Bruton tyrosine kinase (BTK) is a protein tyrosine kinase that is expressed in B cells, macrophages, and neutrophils. The protein encoded by this gene binds to BTK and downregulates BTK's kinase activity. In addition, the encoded protein disrupts BTK-mediated calcium mobilization and negatively regulates the activation of nuclear factor-kappa-B-driven transcription. This gene h... See more...

Aliases for IBTK Gene

Aliases for IBTK Gene

  • Inhibitor Of Bruton Tyrosine Kinase 2 3 4 5
  • Bruton Agammaglobulinemia Tyrosine Kinase Inhibitor 2 3
  • BTBD26 2 3
  • BTKI 3 4
  • Inhibitor Of Bruton Agammaglobulinemia Tyrosine Kinase 2
  • Inhibitor Of Bruton'S Tyrosine Kinase-Alpha 3
  • Inhibitor Of Bruton'S Tyrosine Kinase-Gamma 3
  • Inhibitor Of Bruton'S Tyrosine Kinase-Beta 3
  • BTK-Binding Protein 3
  • DKFZP564B116 2
  • KIAA1417 4
  • IBTK 5
  • IBtk 4

External Ids for IBTK Gene

Previous HGNC Symbols for IBTK Gene

  • BTKI

Previous GeneCards Identifiers for IBTK Gene

  • GC06M082833
  • GC06M082875
  • GC06M082936
  • GC06M082879
  • GC06M080097

Summaries for IBTK Gene

Entrez Gene Summary for IBTK Gene

  • Bruton tyrosine kinase (BTK) is a protein tyrosine kinase that is expressed in B cells, macrophages, and neutrophils. The protein encoded by this gene binds to BTK and downregulates BTK's kinase activity. In addition, the encoded protein disrupts BTK-mediated calcium mobilization and negatively regulates the activation of nuclear factor-kappa-B-driven transcription. This gene has a pseudogene on chromosome 18. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

GeneCards Summary for IBTK Gene

IBTK (Inhibitor Of Bruton Tyrosine Kinase) is a Protein Coding gene. Diseases associated with IBTK include Agammaglobulinemia and Keratoconus. Among its related pathways are B cell receptor signaling pathway (KEGG). Gene Ontology (GO) annotations related to this gene include protein kinase binding and protein tyrosine kinase inhibitor activity.

UniProtKB/Swiss-Prot Summary for IBTK Gene

  • Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization and NF-kappa-B-driven transcription.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for IBTK Gene

Genomics for IBTK Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for IBTK Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J082244 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 260.6 +0.8 798 4.7 SP1 IKZF1 MYC ZNF600 SIX5 SSRP1 ZNF580 ZNF592 KLF9 POLR2A IBTK HSALNG0051552 lnc-TPBG-8 RNU6-130P TPBG PGM3 piR-38051-243 TENT5A
GH06J082259 Enhancer 1.1 Ensembl ENCODE 18.1 -13.3 -13298 4.9 ZNF654 ZNF600 JUND ZNF580 ATF2 ZNF10 ZSCAN16 ZIC2 FEZF1 ZNF639 DOP1A UBE3D PGM3 IBTK TPBG ENSG00000220537 lnc-IBTK-4 HSALNG0051552
GH06J082206 Enhancer 1 Ensembl ENCODE 16.6 +41.6 41553 1.2 NCOR1 IKZF1 ZNF592 NFIC REST FEZF1 MBD2 ARNT FOXA2 NBN IBTK RF00026-917 lnc-FAM46A-5 TENT5A
GH06J081936 Enhancer 1.4 FANTOM5 Ensembl ENCODE 10.6 +308.0 307960 6 MYC NCOR1 JUND ZNF592 ATF2 CEBPA ZNF10 ATF3 BRCA1 YY1 TENT5A IBTK lnc-TPBG-3 piR-33605-399 lnc-FAM46A-4 LINC02542
GH06J082270 Enhancer 0.6 Ensembl 16.5 -23.7 -23746 1 ZNF654 REST ZNF592 CTCF RAD21 CUX1 RFX5 SMC3 ARID3A ZNF660 LOC105377874 lnc-TPBG-2 IBTK TPBG piR-42491-192
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IBTK on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IBTK

Top Transcription factor binding sites by QIAGEN in the IBTK gene promoter:
  • AP-1
  • Bach1
  • CBF(2)
  • CBF-A
  • CBF-B
  • CP1A
  • NF-Y
  • NF-YA
  • NF-YB
  • Pax-3

Genomic Locations for IBTK Gene

Latest Assembly
chr6:82,169,986-82,247,754
(GRCh38/hg38)
Size:
77,769 bases
Orientation:
Minus strand

Previous Assembly
chr6:82,879,704-82,957,461
(GRCh37/hg19 by Entrez Gene)
Size:
77,758 bases
Orientation:
Minus strand

chr6:82,879,700-82,957,471
(GRCh37/hg19 by Ensembl)
Size:
77,772 bases
Orientation:
Minus strand

Alternative Locations (GRCh38/hg38)

  • chr6(PATCHES):29,599-107,356 (-)

