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TTBK2

gene
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Also known as KIAA0847

Summary

TTBK2 (tau tubulin kinase 2, HGNC:19141) is a protein-coding gene on chromosome 15q15.2, encoding Tau-tubulin kinase 2 (Q6IQ55). 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 recruitment of IFT proteins, which bu….

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 cerebellum and brainstem.

Source: NCBI Gene 146057 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): spinocerebellar ataxia type 11 (Strong, GenCC)
  • GWAS associations: 3
  • Clinical variants (ClinVar): 544 total — 6 pathogenic, 4 likely-pathogenic
  • Phenotypes (HPO): 21
  • Druggable target: yes
  • MANE Select transcript: NM_173500

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:19141
Approved symbolTTBK2
Nametau tubulin kinase 2
Location15q15.2
Locus typegene with protein product
StatusApproved
AliasesKIAA0847
Ensembl geneENSG00000128881
Ensembl biotypeprotein_coding
OMIM611695
Entrez146057

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000267890, ENST00000562880, ENST00000564431, ENST00000566931, ENST00000567274, ENST00000567485, ENST00000567840, ENST00000903061, ENST00000903062

RefSeq mRNA: 1 — MANE Select: NM_173500 NM_173500

CCDS: CCDS42029

Canonical transcript exons

ENST00000267890 — 15 exons

ExonStartEnd
ENSE000008841794275197442753247
ENSE000009424764282792842828032
ENSE000009424774281703242817097
ENSE000009424804279464442794801
ENSE000012934434281061442810739
ENSE000013008024277703142777242
ENSE000013261884277513542775723
ENSE000013273104278341942783635
ENSE000016609224281168842811780
ENSE000017874634287261142872758
ENSE000025994304273873042746257
ENSE000026115754292043842920778
ENSE000034758064282993842830078
ENSE000036574584284036042840433
ENSE000036887154287854942878684

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 94.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8545 / max 172.2434, expressed in 1700 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
1495726.10931569
1495731.4426785
1495741.2984728
2074880.00423

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
lateral nuclear group of thalamusUBERON:000273694.24gold quality
Brodmann (1909) area 23UBERON:001355493.35gold quality
ponsUBERON:000098893.11gold quality
parietal lobeUBERON:000187291.18gold quality
postcentral gyrusUBERON:000258191.12gold quality
substantia nigra pars compactaUBERON:000196589.72gold quality
cerebellar vermisUBERON:000472089.72gold quality
spermCL:000001989.37gold quality
superior vestibular nucleusUBERON:000722789.00gold quality
primary visual cortexUBERON:000243688.95gold quality
superior frontal gyrusUBERON:000266188.49gold quality
secondary oocyteCL:000065588.29gold quality
occipital lobeUBERON:000202188.03gold quality
middle temporal gyrusUBERON:000277187.36gold quality
substantia nigra pars reticulataUBERON:000196686.57gold quality
male germ cellCL:000001586.00gold quality
entorhinal cortexUBERON:000272885.86gold quality
ventral tegmental areaUBERON:000269185.48gold quality
dorsal root ganglionUBERON:000004485.33gold quality
inferior vagus X ganglionUBERON:000536385.20gold quality
mucosa of paranasal sinusUBERON:000503085.00gold quality
lateral globus pallidusUBERON:000247684.84gold quality
calcaneal tendonUBERON:000370184.64gold quality
monocyteCL:000057684.34gold quality
left testisUBERON:000453384.14gold quality
mononuclear cellCL:000084284.02gold quality
right testisUBERON:000453483.70gold quality
trigeminal ganglionUBERON:000167583.44gold quality
leukocyteCL:000073883.32gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099183.29gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

ExperimentMarker?Max mean expression
E-GEOD-100618yes428.27
E-ANND-3yes6.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

121 targeting TTBK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-5692A100.0074.406850
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-6833-3P100.0070.633197
HSA-MIR-8485100.0077.574731
HSA-MIR-5692B100.0071.322622
HSA-MIR-5692C100.0071.322622
HSA-MIR-4768-5P100.0069.492861
HSA-MIR-6798-5P100.0065.77699
HSA-MIR-340-5P100.0072.504437
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-548N99.9871.944170
HSA-MIR-60799.9773.625593
HSA-MIR-590-3P99.9674.346478
HSA-LET-7C-3P99.9573.422862
HSA-MIR-96-5P99.9572.802140
HSA-MIR-548AB99.9571.313488
HSA-MIR-55999.9572.283609
HSA-MIR-141-3P99.9472.792421
HSA-MIR-200A-3P99.9472.682420
HSA-MIR-548I99.9471.253481
HSA-MIR-548A-5P99.9471.273482
HSA-MIR-548AD-5P99.9471.233502
HSA-MIR-548AE-5P99.9471.233502
HSA-MIR-548AK99.9471.243488
HSA-MIR-548AM-5P99.9471.243488
HSA-MIR-548AP-5P99.9471.143489
HSA-MIR-548AQ-5P99.9471.343426

