TXK

protein-coding

TXK tyrosine kinase, the group of Tec family tyrosine kinases|SH2 domain containing

Gene summary

Predicted to enable non-membrane spanning protein tyrosine kinase activity. Involved in positive regulation of type II interferon-mediated signaling pathway; protein autophosphorylation; and regulation of gene expression. Located in cytosol; nuclear lumen; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

PTK4

MANE transcript

NM_003328.3

Inheritance

—

ClinVar variants

U:90B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr4:48,063,158-48,134,250

External References & Databases

Ensembl (ENSG00000074966)

Transcript & Mutation Effects

hg38 • Region Span ~71.1 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 TXK variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 88

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003328.3. 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			1 clinvar			1
missense			88 clinvar	2 clinvar		90
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	90	2	0	92

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003328.3	RefSeq	NP_003319.2	15	MANE Select
ENST00000264316.9	Ensembl	ENSP00000264316.4	15	MANE Select
ENST00000506073.2	Ensembl	ENSP00000422798.2	14	Standard
ENST00000506073.3	Ensembl	ENSP00000422798.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Leukocyte transendothelial migration - Homo sapiens (human)
Focal Adhesion
FCERI mediated Ca+2 mobilization
Fc epsilon receptor (FCERI) signaling
TCR

Biological Process

cytokine production
adaptive immune response
regulation of transcription by RNA polymerase II
protein phosphorylation
activation of phospholipase C activity

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
RNA polymerase II regulatory region DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
non-membrane spanning protein tyrosine kinase activity
protein binding

Cellular Component

nucleus
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264316
Coding exons: 15
Length: 67864
Individuals with no LoFs: 125683
Homozygous LoFs: 0
Heterozygous LoFs: 65
Defined: 125748
p: 0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.917	247	291	0.849	0.0000152	3452
Missense (PolyPhen)		72	110.95	0.64894		1390
Synonymous	-0.519	105	98.4	1.07	0.00000507	935
Loss of Function	2.59	19	35.7	0.533	0.00000178	431

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00063	0.00061	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00027	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T- cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. With PARP1 and EEF1A1, TXK forms a complex that acts as a T-helper 1 (Th1) cell- specific transcription factor and binds the promoter of IFNG to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Phosphorylates both PARP1 and EEF1A1. Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr- 201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor. {ECO:0000269|PubMed:10523612, ECO:0000269|PubMed:11564877, ECO:0000269|PubMed:11859127, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:9813138}.;

Recessive Scores

pRec: 0.0980

Intolerance Scores

LoFtool: 0.489
RVIS EVS: -0.16
RVIS percentile EVS: 42.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.584

Gene Damage Prediction

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