TXK

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

Basic information

Region (hg38): 4:48063158-48134250

Previous symbols: [ "PTK4" ]

Links

ENSG00000074966 ∙ NCBI:7294 ∙ OMIM:600058 ∙ HGNC:12434 ∙ Uniprot:P42681 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TXK gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TXK gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			33			33
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	33	0	0

Variants in TXK

This is a list of pathogenic ClinVar variants found in the TXK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-48067666-C-T		not specified	Uncertain significance (Jan 31, 2022)
4-48067669-G-A		not specified	Uncertain significance (Jun 06, 2022)
4-48067678-C-T		not specified	Uncertain significance (Jul 14, 2022)
4-48071520-A-C		not specified	Uncertain significance (Jun 24, 2022)
4-48071561-C-T		not specified	Uncertain significance (Jun 17, 2024)
4-48071597-T-C		not specified	Uncertain significance (Dec 13, 2023)
4-48071606-C-T		not specified	Uncertain significance (Feb 23, 2023)
4-48071618-T-C		not specified	Uncertain significance (Feb 27, 2024)
4-48071618-T-G		not specified	Uncertain significance (Jun 26, 2023)
4-48071671-A-T		not specified	Uncertain significance (Mar 07, 2024)
4-48074028-T-C		not specified	Uncertain significance (Aug 12, 2021)
4-48076445-T-C		not specified	Uncertain significance (Dec 27, 2023)
4-48076453-C-T		not specified	Uncertain significance (Jan 16, 2024)
4-48076460-T-C		not specified	Uncertain significance (Aug 12, 2021)
4-48079982-A-T		not specified	Uncertain significance (Jun 22, 2023)
4-48080024-T-G		not specified	Uncertain significance (Dec 01, 2022)
4-48080126-T-C		not specified	Uncertain significance (Dec 03, 2021)
4-48080127-T-G		not specified	Uncertain significance (Mar 16, 2022)
4-48086517-T-C		not specified	Uncertain significance (Dec 06, 2022)
4-48086545-G-A		not specified	Uncertain significance (Jul 16, 2021)
4-48086586-C-T		not specified	Uncertain significance (May 30, 2023)
4-48086629-C-T		not specified	Uncertain significance (Jul 15, 2021)
4-48094103-A-T		not specified	Uncertain significance (Jul 20, 2022)
4-48094116-T-C		not specified	Uncertain significance (Feb 05, 2024)
4-48094121-T-C		not specified	Uncertain significance (Oct 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TXK	protein_coding	protein_coding	ENST00000264316	15	67864

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.57e-9	0.995	125683	0	65	125748	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.917	247	291	0.849	0.0000152	3452
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000689	0.000688
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000163	0.000163
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000163	0.000163
South Asian	0.000267	0.000261
Other	0.000326	0.000326

dbNSFP

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}.
• Pathway: Leukocyte transendothelial migration - Homo sapiens (human);Focal Adhesion;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System (Consensus)

Recessive Scores

• pRec: 0.0980

Intolerance Scores

• loftool: 0.489
• rvis_EVS: -0.16
• rvis_percentile_EVS: 42.06

Haploinsufficiency Scores

• pHI: 0.0682
• hipred: N
• hipred_score: 0.196
• ghis: 0.498

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.584

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Txk
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: cytokine production;adaptive immune response;regulation of transcription by RNA polymerase II;protein phosphorylation;activation of phospholipase C activity;positive regulation of interferon-gamma production;peptidyl-tyrosine autophosphorylation;positive regulation of transcription by RNA polymerase II;protein autophosphorylation;T cell receptor signaling pathway;positive regulation of interferon-gamma-mediated signaling pathway
• Cellular component: nucleus;cytoplasm;plasma membrane
• 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;ATP binding