Spinocerebellar ataxia type 13

disease

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Also known as autosomal dominant cerebellar ataxia with intellectual disabilityautosomal dominant cerebellar ataxia with mental retardationcerebellar ataxia, autosomal dominant with intellectual disabilitycerebellar ataxia, autosomal dominant with mental retardationSCA13spinocerebellar ataxia 13

Summary

Spinocerebellar ataxia type 13 (MONDO:0011529) is a disease caused by KCNC3 (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Causal gene: KCNC3 (GenCC Strong)
Cohort genes: 2
ClinVar variants: 47
Phenotypes (HPO): 32
Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		20	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001256	Intellectual disability, mild	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0002066	Gait ataxia	Frequent (30-79%)
HP:0002070	Limb ataxia	Frequent (30-79%)
HP:0006886	Impaired distal vibration sensation	Frequent (30-79%)
HP:0009046	Difficulty running	Frequent (30-79%)
HP:0010794	Impaired visuospatial constructive cognition	Frequent (30-79%)
HP:0030187	Titubation	Frequent (30-79%)
HP:0000012	Urinary urgency	Occasional (5-29%)
HP:0000020	Urinary incontinence	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000473	Torticollis	Occasional (5-29%)
HP:0000543	Optic disc pallor	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002172	Postural instability	Occasional (5-29%)
HP:0002312	Clumsiness	Occasional (5-29%)
HP:0006801	Hyperactive deep tendon reflexes	Occasional (5-29%)
HP:0008003	Jerky ocular pursuit movements	Occasional (5-29%)
HP:0001250	Seizure	Very rare (<1-4%)
HP:0001999	Abnormal facial shape	Very rare (<1-4%)
HP:0002067	Bradykinesia	Very rare (<1-4%)
HP:0004322	Short stature	Very rare (<1-4%)
HP:0025331	Upgaze palsy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 13
Mondo ID	MONDO:0011529
MeSH	C537195
OMIM	605259
Orphanet	98768
DOID	DOID:0050963
ICD-11	1191033828
SNOMED CT	719209002
UMLS	C1854488
MedGen	344297
GARD	0009611
Is cancer (heuristic)	no

Also known as: autosomal dominant cerebellar ataxia with intellectual disability · autosomal dominant cerebellar ataxia with mental retardation · cerebellar ataxia, autosomal dominant with intellectual disability · cerebellar ataxia, autosomal dominant with mental retardation · SCA13 · spinocerebellar ataxia 13 · spinocerebellar ataxia type 13

Data availability: 47 ClinVar variants · 5 GenCC gene-disease records · 3 cell lines.

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 I › spinocerebellar ataxia type 13

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

47 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 8 benign/likely benign, 5 pathogenic, 5 conflicting classifications of pathogenicity, 1 benign, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13473	NM_004977.3(KCNC3):c.1259G>A (p.Arg420His)	KCNC3	Pathogenic	criteria provided, multiple submitters, no conflicts
13474	NM_004977.3(KCNC3):c.1344C>A (p.Phe448Leu)	KCNC3	Pathogenic	no assertion criteria provided
208671	NM_004977.3(KCNC3):c.1268G>A (p.Arg423His)	KCNC3	Pathogenic	criteria provided, multiple submitters, no conflicts
245604	NM_004977.3(KCNC3):c.1283C>T (p.Thr428Ile)	KCNC3	Pathogenic	no assertion criteria provided
522615	NM_004977.3(KCNC3):c.11_12del (p.Ser4fs)	KCNC3	Pathogenic	criteria provided, single submitter
976029	NM_004977.3(KCNC3):c.1223A>G (p.Asp408Gly)	KCNC3	Likely pathogenic	criteria provided, single submitter
1389489	NM_004977.3(KCNC3):c.34G>T (p.Gly12Trp)	KCNC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1509315	NM_004977.3(KCNC3):c.781GCGGGCGGC[3] (p.261AGG[3])	KCNC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1573340	NM_004977.3(KCNC3):c.1876G>C (p.Gly626Arg)	KCNC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2442148	NM_004977.3(KCNC3):c.1255G>A (p.Val419Ile)	KCNC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
803573	NM_004977.3(KCNC3):c.1737ACCCCCGCC[1] (p.Pro583_Pro585del)	KCNC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3654731	NM_004369.4(COL6A3):c.967G>A (p.Gly323Ser)	COL6A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029909	NM_004977.3(KCNC3):c.140G>A (p.Gly47Asp)	KCNC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1064691	NM_004977.3(KCNC3):c.1850C>T (p.Pro617Leu)	KCNC3	Uncertain significance	criteria provided, single submitter
1298307	NM_004977.3(KCNC3):c.1130T>C (p.Leu377Pro)	KCNC3	Uncertain significance	no assertion criteria provided
1298308	NM_004977.3(KCNC3):c.1876G>T (p.Gly626Trp)	KCNC3	Uncertain significance	no assertion criteria provided
1298784	NM_004977.3(KCNC3):c.2245G>A (p.Ala749Thr)	KCNC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1383414	NM_004977.3(KCNC3):c.691G>A (p.Gly231Ser)	KCNC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679719	NM_004977.3(KCNC3):c.751G>A (p.Gly251Ser)	KCNC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2302628	NM_004977.3(KCNC3):c.1822A>G (p.Thr608Ala)	KCNC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2432992	NM_004977.3(KCNC3):c.98C>G (p.Pro33Arg)	KCNC3	Uncertain significance	criteria provided, single submitter
2432993	NM_004977.3(KCNC3):c.2143C>T (p.Pro715Ser)	KCNC3	Uncertain significance	criteria provided, single submitter
2432994	NM_004977.3(KCNC3):c.1627G>A (p.Gly543Ser)	KCNC3	Uncertain significance	criteria provided, single submitter
2684248	NM_004977.3(KCNC3):c.1474A>G (p.Ile492Val)	KCNC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689283	NM_004977.3(KCNC3):c.2014C>G (p.Leu672Val)	KCNC3	Uncertain significance	criteria provided, single submitter
2689284	NM_004977.3(KCNC3):c.1903G>A (p.Gly635Arg)	KCNC3	Uncertain significance	criteria provided, single submitter
3236372	NM_004977.3(KCNC3):c.574C>G (p.His192Asp)	KCNC3	Uncertain significance	criteria provided, single submitter
3393308	NM_004977.3(KCNC3):c.1951G>C (p.Glu651Gln)	KCNC3	Uncertain significance	criteria provided, single submitter
3779779	NM_004977.3(KCNC3):c.186_192del (p.Asp63fs)	KCNC3	Uncertain significance	criteria provided, single submitter
3891441	NM_004977.3(KCNC3):c.559A>T (p.Met187Leu)	KCNC3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 5 · 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
KCNC3	Strong	Autosomal dominant	spinocerebellar ataxia type 13	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNC3	Orphanet:98768	Spinocerebellar ataxia type 13
COL6A3	Orphanet:464440	Primary dystonia, DYT27 type
COL6A3	Orphanet:610	Bethlem muscular dystrophy
COL6A3	Orphanet:646113	Intermediate collagen VI-related muscular dystrophy
COL6A3	Orphanet:75840	Ullrich congenital muscular dystrophy

