Spinocerebellar ataxia, autosomal recessive 32

Summary

Spinocerebellar ataxia, autosomal recessive 32 (MONDO:0859245) is a disease caused by PRDX3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PRDX3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia, autosomal recessive 32
Mondo ID	MONDO:0859245
OMIM	619862
DOID	DOID:0070413
UMLS	C5676978
MedGen	1802496
GARD	0026679
Is cancer (heuristic)	no

Data availability: 13 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 32

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 22, 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 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

13 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1325883	NM_006793.5(PRDX3):c.43C>T (p.Arg15Ter)	PRDX3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686990	NM_006793.5(PRDX3):c.604G>A (p.Asp202Asn)	PRDX3	Pathogenic	no assertion criteria provided
1686991	NM_006793.5(PRDX3):c.340dup (p.Ala114fs)	PRDX3	Pathogenic	no assertion criteria provided
1686994	NM_006793.5(PRDX3):c.37-2A>G	PRDX3	Pathogenic	no assertion criteria provided
2443837	NM_006793.5(PRDX3):c.658C>T (p.Gln220Ter)	PRDX3	Pathogenic	no assertion criteria provided
2446414	NM_006793.5(PRDX3):c.489C>G (p.Asp163Glu)	PRDX3	Pathogenic	no assertion criteria provided
1686992	NM_006793.5(PRDX3):c.508C>T (p.Arg170Ter)	PRDX3	Likely pathogenic	criteria provided, single submitter
1686993	NM_006793.5(PRDX3):c.425C>G (p.Ala142Gly)	PRDX3	Uncertain significance	criteria provided, single submitter
1705298	NM_006793.5(PRDX3):c.451G>A (p.Gly151Ser)	PRDX3	Uncertain significance	criteria provided, single submitter
3218489	NM_006793.5(PRDX3):c.169+1G>A	PRDX3	Uncertain significance	criteria provided, single submitter
3218495	NM_006793.5(PRDX3):c.539G>A (p.Gly180Asp)	PRDX3	Uncertain significance	criteria provided, single submitter
3897944	NM_006793.5(PRDX3):c.266A>G (p.Asp89Gly)	PRDX3	Uncertain significance	criteria provided, single submitter
4293965	NM_006793.5(PRDX3):c.36+5G>A	PRDX3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
PRDX3	Strong	Autosomal recessive	spinocerebellar ataxia, autosomal recessive 32	5

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
PRDX3	HGNC:9354	ENSG00000165672	P30048	Thioredoxin-dependent peroxide reductase, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRDX3	Thioredoxin-dependent peroxide reductase, mitochondrial	Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.

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)
PRDX3	Other/Unknown	no		AhpC/TSA, Thioredoxin_domain, Peroxiredoxin_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
adrenal tissue	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRDX3	294	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRDX3	4,736

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRDX3	P30048	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Detoxification of Reactive Oxygen Species	1	300.5×	0.003	PRDX3

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 kinase activity	1	4213.0×	0.004	PRDX3
maternal placenta development	1	1532.0×	0.005	PRDX3
hydrogen peroxide catabolic process	1	674.1×	0.005	PRDX3
myeloid cell differentiation	1	648.1×	0.005	PRDX3
regulation of mitochondrial membrane potential	1	543.6×	0.005	PRDX3
response to hydrogen peroxide	1	468.1×	0.005	PRDX3
cellular response to reactive oxygen species	1	411.0×	0.005	PRDX3
cell redox homeostasis	1	343.9×	0.005	PRDX3
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.008	PRDX3
cellular response to oxidative stress	1	154.6×	0.009	PRDX3
mitochondrion organization	1	151.8×	0.009	PRDX3
response to oxidative stress	1	130.6×	0.009	PRDX3
response to lipopolysaccharide	1	124.8×	0.009	PRDX3
negative regulation of apoptotic process	1	34.8×	0.030	PRDX3
positive regulation of cell population proliferation	1	33.6×	0.030	PRDX3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
PRDX3	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
PRDX3	8	Binding:8

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	PRDX3

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)
PRDX3	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.