TRAF2- and NCK-Interacting Kinase

Alternative Names

  • TNIK
  • KIAA0551
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OMIM Number

610005

Gene Map Locus
3q26.2-q26.3

Description

The TNIK gene codes for a member of the serine/threonine kinase of the Ste20 family of It belongs to the germinal center kinase subgroup of this family that is involved in cytoskeleton organization and neuronal dendrite extension.  It functions as a tumor suppressor by activation of the c-Jun N-terminal kinase (JNK) pathway, and is associated with Rap2 to regulate cytoskeleton organization and cell spreading.  It also localizes in the nuclei and functions as transcription activator of the Wnt signaling pathway in a β-catenin-dependent manner.  In addition, recent studies have hinted at a possible role as a scaffold that assembles molecular complexes for downstream signal transduction

Defects in this gene have been associated with colorectal cancer as well as a specific form of autosomal recessive mental retardation.  

Molecular Genetics

The TNIK gene has been mapped to the 3q26.2-q26.3 chromosome.  It has 33 coding exons spanning about 399 kb within the genomic DNA.  The encoded protein comprises 1360 amino acids with a molecular weight of 155 kDa.  Like other members of the germinal center kinase (GCK) proteins family, TNIK is also characterized by the presence of an N-terminal kinase domain and a regulatory C-terminal GCK domain.  The protein is expressed ubiquitously, but maximum expression levels are seen in heart, brain and skeletal muscle cells, as well as in colorectal cancers.  

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Anazi et al., (2016) reported on two multiplex consanguineous Saudi family siblings affected with autosomal recessive intellectual disability.  The first family consisted of two affected and two normal siblings, while the second family had three affected and four normal siblings.  Autozygome analysis on the first family revealed six autozygous intervals that were exclusive to the two affected brothers.  Within the second family, only one autozygous block exclusive to the affected patients was identified.  Interestingly, this block on chromosome 3 was also one of the three identified in the first family.  Linkage analysis verified this as the critical locus with a lod score of 4.  The two families shared the same haplotype around the critical locus, indicating the presence of a founder mutation.  Exome sequencing was able to identify the same variant (c.538C>T) in the TNIK gene in both the index cases.  This mutation was predicted to result in a premature stop codon and was not found in 734 Saudi exomes or in the ExAC browser.  Western blot using antibody against the N-terminus revealed a total lack of the full-length TNIK as well as the 20 kD truncated TNIK, supporting the null nature of the mutation.  

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