Autosomal recessive spinocerebellar ataxia 17

Summary

Autosomal recessive spinocerebellar ataxia 17 (MONDO:0014503) is a disease caused by CWF19L1 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CWF19L1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 30
• Phenotypes (HPO): 24

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)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0000657	Oculomotor apraxia	Frequent (30-79%)
HP:0000664	Synophrys	Frequent (30-79%)
HP:0000666	Horizontal nystagmus	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001310	Dysmetria	Frequent (30-79%)
HP:0001320	Cerebellar vermis hypoplasia	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0001350	Slurred speech	Frequent (30-79%)
HP:0002066	Gait ataxia	Frequent (30-79%)
HP:0002078	Truncal ataxia	Frequent (30-79%)
HP:0002080	Intention tremor	Frequent (30-79%)
HP:0002312	Clumsiness	Frequent (30-79%)
HP:0002317	Unsteady gait	Frequent (30-79%)
HP:0002342	Intellectual disability, moderate	Frequent (30-79%)
HP:0002359	Frequent falls	Frequent (30-79%)
HP:0002470	Nonprogressive cerebellar ataxia	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0008947	Floppy infant	Frequent (30-79%)
HP:0009617	Abnormality of the distal phalanx of the thumb	Frequent (30-79%)
HP:0031435	Monotonic speech	Frequent (30-79%)
HP:0040196	Mild microcephaly	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive spinocerebellar ataxia 17
Mondo ID	MONDO:0014503
OMIM	616127
Orphanet	453521
DOID	DOID:0080064
UMLS	C4015301
MedGen	863738
GARD	0017786
Is cancer (heuristic)	no

Also known as: autosomal recessive congenital cerebellar ataxia caused by mutation in CWF19L1 · autosomal recessive spinocerebellar ataxia type 17 · CWF19L1 autosomal recessive congenital cerebellar ataxia · SCAR17 · spinocerebellar ataxia autosomal recessive type 17 · spinocerebellar ataxia, autosomal recessive 17 · spinocerebellar ataxia, autosomal recessive type 17

Data availability: 30 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 congenital cerebellar ataxia › autosomal recessive spinocerebellar ataxia 17

Related subtypes (6): autosomal recessive spinocerebellar ataxia 2, cerebellar ataxia, intellectual disability, and dysequilibrium, Cayman type cerebellar ataxia, Joubert syndrome and related disorders, CAMOS syndrome, congenital cerebellar ataxia due to RNU12 mutation

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

30 retrieved; paginated sample, class counts are floors:

9 pathogenic, 8 uncertain significance, 8 likely pathogenic, 2 pathogenic/likely pathogenic, 1 benign, 1 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
128882	NM_018294.6(CWF19L1):c.964+1G>A	CWF19L1	Pathogenic	criteria provided, multiple submitters, no conflicts
1322180	NM_018294.6(CWF19L1):c.520A>T (p.Lys174Ter)	CWF19L1	Pathogenic	criteria provided, single submitter
1711123	NM_018294.6(CWF19L1):c.1070G>T (p.Gly357Val)	CWF19L1	Pathogenic	no assertion criteria provided
2497675	NM_018294.6(CWF19L1):c.1375-2A>G	CWF19L1	Pathogenic	criteria provided, single submitter
253210	NM_018294.6(CWF19L1):c.946A>T (p.Lys316Ter)	CWF19L1	Pathogenic	no assertion criteria provided
253212	NM_018294.6(CWF19L1):c.467del (p.Pro156fs)	CWF19L1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4687749	NM_018294.6(CWF19L1):c.1372C>T (p.Gln458Ter)	CWF19L1	Pathogenic	criteria provided, single submitter
800879	NM_018294.6(CWF19L1):c.605dup (p.Tyr202Ter)	CWF19L1	Pathogenic	criteria provided, multiple submitters, no conflicts
813893	NM_018294.6(CWF19L1):c.1158dup (p.Lys387fs)	CWF19L1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
976765	NM_018294.6(CWF19L1):c.1114C>T (p.Gln372Ter)	CWF19L1	Pathogenic	criteria provided, single submitter
996893	NM_018294.6(CWF19L1):c.708+294_1044+1540del	CWF19L1	Pathogenic	criteria provided, single submitter
1685293	NM_018294.6(CWF19L1):c.187+1G>T	CWF19L1	Likely pathogenic	criteria provided, single submitter
1711160	NM_018294.6(CWF19L1):c.820dup (p.Ser274fs)	CWF19L1	Likely pathogenic	criteria provided, single submitter
2429271	NM_018294.6(CWF19L1):c.1045-2A>C	CWF19L1	Likely pathogenic	criteria provided, single submitter
2497673	NM_018294.6(CWF19L1):c.452T>G (p.Ile151Ser)	CWF19L1	Likely pathogenic	criteria provided, single submitter
3775832	NM_018294.6(CWF19L1):c.1299del (p.Asp434fs)	CWF19L1	Likely pathogenic	criteria provided, single submitter
488454	NM_018294.6(CWF19L1):c.1150G>T (p.Glu384Ter)	CWF19L1	Likely pathogenic	no assertion criteria provided
806557	NM_018294.6(CWF19L1):c.942del (p.Pro315fs)	CWF19L1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
984934	NM_018294.6(CWF19L1):c.349G>T (p.Glu117Ter)	CWF19L1	Likely pathogenic	criteria provided, single submitter
976766	NM_018294.6(CWF19L1):c.665G>A (p.Arg222Gln)	CWF19L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1678602	NM_018294.6(CWF19L1):c.1523G>A (p.Trp508Ter)	CHUK-DT	Uncertain significance	criteria provided, single submitter
3256766	NM_018294.6(CWF19L1):c.1552G>A (p.Glu518Lys)	CHUK-DT	Uncertain significance	criteria provided, single submitter
488455	NM_018294.6(CWF19L1):c.1552GAG[1] (p.Glu519del)	CHUK-DT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1678624	NM_018294.6(CWF19L1):c.1063A>G (p.Lys355Glu)	CWF19L1	Uncertain significance	criteria provided, single submitter
1711159	NM_018294.6(CWF19L1):c.1394C>T (p.Ala465Val)	CWF19L1	Uncertain significance	criteria provided, single submitter
3589901	NM_018294.6(CWF19L1):c.779A>G (p.Asp260Gly)	CWF19L1	Uncertain significance	criteria provided, single submitter
3901934	NM_018294.6(CWF19L1):c.62T>C (p.Leu21Ser)	CWF19L1	Uncertain significance	criteria provided, single submitter
981166	NM_018294.6(CWF19L1):c.1045T>G (p.Cys349Gly)	CWF19L1	Uncertain significance	criteria provided, single submitter
3056968	NM_018294.6(CWF19L1):c.1568G>A (p.Arg523His)	CHUK-DT	Benign	criteria provided, multiple submitters, no conflicts
730375	NM_018294.6(CWF19L1):c.940C>T (p.His314Tyr)	CWF19L1	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
CWF19L1	Strong	Autosomal recessive	autosomal recessive spinocerebellar ataxia 17	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CWF19L1	Orphanet:453521	Autosomal recessive cerebellar ataxia due to CWF19L1 deficiency

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CWF19L1	HGNC:25613	ENSG00000095485	Q69YN2	CWF19-like protein 1	gencc,clinvar
CHUK-DT	HGNC:55813	ENSG00000227492		CHUK divergent transcript	clinvar

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CWF19L1	Other/Unknown	no		Cwf19-like_C_dom-2, Cwf19-like_C_dom-1, HIT-like_sf
CHUK-DT	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1
blood	1
male germ line stem cell (sensu Vertebrata) in testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CWF19L1	216	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
CHUK-DT	130		yes	male germ line stem cell (sensu Vertebrata) in testis, blood, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CWF19L1	1,306
CHUK-DT	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CWF19L1	Q69YN2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
mRNA splicing, via spliceosome	1	91.6×	0.011	CWF19L1

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
CWF19L1	0	0
CHUK-DT	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	2	CWF19L1, CHUK-DT

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)
CWF19L1	0	—
CHUK-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.