The TNIK gene size is 397827bp encoding by 33 exons. This gene has 15 transcripts (splice variants), 312 orthologues, 35 paralogues (http://www.ensembl.org/).The protein encoded by this gene is a serine/threonine kinase that functions as an activator of the Wnt signaling pathway.

15 transcripts variant have been found for this gene (http://www.ensembl.org/).
TNIK-204 ENST00000436636.7 : mRNA 9892bp, protein 1360aa
TNIK-202 ENST00000341852.10 : mRNA 4727, protein 1276aa
TNIK-201 ENST00000284483.12 : mRNA 4059, protein 1352aa
TNIK-203 ENST00000357327.9 : mRNA 3996, protein 1331aa
TNIK-210 ENST00000470834.5 : mRNA 3972, protein 1323aa
TNIK-214 ENST00000488470.5 : mRNA 3918, protein 1305aa
TNIK-206 ENST00000460047.5 : mRNA 3894, protein 1297aa
TNIK-211 ENST00000475336.5 : mrNA 3807, protein 1268aa
TNIK-209 ENST00000468757.1 : mRNA1128, protein 350aa
TNIK-208 ENST00000465393.1 : mRNA 750, protein 45aa
TNIK-207 ENST00000464785.1 : mRNA 437, no protein
TNIK-215 ENST00000496492.5 : mRNA 2736, no protein
TNIK-212 ENST00000484051.5 : mRNA 1180, no protein
TNIK-205 ENST00000459881.1 : mRNA 583, no protein
TNIK-213 ENST00000487846.1 : mRNA 573, no protein

The serine/threonine kinase Traf2- and Nck interacting kinase (TNIK), is a member of the germinal center kinase (GCK) family, that it was isolated by yeast two-hybrid screening for proteins that interact with TRAF2 and NCK (Fu CA et al.,1999). It was demonstrated that TNIK regulates Jun N-terminal kinase pathway (JNK), the actin cytoskeleton, it is an important activator of Wnt signaling and it is involved in in the survival of many human cancer cells (Lee Y. et al., 2017).
The gene TNIK encodes a 1360 aa protein with several spliced isoforms. This protein has an N-terminal kinase domain, an intermediate domain and an C-terminal germinal center kinase homology (GCKH) region, later called Citron homology (CNH) domain (Fu CA et al.,1999; Taira K. et al., 2004) It was observed that it shared about 90% amino acid identity with other two previously cloned GCK family member, NIK and MAPK4, in both its kinase and CNH domains. However, this homology goes down to about 50% in the intermediate region suggesting potentially different signaling role for these GCK proteins (Su YC. et al.,1997; Taira K. et al., 2004).

TNIK is ubiquitously expressed in human. It is expressed with high level in brain, small intestine, duodenum, testis, heart, normal and cancer epithelia colon tissues. Its expression it also observed in endometrium, lung, lymph node, kidney, spleen, thyroid, urinary bladder, gall bladder, prostate, endometrium, adrenal, bone marrow (https://www.ncbi.nlm.nih.gov/)

TNIK is mainly localized in the nucleoplasm and cytosol (https://www.uniprot.org/)

TNIK was discovered by Fu CA et al. in 1999, with a yeast-two-hybrid screen for interaction partners of the adapter proteins TRAF2 and NCK. Like several other GCK family members, TNIK regulates activation of JNK pathway which is induced through the CNH domain by a yet undefined mechanism (Fu CA et al., 1999). TNIK overexpression also modulates the actin cytoskeleton; through its kinase domain, inducing disruption of F-actin structure and inhibiting cell spreading (Taira K et al., 2004). TNIK protein is known to be implicated in Wnt pathway activation. Mahmoudi T. et al. in 2009, have identified TNIK as a co-activator protein that interact both TCF4/β-catenin complex in the proliferative cripts of mouse small intestine. Through in vitro assays they showed that TNIK directly bind both TCF4 and β-catenin and phosphorylates TCF4 leading to transcriptional activation of Wnt target genes. This protein is also involved in the dendrite development. NEDD4, the TNIK, and RAP2A form a complex that controls NEDD4-mediated ubiquitination of RAP2A. Ubiquitination by NEDD4 inhibits RAP2A function, which reduces the activity of Rap2 effector kinases of the TNIK family and promotes dendrite growth (Kawabe H. et al., 2010).

TNIK is conserved in human, mouse, chicken, C. Elegans

Recently, Anazi S. et al. in 2016 have identified in 2 unrelated consanguineous Saudi families affected with autosomal recessive mental retardation-54 (MRT54) the same homozygous truncating mutation in the TNIK gene that results in complete loss of the protein, indicating that the mutation resulted in a null allele.

Some somatic mutations have been identified and described by COSMIC (Catalogue of Somatic Mutation In Cancer) and they are listed mostly as substitution; their role in disease has not yet been fully elucidated.