Genomic View for IBTK Gene

Genes around IBTK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IBTK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IBTK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IBTK Gene

Proteins for IBTK Gene

  • Protein details for IBTK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P2D0-IBTK_HUMAN
    Recommended name:
    Inhibitor of Bruton tyrosine kinase
    Protein Accession:
    Q9P2D0
    Secondary Accessions:
    • Q2QKU2
    • Q2QKU3
    • Q2QKU4
    • Q5TFD7
    • Q5TFD9
    • Q8IUQ9
    • Q8IUY7
    • Q8TAI4
    • Q9HBI8
    • Q9Y3T8

    Protein attributes for IBTK Gene

    Size:
    1353 amino acids
    Molecular mass:
    150528 Da
    Quaternary structure:
    • Interacts with the PH domain of BTK. Isoform 2 does not interact with BTK.
    SequenceCaution:
    • Sequence=AAG27170.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; Sequence=BAA92655.2; Type=Erroneous initiation; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 2]: Due to a partial intron retention.
    • [Isoform 3]: Due to a partial intron retention.

    Alternative splice isoforms for IBTK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IBTK Gene

Post-translational modifications for IBTK Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for IBTK Gene

Domains & Families for IBTK Gene

Gene Families for IBTK Gene

Protein Domains for IBTK Gene

Suggested Antigen Peptide Sequences for IBTK Gene

GenScript: Design optimal peptide antigens:
  • IBTK protein (B7ZLD4_HUMAN)
  • IBTK protein (B7ZLE0_HUMAN)
  • Inhibitor of Bruton tyrosine kinase (IBTK_HUMAN)
genes like me logo Genes that share domains with IBTK: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for IBTK Gene

Function for IBTK Gene

Molecular function for IBTK Gene

UniProtKB/Swiss-Prot Function:
Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization and NF-kappa-B-driven transcription.

Phenotypes From GWAS Catalog for IBTK Gene

Gene Ontology (GO) - Molecular Function for IBTK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA --
GO:0019901 protein kinase binding IDA 11577348
GO:0030292 protein tyrosine kinase inhibitor activity IDA 11577348
genes like me logo Genes that share ontologies with IBTK: view
genes like me logo Genes that share phenotypes with IBTK: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IBTK

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for IBTK Gene

Localization for IBTK Gene

Subcellular locations from UniProtKB/Swiss-Prot for IBTK Gene

Cytoplasm. Membrane. Peripheral membrane protein. Note=Translocates to the plasma membrane upon IgM stimulation.
[Isoform 2]: Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IBTK gene
Compartment Confidence
nucleus 5
cytosol 3
plasma membrane 2
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for IBTK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA 11577348
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with IBTK: view

Pathways & Interactions for IBTK Gene

PathCards logo

SuperPathways for IBTK Gene

SuperPathway Contained pathways
1 B cell receptor signaling pathway (KEGG)
genes like me logo Genes that share pathways with IBTK: view

Pathways by source for IBTK Gene

1 BioSystems pathway for IBTK Gene

SIGNOR curated interactions for IBTK Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for IBTK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001933 negative regulation of protein phosphorylation IDA 11577348
GO:0051209 release of sequestered calcium ion into cytosol IDA 11577348
GO:0061099 negative regulation of protein tyrosine kinase activity IEA --
genes like me logo Genes that share ontologies with IBTK: view

Drugs & Compounds for IBTK Gene

(4) Drugs for IBTK Gene - From: ApexBio and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
AVL-292 Pharma Btk inhibitor 0
CGI-1746 Pharma Btk inhibitor 0
RN486 Pharma Btk inhibitor,potent and selective 0
Calcium Nutra 6959

(3) ApexBio Compounds for IBTK Gene

Compound Action Cas Number
AVL-292 Btk inhibitor 1202757-89-8
CGI-1746 Btk inhibitor 910232-84-7
RN486 Btk inhibitor,potent and selective 1242156-23-5
genes like me logo Genes that share compounds with IBTK: view

Drug products for research

Transcripts for IBTK Gene

mRNA/cDNA for IBTK Gene

2 REFSEQ mRNAs :
25 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IBTK

Alternative Splicing Database (ASD) splice patterns (SP) for IBTK Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b · 17c ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23a · 23b ^
SP1: -
SP2:
SP3:
SP4: -
SP5:
SP6:

ExUns: 24 ^ 25 ^ 26 ^ 27 ^ 28 ^ 29a · 29b ^ 30
SP1: - -
SP2: - -
SP3:
SP4:
SP5: -
SP6:

Relevant External Links for IBTK Gene

GeneLoc Exon Structure for
IBTK

Expression for IBTK Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for IBTK Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for IBTK Gene

This gene is overexpressed in Nasal epithelium (59.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for IBTK Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for IBTK

SOURCE GeneReport for Unigene cluster for IBTK Gene:

Hs.306425

mRNA Expression by UniProt/SwissProt for IBTK Gene:

Q9P2D0-IBTK_HUMAN
Tissue specificity: Expressed in DeFew, HEK293T, HeLa and in Jurkat, MC3 and NB4 lymphoid cells (at protein level). Isoform 1 is the predominant isoform expressed in all examined tissues and cell lines. Highly expressed in hemopoietic tissues (fetal liver, spleen, lymph node, thymus, peripheral blood leukocytes and bone marrow). Weakly or not expressed in other tissues.

