TNIK (TRAF2 and NCK interacting kinase)

Gene

• Entrez ID: 23043
• Gene name: TRAF2 and NCK interacting kinase
• Gene symbol: TNIK
• Synonyms (NCBI Gene): MRT54
• Chromosome: 3
• Chromosome location: 3q26.2-q26.31
• Summary: Wnt signaling plays important roles in carcinogenesis and embryonic development. The protein encoded by this gene is a serine/threonine kinase that functions as an activator of the Wnt signaling pathway. Mutations in this gene are associated with an autos

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs886037841	G>A	Pathogenic	Genic downstream transcript variant, stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017299	hsa-miR-335-5p	Microarray	18185580
MIRT1443606	hsa-miR-3125	CLIP-seq
MIRT1443607	hsa-miR-3148	CLIP-seq
MIRT1443608	hsa-miR-3153	CLIP-seq
MIRT1443609	hsa-miR-3916	CLIP-seq
MIRT1443610	hsa-miR-3978	CLIP-seq
MIRT1443611	hsa-miR-4270	CLIP-seq
MIRT1443612	hsa-miR-4419a	CLIP-seq
MIRT1443613	hsa-miR-4441	CLIP-seq
MIRT1443614	hsa-miR-4510	CLIP-seq
MIRT1443615	hsa-miR-4514	CLIP-seq
MIRT1443616	hsa-miR-4692	CLIP-seq
MIRT1443617	hsa-miR-590-3p	CLIP-seq
MIRT1443618	hsa-miR-658	CLIP-seq
MIRT2132743	hsa-miR-4536	CLIP-seq
MIRT2132744	hsa-miR-4719	CLIP-seq
MIRT2132745	hsa-miR-4796-3p	CLIP-seq
MIRT2132746	hsa-miR-513b	CLIP-seq
MIRT2132747	hsa-miR-548t	CLIP-seq
MIRT2647943	hsa-miR-1237	CLIP-seq
MIRT2647944	hsa-miR-1248	CLIP-seq
MIRT2647945	hsa-miR-4715-3p	CLIP-seq
MIRT2647946	hsa-miR-4768-5p	CLIP-seq
MIRT2647947	hsa-miR-513c	CLIP-seq
MIRT2647948	hsa-miR-514b-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IBA
GO:0000166	Function	Nucleotide binding	IEA
GO:0004672	Function	Protein kinase activity	IDA	22797597
GO:0004672	Function	Protein kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	IBA
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	10521462, 15342639
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0005515	Function	Protein binding	IPI	10521462, 15342639, 17474147, 18930710, 19816403, 20159449, 22904686, 29961565, 31413325, 32707033, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IDA	19816403
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	15342639, 19061864
GO:0005737	Component	Cytoplasm	IEA
GO:0005768	Component	Endosome	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005856	Component	Cytoskeleton	IDA	15342639
GO:0005856	Component	Cytoskeleton	IEA
GO:0006468	Process	Protein phosphorylation	IDA	10521462, 15342639
GO:0007010	Process	Cytoskeleton organization	IMP	10521462
GO:0007399	Process	Nervous system development	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0016324	Component	Apical plasma membrane	IDA	22797597
GO:0016740	Function	Transferase activity	IEA
GO:0030036	Process	Actin cytoskeleton organization	IDA	15342639
GO:0035556	Process	Intracellular signal transduction	IDA	10521462
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0043408	Process	Regulation of MAPK cascade	IBA
GO:0046328	Process	Regulation of JNK cascade	IEA
GO:0046330	Process	Positive regulation of JNK cascade	IDA	15342639
GO:0046330	Process	Positive regulation of JNK cascade	IMP	10521462
GO:0046777	Process	Protein autophosphorylation	IDA	10521462, 15342639
GO:0048812	Process	Neuron projection morphogenesis	IBA
GO:0048814	Process	Regulation of dendrite morphogenesis	IDA	20159449
GO:0055037	Component	Recycling endosome	IEA
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0098793	Component	Presynapse	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099092	Component	Postsynaptic density, intracellular component	IEA
GO:0106310	Function	Protein serine kinase activity	IEA
GO:1902533	Process	Positive regulation of intracellular signal transduction	IEA
GO:1903698	Process	Positive regulation of microvillus assembly	IMP	22797597

Other IDs

• MIM: 610005
• HGNC: 30765
• e!Ensembl: ENSG00000154310

Protein

• UniProt ID: Q9UKE5
• Protein name: TRAF2 and NCK-interacting protein kinase (EC 2.7.11.1)
• Protein 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 th
• PDB: 2X7F, 5AX9, 5CWZ, 5D7A, 6RA5, 6RA7, 7XZQ, 7XZR, 8WM0, 8X88
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	25 → 289	Protein kinase domain	Domain
  PF00780	CNH	1051 → 1331	CNH domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed ubiquitously. Highest levels observed in heart, brain and skeletal muscle. Expressed in normal colonic epithelia and colorectal cancer tissues. {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:19816403}.
• Sequence:

