Spinocerebellar ataxia type 11

Summary

Spinocerebellar ataxia type 11 (MONDO:0011464) is a disease caused by TTBK2 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TTBK2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 102
• Phenotypes (HPO): 11
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		51	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0000666	Horizontal nystagmus	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0002015	Dysphagia	Very frequent (80-99%)
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0002141	Gait imbalance	Very frequent (80-99%)
HP:0008003	Jerky ocular pursuit movements	Very frequent (80-99%)
HP:0010544	Vertical nystagmus	Very frequent (80-99%)
HP:0001332	Dystonia	Very rare (<1-4%)
HP:0007256	Abnormal pyramidal sign	Very rare (<1-4%)
HP:0009830	Peripheral neuropathy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 11
Mondo ID	MONDO:0011464
MeSH	C565772
OMIM	604432
Orphanet	98767
DOID	DOID:0050961
ICD-11	743674840
SNOMED CT	719207000
UMLS	C1858351
MedGen	346799
GARD	0010475
Is cancer (heuristic)	no

Also known as: SCA11 · spinocerebellar ataxia 11 · spinocerebellar ataxia type 11

Data availability: 102 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant cerebellar ataxia › autosomal dominant cerebellar ataxia type III › spinocerebellar ataxia type 11

Related subtypes (9): spinocerebellar ataxia type 31, spinocerebellar ataxia type 6, spinocerebellar ataxia type 5, spinocerebellar ataxia type 26, spinocerebellar ataxia type 30, spinocerebellar ataxia type 38, spinocerebellar ataxia type 41, spinocerebellar ataxia type 42, spinocerebellar ataxia 45

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

102 retrieved; paginated sample, class counts are floors:

47 uncertain significance, 16 conflicting classifications of pathogenicity, 13 benign/likely benign, 11 benign, 9 likely benign, 3 likely pathogenic, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
41375	NM_173500.4(TTBK2):c.1306_1307del (p.Asp436fs)	TTBK2	Pathogenic	no assertion criteria provided
847	NM_173500.4(TTBK2):c.1329dup (p.Arg444fs)	TTBK2	Pathogenic	criteria provided, multiple submitters, no conflicts
848	NM_173500.4(TTBK2):c.1287_1288del (p.Glu429fs)	TTBK2	Pathogenic	no assertion criteria provided
1027488	NM_173500.4(TTBK2):c.239T>A (p.Phe80Tyr)	TTBK2	Likely pathogenic	criteria provided, single submitter
1298326	NM_173500.4(TTBK2):c.3466C>T (p.Arg1156Ter)	TTBK2	Likely pathogenic	no assertion criteria provided
1679151	NM_173500.4(TTBK2):c.1675del (p.Gln559fs)	TTBK2	Likely pathogenic	criteria provided, single submitter
1325245	NM_173500.4(TTBK2):c.322C>T (p.Gln108Ter)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315961	NM_173500.4(TTBK2):c.*1153G>A	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315975	NM_173500.4(TTBK2):c.3543G>A (p.Ser1181=)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315977	NM_173500.4(TTBK2):c.3418C>T (p.Pro1140Ser)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315978	NM_173500.4(TTBK2):c.3331C>G (p.Leu1111Val)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315980	NM_173500.4(TTBK2):c.3185C>T (p.Thr1062Ile)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315987	NM_173500.4(TTBK2):c.2278C>T (p.Pro760Ser)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315988	NM_173500.4(TTBK2):c.2210T>C (p.Ile737Thr)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315992	NM_173500.4(TTBK2):c.1555G>C (p.Ala519Pro)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315998	NM_173500.4(TTBK2):c.595C>T (p.Arg199Trp)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
425066	NM_173500.4(TTBK2):c.3722A>C (p.Lys1241Thr)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
448746	NM_173500.4(TTBK2):c.1274G>A (p.Arg425His)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
71891	NM_173500.4(TTBK2):c.3329G>A (p.Arg1110His)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
805613	NM_173500.4(TTBK2):c.1100A>T (p.Lys367Ile)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
884308	NM_173500.4(TTBK2):c.1499G>T (p.Arg500Leu)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
888522	NM_173500.4(TTBK2):c.2344A>G (p.Ile782Val)	TTBK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030321	NM_173500.4(TTBK2):c.2720A>G (p.Glu907Gly)	TTBK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1334080	NM_173500.4(TTBK2):c.3329G>T (p.Arg1110Leu)	TTBK2	Uncertain significance	criteria provided, single submitter
1709189	NM_173500.4(TTBK2):c.2107G>A (p.Glu703Lys)	TTBK2	Uncertain significance	criteria provided, single submitter
2437391	NM_173500.4(TTBK2):c.820C>A (p.Gln274Lys)	TTBK2	Uncertain significance	criteria provided, single submitter
2585448	NM_173500.4(TTBK2):c.331G>A (p.Gly111Ser)	TTBK2	Uncertain significance	criteria provided, single submitter
2664698	NM_173500.4(TTBK2):c.2476A>G (p.Thr826Ala)	TTBK2	Uncertain significance	criteria provided, single submitter
315962	NM_173500.4(TTBK2):c.*967G>A	TTBK2	Uncertain significance	criteria provided, single submitter
315964	NM_173500.4(TTBK2):c.*847T>C	TTBK2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TTBK2	Strong	Autosomal dominant	spinocerebellar ataxia type 11	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TTBK2	Orphanet:98767	Spinocerebellar ataxia type 11

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TTBK2	HGNC:19141	ENSG00000128881	Q6IQ55	Tau-tubulin kinase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TTBK2	Tau-tubulin kinase 2	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 t…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TTBK2	Kinase	yes	2.7.11.26	Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
pons	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TTBK2	275	ubiquitous	marker	lateral nuclear group of thalamus, Brodmann (1909) area 23, pons

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TTBK2	1,510

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTBK2	Q6IQ55	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring of the basal body to the plasma membrane	1	113.1×	0.009	TTBK2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cerebellar granule cell precursor tangential migration	1	8426.0×	0.002	TTBK2
cerebellar granular layer development	1	5617.3×	0.002	TTBK2
negative regulation of protein localization to microtubule	1	3370.4×	0.002	TTBK2
positive regulation of non-motile cilium assembly	1	1872.4×	0.002	TTBK2
embryonic brain development	1	802.5×	0.004	TTBK2
regulation of smoothened signaling pathway	1	624.1×	0.004	TTBK2
neural tube development	1	526.6×	0.004	TTBK2
negative regulation of microtubule depolymerization	1	495.6×	0.004	TTBK2
peptidyl-serine phosphorylation	1	495.6×	0.004	TTBK2
cerebellum development	1	358.6×	0.005	TTBK2
forebrain development	1	351.1×	0.005	TTBK2
embryonic digit morphogenesis	1	300.9×	0.005	TTBK2
smoothened signaling pathway	1	181.2×	0.008	TTBK2
regulation of cell migration	1	157.5×	0.008	TTBK2
microtubule cytoskeleton organization	1	121.2×	0.010	TTBK2
intracellular protein localization	1	104.7×	0.011	TTBK2
cilium assembly	1	73.6×	0.014	TTBK2
signal transduction	1	16.1×	0.062	TTBK2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TTBK2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TTBK2	56	Binding:56

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTBK2	2.7.11.26	tau-protein kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	TTBK2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TTBK2	56	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford