IBTK

protein-coding

inhibitor of Bruton tyrosine kinase, the group of BTB domain containing|Ankyrin repeat domain containing

Gene summary

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]

Previous symbols:

BTKI

MANE transcript

NM_015525.4

Inheritance

—

ClinVar variants

U:140B:7

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr6:82,169,986-82,247,754

External References & Databases

Ensembl (ENSG00000005700)

Transcript & Mutation Effects

hg38 • Region Span ~77.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IBTK variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 125

not providedTotal: 3

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015525.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	1 clinvar		4
missense			126 clinvar	5 clinvar	1 clinvar	132
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	140	6	1	147

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015525.4	RefSeq	NP_056340.2	28	MANE Select
ENST00000306270.12	Ensembl	ENSP00000305721.7	28	MANE Select
NM_001300906.2	RefSeq	NP_001287835.1	28	Standard
ENST00000471036.1	Ensembl	ENSP00000424634.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

BCR signaling pathway

Biological Process

negative regulation of protein phosphorylation
release of sequestered calcium ion into cytosol
negative regulation of protein tyrosine kinase activity

Molecular Function

protein kinase binding
protein tyrosine kinase inhibitor activity

Cellular Component

nucleoplasm
cytoplasm
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306270
Coding exons: 28
Length: 77772
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125748
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.28	506	672	0.753	0.0000319	8884
Missense (PolyPhen)		81	162.46	0.49858		2094
Synonymous	1.84	200	236	0.848	0.0000114	2530
Loss of Function	5.37	18	64.6	0.279	0.00000325	883

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0.000065	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:11577348}.;

Recessive Scores

pRec: 0.0888

Intolerance Scores

LoFtool: 0.641
RVIS EVS: -0.66
RVIS percentile EVS: 16.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.447

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium