TNIK

TRAF2 and NCK interacting kinase, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 3:171058414-171460408

Links

ENSG00000154310 ∙ NCBI:23043 ∙ OMIM:610005 ∙ HGNC:30765 ∙ Uniprot:Q9UKE5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 54 (Limited), mode of inheritance: AR
• intellectual disability, autosomal recessive 54 (Limited), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 54 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 54	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	27106596

ClinVar

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

• Intellectual disability, autosomal recessive 54 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNIK 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				21	8	29
missense			48	2	1	51
nonsense	1		1			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	4	1	8
non coding				6	4	10
Total	1	0	49	29	13

Variants in TNIK

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

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

Position	Type	Phenotype	Significance	ClinVar
3-171063906-T-C		not specified	Uncertain significance (Aug 17, 2021)
3-171066592-T-C			Likely benign (Dec 01, 2021)
3-171066601-T-C			Likely benign (Mar 29, 2018)
3-171066626-C-T		TNIK-related disorder	Uncertain significance (May 23, 2023)
3-171066641-A-G		not specified	Uncertain significance (Dec 14, 2021)
3-171066728-C-T			Uncertain significance (Nov 02, 2016)
3-171071247-C-T		TNIK-related disorder	Benign (Dec 31, 2019)
3-171071330-T-A			Benign (Apr 01, 2024)
3-171079538-C-T		not specified	Uncertain significance (May 08, 2023)
3-171082284-G-A			Likely benign (Oct 10, 2018)
3-171082339-C-T			Likely benign (Apr 01, 2022)
3-171084312-G-A		Intellectual disability, autosomal recessive 54 • TNIK-related disorder	Benign/Likely benign (Feb 15, 2022)
3-171085120-G-A		not specified	Uncertain significance (Mar 14, 2023)
3-171085121-C-T		Intellectual disability, autosomal recessive 54	Benign (May 18, 2021)
3-171085122-G-A			Likely benign (Oct 01, 2023)
3-171085124-C-T		not specified	Uncertain significance (Dec 21, 2022)
3-171085143-T-G		not specified	Uncertain significance (Nov 02, 2021)
3-171085164-C-T			Likely benign (Mar 01, 2023)
3-171085165-G-T		not specified	Uncertain significance (May 26, 2024)
3-171087359-T-C		Intellectual disability, autosomal recessive 54	Uncertain significance (Mar 07, 2019)
3-171087456-A-T			Likely benign (Dec 31, 2019)
3-171087466-T-C		not specified	Uncertain significance (Apr 19, 2023)
3-171087473-C-G		not specified	Uncertain significance (Aug 02, 2023)
3-171087487-C-T		not specified	Uncertain significance (Dec 14, 2023)
3-171087491-T-G		Intellectual disability, autosomal recessive 54	Uncertain significance (Jan 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNIK	protein_coding	protein_coding	ENST00000436636	33	399070

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.68e-8	124696	0	13	124709	0.0000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.10	436	753	0.579	0.0000427	8865
Missense in Polyphen		160	294.46	0.54336		3558
Synonymous	0.423	262	271	0.967	0.0000148	2555
Loss of Function	7.75	9	87.0	0.103	0.00000533	945

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000876	0.0000876
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000558	0.0000555
Finnish	0.0000465	0.0000464
European (Non-Finnish)	0.0000720	0.0000708
Middle Eastern	0.0000558	0.0000555
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388}.
• Disease: DISEASE: Mental retardation, autosomal recessive 54 (MRT54) [MIM:617028]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT54 patients manifest intellectual disability, delayed speech and hyperactivity. {ECO:0000269|PubMed:27106596}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Oxidative Stress Induced Senescence;Oxidative Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;Cellular responses to external stimuli;Regulation of nuclear beta catenin signaling and target gene transcription;TNF receptor signaling pathway (Consensus)

Recessive Scores

• pRec: 0.188

Intolerance Scores

• loftool: 0.467
• rvis_EVS: -1.44
• rvis_percentile_EVS: 3.97

Haploinsufficiency Scores

• pHI: 0.855
• hipred: Y
• hipred_score: 0.706
• ghis: 0.573

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.978

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnik
• Phenotype: digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; hematopoietic system phenotype; growth/size/body region phenotype; normal phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: tnika
• Affected structure: EVL
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• Biological process: MAPK cascade;positive regulation of protein phosphorylation;protein phosphorylation;cytoskeleton organization;activation of JNKK activity;Wnt signaling pathway;signal transduction by protein phosphorylation;microvillus assembly;stress-activated protein kinase signaling cascade;actin cytoskeleton reorganization;activation of protein kinase activity;intracellular signal transduction;protein autophosphorylation;neuron projection morphogenesis;regulation of dendrite morphogenesis;protein localization to plasma membrane
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;cytoskeleton;apical plasma membrane;recycling endosome;extracellular exosome;presynapse;glutamatergic synapse;postsynaptic density, intracellular component
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding