TTBK2

tau tubulin kinase 2

Basic information

Region (hg38): 15:42738730-42920809

Previous symbols: [ "SCA11" ]

Links

ENSG00000128881 ∙ NCBI:146057 ∙ OMIM:611695 ∙ HGNC:19141 ∙ Uniprot:Q6IQ55 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 11 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 11 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 11	AD	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	18037885

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTBK2 gene.

• not_provided (301 variants)
• Inborn_genetic_diseases (129 variants)
• Spinocerebellar_ataxia_type_11 (69 variants)
• not_specified (50 variants)
• TTBK2-related_disorder (11 variants)
• Spastic_ataxia (1 variants)
• Hereditary_ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTBK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000173500.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	59	6	75
missense		1	243	40	3	287
nonsense	1	2	2			5
start loss						0
frameshift	5	2	5			12
splice donor/acceptor (+/-2bp)			1			1
Total	6	5	261	99	9

Highest pathogenic variant AF is 0.00000478831

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTBK2	protein_coding	protein_coding	ENST00000267890	14	182076

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00125	124785	0	15	124800	0.0000601

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	558	659	0.847	0.0000351	8132
Missense in Polyphen		177	269.56	0.65662		3170
Synonymous	0.0958	232	234	0.992	0.0000118	2495
Loss of Function	5.66	7	50.3	0.139	0.00000292	617

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000187	0.000187
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.00	0.00
Finnish	0.0000483	0.0000464
European (Non-Finnish)	0.0000619	0.0000618
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:21548880, ECO:0000269|PubMed:23141541}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:18037885}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.0844

Intolerance Scores

• loftool: 0.435
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.12

Haploinsufficiency Scores

• pHI: 0.354
• hipred: Y
• hipred_score: 0.786
• ghis: 0.494

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ttbk2
• Phenotype: cellular phenotype; growth/size/body region 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); limbs/digits/tail phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: microtubule cytoskeleton organization;negative regulation of microtubule depolymerization;smoothened signaling pathway;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;cerebellum development;cerebellar granular layer development;cerebellar granule cell precursor tangential migration;regulation of cell migration;cilium assembly;ciliary basal body-plasma membrane docking;negative regulation of protein localization to microtubule;negative regulation of microtubule binding
• Cellular component: extracellular space;nucleus;cytoplasm;centriole;cytosol;ciliary transition zone;ciliary basal body
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;kinesin binding;tau protein binding;tau-protein kinase activity;microtubule plus-end binding