Autosomal recessive spinocerebellar ataxia 10

Summary

Autosomal recessive spinocerebellar ataxia 10 (MONDO:0013392) is a disease caused by ANO10 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ANO10 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 125
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		14	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0012379	Abnormal enzyme/coenzyme activity	Very frequent (80-99%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0000608	Macular degeneration	Frequent (30-79%)
HP:0000641	Dysmetric saccades	Frequent (30-79%)
HP:0001152	Saccadic smooth pursuit	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001310	Dysmetria	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0001348	Brisk reflexes	Frequent (30-79%)
HP:0001350	Slurred speech	Frequent (30-79%)
HP:0001761	Pes cavus	Frequent (30-79%)
HP:0002070	Limb ataxia	Frequent (30-79%)
HP:0002078	Truncal ataxia	Frequent (30-79%)
HP:0002197	Generalized-onset seizure	Frequent (30-79%)
HP:0002380	Fasciculations	Frequent (30-79%)
HP:0003457	EMG abnormality	Frequent (30-79%)
HP:0007240	Progressive gait ataxia	Frequent (30-79%)
HP:0008969	Leg muscle stiffness	Frequent (30-79%)
HP:0010545	Downbeat nystagmus	Frequent (30-79%)
HP:0011448	Ankle clonus	Frequent (30-79%)
HP:0000503	Tortuosity of conjunctival vessels	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000651	Diplopia	Occasional (5-29%)
HP:0000666	Horizontal nystagmus	Occasional (5-29%)
HP:0001256	Intellectual disability, mild	Occasional (5-29%)
HP:0002080	Intention tremor	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive spinocerebellar ataxia 10
Mondo ID	MONDO:0013392
OMIM	613728
Orphanet	284289
DOID	DOID:0050999
UMLS	C3150998
MedGen	462348
GARD	0017314
Is cancer (heuristic)	no

Also known as: ANO10 autosomal recessive cerebellar ataxia · autosomal recessive cerebellar ataxia caused by mutation in ANO10 · autosomal recessive spinocerebellar ataxia type 10 · SCAR10 · spinocerebellar ataxia, autosomal recessive 10 · spinocerebellar ataxia, autosomal recessive type 10

Data availability: 125 ClinVar variants · 4 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 recessive disease › autosomal recessive cerebellar ataxia › autosomal recessive spinocerebellar ataxia 10

Related subtypes (28): Charlevoix-Saguenay spastic ataxia, infantile-onset autosomal recessive nonprogressive cerebellar ataxia, autosomal recessive spinocerebellar ataxia 7, autosomal recessive ataxia, Beauce type, RIDDLE syndrome, autosomal recessive ataxia due to ubiquinone deficiency, ataxia with oculomotor apraxia type 3, autosomal recessive spinocerebellar ataxia 14, autosomal recessive spinocerebellar ataxia 16, Lichtenstein-Knorr syndrome, autosomal recessive spinocerebellar ataxia 20, spinocerebellar ataxia, autosomal recessive 22, spinocerebellar ataxia, autosomal recessive 24, autosomal recessive cerebellar ataxia - epilepsy - intellectual disability syndrome, autosomal recessive congenital cerebellar ataxia, autosomal recessive metabolic cerebellar ataxia, autosomal recessive degenerative and progressive cerebellar ataxia, autosomal recessive syndromic cerebellar ataxia, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy, spinocerebellar ataxia, autosomal recessive 29, spinocerebellar ataxia, autosomal recessive 30, spinocerebellar ataxia, autosomal recessive 31, spinocerebellar ataxia, autosomal recessive 27, spinocerebellar ataxia, autosomal recessive 28, spinocerebellar ataxia, autosomal recessive 25, spinocerebellar ataxia, autosomal recessive 26, spinocerebellar ataxia, autosomal recessive 32, spinocerebellar ataxia, autosomal recessive 33

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

125 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 27 conflicting classifications of pathogenicity, 16 pathogenic, 13 likely pathogenic, 11 pathogenic/likely pathogenic, 11 benign, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027440	NM_018075.5(ANO10):c.206T>A (p.Leu69Ter)	ANO10	Pathogenic	criteria provided, single submitter
1064587	NM_018075.5(ANO10):c.1163-9A>G	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323907	NM_018075.5(ANO10):c.139+1G>T	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162016	NM_018075.5(ANO10):c.132dup (p.Asp45fs)	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162018	NM_018075.5(ANO10):c.1144G>T (p.Glu382Ter)	ANO10	Pathogenic	criteria provided, single submitter
1675913	NM_018075.5(ANO10):c.1219-1G>T	ANO10	Pathogenic	criteria provided, multiple submitters, no conflicts
1705343	NM_018075.5(ANO10):c.1056dup (p.Glu353Ter)	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2809084	NM_018075.5(ANO10):c.710G>A (p.Trp237Ter)	ANO10	Pathogenic	criteria provided, multiple submitters, no conflicts
2864526	NM_018075.5(ANO10):c.1519del (p.Tyr507fs)	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2962292	NM_018075.5(ANO10):c.986C>G (p.Ser329Ter)	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2982219	NM_018075.5(ANO10):c.1244C>G (p.Ser415Ter)	ANO10	Pathogenic	criteria provided, multiple submitters, no conflicts
31057	NM_018075.5(ANO10):c.1529T>G (p.Leu510Arg)	ANO10	Pathogenic	no assertion criteria provided
31058	NM_018075.5(ANO10):c.1150_1151del (p.Leu384fs)	ANO10	Pathogenic	criteria provided, multiple submitters, no conflicts
31060	NM_018075.5(ANO10):c.1604del (p.Ala534_Leu535insTer)	ANO10	Pathogenic	criteria provided, multiple submitters, no conflicts
3589163	NM_018075.5(ANO10):c.1121_1145del (p.Asn374fs)	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3902574	NM_018075.5(ANO10):c.1162G>T (p.Glu388Ter)	ANO10	Pathogenic	criteria provided, single submitter
3907035	NC_000003.11:g.(43607220_43616300)_(43621965_43640023)del	ANO10	Pathogenic	criteria provided, single submitter
4081732	NM_018075.5(ANO10):c.1093_1097delinsC (p.Ile365fs)	ANO10	Pathogenic	criteria provided, single submitter
4081740	NM_018075.5(ANO10):c.50_51dup (p.Val19fs)	ANO10	Pathogenic	criteria provided, single submitter
434213	NM_018075.5(ANO10):c.306C>A (p.Tyr102Ter)	ANO10	Pathogenic	criteria provided, single submitter
434215	NM_018075.5(ANO10):c.96del (p.Glu33fs)	ANO10	Pathogenic	criteria provided, multiple submitters, no conflicts
446835	NM_018075.5(ANO10):c.473-2A>G	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
452043	NM_018075.5(ANO10):c.124A>T (p.Lys42Ter)	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
503974	NM_018075.5(ANO10):c.289del (p.Thr96_Met97insTer)	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
807373	NM_018075.5(ANO10):c.1025G>A (p.Trp342Ter)	ANO10	Pathogenic	criteria provided, multiple submitters, no conflicts
976688	NM_018075.5(ANO10):c.1551dup (p.Ala518fs)	ANO10	Pathogenic	criteria provided, multiple submitters, no conflicts
986820	NM_018075.5(ANO10):c.1009T>G (p.Phe337Val)	ANO10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805383	NM_018075.5(ANO10):c.1A>G (p.Met1Val)	ANO10	Likely pathogenic	criteria provided, single submitter
2573043	NM_018075.5(ANO10):c.101G>A (p.Trp34Ter)	ANO10	Likely pathogenic	criteria provided, single submitter
2637529	NC_000003.11:g.(43640159_43641875)_(43647356_43663400)del	ANO10	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ANO10	Strong	Autosomal recessive	autosomal recessive spinocerebellar ataxia 10	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANO10	Orphanet:284289	Adult-onset autosomal recessive cerebellar ataxia

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
ANO10	HGNC:25519	ENSG00000160746	Q9NW15	Anoctamin-10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANO10	Anoctamin-10	Does not exhibit calcium-activated chloride channel (CaCC) activity.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANO10	Other/Unknown	no		Anoctamin, Anoctamin_TM

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
duodenum	1
mucosa of transverse colon	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANO10	271	ubiquitous	marker	stromal cell of endometrium, mucosa of transverse colon, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANO10	766

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANO10	Q9NW15	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Induction of Cell-Cell Fusion	1	878.5×	0.011	ANO10
Late SARS-CoV-2 Infection Events	1	292.8×	0.017	ANO10
Stimuli-sensing channels	1	135.9×	0.025	ANO10
Ion channel transport	1	96.0×	0.025	ANO10
SARS-CoV-2 Infection	1	80.4×	0.025	ANO10
SARS-CoV Infections	1	55.4×	0.030	ANO10
Viral Infection Pathways	1	30.8×	0.045	ANO10
Transport of small molecules	1	25.1×	0.045	ANO10
Infectious disease	1	24.8×	0.045	ANO10
Disease	1	13.1×	0.076	ANO10

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
chloride transmembrane transport	1	237.3×	0.005	ANO10
monoatomic ion transmembrane transport	1	208.1×	0.005	ANO10

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ANO10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ANO10

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)
ANO10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.