TTBK2 (tau tubulin kinase 2)

Gene

• Entrez ID: 146057
• Gene name: Tau tubulin kinase 2
• Gene symbol: TTBK2
• Synonyms (NCBI Gene): SCA11, TTBK
• Chromosome: 15
• Chromosome location: 15q15.2
• Summary: This gene encodes a serine-threonine kinase that putatively phosphorylates tau and tubulin proteins. Mutations in this gene cause spinocerebellar ataxia type 11 (SCA11); a neurodegenerative disease characterized by progressive ataxia and atrophy of the ce

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs80356538	->T	Pathogenic	Coding sequence variant, frameshift variant
rs80356539	CT>-	Pathogenic	Coding sequence variant, frameshift variant
rs199635198	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, synonymous variant
rs318240735	CT>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1460779	hsa-miR-1273d	CLIP-seq
MIRT1460780	hsa-miR-3154	CLIP-seq
MIRT1460781	hsa-miR-410	CLIP-seq
MIRT1460782	hsa-miR-4307	CLIP-seq
MIRT1460783	hsa-miR-4768-5p	CLIP-seq
MIRT2138396	hsa-miR-3152-5p	CLIP-seq
MIRT2138397	hsa-miR-3974	CLIP-seq
MIRT2138398	hsa-miR-4263	CLIP-seq
MIRT2138399	hsa-miR-4320	CLIP-seq
MIRT2138400	hsa-miR-4774-3p	CLIP-seq
MIRT2138401	hsa-miR-520d-5p	CLIP-seq
MIRT2138402	hsa-miR-524-5p	CLIP-seq
MIRT2138403	hsa-miR-596	CLIP-seq
MIRT2138398	hsa-miR-4263	CLIP-seq
MIRT2138399	hsa-miR-4320	CLIP-seq
MIRT2359303	hsa-miR-4690-3p	CLIP-seq
MIRT2138401	hsa-miR-520d-5p	CLIP-seq
MIRT2138402	hsa-miR-524-5p	CLIP-seq
MIRT2359304	hsa-miR-548n	CLIP-seq
MIRT2359305	hsa-miR-548t	CLIP-seq
MIRT2138398	hsa-miR-4263	CLIP-seq
MIRT2396448	hsa-miR-4799-5p	CLIP-seq
MIRT2396449	hsa-miR-576-5p	CLIP-seq
MIRT2138403	hsa-miR-596	CLIP-seq
MIRT2138403	hsa-miR-596	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000226	Process	Microtubule cytoskeleton organization	IGI	26323690
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	21548880, 26323690
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	NAS	28386764
GO:0005515	Function	Protein binding	IPI	22863007, 25416956, 26323690, 32296183, 32814053, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005615	Component	Extracellular space	HDA	22664934
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	21548880
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005814	Component	Centriole	IDA	23141541
GO:0005814	Component	Centriole	IEA
GO:0005829	Component	Cytosol	IDA	21548880
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0005929	Component	Cilium	IDA
GO:0005929	Component	Cilium	IEA
GO:0007026	Process	Negative regulation of microtubule depolymerization	IDA	26323690
GO:0007165	Process	Signal transduction	IBA
GO:0007224	Process	Smoothened signaling pathway	IEA
GO:0007224	Process	Smoothened signaling pathway	ISS
GO:0008104	Process	Intracellular protein localization	IEA
GO:0008589	Process	Regulation of smoothened signaling pathway	IEA
GO:0015630	Component	Microtubule cytoskeleton	IDA
GO:0015630	Component	Microtubule cytoskeleton	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	21548880, 30375385
GO:0019894	Function	Kinesin binding	IPI	26323690
GO:0021549	Process	Cerebellum development	IEA
GO:0021549	Process	Cerebellum development	ISS	26323690
GO:0021681	Process	Cerebellar granular layer development	IEA
GO:0021681	Process	Cerebellar granular layer development	ISS	26323690
GO:0021915	Process	Neural tube development	IEA
GO:0021935	Process	Cerebellar granule cell precursor tangential migration	IEA
GO:0021935	Process	Cerebellar granule cell precursor tangential migration	ISS	26323690
GO:0030030	Process	Cell projection organization	IEA
GO:0030334	Process	Regulation of cell migration	IGI	26323690
GO:0030900	Process	Forebrain development	IEA
GO:0033365	Process	Protein localization to organelle	IEA
GO:0035869	Component	Ciliary transition zone	IBA
GO:0035869	Component	Ciliary transition zone	IDA	23141541
GO:0035869	Component	Ciliary transition zone	IEA
GO:0035869	Component	Ciliary transition zone	ISS
GO:0036064	Component	Ciliary basal body	IBA
GO:0036064	Component	Ciliary basal body	IDA
GO:0036064	Component	Ciliary basal body	IEA
GO:0036064	Component	Ciliary basal body	ISS
GO:0042733	Process	Embryonic digit morphogenesis	IEA
GO:0042995	Component	Cell projection	IEA
GO:0048156	Function	Tau protein binding	NAS	28386764
GO:0050321	Function	Tau-protein kinase activity	NAS	28386764
GO:0050321	Function	Tau-protein kinase activity	TAS	26323690
GO:0051010	Function	Microtubule plus-end binding	TAS	26323690
GO:0060271	Process	Cilium assembly	IBA
GO:0060271	Process	Cilium assembly	IEA
GO:0060271	Process	Cilium assembly	IMP	23141541
GO:0060271	Process	Cilium assembly	ISS
GO:0097546	Component	Ciliary base	IEA
GO:0106310	Function	Protein serine kinase activity	IEA
GO:1902817	Process	Negative regulation of protein localization to microtubule	IMP	26323690
GO:1902857	Process	Positive regulation of non-motile cilium assembly	IEA
GO:1903828	Process	Negative regulation of protein localization	IEA
GO:1990403	Process	Embryonic brain development	IEA

Other IDs

• MIM: 611695
• HGNC: 19141
• e!Ensembl: ENSG00000128881

Protein

• UniProt ID: Q6IQ55
• Protein name: Tau-tubulin kinase 2 (EC 2.7.11.1)
• Protein function: Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the rec
• PDB: 6U0K, 6VRF, 7O3B, 7Q8Y, 7Q8Z, 7Q90
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	21 → 272	Protein kinase domain	Domain

• Sequence:

  MSGGGEQLDILSVGILVKERWKVLRKIGGGGFGEIYDALDMLTRENVALKVESAQQPKQV
  LKMEVAVLKKLQGKDHVCRFIGCGRNDRFNYVVMQLQGRNLADLRRSQSRGTFTISTTLR
  LGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNSCGDVRPP
  RAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKE
  RYDHRLMLKHLPPEFSIFLDHISSLDYFTKPDYQLLTSVFDNSIKTFGVIESDPFDWEKT
  GNDGSLTTTTTSTTPQLHTRLTPAAIGIANATPIPGDLLRENTDEVFPDEQLSDGENGIP
  VGVSPDKLPGSLGHPRPQEKDVWEEMDANKNKIKLGICKAATEEENSHGQANGLLNAPSL
  GSPIRVRSEITQPDRDIPLVRKLRSIHSFELEKRLTLEPKPDTDKFLETCLEKMQKDTSA
  GKESILPALLHKPCVPAVSRTDHIWHYDEEYLPDASKPASANTPEQADGGGSNGFIAVNL
  SSCKQEIDSKEWVIVDKEQDLQDFRTNEAVGHKTTGSPSDEEPEVLQVLEASPQDEKLQL
  GPWAENDHLKKETSGVVLALSAEGPPTAASEQYTDRLELQPGAASQFIAATPTSLMEAQA
  EGPLTAITIPRPSVASTQSTSGSFHCGQQPEKKDLQPMEPTVELYSPRENFSGLVVTEGE
  PPSGGSRTDLGLQIDHIGHDMLPNIRESNKSQDLGPKELPDHNRLVVREFENLPGETEEK
  SILLESDNEDEKLSRGQHCIEISSLPGDLVIVEKDHSATTEPLDVTKTQTFSVVPNQDKN
  NEIMKLLTVGTSEISSRDIDPHVEGQIGQVAEMQKNKISKDDDIMSEDLPGHQGDLSTFL
  HQEGKREKITPRNGELFHCVSENEHGAPTRKDMVRSSFVTRHSRIPVLAQEIDSTLESSS
  PVSAKEKLLQKKAYQPDLVKLLVEKRQFKSFLGDLSSASDKLLEEKLATVPAPFCEEEVL
  TPFSRLTVDSHLSRSAEDSFLSPIISQSRKSKIPRPVSWVNTDQVNSSTSSQFFPRPPPG
  KPPTRPGVEARLRRYKVLGSSNSDSDLFSRLAQILQNGSQKPRSTTQCKSPGSPHNPKTP
  PKSPVVPRRSPSASPRSSSLPRTSSSSPSRAGRPHHDQRSSSPHLGRSKSPPSHSGSSSS
  RRSCQQEHCKPSKNGLKGSGSLHHHSASTKTPQGKSKPASKLSR

