Spinocerebellar ataxia type 31

Summary

Spinocerebellar ataxia type 31 (MONDO:0007296) is a disease caused by BEAN1 (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: BEAN1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 3
• Phenotypes (HPO): 11
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		30	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0001272	Cerebellar atrophy	Very frequent (80-99%)
HP:0002066	Gait ataxia	Very frequent (80-99%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001265	Hyporeflexia	Frequent (30-79%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0002495	Impaired vibratory sensation	Occasional (5-29%)
HP:0006801	Hyperactive deep tendon reflexes	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 31
Mondo ID	MONDO:0007296
MeSH	C566146
OMIM	117210
Orphanet	217012
DOID	DOID:0050980
ICD-11	250956064
NCIT	C176901
SNOMED CT	715826005
UMLS	C1861736
MedGen	348439
GARD	0009975
Is cancer (heuristic)	no

Also known as: SCA31 · spinocerebellar ataxia 16q22-linked · spinocerebellar ataxia 31 · spinocerebellar ataxia type 31

Data availability: 3 ClinVar variants · 3 GenCC gene-disease records · 5 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 III › spinocerebellar ataxia type 31

Related subtypes (9): spinocerebellar ataxia type 6, spinocerebellar ataxia type 5, spinocerebellar ataxia type 11, spinocerebellar ataxia type 26, spinocerebellar ataxia type 30, spinocerebellar ataxia type 38, spinocerebellar ataxia type 41, spinocerebellar ataxia type 42, spinocerebellar ataxia 45

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

3 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
733	NG_021403.2:g.68486_68487insN[2500_3800]	BEAN1	Pathogenic	no assertion criteria provided
1635	NM_001129729.3(PLEKHG4):c.-16C>T	PLEKHG4	Uncertain significance	no assertion criteria provided
3242610	NM_001178020.3(BEAN1):c.90T>G (p.His30Gln)	BEAN1	Benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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
BEAN1	Strong	Autosomal dominant	spinocerebellar ataxia type 31	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BEAN1	Orphanet:217012	Spinocerebellar ataxia type 31
PLEKHG4	Orphanet:98765	Spinocerebellar ataxia type 4

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
BEAN1	HGNC:24160	ENSG00000166546	Q3B7T3	Protein BEAN1	gencc,clinvar
PLEKHG4	HGNC:24501	ENSG00000196155	Q58EX7	Puratrophin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLEKHG4	Puratrophin-1	Possible role in intracellular signaling and cytoskeleton dynamics at the Golgi.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BEAN1	Other/Unknown	no		BEAN1
PLEKHG4	Scaffold/PPI	no		DH_dom, PH_domain, PH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

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
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BEAN1	180	broad	yes	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
PLEKHG4	195	ubiquitous	yes	right testis, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLEKHG4	1,160
BEAN1	446

Intra-cohort edges

A	B	Sources
BEAN1	PLEKHG4	string_interaction

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLEKHG4	Q58EX7	69.68
BEAN1	Q3B7T3	58.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
RHOA GTPase cycle	1	74.6×	0.016	PLEKHG4
CDC42 GTPase cycle	1	72.3×	0.016	PLEKHG4
RAC1 GTPase cycle	1	61.1×	0.016	PLEKHG4

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 small GTPase mediated signal transduction	1	144.0×	0.011	PLEKHG4
axon guidance	1	90.6×	0.011	PLEKHG4

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
BEAN1	0	0
PLEKHG4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	BEAN1, PLEKHG4

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)
BEAN1	0	—
PLEKHG4	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