Spastic ataxia 11, autosomal dominant

Summary

Spastic ataxia 11, autosomal dominant (MONDO:0979230) is a disease caused by TUBA4A (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TUBA4A (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic ataxia 11, autosomal dominant
Mondo ID	MONDO:0979230
OMIM	621226
UMLS	C6012733
MedGen	1876498
GARD	0028108
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants · 1 GenCC gene-disease record.

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 spastic ataxia › spastic ataxia 11, autosomal dominant

Related subtypes (2): spastic ataxia 1, spastic ataxia 7

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3901248	E415K	TUBA4A	Pathogenic	no assertion criteria provided
3901249	NM_006000.3(TUBA4A):c.517C>T (p.Pro173Ser)	TUBA4A	Pathogenic	no assertion criteria provided
3901250	NM_006000.3(TUBA4A):c.518C>G (p.Pro173Arg)	TUBA4A	Pathogenic	no assertion criteria provided
2578200	NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys)	STK16	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 0 · 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
TUBA4A	Strong	Autosomal dominant	spastic ataxia 11, autosomal dominant	8

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TUBA4A	HGNC:12407	ENSG00000127824	P68366	Tubulin alpha-4A chain	gencc,clinvar
STK16	HGNC:11394	ENSG00000115661	O75716	Serine/threonine-protein kinase 16	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUBA4A	Tubulin alpha-4A chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
STK16	Serine/threonine-protein kinase 16	Membrane-associated protein kinase that phosphorylates on serine and threonine residues.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TUBA4A	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
STK16	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
frontal pole	1
gingiva	1
gingival epithelium	1
body of pancreas	1
mucosa of transverse colon	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBA4A	299	ubiquitous	marker	gingival epithelium, frontal pole, gingiva
STK16	192	ubiquitous	marker	mucosa of transverse colon, body of pancreas, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STK16	1,722
TUBA4A	1,118

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STK16	O75716	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBA4A	P68366	92.02

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 96. Enrichment computed across 2 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
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	543.8×	0.016	TUBA4A
Transport of connexons to the plasma membrane	1	543.8×	0.016	TUBA4A
Gap junction trafficking and regulation	1	475.8×	0.016	TUBA4A
Gap junction trafficking	1	475.8×	0.016	TUBA4A
Post-chaperonin tubulin folding pathway	1	475.8×	0.016	TUBA4A
Formation of tubulin folding intermediates by CCT/TriC	1	423.0×	0.016	TUBA4A
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	407.9×	0.016	TUBA4A
Prefoldin mediated transfer of substrate to CCT/TriC	1	393.8×	0.016	TUBA4A
Activation of AMPK downstream of NMDARs	1	380.7×	0.016	TUBA4A
RHO GTPases activate IQGAPs	1	346.1×	0.016	TUBA4A
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.016	TUBA4A
HCMV Infection	1	326.3×	0.016	TUBA4A
Chaperonin-mediated protein folding	1	300.5×	0.016	TUBA4A
Gap junction assembly	1	292.8×	0.016	TUBA4A
Nuclear Envelope (NE) Reassembly	1	292.8×	0.016	TUBA4A
Selective autophagy	1	278.5×	0.016	TUBA4A
Protein folding	1	259.6×	0.016	TUBA4A
Centrosome maturation	1	253.8×	0.016	TUBA4A
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.016	TUBA4A
Cargo trafficking to the periciliary membrane	1	248.3×	0.016	TUBA4A
Aggrephagy	1	248.3×	0.016	TUBA4A
Carboxyterminal post-translational modifications of tubulin	1	237.9×	0.016	TUBA4A
Recycling pathway of L1	1	223.9×	0.016	TUBA4A
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.016	TUBA4A
Post NMDA receptor activation events	1	203.9×	0.016	TUBA4A
Intraflagellar transport	1	200.3×	0.016	TUBA4A
Antimicrobial mechanism of IFN-stimulated genes	1	196.9×	0.016	TUBA4A
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	193.6×	0.016	TUBA4A
Activation of NMDA receptors and postsynaptic events	1	184.2×	0.016	TUBA4A
Signaling by Hedgehog	1	184.2×	0.016	TUBA4A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to transforming growth factor beta stimulus	1	138.1×	0.021	STK16
protein autophosphorylation	1	72.6×	0.021	STK16
mitotic cell cycle	1	66.9×	0.021	TUBA4A
microtubule cytoskeleton organization	1	60.6×	0.021	TUBA4A
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	STK16

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TUBA4A	COLCHICINE
STK16	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STK16	35	4
TUBA4A	22	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBA4A
VINBLASTINE	4	TUBA4A
LEVOFLOXACIN ANHYDROUS	4	TUBA4A
DOCETAXEL	4	TUBA4A
NOSCAPINE	4	TUBA4A
VINBLASTINE SULFATE	4	TUBA4A
PACLITAXEL	4	TUBA4A
LEVOFLOXACIN	4	TUBA4A
VINORELBINE	4	TUBA4A
TIRBANIBULIN	4	TUBA4A
PODOFILOX	4	TUBA4A
VINCRISTINE	4	TUBA4A
DOCETAXEL ANHYDROUS	4	TUBA4A
MOMELOTINIB	4	STK16
FEDRATINIB	4	STK16
AXITINIB	4	STK16
RUXOLITINIB	4	STK16
PALBOCICLIB	4	STK16
PACRITINIB	4	STK16
FOSTAMATINIB	4	STK16
ABEMACICLIB	4	STK16
GILTERITINIB	4	STK16
UPADACITINIB	4	STK16
PAZOPANIB	4	STK16
NINTEDANIB	4	STK16
SUNITINIB	4	STK16
MIDOSTAURIN	4	STK16
PATUPILONE	3	TUBA4A
ENZASTAURIN	3	STK16
DEFACTINIB	3	STK16

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TUBA4A	1,695	Binding:1654, Functional:35, ADMET:6
STK16	244	Binding:244

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STK16	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TUBA4A	1,695
STK16	244

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
COLCHICINE	4	TUBA4A
VINBLASTINE	4	TUBA4A
LEVOFLOXACIN ANHYDROUS	4	TUBA4A
DOCETAXEL	4	TUBA4A
NOSCAPINE	4	TUBA4A
VINBLASTINE SULFATE	4	TUBA4A
PACLITAXEL	4	TUBA4A
LEVOFLOXACIN	4	TUBA4A
VINORELBINE	4	TUBA4A
TIRBANIBULIN	4	TUBA4A
PODOFILOX	4	TUBA4A
VINCRISTINE	4	TUBA4A
DOCETAXEL ANHYDROUS	4	TUBA4A
MOMELOTINIB	4	STK16
FEDRATINIB	4	STK16
AXITINIB	4	STK16
RUXOLITINIB	4	STK16
PALBOCICLIB	4	STK16
PACRITINIB	4	STK16
FOSTAMATINIB	4	STK16
ABEMACICLIB	4	STK16
GILTERITINIB	4	STK16
UPADACITINIB	4	STK16
PAZOPANIB	4	STK16
NINTEDANIB	4	STK16
SUNITINIB	4	STK16
MIDOSTAURIN	4	STK16
PATUPILONE	3	TUBA4A
ENZASTAURIN	3	STK16
DEFACTINIB	3	STK16

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TUBA4A, STK16
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.