Spinocerebellar ataxia, autosomal recessive 22

Summary

Spinocerebellar ataxia, autosomal recessive 22 (MONDO:0014845) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia, autosomal recessive 22
Mondo ID	MONDO:0014845
OMIM	616948
DOID	DOID:0111614
UMLS	C4310781
MedGen	934748
GARD	0025026
Is cancer (heuristic)	no

Also known as: autosomal recessive cerebellar ataxia caused by mutation in VWA3B · SCAR22 · spinocerebellar ataxia, autosomal recessive 22 · spinocerebellar ataxia, autosomal recessive 22; SCAR22 · spinocerebellar ataxia, autosomal recessive type 22 · VWA3B autosomal recessive cerebellar ataxia

Data availability: 17 ClinVar variants · 3 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 › spinocerebellar ataxia, autosomal recessive 22

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, autosomal recessive spinocerebellar ataxia 10, 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 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

17 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 likely pathogenic, 4 benign, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1030231	NM_144992.5(VWA3B):c.1191T>G (p.Tyr397Ter)	VWA3B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
226428	NM_144992.5(VWA3B):c.1865A>C (p.Lys622Thr)	VWA3B	Pathogenic	no assertion criteria provided
4845934	NM_144992.5(VWA3B):c.402del (p.Phe134fs)	VWA3B	Likely pathogenic	criteria provided, single submitter
4849280	NM_144992.5(VWA3B):c.2072del (p.Leu691fs)	VWA3B	Likely pathogenic	criteria provided, single submitter
4849329	NM_144992.5(VWA3B):c.3688_3713delinsTGCC (p.Gly1230fs)	VWA3B	Likely pathogenic	criteria provided, single submitter
4849369	NM_144992.5(VWA3B):c.3014del (p.Lys1005fs)	VWA3B	Likely pathogenic	criteria provided, single submitter
4849393	NM_144992.5(VWA3B):c.592dup (p.Glu198fs)	VWA3B	Likely pathogenic	criteria provided, single submitter
1034286	NM_144992.5(VWA3B):c.3068C>G (p.Pro1023Arg)	VWA3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1213771	NM_144992.5(VWA3B):c.544G>A (p.Val182Ile)	VWA3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1213772	NM_144992.5(VWA3B):c.2243A>G (p.Asn748Ser)	VWA3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2572060	NM_144992.5(VWA3B):c.2951A>C (p.Glu984Ala)	VWA3B	Uncertain significance	no assertion criteria provided
3897058	NM_144992.5(VWA3B):c.364C>T (p.Arg122Ter)	VWA3B	Uncertain significance	criteria provided, single submitter
3897059	NM_144992.5(VWA3B):c.760del (p.Leu254fs)	VWA3B	Uncertain significance	criteria provided, single submitter
1684216	NM_144992.5(VWA3B):c.2029C>G (p.Leu677Val)	VWA3B	Benign	criteria provided, multiple submitters, no conflicts
1684217	NM_144992.5(VWA3B):c.2653G>A (p.Val885Met)	VWA3B	Benign	criteria provided, multiple submitters, no conflicts
1684219	NM_144992.5(VWA3B):c.2843+36dup	VWA3B	Benign	criteria provided, single submitter
1684220	NM_144992.5(VWA3B):c.3734G>A (p.Arg1245Lys)	VWA3B	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
VWA3B	Limited	Autosomal recessive	spinocerebellar ataxia, autosomal recessive 22	3

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
VWA3B	HGNC:28385	ENSG00000168658	Q502W6	von Willebrand factor A domain-containing protein 3B	gencc,clinvar

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)
VWA3B	Other/Unknown	no		VWF_A, DUF4537, vWFA_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
bronchial epithelial cell	1
bronchus	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VWA3B	165	tissue_specific	marker	bronchial epithelial cell, sperm, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VWA3B	693

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VWA3B	Q502W6	69.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
VWA3B	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	VWA3B

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)
VWA3B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.