Spinocerebellar ataxia type 14

Summary

Spinocerebellar ataxia type 14 (MONDO:0011540) is a disease caused by PRKCG (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PRKCG (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 122
• Phenotypes (HPO): 15
• 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)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0002066	Gait ataxia	Very frequent (80-99%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0002070	Limb ataxia	Frequent (30-79%)
HP:0002073	Progressive cerebellar ataxia	Frequent (30-79%)
HP:0005109	Abnormality of the Achilles tendon	Frequent (30-79%)
HP:0006855	Cerebellar vermis atrophy	Frequent (30-79%)
HP:0000640	Gaze-evoked nystagmus	Occasional (5-29%)
HP:0001152	Saccadic smooth pursuit	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0002063	Rigidity	Occasional (5-29%)
HP:0002600	Hyporeflexia of lower limbs	Occasional (5-29%)
HP:0003474	Somatic sensory dysfunction	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 14
Mondo ID	MONDO:0011540
MeSH	C537196
OMIM	605361
Orphanet	98763
DOID	DOID:0050964
ICD-11	736357100
SNOMED CT	719210007
UMLS	C1854369
MedGen	343106
GARD	0009867
Is cancer (heuristic)	no

Also known as: SCA14 · spinocerebellar ataxia 14 · spinocerebellar ataxia type 14

Data availability: 122 ClinVar variants · 4 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 14

Related subtypes (29): Machado-Joseph disease, spinocerebellar ataxia type 29, spinocerebellar ataxia type 34, spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 4, cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome, autosomal dominant cerebellar ataxia, deafness and narcolepsy, spinocerebellar ataxia type 12, spinocerebellar ataxia type 13, spinocerebellar ataxia type 15/16, spinocerebellar ataxia type 17, spinocerebellar ataxia type 19/22, spinocerebellar ataxia type 21, spinocerebellar ataxia type 18, spinocerebellar ataxia type 20, spinocerebellar ataxia type 25, spinocerebellar ataxia type 8, spinocerebellar ataxia type 27, spinocerebellar ataxia type 23, spinocerebellar ataxia type 28, spinocerebellar ataxia type 35, spinocerebellar ataxia type 32, spinocerebellar ataxia type 36, cerebellar dysfunction with variable cognitive and behavioral abnormalities, spinocerebellar ataxia type 37, spinocerebellar ataxia type 40, spinocerebellar ataxia 46, neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism

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

122 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 24 likely pathogenic, 20 pathogenic, 13 benign, 9 conflicting classifications of pathogenicity, 6 benign/likely benign, 5 likely benign, 3 not provided, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027481	NM_002739.5(PRKCG):c.1308C>G (p.Tyr436Ter)	PRKCG	Pathogenic	criteria provided, single submitter
1298291	NM_002739.5(PRKCG):c.107A>G (p.His36Arg)	PRKCG	Pathogenic	no assertion criteria provided
13244	NM_002739.5(PRKCG):c.301C>T (p.His101Tyr)	PRKCG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13245	NM_002739.5(PRKCG):c.355T>C (p.Ser119Pro)	PRKCG	Pathogenic	criteria provided, single submitter
13246	NM_002739.5(PRKCG):c.383G>A (p.Gly128Asp)	PRKCG	Pathogenic	criteria provided, single submitter
13247	NM_002739.5(PRKCG):c.353G>A (p.Gly118Asp)	PRKCG	Pathogenic	criteria provided, single submitter
13248	NM_002739.5(PRKCG):c.380A>G (p.Gln127Arg)	PRKCG	Pathogenic	criteria provided, multiple submitters, no conflicts
13249	NM_002739.5(PRKCG):c.1927T>C (p.Phe643Leu)	PRKCG	Pathogenic	criteria provided, single submitter
13251	NM_002739.5(PRKCG):c.303C>G (p.His101Gln)	PRKCG	Pathogenic	no assertion criteria provided
13252	NM_002739.5(PRKCG):c.2091_*98del (p.Met697_Ter698delinsXaa)	PRKCG	Pathogenic	no assertion criteria provided
29857	NM_002739.5(PRKCG):c.530_919del	PRKCG	Pathogenic	no assertion criteria provided
29858	NM_002739.5(PRKCG):c.1438G>T (p.Asp480Tyr)	PRKCG	Pathogenic	no assertion criteria provided
42129	NM_002739.5(PRKCG):c.1078G>A (p.Gly360Ser)	PRKCG	Pathogenic	no assertion criteria provided
42148	NM_002739.5(PRKCG):c.229T>A (p.Cys77Ser)	PRKCG	Pathogenic	no assertion criteria provided
42157	NM_002739.5(PRKCG):c.300_305del (p.His101_Lys102del)	PRKCG	Pathogenic	no assertion criteria provided
42161	NM_002739.5(PRKCG):c.341G>A (p.Cys114Tyr)	PRKCG	Pathogenic	no assertion criteria provided
42163	NM_002739.5(PRKCG):c.356C>T (p.Ser119Phe)	PRKCG	Pathogenic	criteria provided, single submitter
42164	NM_002739.5(PRKCG):c.367G>A (p.Gly123Arg)	PRKCG	Pathogenic	no assertion criteria provided
42169	NM_002739.5(PRKCG):c.413T>A (p.Val138Glu)	PRKCG	Pathogenic	criteria provided, multiple submitters, no conflicts
42170	NM_002739.5(PRKCG):c.449_450delinsTT (p.Cys150Phe)	PRKCG	Pathogenic	no assertion criteria provided
42171	NM_002739.5(PRKCG):c.417C>A (p.His139Gln)	PRKCG	Pathogenic	no assertion criteria provided
1027477	NM_002739.5(PRKCG):c.358C>T (p.Leu120Phe)	PRKCG	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027478	NM_002739.5(PRKCG):c.1928T>G (p.Phe643Cys)	PRKCG	Likely pathogenic	criteria provided, single submitter
1027479	NM_002739.5(PRKCG):c.1381G>A (p.Ala461Thr)	PRKCG	Likely pathogenic	criteria provided, single submitter
1027509	NM_002739.5(PRKCG):c.380A>C (p.Gln127Pro)	PRKCG	Likely pathogenic	criteria provided, single submitter
1184519	NM_002739.5(PRKCG):c.323A>G (p.Tyr108Cys)	PRKCG	Likely pathogenic	no assertion criteria provided
1184520	NM_002739.5(PRKCG):c.381G>T (p.Gln127His)	PRKCG	Likely pathogenic	no assertion criteria provided
1184521	NM_002739.5(PRKCG):c.394T>C (p.Ser132Pro)	PRKCG	Likely pathogenic	no assertion criteria provided
13250	NM_002739.5(PRKCG):c.1081A>G (p.Ser361Gly)	PRKCG	Likely pathogenic	criteria provided, single submitter
1333855	NM_002739.5(PRKCG):c.220C>T (p.His74Tyr)	PRKCG	Likely pathogenic	criteria provided, multiple submitters, no conflicts

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
PRKCG	Definitive	Autosomal dominant	spinocerebellar ataxia type 14	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRKCG	Orphanet:98763	Spinocerebellar ataxia type 14

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
PRKCG	HGNC:9402	ENSG00000126583	P05129	Protein kinase C gamma type	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRKCG	Protein kinase C gamma type	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modu…

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)
PRKCG	Kinase	yes	2.7.11.13	C2_dom, Prot_kinase_dom, AGC-kinase_C

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
nucleus accumbens	1
prefrontal cortex	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRKCG	141	broad	marker	right frontal lobe, nucleus accumbens, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKCG	2,212

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKCG	P05129	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. 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
Disinhibition of SNARE formation	1	2284.0×	0.007	PRKCG
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	761.3×	0.007	PRKCG
WNT5A-dependent internalization of FZD4	1	761.3×	0.007	PRKCG
Trafficking of GluR2-containing AMPA receptors	1	671.8×	0.007	PRKCG
Trafficking of AMPA receptors	1	543.8×	0.007	PRKCG
Calmodulin induced events	1	380.7×	0.007	PRKCG
CaM pathway	1	380.7×	0.007	PRKCG
Ca-dependent events	1	368.4×	0.007	PRKCG
G-protein mediated events	1	326.3×	0.007	PRKCG
DAG and IP3 signaling	1	317.2×	0.007	PRKCG
PCP/CE pathway	1	300.5×	0.007	PRKCG
Beta-catenin independent WNT signaling	1	292.8×	0.007	PRKCG
Opioid Signalling	1	265.6×	0.007	PRKCG
PLC beta mediated events	1	265.6×	0.007	PRKCG
G alpha (z) signalling events	1	233.1×	0.008	PRKCG
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.010	PRKCG
Signaling by WNT	1	112.0×	0.014	PRKCG
Platelet activation, signaling and aggregation	1	105.7×	0.014	PRKCG
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.014	PRKCG
Intracellular signaling by second messengers	1	91.4×	0.015	PRKCG
Transmission across Chemical Synapses	1	76.1×	0.017	PRKCG
Neuronal System	1	44.3×	0.027	PRKCG
GPCR downstream signalling	1	43.4×	0.027	PRKCG
Signaling by GPCR	1	40.1×	0.028	PRKCG
G alpha (i) signalling events	1	39.0×	0.028	PRKCG
Hemostasis	1	36.0×	0.029	PRKCG
Signal Transduction	1	10.2×	0.098	PRKCG

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
regulation of response to food	1	5617.3×	0.002	PRKCG
positive regulation of mismatch repair	1	5617.3×	0.002	PRKCG
chemosensory behavior	1	3370.4×	0.002	PRKCG
response to psychosocial stress	1	3370.4×	0.002	PRKCG
response to angiotensin	1	1872.4×	0.002	PRKCG
regulation of phagocytosis	1	1685.2×	0.002	PRKCG
synaptic signaling via neuropeptide	1	1532.0×	0.002	PRKCG
negative regulation of proteasomal protein catabolic process	1	1404.3×	0.002	PRKCG
response to morphine	1	1203.7×	0.002	PRKCG
response to pain	1	887.0×	0.002	PRKCG
innervation	1	887.0×	0.002	PRKCG
presynaptic modulation of chemical synaptic transmission	1	455.5×	0.004	PRKCG
regulation of synaptic vesicle exocytosis	1	455.5×	0.004	PRKCG
negative regulation of protein catabolic process	1	366.4×	0.005	PRKCG
negative regulation of protein ubiquitination	1	285.6×	0.005	PRKCG
long-term synaptic potentiation	1	280.9×	0.005	PRKCG
regulation of circadian rhythm	1	259.3×	0.005	PRKCG
rhythmic process	1	251.5×	0.005	PRKCG
learning or memory	1	240.7×	0.005	PRKCG
response to toxic substance	1	210.7×	0.006	PRKCG
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.009	PRKCG
negative regulation of neuron apoptotic process	1	110.9×	0.010	PRKCG
chemical synaptic transmission	1	77.3×	0.013	PRKCG
intracellular signal transduction	1	38.1×	0.026	PRKCG

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
PRKCG	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKCG	23	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKCG
MIDOSTAURIN	4	PRKCG
TAMOXIFEN	4	PRKCG
ENTRECTINIB	4	PRKCG
SURAMIN	3	PRKCG
FASUDIL	3	PRKCG
ALVOCIDIB	3	PRKCG
ENZASTAURIN HYDROCHLORIDE	3	PRKCG
ENZASTAURIN	3	PRKCG
RUBOXISTAURIN	3	PRKCG
PHORBOL MYRISTATE ACETATE	2	PRKCG
EDELFOSINE	2	PRKCG
UPROSERTIB	2	PRKCG
UCN-01	2	PRKCG
CENISERTIB	2	PRKCG
LAUROGUADINE	2	PRKCG
LY-2090314	2	PRKCG
DAROVASERTIB	2	PRKCG
R-406	2	PRKCG
SOTRASTAURIN	2	PRKCG
PF-00562271	1	PRKCG
RG-1530	1	PRKCG
PF-03758309	1	PRKCG

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRKCG	627	Binding:611, Functional:15, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRKCG	2.7.11.13	protein kinase C

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRKCG	627

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

23 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)
INGENOL MEBUTATE	4	PRKCG
MIDOSTAURIN	4	PRKCG
TAMOXIFEN	4	PRKCG
ENTRECTINIB	4	PRKCG
SURAMIN	3	PRKCG
FASUDIL	3	PRKCG
ALVOCIDIB	3	PRKCG
ENZASTAURIN HYDROCHLORIDE	3	PRKCG
ENZASTAURIN	3	PRKCG
RUBOXISTAURIN	3	PRKCG
PHORBOL MYRISTATE ACETATE	2	PRKCG
EDELFOSINE	2	PRKCG
UPROSERTIB	2	PRKCG
UCN-01	2	PRKCG
CENISERTIB	2	PRKCG
LAUROGUADINE	2	PRKCG
LY-2090314	2	PRKCG
DAROVASERTIB	2	PRKCG
R-406	2	PRKCG
SOTRASTAURIN	2	PRKCG
PF-00562271	1	PRKCG
RG-1530	1	PRKCG
PF-03758309	1	PRKCG

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKCG
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: 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