Information on BTK

Basic details

Alt. symbols: AGMX1 | IMD1 | ATK | XLA | PSCTK1

Approved name: Bruton tyrosine kinase
Alt. names: Bruton agammaglobulinemia tyrosine kinase | Bruton's tyrosine kinase

Location: Xq22.1: 101349338 - 101390796 (-)
Gene type: protein_coding, 31 transcripts.

Scores: LoFtool: | pLI: 0.99956322 | LOEUF: 0.103

HGNC: 1133

NCBI: 695, RefSeq: NG_009616.1

Ensembl: ENSG00000010671.18

LRG_128 | Status: public

OMIM: 300300

Expression | ProteinAtlas

Normal function

The BTK gene encodes the Bruton tyrosine kinase (BTK), which is a protein essential for the development and maturation of B cells to antibody-secreting cells. BTK is required for transmitting signals from the pre-B cell receptor that forms after successful immunoglobulin heavy chain rearrangement. It also has a role in mast cell activation through the high-affinity IgE receptor.

Dysfunction and disease

Hemizygous BTK null mutations are classically associated with X-linked recessive agammaglobulinemia (XLA), with or without metabolic abnormalities. These conditions are known as X-linked agammaglobulinemia 1 [OMIM:300755], and isolated growth hormone deficiency, type III, with agammaglobulinemia [OMIM:307200]. The absence of functional BTK protein leads to a block in B cell differentiation and lack of antibody production, causing increased susceptibility to infections. More than 600 different mu tations in the BTK gene have been identified to date, with most resulting in absent BTK protein. However, hypomorphic mutations have also been reported, leading to milder B cell- and antibody-deficient phenotypes than classic XLA, including some patients with clinical diagnoses of CVID (PMID: 10792386, 15821893, 18518992, 29709555, 31942606, 32499645, 32615565, 34182127, 34975878). [Load More]

[Reviewed by Xiao P. Peng on 2022-08-11 02:37:51]

Associated conditions

Acronym Condition's_name MOI Mode_of_actionwww icon OMIM_ID No.cases
IGHD3 Isolated growth hormone deficiency, type III with agammaglobulinemia XLRdict. icon 307200www icon 0 (0 fams)
AGMX1 Agammaglobulinemia, X-linked 1 XLRdict. icon Loss of Function 300755www icon 3 (3 fams)

Please mind that full curation (inclusion of all published patients) of this gene has not been completed yet. It is currently ongoing.

Transcripts of BTK

Name ENSEMBL_ID LRG_ID CCDS_ID MANE Transcript.type Exons Canonical CDS_length REFSEQ_ID
201 ENST00000308731.8 1 CCDS14482 Select protein_coding 19 Yes 2575 NM_000061
208 ENST00000621635.4 CCDS76003 protein_coding 19 No 2767 NM_001287344
231 ENST00000703407.1 protein_coding No NM_001287345

Published variants

Found 5 variants

Var.name Exon/Intron cDNA_pos. CDS_change Prot.change Var.type Var.class. Patients
G541C EX16 1781 c.1621G>T p.Gly541Cys missense_variant Likely Pathogenic 1
V253* EX8 1004 c.757del p.Val253LeufsTer10 frameshift_variant Pathogenic 1
Y74C EX2 468 c.221A>G p.Tyr74Cys missense_variant Pathogenic 0
R62C EX2 431 c.184C>T p.Arg62Cys missense_variant Pathogenic 1
R47* EX2 386 c.139C>T p.Arg47Ter stop_gained Pathogenic 0

Please mind that full curation (inclusion of all published variants) of this gene has not been completed yet. It is currently ongoing.

Diagnostic pitfalls & paradigms

Considerations to take into account when analyzing this gene

Year Paradigm ⓘ PMID Notes
- Regions of Homology -
2004Skewed X-linked inactivation12958074
2024Skewed X-linked inactivation38265673Study reports a 71-yo female patient who carried the heterozygous hypomorphic (p.Tyr418His) variant but was affected with CVID (starting at age 35) because of her skewed X-linked inactivation. mRNA expression studies showed a 20:80 ratio for the WT:MUT alleles.
-Cryptic splicing-Unreported or not recorded in our DB.
-Uniparental disomy-Unreported or not recorded in our DB.
-Mosaicism-Unreported or not recorded in our DB.
-Incomplete penetrance-Unreported or not recorded in our DB.
-Di-/oligo-genic inheritance-Unreported or not recorded in our DB.
-Somatic reversion-Unreported or not recorded in our DB.

References linked to variants in BTK

ID Year Title Journal PMID Variants
118 2021 Establishing the Molecular Diagnoses in a Cohort of 291 Pati... Front. Immunol. 34975878 3
219 1997 Molecular and structural characterization of five novel muta... Mol. Med. 9260159 1
220 1998 Mutations in Btk in patients with presumed X-linked agammagl... Am. J. Hum. Genet. 9545398 2
221 2002 Identification of mutations of Bruton's tyrosine kinase gene... Hum. Mut. 12204007 2
222 2001 Clinical and mutational characteristics of X-linked agammagl... JACI 11742281 2
223 2015 Btk mutations selectively regulate btk expression and upregu... Imm. Inflam. Dis. 26417435 1
397 1999 Regulation of Nuclear Localization and Transcriptional Activ... MCB 10373551 1
398 2018 Chronic Aichi Virus Infection in a Patient with X-Linked Aga... JoCI 30311057 1
399 2010 Clinical characteristics and genotype-phenotype correlation ... JoCI 19904586 2
527 2006 Bruton's tyrosine kinase is not essential for LPS-induced ac... JACI 16751014 1
528 2011 Quantification of ?-deleting recombination excision circles ... JACI 21397315 1
532 2000 Genetic defect in human X-linked agammaglobulinemia impedes ... Blood 10887125 1
534 2005 Genetic analysis of patients with defects in early B-cell de... Imm. Rev. 15661032 1
535 2009 Mutation of the BTK gene and clinical feature of X-linked ag... JoCI 19039656 1
536 2005 Severe neutropenia in Japanese patients with x-linked agamma... JoCI 16160918 1
540 2001 Analysis of Btk mutations in patients with X-linked agammagl... Scan. J. Immunol. 11555397 1
541 2006 Identification of Bruton tyrosine kinase mutations in 12 Chi... Int. J. Immunogen 16712653 1
554 1994 Screening of genomic DNA to identify mutations in the gene f... Hum. Mol. Genet. 7849697 1
573 1995 The spectrum of mutations in Btk that cause X-linked agammag... Clin. Immun. Immunopath. 7554467 1

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