Literature-anchored findings (GeneRIF, showing 25)

  • These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration. (PMID:18037885)
  • that SCA11 is an extremely rare cause for dominantly inherited ataxias (TTBK2) in the German population. (PMID:19533200)
  • Examination the TTBK2 gene in 68 unrelated spinocerebellar ataxia patients displayed the normal elution profile, which denoted that no disease-related mutation was identified. We provided the evidence that SCA11 is a rare form of ataxia in China. (PMID:19768375)
  • two-basepair deletion (c.1306_1307delGA, p.D435fs448X in exon 12) lead to a premature stop codon in the TTBK2 gene; spinocerebellar ataxia patients had phenotypic of slowly progressive almost pure cerebellar ataxia with normal life expectancy (PMID:20667868)
  • findings reveals a major role of PRKX, TTBK2 and RSK4 in triggering Sunitinib resistance formation; data suggest transcriptional regulation of these kinases together with other proteins might play an important role in formation of Sunitinib resistance by affecting transcription factors (PMID:22020623)
  • TTBK2 is a completely novel regulator of Na(+)-coupled glucose transport. (PMID:22814243)
  • Dominant truncating mutations in human TTBK2 cause spinocerebellar ataxia type 11 (SCA11); these mutant proteins do not promote ciliogenesis and inhibit ciliogenesis in wild-type cells. (PMID:23141541)
  • data suggest that TTBK2 also acts upstream of Cep164, contributing to the assembly of distal appendages (PMID:24982133)
  • TTBK2 bound EB1 and Cep164 through its SxIP motifs and a proline-rich motif, respectively. (PMID:25297623)
  • TTBK1/2 kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as Amyotrophic lateral sclerosis and Frontotemporal lobar degeneration-TDP. (PMID:25473830)
  • TTBK2 is a multifunctional kinase involved in important cellular processes and demands augmented efforts in investigating its functions (PMID:25950000)
  • TTBK2 phosphorylates KIF2A and antagonizes KIF2A-induced depolymerization at microtubules plus ends for cell migration. (PMID:26323690)
  • TTBK2 down-regulates GluK2 activity by decreasing the receptor protein abundance in the cell membrane via RAB5-dependent endocytosis. (PMID:27607061)
  • Enhanced expression of circ-TTBK2 promoted cell proliferation, migration, and invasion, while inhibited apoptosis in glioma cells. (PMID:28219405)
  • Our findings suggest a possible etiology for the two most common frontotemporal lobar degeneration subtypes through a TTBK1/2 activation driven mechanism of neurodegeneration (PMID:29409526)
  • Spinocerebellar ataxia type 11 (SCA11)-associated mutations are dominant negative alleles and the resulting truncated protein (TTBK2SCA11) interferes with the function of full length TTBK2 in mediating ciliogenesis. (PMID:30532139)
  • The TTBK2-dependent CEP83 phosphorylation is important for early ciliogenesis steps, including ciliary vesicle docking and CP110 removal. (PMID:31455668)
  • Circular RNA TTBK2 promotes the development of human glioma cells via miR-520b/EZH2 axis. (PMID:31858557)
  • Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin kinase 2. (PMID:32129703)
  • Circular RNA TTBK2 regulates cell proliferation, invasion and ferroptosis via miR-761/ITGB8 axis in glioma. (PMID:32196629)
  • A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability. (PMID:33846249)
  • Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies. (PMID:34499853)
  • Spinocerebellar ataxia type 11 (SCA11): TTBK2 variants, functions and associated disease mechanisms. (PMID:36892783)
  • Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis. (PMID:37059819)
  • A Novel TTBK2 Mutation in a Chinese Pedigree with Spinocerebellar Ataxia 11. (PMID:37848700)

Cross-species orthologs

65 orthologs

OrganismSymbolGene ID
mus_musculusTtbk2ENSMUSG00000090100
rattus_norvegicusTtbk2ENSRNOG00000011059
drosophila_melanogasterAsatorFBGN0039908
caenorhabditis_elegansWBGENE00007049
caenorhabditis_elegansWBGENE00007269
caenorhabditis_elegansWBGENE00007305
caenorhabditis_elegansWBGENE00007335
caenorhabditis_elegansWBGENE00007448
caenorhabditis_elegansWBGENE00007777
caenorhabditis_elegansWBGENE00007791
caenorhabditis_elegansWBGENE00008088
caenorhabditis_elegansWBGENE00008423
caenorhabditis_elegansWBGENE00008464
caenorhabditis_elegansF10G8.2WBGENE00008662
caenorhabditis_elegansWBGENE00008883
caenorhabditis_elegansWBGENE00009324
caenorhabditis_elegansWBGENE00009402
caenorhabditis_elegansWBGENE00010555
caenorhabditis_elegansWBGENE00010692
caenorhabditis_elegansWBGENE00010874
caenorhabditis_elegansWBGENE00011283
caenorhabditis_elegansWBGENE00012169
caenorhabditis_elegansWBGENE00012637
caenorhabditis_elegansWBGENE00012731
caenorhabditis_elegansWBGENE00013868
caenorhabditis_elegansWBGENE00014007
caenorhabditis_elegansWBGENE00015893
caenorhabditis_elegansWBGENE00016111
caenorhabditis_elegansC34B2.3WBGENE00016388
caenorhabditis_elegansWBGENE00016513
caenorhabditis_elegansWBGENE00016541
caenorhabditis_elegansWBGENE00016673
caenorhabditis_elegansWBGENE00016765
caenorhabditis_elegansC55B7.10WBGENE00016946
caenorhabditis_elegansWBGENE00016963
caenorhabditis_elegansWBGENE00017050
caenorhabditis_elegansWBGENE00017714
caenorhabditis_elegansWBGENE00017725
caenorhabditis_elegansWBGENE00017803
caenorhabditis_elegansF33D11.7WBGENE00018004
caenorhabditis_elegansWBGENE00018122
caenorhabditis_elegansWBGENE00018123
caenorhabditis_elegansWBGENE00018202
caenorhabditis_elegansWBGENE00018203
caenorhabditis_elegansWBGENE00018745
caenorhabditis_elegansWBGENE00018839
caenorhabditis_elegansWBGENE00019086
caenorhabditis_elegansWBGENE00019119
caenorhabditis_elegansWBGENE00019459
caenorhabditis_elegansWBGENE00019556
caenorhabditis_elegansWBGENE00019561
caenorhabditis_elegansWBGENE00019562
caenorhabditis_elegansWBGENE00019642
caenorhabditis_eleganskin-35WBGENE00019769
caenorhabditis_elegansWBGENE00020071
caenorhabditis_elegansWBGENE00020072
caenorhabditis_elegansWBGENE00020223
caenorhabditis_elegansWBGENE00020580
caenorhabditis_elegansW09C3.1WBGENE00021109
caenorhabditis_elegansY47G6A.13WBGENE00021639
caenorhabditis_elegansY65B4A.9WBGENE00022032
caenorhabditis_elegansWBGENE00022102
caenorhabditis_elegansY71F9AL.2WBGENE00022108
caenorhabditis_elegansWBGENE00022705
caenorhabditis_elegansWBGENE00022707

Paralogs (12): VRK2 (ENSG00000028116), CDC7 (ENSG00000097046), VRK1 (ENSG00000100749), VRK3 (ENSG00000105053), CSNK1A1 (ENSG00000113712), CSNK1G2 (ENSG00000133275), CSNK1D (ENSG00000141551), TTBK1 (ENSG00000146216), CSNK1G3 (ENSG00000151292), CSNK1G1 (ENSG00000169118), CSNK1A1L (ENSG00000180138), CSNK1E (ENSG00000213923)

Protein

Protein identifiers

Tau-tubulin kinase 2 — Q6IQ55 (reviewed: Q6IQ55)

All UniProt accessions (5): Q6IQ55, A0A0B4J292, H3BMY7, H3BQ25, H3BTY5

UniProt curated annotations — full annotation on UniProt →

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 recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro. Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis. Required for recruitment of CPLANE2 and INTU to the mother centriole.

Subunit / interactions. Interacts with CEP164. Interacts with MCRS1; the interaction is required for recruitment of TTBK2 to the mother centriole.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Cilium basal body. Microtubule organizing center. Centrosome. Centriole. Cytosol. Nucleus.

Disease relevance. Spinocerebellar ataxia 11 (SCA11) [MIM:604432] Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA11 is an autosomal dominant cerebellar ataxia (ADCA). It is a relatively benign, late-onset, slowly progressive neurologic disorder. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family.