  MASDSPARSLDEIDLSALRDPAGIFELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTG
  DEEEEIKQEINMLKKYSHHRNIATYYGAFIKKNPPGMDDQLWLVMEFCGAGSVTDLIKNT
  KGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR
  TVGRRNTFIGTPYWMAPEVIACDENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMR
  ALFLIPRNPAPRLKSKKWSKKFQSFIESCLVKNHSQRPATEQLMKHPFIRDQPNERQVRI
  QLKDHIDRTKKKRGEKDETEYEYSGSEEEEEENDSGEPSSILNLPGESTLRRDFLRLQLA
  NKERSEALRRQQLEQQQRENEEHKRQLLAERQKRIEEQKEQRRRLEEQQRREKELRKQQE
  REQRRHYEEQMRREEERRRAEHEQEYIRRQLEEEQRQLEILQQQLLHEQALLLEYKRKQL
  EEQRQAERLQRQLKQERDYLVSLQHQRQEQRPVEKKPLYHYKEGMSPSEKPAWAKEVEER
  SRLNRQSSPAMPHKVANRISDPNLPPRSESFSISGVQPARTPPMLRPVDPQIPHLVAVKS
  QGPALTASQSVHEQPTKGLSGFQEALNVTSHRVEMPRQNSDPTSENPPLPTRIEKFDRSS
  WLRQEEDIPPKVPQRTTSISPALARKNSPGNGSALGPRLGSQPIRASNPDLRRTEPILES
  PLQRTSSGSSSSSSTPSSQPSSQGGSQPGSQAGSSERTRVRANSKSEGSPVLPHEPAKVK
  PEESRDITRPSRPASYKKAIDEDLTALAKELRELRIEETNRPMKKVTDYSSSSEESESSE
  EEEEDGESETHDGTVAVSDIPRLIPTGAPGSNEQYNVGMVGTHGLETSHADSFSGSISRE
  GTLMIRETSGEKKRSGHSDSNGFAGHINLPDLVQQSHSPAGTPTEGLGRVSTHSQEMDSG
  TEYGMGSSTKASFTPFVDPRVYQTSPTDEDEEDEESSAAALFTSELLRQEQAKLNEARKI
  SVVNVNPTNIRPHSDTPEIRKYKKRFNSEILCAALWGVNLLVGTENGLMLLDRSGQGKVY
  NLINRRRFQQMDVLEGLNVLVTISGKKNKLRVYYLSWLRNRILHNDPEVEKKQGWITVGD
  LEGCIHYKVVKYERIKFLVIALKNAVEIYAWAPKPYHKFMAFKSFADLQHKPLLVDLTVE
  EGQRLKVIFGSHTGFHVIDVDSGNSYDIYIPSHIQGNITPHAIVILPKTDGMEMLVCYED
  EGVYVNTYGRITKDVVLQWGEMPTSVAYIHSNQIMGWGEKAIEIRSVETGHLDGVFMHKR
  AQRLKFLCERNDKVFFASVRSGGSSQVFFMTLNRNSMMNW

• Sequence length: 1360

Pathways

Reactome:

Oxidative Stress Induced Senescence

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Intellectual disability, autosomal recessive 54	Pathogenic	rs886037841	RCV000235017	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ARTHRITIS, JUVENILE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE NON-SYNDROMIC INTELLECTUAL DISABILITY	—	CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DERMATOLOGIC DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DYSHIDROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTOTEMPORAL DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 54	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JUVENILE CHRONIC POLYARTHRITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MONOARTICULAR JUVENILE RHEUMATOID ARTHRITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PAUCIARTICULAR JUVENILE RHEUMATOID ARTHRITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL ARTERIAL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet, GWAS catalog Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASES, GENETIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TNIK-related disorder	Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absence of septum pellucidum	Absence Of Septum Pellucidum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	29186589	Associate	★☆☆☆☆ Found in Text Mining only
Arsenic Encephalopathy	Arsenic Encephalopathy	CTD_human_DG	16835338		★☆☆☆☆ Found in Text Mining only
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal recessive non-syndromic intellectual disability	Non-Syndromic Intellectual Disability	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	23496902		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	23496902	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	26269113	Associate	★☆☆☆☆ Found in Text Mining only
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	29186589	Associate	★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	21710359		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	20530691, 26542362, 27562646		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	26499327	Associate	★☆☆☆☆ Found in Text Mining only
Cortical Dysplasia	Cortical Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dermatologic disorders	Dermatologic Disorders	CTD_human_DG	16835338		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Frontotemporal dementia	Frontotemporal dementia	GWASCAT_DG	29724592		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Generalized seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	20530691		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	27106596, 31382054		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	31382054	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Juvenile arthritis	Arthritis	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Juvenile psoriatic arthritis	Juvenile arthritis	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Juvenile-Onset Still Disease	Still Disease	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	23496902		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	26269113		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	30901730		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	23496902, 26269113, 26995282, 28208209		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	21710359		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 54	Mental retardation	GENOMICS_ENGLAND_DG	27106596		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 54	Mental retardation	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 54	Mental retardation	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	28467797		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	28467797	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	20530691, 25250919, 27562646		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	31153805		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	31382054	Associate	★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	29301492	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	26269113		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	26269113	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	29241837		★☆☆☆☆ Found in Text Mining only
Peripheral Arterial Diseases	Vascular Diseases	GWASCAT_DG	27082954		★☆☆☆☆ Found in Text Mining only
Polyarthritis, Juvenile, Rheumatoid Factor Negative	Seronegative polyarthritis	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Polyarthritis, Juvenile, Rheumatoid Factor Positive	Polyarthritis, Rheumatoid Factor Positive	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	39284759	Associate	★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	30901730		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	30901730	Associate	★☆☆☆☆ Found in Text Mining only
Salaam Seizures	Salaam Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	21440632, 31382054		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	21440632		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	GWASCAT_DG	29503163		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	31382054	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	33879700	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	30442712		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	30442712	Associate	★☆☆☆☆ Found in Text Mining only