• Sequence length: 1244

Pathways

Reactome:

Anchoring of the basal body to the plasma membrane

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
Spinocerebellar ataxia type 11	Likely pathogenic; Pathogenic	rs778218227, rs770444240, rs80356538, rs80356539, rs2140757755, rs318240735	RCV001647210 RCV001849234 RCV000000895 RCV000000896 RCV002226594 RCV000034277	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA, SPINOCEREBELLAR	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal dominant cerebellar ataxia	Likely benign; Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic ataxia	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 11	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIAS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TTBK2-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	25473830		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic lateral sclerosis	Pubtator	37059819	Associate	★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	24030952	Associate	★☆☆☆☆ Found in Text Mining only
Ataxia, Spinocerebellar	Spinocerebellar Ataxia	BEFREE	18037885, 21548880, 23141541, 27165044		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ataxia, Spinocerebellar	Spinocerebellar Ataxia	CTD_human_DG	18037885		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cerebellar atrophy	Cerebellar atrophy	BEFREE	31485862		★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathy	Pubtator	34499853	Associate	★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Frontotemporal dementia	Frontotemporal dementia	BEFREE	25473830		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	28219405		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	28219405, 31858557, 32196629	Associate	★☆☆☆☆ Found in Text Mining only
Horizontal Nystagmus	Horizontal nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28219405		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	BEFREE	21548880		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	28219405		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	31034749		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progressive cerebellar ataxia	Cerebellar Ataxia	BEFREE	31485862		★☆☆☆☆ Found in Text Mining only
Progressive cerebellar ataxia	Cerebellar Ataxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal carcinoma	Renal Carcinoma	BEFREE	22020623		★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	22020623		★☆☆☆☆ Found in Text Mining only
Small cell carcinoma of lung	Lung carcinoma	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
SPINOCEREBELLAR ATAXIA 11	Spinocerebellar Ataxia	BEFREE	18037885, 20667868, 23141541, 27165044, 30532139, 31455668		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 11	Spinocerebellar Ataxia	CLINVAR_DG	18037885		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 11	Spinocerebellar Ataxia	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 11	Spinocerebellar Ataxia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spinocerebellar Ataxia Type 1	Spinocerebellar Ataxia	CTD_human_DG	18037885		★☆☆☆☆ Found in Text Mining only
Spinocerebellar ataxia type 11	Spinocerebellar Ataxia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Spinocerebellar Ataxia Type 2	Spinocerebellar Ataxia	CTD_human_DG	18037885		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 4	Spinocerebellar Ataxia	CTD_human_DG	18037885		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 5	Spinocerebellar Ataxia	CTD_human_DG	18037885		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 6 (disorder)	Spinocerebellar Ataxia	CTD_human_DG	18037885		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 7	Spinocerebellar Ataxia	CTD_human_DG	18037885		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxias	Spinocerebellar ataxia	Pubtator	39930500	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spinocerebellar Degeneration	Spinocerebellar Degeneration	BEFREE	18037885		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Degeneration	Spinocerebellar Degeneration	LHGDN	18037885		★☆☆☆☆ Found in Text Mining only
Spinocerebellar tract degeneration	Spinocerebellar Degeneration	BEFREE	18037885		★☆☆☆☆ Found in Text Mining only
Tauopathies	Tauopathies	BEFREE	29409526		★☆☆☆☆ Found in Text Mining only
Vertical Nystagmus	Vertical nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only