Isoforms (3)

UniProt IDNamesCanonical?
Q6IQ55-11yes
Q6IQ55-22
Q6IQ55-33

RefSeq proteins (1): NP_775771* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR017441Protein_kinase_ATP_BSBinding_site
IPR047915TTBK2_STKcDomain
IPR050235CK1_Ser-Thr_kinase-likeFamily

Pfam: PF00069

Enzyme classification (BRENDA):

  • EC 2.7.11.26 — tau-protein kinase (BRENDA: 18 organisms, 200 substrates, 549 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

  • L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
  • L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (71 total): sequence variant 15, helix 14, strand 8, compositionally biased region 6, mutagenesis site 5, turn 5, splice variant 4, modified residue 3, region of interest 3, sequence conflict 3, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDBMethodResolution (Å)
6VRFX-RAY DIFFRACTION1.5
7Q8ZX-RAY DIFFRACTION1.57
7Q8YX-RAY DIFFRACTION1.6
7Q90X-RAY DIFFRACTION1.6
6U0KX-RAY DIFFRACTION1.74
7O3BX-RAY DIFFRACTION2.4

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6IQ55-F149.550.24

Antibody-complex structures (SAbDab): 1 — 7O3B

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 141 (proton acceptor)

Ligand- & substrate-binding residues (2): 27–35; 50

Post-translational modifications (3): 445, 786, 1103

Mutagenesis-validated functional residues (5):

PositionPhenotype
50leads to inactivation/destabilization of the protein.
143leads to inactivation/destabilization of the protein.
163abolishes serine/threonine-protein kinase activity.
181impaired serine/threonine-protein kinase activity.
184impaired serine/threonine-protein kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-5620912Anchoring of the basal body to the plasma membrane

MSigDB gene sets: 260 (showing top): RNGTGGGC_UNKNOWN, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RORA1_01, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_PEPTIDYL_SERINE_MODIFICATION, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION

GO Biological Process (21): microtubule cytoskeleton organization (GO:0000226), negative regulation of microtubule depolymerization (GO:0007026), signal transduction (GO:0007165), smoothened signaling pathway (GO:0007224), intracellular protein localization (GO:0008104), regulation of smoothened signaling pathway (GO:0008589), peptidyl-serine phosphorylation (GO:0018105), cerebellum development (GO:0021549), cerebellar granular layer development (GO:0021681), neural tube development (GO:0021915), cerebellar granule cell precursor tangential migration (GO:0021935), regulation of cell migration (GO:0030334), forebrain development (GO:0030900), embryonic digit morphogenesis (GO:0042733), cilium assembly (GO:0060271), negative regulation of protein localization to microtubule (GO:1902817), positive regulation of non-motile cilium assembly (GO:1902857), embryonic brain development (GO:1990403), protein phosphorylation (GO:0006468), cell projection organization (GO:0030030), negative regulation of protein localization (GO:1903828)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), kinesin binding (GO:0019894), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), microtubule plus-end binding (GO:0051010), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), centriole (GO:0005814), cytosol (GO:0005829), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), ciliary base (GO:0097546), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Assembly of the 9+0 primary cilium1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure5
anatomical structure development3
cilium3
protein kinase activity2
cytoskeletal protein binding2
microtubule organizing center2
intracellular membraneless organelle2
cytoskeleton organization1
microtubule-based process1
microtubule depolymerization1
negative regulation of microtubule polymerization or depolymerization1
regulation of microtubule depolymerization1
negative regulation of protein depolymerization1
negative regulation of supramolecular fiber organization1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
cell surface receptor signaling pathway1
macromolecule localization1
smoothened signaling pathway1
regulation of signal transduction1
protein phosphorylation1
peptidyl-serine modification1
metencephalon development1
cerebellar cortex development1
nervous system development1
tube development1
chordate embryonic development1
epithelium development1
hindbrain tangential cell migration1
cell migration1
regulation of cell motility1
brain development1
embryonic limb morphogenesis1
embryonic morphogenesis1
axoneme assembly1
intraciliary transport involved in cilium assembly1
cilium organization1

Protein interactions and networks

STRING

1452 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
TTBK2CEP164Q9UPV0985
TTBK2SPTBN2O15020876
TTBK2ATXN10Q9UBB4837
TTBK2ATXN7O15265782
TTBK2CACNA1AP78510765
TTBK2FBF1Q8TES7738
TTBK2CCP110O43303735
TTBK2CEP83Q9Y592732
TTBK2SCLT1Q96NL6690
TTBK2PPP2R2BQ00005684
TTBK2CEP97Q8IW35677
TTBK2CEP89Q96ST8669
TTBK2KCNC3Q14003661
TTBK2ATXN1P54253620
TTBK2KIF24Q5T7B8606

IntAct

28 interactions, top by confidence:

ABTypeScore
KLHL12TTBK2psi-mi:“MI:0915”(physical association)0.720
TTBK2KLHL12psi-mi:“MI:0915”(physical association)0.720
CFTRESYT2psi-mi:“MI:0914”(association)0.710
GABARAPL2IPO5psi-mi:“MI:0914”(association)0.690
CEP164TTBK2psi-mi:“MI:0914”(association)0.680
TTBK2CEP164psi-mi:“MI:0915”(physical association)0.680
CEP164TTBK2psi-mi:“MI:0915”(physical association)0.680
GNG2GNB5psi-mi:“MI:0914”(association)0.530
CRKBCR/ABL fusionpsi-mi:“MI:0914”(association)0.460
COPS5FBLL1psi-mi:“MI:0914”(association)0.350
GABARAPL2psi-mi:“MI:0914”(association)0.350
CFTRMYH7Bpsi-mi:“MI:0914”(association)0.350
CSNK2A1RPS3Apsi-mi:“MI:0914”(association)0.350
MAPRE1SCAMP1psi-mi:“MI:0914”(association)0.350
FTLSH3PXD2Bpsi-mi:“MI:0914”(association)0.350
TTBK1GABARAPpsi-mi:“MI:0914”(association)0.350
TTBK2psi-mi:“MI:0915”(physical association)0.000
TTBK2KLHL12psi-mi:“MI:0915”(physical association)0.000