Evidence on tissue expression from TISSUES for IBTK Gene

  • Nervous system(4.6)
  • Liver(4.4)
  • Skin(4.3)
  • Spleen(2)
genes like me logo Genes that share expression patterns with IBTK: view

Primer products for research

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for IBTK Gene

Orthologs for IBTK Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for IBTK Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia IBTK 29 30
  • 99.66 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia IBTK 29 30
  • 92.5 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia IBTK 29 30
  • 92.09 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Ibtk 29 16 30
  • 85.2 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ibtk 29
  • 81.63 (n)
Oppossum
(Monodelphis domestica)
Mammalia IBTK 30
  • 78 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 76 (a)
OneToMany
-- 30
  • 68 (a)
OneToMany
Chicken
(Gallus gallus)
Aves IBTK 29 30
  • 74.74 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia IBTK 30
  • 68 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ibtk 29
  • 67.77 (n)
Str.16202 29
Zebrafish
(Danio rerio)
Actinopterygii ibtk 29 30
  • 60.1 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009939 29
  • 43.96 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG8060 29 30 31
  • 42.41 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea glo-4 30
  • 13 (a)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SRM1 30
  • 14 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 38 (a)
OneToOne
Species where no ortholog for IBTK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for IBTK Gene

ENSEMBL:
Gene Tree for IBTK (if available)
TreeFam:
Gene Tree for IBTK (if available)
Aminode:
Evolutionary constrained regions (ECRs) for IBTK: view image
Alliance of Genome Resources:
Additional Orthologs for IBTK

Paralogs for IBTK Gene

(4) SIMAP similar genes for IBTK Gene using alignment to 7 proteins:

  • IBTK_HUMAN
  • B7ZLD4_HUMAN
  • B7ZLE0_HUMAN
  • D6R9F4_HUMAN
  • E7EPI0_HUMAN
  • E9PDR5_HUMAN
  • H0Y9N7_HUMAN

Pseudogenes.org Pseudogenes for IBTK Gene

genes like me logo Genes that share paralogs with IBTK: view

No data available for Paralogs for IBTK Gene

Variants for IBTK Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for IBTK Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
rs116533551 Benign: not provided 82,191,797(-) A/T
NM_015525.4(IBTK):c.3421T>A (p.Ser1141Thr)
MISSENSE
rs142130349 Benign: not provided 82,191,889(-) A/G
NM_015525.4(IBTK):c.3339-10T>C
INTRON
rs193921029 Uncertain Significance: Malignant tumor of prostate 82,191,142(-) T/A
NM_015525.4(IBTK):c.3506A>T (p.Asn1169Ile)
MISSENSE
rs12662902 -- p.Val1065Ile
rs9449444 -- p.Ala1185Val

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for IBTK Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for IBTK Gene

Variant ID Type Subtype PubMed ID
nsv470837 CNV gain 18288195
nsv476270 CNV novel sequence insertion 20440878
nsv479557 CNV novel sequence insertion 20440878
nsv479739 CNV novel sequence insertion 20440878
nsv480516 CNV novel sequence insertion 20440878
nsv481119 CNV novel sequence insertion 20440878
nsv481542 CNV novel sequence insertion 20440878
nsv510926 OTHER complex 20534489
nsv5373 CNV insertion 18451855
nsv7937 CNV loss 18304495
nsv830713 CNV gain 17160897
nsv830715 CNV loss 17160897

Variation tolerance for IBTK Gene

Residual Variation Intolerance Score: 15.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.64; 82.79% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for IBTK Gene

Human Gene Mutation Database (HGMD)
IBTK
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IBTK
Leiden Open Variation Database (LOVD)
IBTK

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IBTK Gene

Disorders for IBTK Gene

MalaCards: The human disease database

(3) MalaCards diseases for IBTK Gene - From: COP and GCD

Disorder Aliases PubMed IDs
agammaglobulinemia
  • hypogammaglobulinemia
keratoconus
  • conical cornea
leukemia, chronic lymphocytic
  • cll
- elite association - COSMIC cancer census association via MalaCards
Search IBTK in MalaCards View complete list of genes associated with diseases

Additional Disease Information for IBTK

genes like me logo Genes that share disorders with IBTK: view

No data available for UniProtKB/Swiss-Prot and Genatlas for IBTK Gene

Publications for IBTK Gene

  1. Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding protein. (PMID: 11577348) Liu W … Scala G (Nature immunology 2001) 2 3 4 22
  2. Physical and functional characterization of the genetic locus of IBtk, an inhibitor of Bruton's tyrosine kinase: evidence for three protein isoforms of IBtk. (PMID: 18596081) Spatuzza C … Scala G (Nucleic acids research 2008) 3 4 22
  3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  4. The DNA sequence and analysis of human chromosome 6. (PMID: 14574404) Mungall AJ … Beck S (Nature 2003) 3 4
  5. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10718198) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 2000) 3 4

Products for IBTK Gene

Sources for IBTK Gene