Spinocerebellar ataxia, autosomal recessive 26

Summary

Spinocerebellar ataxia, autosomal recessive 26 (MONDO:0033116) is a disease caused by XRCC1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: XRCC1 (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 26
Mondo ID	MONDO:0033116
OMIM	617633
DOID	DOID:0080260
UMLS	C4539948
MedGen	1617917
GARD	0025787
Is cancer (heuristic)	no

Also known as: SCAR26 · spinocerebellar ataxia, autosomal recessive 26

Data availability: 13 ClinVar variants · 2 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 26

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 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

13 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 3 benign, 2 likely pathogenic, 1 drug response, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
433532	NM_006297.3(XRCC1):c.1393C>T (p.Gln465Ter)	XRCC1	Pathogenic	no assertion criteria provided
2573207	NM_006297.3(XRCC1):c.1015C>T (p.Arg339Ter)	XRCC1	Likely pathogenic	criteria provided, single submitter
433531	NM_006297.3(XRCC1):c.1293G>C (p.Lys431Asn)	XRCC1	Likely pathogenic	criteria provided, single submitter
225976	NM_006297.3(XRCC1):c.1196A>G (p.Gln399Arg)	XRCC1	drug response	reviewed by expert panel
1032426	NM_006297.3(XRCC1):c.1738C>T (p.Arg580Trp)	XRCC1	Uncertain significance	criteria provided, single submitter
2438628	NM_006297.3(XRCC1):c.89dup (p.Tyr30Ter)	XRCC1	Uncertain significance	criteria provided, single submitter
2438629	NM_006297.3(XRCC1):c.352C>T (p.Arg118Trp)	XRCC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3068604	NM_006297.3(XRCC1):c.209_233dup (p.Glu81fs)	XRCC1	Uncertain significance	criteria provided, single submitter
3776271	NM_006297.3(XRCC1):c.1788+6T>C	XRCC1	Uncertain significance	criteria provided, single submitter
548581	NM_006297.3(XRCC1):c.764AGA[1] (p.Lys256del)	XRCC1	Uncertain significance	criteria provided, single submitter
1245878	NM_006297.3(XRCC1):c.1481+9G>A	XRCC1	Benign	criteria provided, multiple submitters, no conflicts
1684239	NM_006297.3(XRCC1):c.1896A>G (p.Gln632=)	XRCC1	Benign	criteria provided, multiple submitters, no conflicts
1684240	NM_006297.3(XRCC1):c.618A>G (p.Pro206=)	XRCC1	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
XRCC1	Strong	Autosomal recessive	spinocerebellar ataxia, autosomal recessive 26	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
XRCC1	HGNC:12828	ENSG00000073050	P18887	DNA repair protein XRCC1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XRCC1	DNA repair protein XRCC1	Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes.

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)
XRCC1	Other/Unknown	no		BRCT_dom, Xrcc1_N, Galactose-bd-like_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
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XRCC1	276	ubiquitous	marker	ventricular zone, tendon of biceps brachii, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
XRCC1	2,591

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XRCC1	P18887	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Resolution of AP sites via the single-nucleotide replacement pathway	1	2284.0×	0.002	XRCC1
APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway	1	1631.4×	0.002	XRCC1
HDR through MMEJ (alt-NHEJ)	1	878.5×	0.002	XRCC1
Gap-filling DNA repair synthesis and ligation in GG-NER	1	439.2×	0.003	XRCC1
Gap-filling DNA repair synthesis and ligation in TC-NER	1	178.4×	0.006	XRCC1

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 protein ADP-ribosylation	1	8426.0×	6e-04	XRCC1
regulation of base-excision repair	1	8426.0×	6e-04	XRCC1
telomeric DNA-containing double minutes formation	1	4213.0×	6e-04	XRCC1
negative regulation of protection from non-homologous end joining at telomere	1	4213.0×	6e-04	XRCC1
response to hydroperoxide	1	1685.2×	0.001	XRCC1
single strand break repair	1	1404.3×	0.001	XRCC1
base-excision repair	1	468.1×	0.003	XRCC1
double-strand break repair via nonhomologous end joining	1	421.3×	0.003	XRCC1
hippocampus development	1	230.8×	0.005	XRCC1
double-strand break repair	1	203.0×	0.005	XRCC1

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
XRCC1	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	XRCC1

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)
XRCC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.