Autosomal recessive spinocerebellar ataxia 15
diseaseOn this page
Also known as autosomal recessive cerebellar ataxia - epilepsy - intellectual disability syndrome caused by mutation in RUBCNautosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome caused by mutation in RUBCNautosomal recessive spinocerebellar ataxia type 15RUBCN autosomal recessive cerebellar ataxia - epilepsy - intellectual disability syndromeRUBCN autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndromeSCAR15spinocerebellar ataxia, autosomal recessive 15spinocerebellar ataxia, autosomal recessive type 15
Summary
Autosomal recessive spinocerebellar ataxia 15 (MONDO:0014311) is a disease caused by RUBCN (GenCC Strong), with 1 cohort gene.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: RUBCN (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 17
- Phenotypes (HPO): 11
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 2 | 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:0000750 | Delayed speech and language development | Very frequent (80-99%) |
| HP:0001260 | Dysarthria | Very frequent (80-99%) |
| HP:0001265 | Hyporeflexia | Very frequent (80-99%) |
| HP:0002066 | Gait ataxia | Very frequent (80-99%) |
| HP:0002070 | Limb ataxia | Very frequent (80-99%) |
| HP:0002194 | Delayed gross motor development | Very frequent (80-99%) |
| HP:0001152 | Saccadic smooth pursuit | Frequent (30-79%) |
| HP:0001249 | Intellectual disability | Frequent (30-79%) |
| HP:0001250 | Seizure | Frequent (30-79%) |
| HP:0000639 | Nystagmus | Occasional (5-29%) |
| HP:0002172 | Postural instability | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | autosomal recessive spinocerebellar ataxia 15 |
| Mondo ID | MONDO:0014311 |
| OMIM | 615705 |
| Orphanet | 404499 |
| DOID | DOID:0080057 |
| UMLS | C3810326 |
| MedGen | 816656 |
| GARD | 0017678 |
| Is cancer (heuristic) | no |
Also known as: autosomal recessive cerebellar ataxia - epilepsy - intellectual disability syndrome caused by mutation in RUBCN · autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome caused by mutation in RUBCN · autosomal recessive spinocerebellar ataxia type 15 · RUBCN autosomal recessive cerebellar ataxia - epilepsy - intellectual disability syndrome · RUBCN autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome · SCAR15 · spinocerebellar ataxia, autosomal recessive 15 · spinocerebellar ataxia, autosomal recessive type 15
Data availability: 17 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 cerebellar ataxia - epilepsy - intellectual disability syndrome › autosomal recessive spinocerebellar ataxia 15
Related subtypes (2): autosomal recessive spinocerebellar ataxia 12, spinocerebellar ataxia, autosomal recessive 23
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
17 retrieved; paginated sample, class counts are floors:
10 uncertain significance, 3 conflicting classifications of pathogenicity, 2 pathogenic, 1 benign/likely benign, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 120216 | NM_014687.4(RUBCN):c.2624del (p.Ala875fs) | RUBCN | Pathogenic | criteria provided, single submitter |
| 2775435 | NM_014687.4(RUBCN):c.2647-2A>G | RUBCN | Pathogenic | criteria provided, single submitter |
| 2505356 | NM_014687.4(RUBCN):c.1847+2T>G | RUBCN | Likely pathogenic | criteria provided, single submitter |
| 2251002 | NM_014687.4(RUBCN):c.2284G>T (p.Val762Phe) | RUBCN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 548452 | NM_014687.4(RUBCN):c.593C>T (p.Pro198Leu) | RUBCN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 809598 | NM_014687.4(RUBCN):c.2075A>T (p.Glu692Val) | RUBCN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1030346 | NM_014687.4(RUBCN):c.124A>G (p.Thr42Ala) | RUBCN | Uncertain significance | criteria provided, single submitter |
| 1297540 | NM_014687.4(RUBCN):c.397C>T (p.His133Tyr) | RUBCN | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1333863 | NM_014687.4(RUBCN):c.2537A>G (p.Asp846Gly) | RUBCN | Uncertain significance | criteria provided, single submitter |
| 242883 | NM_014687.4(RUBCN):c.1642A>G (p.Thr548Ala) | RUBCN | Uncertain significance | criteria provided, single submitter |
| 242884 | NM_014687.4(RUBCN):c.319G>A (p.Glu107Lys) | RUBCN | Uncertain significance | criteria provided, single submitter |
| 2435492 | NM_014687.4(RUBCN):c.1474-5G>T | RUBCN | Uncertain significance | criteria provided, single submitter |
| 2505573 | NM_014687.4(RUBCN):c.1262-1G>C | RUBCN | Uncertain significance | criteria provided, single submitter |
| 2570690 | NM_014687.4(RUBCN):c.1464C>A (p.Asp488Glu) | RUBCN | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3067820 | NM_014687.4(RUBCN):c.1786+2595_1786+2596del | RUBCN | Uncertain significance | criteria provided, single submitter |
| 3896970 | NM_014687.4(RUBCN):c.2507T>C (p.Phe836Ser) | RUBCN | Uncertain significance | criteria provided, single submitter |
| 1175170 | NM_014687.4(RUBCN):c.2126C>T (p.Thr709Met) | RUBCN | Benign/Likely benign | 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 |
|---|---|---|---|---|
| RUBCN | Strong | Autosomal recessive | autosomal recessive spinocerebellar ataxia 15 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| RUBCN | Orphanet:404499 | Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to RUBCN deficiency |
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 |
|---|---|---|---|---|---|
| RUBCN | HGNC:28991 | ENSG00000145016 | Q92622 | Run domain Beclin-1-interacting and cysteine-rich domain-containing protein | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| RUBCN | Run domain Beclin-1-interacting and cysteine-rich domain-containing protein | Inhibits PIK3C3 activity; under basal conditions negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy. |
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) |
|---|---|---|---|---|
| RUBCN | Other/Unknown | no | Run_dom, RH_dom, Run_dom_sf |
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 |
|---|---|
| middle frontal gyrus | 1 |
| postcentral gyrus | 1 |
| sural nerve | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| RUBCN | 285 | ubiquitous | marker | sural nerve, postcentral gyrus, middle frontal gyrus |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| RUBCN | 925 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| RUBCN | Q92622 | 2 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|---|---|
| negative regulation of autophagosome maturation | 1 | 3370.4× | 0.002 | RUBCN |
| negative regulation of endocytosis | 1 | 936.2× | 0.003 | RUBCN |
| multivesicular body sorting pathway | 1 | 802.5× | 0.003 | RUBCN |
| immune system process | 1 | 391.9× | 0.005 | RUBCN |
| negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1 | 263.3× | 0.005 | RUBCN |
| negative regulation of autophagy | 1 | 259.3× | 0.005 | RUBCN |
| phagocytosis | 1 | 240.7× | 0.005 | RUBCN |
| autophagy | 1 | 110.1× | 0.009 | RUBCN |
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 |
|---|---|---|
| RUBCN | 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 | RUBCN |
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) |
|---|---|---|
| RUBCN | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: RUBCN