BioGRID (30): TTBK2 (Two-hybrid), TTBK2 (Affinity Capture-MS), TTBK2 (Affinity Capture-MS), TTBK2 (Affinity Capture-MS), TTBK2 (Affinity Capture-MS), TTBK2 (Co-localization), TTBK2 (Affinity Capture-RNA), TTBK2 (Affinity Capture-RNA), TTBK2 (Synthetic Lethality), TTBK2 (Affinity Capture-Western), TTBK2 (Affinity Capture-MS), TTBK2 (Two-hybrid), TTBK2 (Proximity Label-MS), TTBK2 (Proximity Label-MS), TTBK2 (Proximity Label-MS)

ESM2 similar proteins: A0A087WXM9, A0A1B0GVH6, A0A2K1J5A5, A0A2K1JJ00, A2AWL7, B0S6S9, B3DHS1, B4GBA9, B4P8I0, D3Z3C6, E9Q286, O14513, O60673, Q0P4G8, Q0P4S0, Q1LV19, Q28DZ0, Q290S5, Q3UVR3, Q4V7J0, Q5EXX3, Q5RD08, Q5VWN6, Q5VYV7, Q61493, Q641I1, Q6IQ55, Q6NS59, Q6P6I6, Q6ZPK7, Q703I1, Q7TSH4, Q80U59, Q86XD8, Q8IWI9, Q8MJ06, Q8NAP3, Q8TAL5, Q90ZS6, Q92628

Diamond homologs: A7E3X2, B9VVJ6, O15726, O19175, O74135, O76324, O80888, P16912, P22517, P23291, P23292, P28327, P29295, P34516, P34633, P35507, P35508, P35509, P39962, P40230, P40233, P40234, P40235, P40236, P42158, P42168, P48729, P48730, P49615, P49674, P51166, P54367, P67827, P67828, P67829, P67962, P67963, P78368, P81123, P97633

SIGNOR signaling

2 interactions.

AEffectBMechanism
TTBK2“down-regulates quantity”MPHOSPH9phosphorylation
TTBK2“down-regulates activity”KIF2Aphosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

544 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic6
Likely pathogenic4
Uncertain significance310
Likely benign99
Benign39

Top pathogenic / likely-pathogenic (10)

Variant IDHGVSClassification
1256330NM_173500.4(TTBK2):c.1232dup (p.Asn412fs)Pathogenic
1256335NM_173500.4(TTBK2):c.2983del (p.Leu995fs)Pathogenic
41375NM_173500.4(TTBK2):c.1306_1307del (p.Asp436fs)Pathogenic
847NM_173500.4(TTBK2):c.1329dup (p.Arg444fs)Pathogenic
848NM_173500.4(TTBK2):c.1287_1288del (p.Glu429fs)Pathogenic
872174NM_173500.4(TTBK2):c.2450C>G (p.Ser817Ter)Pathogenic
1027488NM_173500.4(TTBK2):c.239T>A (p.Phe80Tyr)Likely pathogenic
1298326NM_173500.4(TTBK2):c.3466C>T (p.Arg1156Ter)Likely pathogenic
1679151NM_173500.4(TTBK2):c.1675del (p.Gln559fs)Likely pathogenic
4082536NM_173500.4(TTBK2):c.1229_1230insACCA (p.Ala411fs)Likely pathogenic

SpliceAI

3565 predictions. Top by Δscore:

VariantEffectΔscore
15:42775725:T:Cacceptor_gain1.0000
15:42775725:T:TCacceptor_gain1.0000
15:42777239:CAGC:Cacceptor_gain1.0000
15:42777243:C:CCacceptor_gain1.0000
15:42777248:C:CTacceptor_gain1.0000
15:42783417:A:Cdonor_loss1.0000
15:42783418:C:Adonor_loss1.0000
15:42783439:T:Cdonor_gain1.0000
15:42783631:CAATT:Cacceptor_gain1.0000
15:42783632:AATT:Aacceptor_gain1.0000
15:42783633:ATT:Aacceptor_gain1.0000
15:42783634:TT:Tacceptor_gain1.0000
15:42783635:TCT:Tacceptor_loss1.0000
15:42783636:C:Aacceptor_loss1.0000
15:42783636:C:CCacceptor_gain1.0000
15:42783639:CA:Cacceptor_gain1.0000
15:42783640:A:ACacceptor_gain1.0000
15:42783640:A:Cacceptor_gain1.0000
15:42783642:A:ACacceptor_gain1.0000
15:42783642:A:Cacceptor_gain1.0000
15:42811784:CA:Cacceptor_gain1.0000
15:42811785:A:Cacceptor_gain1.0000
15:42817030:AC:Adonor_gain1.0000
15:42817031:CC:Cdonor_gain1.0000
15:42817109:CCA:Cacceptor_gain1.0000
15:42817110:CA:Cacceptor_gain1.0000
15:42817111:A:ACacceptor_gain1.0000
15:42817111:A:Cacceptor_gain1.0000
15:42827926:A:ACdonor_gain1.0000
15:42827927:C:CCdonor_gain1.0000

AlphaMissense

8157 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
15:42794733:C:AW297C1.000
15:42794733:C:GW297C1.000
15:42794735:A:GW297R1.000
15:42794735:A:TW297R1.000
15:42811703:T:AR227S1.000
15:42811703:T:GR227S1.000
15:42811704:C:GR227T1.000
15:42811706:C:AW226C1.000
15:42811706:C:GW226C1.000
15:42811707:C:GW226S1.000
15:42811708:A:GW226R1.000
15:42811708:A:TW226R1.000
15:42811731:T:AE218V1.000
15:42811732:C:TE218K1.000
15:42811756:A:GW210R1.000
15:42811756:A:TW210R1.000
15:42811758:A:GL209P1.000
15:42811761:T:AD208V1.000
15:42811761:T:CD208G1.000
15:42811761:T:GD208A1.000
15:42811762:C:AD208Y1.000
15:42811762:C:GD208H1.000
15:42811764:T:AD207V1.000
15:42811765:C:GD207H1.000
15:42811774:C:GG204R1.000
15:42811774:C:TG204R1.000
15:42817057:G:TA193E1.000
15:42817061:A:GY192H1.000
15:42817064:G:TR191S1.000
15:42817066:A:TV190D1.000

dbSNP variants (sampled 300 via entrez): RS1000002157 (15:42862678 C>T), RS1000019062 (15:42894008 C>T), RS1000019825 (15:42850366 T>C), RS1000045139 (15:42775419 G>A), RS1000100463 (15:42825355 T>C), RS1000102588 (15:42869249 G>C), RS1000102918 (15:42765493 C>T), RS1000107632 (15:42852839 G>A,T), RS1000137687 (15:42752844 T>A), RS1000140198 (15:42796393 C>A,T), RS1000149345 (15:42843566 C>T), RS1000218600 (15:42745572 T>C), RS1000225290 (15:42843692 GAGGCTGC>G), RS1000229078 (15:42799820 T>C), RS1000247286 (15:42790924 T>A,C)

Disease associations

OMIM: gene MIM:611695 | disease phenotypes: MIM:604432, MIM:108600

GenCC curated gene-disease

DiseaseClassificationInheritance
spinocerebellar ataxia type 11StrongAutosomal dominant

Mondo (3): spinocerebellar ataxia type 11 (MONDO:0011464), spastic ataxia (MONDO:0017845), hereditary ataxia (MONDO:0100309)

Orphanet (3): Spinocerebellar ataxia type 11 (Orphanet:98767), Spastic ataxia (Orphanet:316226), Hereditary ataxia (Orphanet:183518)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000639Nystagmus
HP:0000666Horizontal nystagmus
HP:0001260Dysarthria
HP:0001272Cerebellar atrophy
HP:0001288Gait disturbance
HP:0001332Dystonia
HP:0001347Hyperreflexia
HP:0002015Dysphagia
HP:0002066Gait ataxia
HP:0002070Limb ataxia
HP:0002073Progressive cerebellar ataxia
HP:0002078Truncal ataxia
HP:0002141Gait imbalance
HP:0003584Late onset
HP:0003621Juvenile onset
HP:0007256Abnormal pyramidal sign
HP:0008003Jerky ocular pursuit movements
HP:0009830Peripheral neuropathy
HP:0010544Vertical nystagmus
HP:0011462Young adult onset

GWAS associations

3 associations (top):

StudyTraitp-value
GCST003031_1MGMT methylation in smokers3.000000e-07
GCST008103_43Bipolar disorder2.000000e-07
GCST90002383_266Hematocrit6.000000e-10

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0006959gene methylation measurement
EFO:0004348hematocrit

MeSH disease descriptors (3)