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
KCNC3	HGNC:6235	ENSG00000131398	Q14003	Voltage-gated potassium channel KCNC3	gencc,clinvar
COL6A3	HGNC:2213	ENSG00000163359	P12111	Collagen alpha-3(VI) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNC3	Voltage-gated potassium channel KCNC3	Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons.
COL6A3	Collagen alpha-3(VI) chain	Collagen VI acts as a cell-binding protein.

Protein-family classification

Druggable: 2 · 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
Ion channel	1	55.8×	0.036
Antibody/Immunoglobulin	1	14.6×	0.067

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNC3	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
COL6A3	Antibody/Immunoglobulin	yes		VWF_A, Kunitz_BPTI, FN3_dom

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar vermis	1
kidney epithelium	1
right uterine tube	1
skin of hip	1
stromal cell of endometrium	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNC3	192	ubiquitous	yes	kidney epithelium, right uterine tube, cerebellar vermis
COL6A3	264	broad	marker	stromal cell of endometrium, visceral pleura, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL6A3	2,267
KCNC3	2,099

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL6A3	P12111	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNC3	Q14003	66.01

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Collagen chain trimerization	1	129.8×	0.016	COL6A3
Signaling by PDGF	1	126.9×	0.016	COL6A3
NCAM1 interactions	1	124.1×	0.016	COL6A3
Voltage gated Potassium channels	1	121.5×	0.016	KCNC3
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.016	COL6A3
Collagen degradation	1	87.8×	0.016	COL6A3
Collagen biosynthesis and modifying enzymes	1	85.2×	0.016	COL6A3
ECM proteoglycans	1	75.1×	0.016	COL6A3
Potassium Channels	1	67.2×	0.016	KCNC3
Integrin cell surface interactions	1	67.2×	0.016	COL6A3
Neuronal System	1	22.1×	0.045	KCNC3

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein tetramerization	1	312.1×	0.016	KCNC3
cortical actin cytoskeleton organization	1	300.9×	0.016	KCNC3
response to UV	1	183.2×	0.016	COL6A3
action potential	1	179.3×	0.016	KCNC3
response to glucose	1	127.7×	0.016	COL6A3
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	105.3×	0.016	COL6A3
potassium ion transport	1	95.8×	0.016	KCNC3
neuron apoptotic process	1	92.6×	0.016	COL6A3
muscle organ development	1	83.4×	0.016	COL6A3
potassium ion transmembrane transport	1	68.0×	0.018	KCNC3
protein homooligomerization	1	61.1×	0.018	KCNC3
cell adhesion	1	18.7×	0.053	COL6A3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
KCNC3	0	0
COL6A3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KCNC3	21	Binding:20, Toxicity:1

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

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	COL6A3
D	Druggable family + AlphaFold only, no drug	1	KCNC3
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KCNC3	21	—
COL6A3	0	—

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

Cohort genes: KCNC3, COL6A3