitution causes super-resistance to irreversible inhibitors acalabrutinib, ibrutinib and zanubrutinib.
Title: BTK gatekeeper residue variation combined with cysteine 481 substitution causes super-resistance to irreversible inhibitors acalabrutinib, ibrutinib and zanubrutinib.
Acalabrutinib plus Obinutuzumab in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia.
Title: Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia.
BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy.
Title: BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy.

Submit: New GeneRIF Correction See all GeneRIFs (171)

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 2021-03-24) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-03-24) ClinGen Genome Curation PagePubMed

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: 426 organisms have orthologs with human gene BTK
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	TAS Traceable Author Statement more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables non-membrane spanning protein tyrosine kinase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables non-membrane spanning protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed
enables phosphatidylinositol-3,4,5-trisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phospholipase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables phospholipase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine/tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	EXP Inferred from Experiment more info	PubMed
enables protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed

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

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

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

ENSP00000308176.8, ENST00000308731.8

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_001287344.2 → 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_001287345.2 → 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 (4) 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

cl15255
Location:274 → 350

SH2; Src homology 2 (SH2) domain

cl21453
Location:346 → 476

PKc_like; Protein Kinases, catalytic domain