DescriptorNameTree numbers
C531684Hereditary spinal ataxia (supp.)
C564815Spastic Ataxia (supp.)
C565772Spinocerebellar Ataxia 11 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3337327 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Tau tubulin kinase (TTBK) family

ChEMBL bioactivities

45 potent at pChembl≥5 of 54 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.85IC501.4nMCHEMBL5283456
8.80IC501.6nMCHEMBL5280210
8.80IC501.6nMCHEMBL5193906
8.57IC502.7nMCHEMBL5182036
7.89IC5013nMCHEMBL5273263
6.77IC50170nMCHEMBL4528881
6.77IC50170nMCHEMBL5193906
6.31IC50490nMCHEMBL5200069
6.07IC50850nMCHEMBL5198544
6.01IC50970nMCHEMBL5193488
5.92IC501210nMCHEMBL5197789
5.92IC501210nMCHEMBL5200160
5.91IC501240nMCHEMBL5209196
5.88IC501320nMCHEMBL5185704
5.78IC501680nMCHEMBL5207783
5.76IC501750nMCHEMBL5178462
5.69IC502030nMCHEMBL5197012
5.67IC502140nMCHEMBL5187459
5.58IC502610nMCHEMBL5178965
5.57IC502700nMCHEMBL5187125
5.56IC502750nMCHEMBL5181249
5.54IC502870nMCHEMBL5193034
5.52IC503020nMCHEMBL5208565
5.52IC503050nMCHEMBL5184336
5.41IC503900nMCHEMBL5178871
5.38IC504220nMCHEMBL5204869
5.38IC504200nMCHEMBL4517951
5.35IC504490nMCHEMBL5180098
5.31IC504900nMCHEMBL5171328
5.31IC504940nMCHEMBL5188513
5.27IC505400nMCHEMBL5209161
5.24IC505700nMCHEMBL5171736
5.24IC505720nMCHEMBL5169390
5.22IC506050nMCHEMBL5206548
5.19IC506400nMCHEMBL5207918
5.17IC506700nMCHEMBL5204443
5.17IC506790nMCHEMBL5196033
5.13IC507400nMCHEMBL5186693
5.12IC507580nMCHEMBL5182006
5.08IC508400nMCHEMBL5202436
5.06IC508800nMCHEMBL1257781
5.06IC508790nMCHEMBL5179559
5.03IC509340nMSB-202190
5.03IC509300nMCHEMBL5209114
5.02IC509540nMCHEMBL5193008

PubChem BioAssay actives

45 with measured affinity, of 117 total; 44 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(3S)-1-[1-(2-aminopyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol1933482: Inhibition of TTBK2 (unknown origin)ic500.0014uM
3-[[5-[(4-amino-4-methylpiperidin-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-5-bromophenol2124223: Inhibition of TTBK2 (unknown origin)ic500.0016uM
(3S)-1-[1-(2-amino-6-methoxypyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol1933482: Inhibition of TTBK2 (unknown origin)ic500.0016uM
(3R)-1-[1-(2-amino-6-methoxypyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol1900239: Inhibition of TTBK2 (unknown origin)ic500.0027uM
(3S)-1-[1-(2-aminopyrimidin-4-yl)pyrazolo[4,5-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol1933482: Inhibition of TTBK2 (unknown origin)ic500.0130uM
3-[[5-[(4-amino-4-methylcyclohexyl)amino]pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-5-bromophenol1529981: Inhibition of TTBK2 (unknown origin)ic500.1700uM
N-[4-(2-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic500.4900uM
N-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic500.8500uM
N-[4-(4-methoxyphenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic500.9700uM
N-(4-phenylmethoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic501.2100uM
N-[4-(4-bromophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic501.2100uM
N-[4-(4-nitrophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic501.2400uM
N-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic501.3200uM
N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic501.6800uM
N-[4-[[1-[(4-methylphenyl)methyl]triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic501.7500uM
N-[4-[[1-[(3-chlorophenyl)methyl]triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic502.0300uM
4-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)phenoxy]benzonitrile1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic502.1400uM
N-[4-[[1-(2-phenylethyl)triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic502.6100uM
4-N-[4-(4-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic502.7000uM
N-[4-[[1-[(2-chlorophenyl)methyl]triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic502.7500uM
N-[4-[[1-[(4-chlorophenyl)methyl]triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic502.8700uM
N-[4-(4-fluorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic503.0200uM
4-N-[4-(3-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic503.0500uM
4-N-[4-[3-(trifluoromethyl)phenoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic503.9000uM
methyl 2-bromo-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzoate1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic504.2000uM
N-[4-(4-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic504.2200uM
4-N-[4-[4-(trifluoromethyl)phenoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic504.4900uM
N-[4-(4-aminophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic504.9000uM
N-[4-(4-aminophenyl)sulfanylphenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic504.9400uM
(4-fluorophenyl)-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)phenyl]methanone1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic505.4000uM
N-(3-morpholin-4-ylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic505.7000uM
N-[4-(3,4-dichlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic505.7200uM
N-(4-pyridin-3-yloxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic506.0500uM
N-[4-(3-methylphenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic506.4000uM
3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)phenol1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic506.7000uM
N-[4-(3-methoxyphenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic506.7900uM
4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)phenol1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic507.4000uM
N-(1,3-benzodioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic507.5800uM
N-(4-propan-2-yloxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic508.4000uM
N-[4-(4-methylphenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic508.7900uM
N-[4-(trifluoromethoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic508.8000uM
1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)phenyl]ethanone1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic509.3000uM
4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]phenol1531918: Inhibition of human TTBK2 using MBP as substrate by [gamma-33P]-ATP assayic509.3400uM
N-[4-(2-methoxyphenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine1900244: Inhibition of recombinant human TTBK2 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATPic509.5400uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
trichostatin Aaffects cotreatment, decreases expression2
sodium arsenitedecreases expression, increases expression2
Valproic Acidaffects cotreatment, decreases expression2
FR900359increases phosphorylation1
methylmercuric chloridedecreases expression1
triphenyl phosphateaffects expression1
alpha-pineneaffects cotreatment, increases oxidation, increases abundance1
cobaltous chlorideincreases expression1
benzo(e)pyreneincreases methylation1
methacrylaldehydeaffects cotreatment, increases oxidation, increases abundance1
avobenzoneincreases expression1
di-n-butylphosphoric acidaffects expression1
pentabromodiphenyl etherincreases expression1
CGP 52608affects binding, increases reaction1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
abrineincreases expression1
dorsomorphindecreases expression, affects cotreatment1
(+)-JQ1 compoundincreases expression1
Decitabineaffects expression1
Sunitinibincreases expression1
Vorinostatdecreases expression1
Acroleinaffects cotreatment, increases oxidation, increases abundance1
Air Pollutantsaffects cotreatment, increases abundance, increases oxidation1
Amiodaroneincreases expression1
Benzo(a)pyreneaffects methylation1
Ethyl Methanesulfonateincreases expression1
Methapyrileneincreases methylation1
Methyl Methanesulfonateincreases expression1
Ozoneaffects cotreatment, increases oxidation, increases abundance1
Tobacco Smoke Pollutiondecreases expression1

ChEMBL screening assays

56 unique, capped per target: 56 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3388062BindingInhibition of TTBK2 (unknown origin) assessed as remaining enzyme activity at 10 uM by radioactive [33P]-ATP filter binding assaySynthesis and preliminary mechanistic evaluation of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid amides with potent antiproliferative activity on human cancer cell lines. — Eur J Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_D0MWTMOi001-A-9Induced pluripotent stem cellFemale
CVCL_D0MXTMOi001-A-10Induced pluripotent stem cellFemale
CVCL_TV03HAP1 TTBK2 (-) 1Cancer cell lineMale
CVCL_TV04HAP1 TTBK2 (-) 2Cancer cell lineMale
CVCL_TV05HAP1 TTBK2 (-) 3Cancer cell lineMale

Clinical trials (associated diseases)

13 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT00202397PHASE2COMPLETEDEffect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT01793168Not specifiedRECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04297891Not specifiedUNKNOWNPhenotypes, Biomarkers and Pathophysiology in Spastic Ataxias
NCT01360164PHASE1/PHASE2UNKNOWNSafety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Hereditary Ataxia
NCT00004306Not specifiedCOMPLETEDClinical and Molecular Correlations in Spinocerebellar Ataxia Type 10 (SCA10)
NCT04750850Not specifiedCOMPLETEDCore Stability Exercises and Hereditary Ataxia
NCT05160870Not specifiedUNKNOWNGenotype-phenotype Correlation and Pathogenic Mechanism in Hereditary Ataxia
NCT05160883Not specifiedUNKNOWNNeuroimaging Changes in Hereditary Ataxia
NCT06034886Not specifiedAVAILABLEExpanded Access Protocol of Troriluzole in Patients With Spinocerebellar Ataxia (SCA)
NCT06152133Not specifiedCOMPLETEDTelerehabilitation, Core Stability Exercises and Hereditary Ataxia (TRCore-ataxia)
NCT06267222Not specifiedENROLLING_BY_INVITATIONTrans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia
NCT07092358Not specifiedRECRUITINGHereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta
NCT07200505Not specifiedNOT_YET_RECRUITINGTelerehabilitation for Core Stability and Strength in Hereditary Ataxia

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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BioBTree
v2.0.2

Sources 79

This page pulls from 79 datasets indexed by BioBTree:

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