Spinocerebellar ataxia type 37

disease

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Also known as SCA37spinocerebellar ataxia 37spinocerebellar ataxia with altered vertical eye movements

Summary

Spinocerebellar ataxia type 37 (MONDO:0014410) is a disease caused by DAB1 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Causal gene: DAB1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 7
Phenotypes (HPO): 16
Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000549	Abnormal conjugate eye movement	Very frequent (80-99%)
HP:0002396	Cogwheel rigidity	Very frequent (80-99%)
HP:0002527	Falls	Very frequent (80-99%)
HP:0000407	Sensorineural hearing impairment	Frequent (30-79%)
HP:0000666	Horizontal nystagmus	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001336	Myoclonus	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0002075	Dysdiadochokinesis	Frequent (30-79%)
HP:0002078	Truncal ataxia	Frequent (30-79%)
HP:0002167	Abnormality of speech or vocalization	Frequent (30-79%)
HP:0002168	Scanning speech	Frequent (30-79%)
HP:0002406	Limb dysmetria	Frequent (30-79%)
HP:0003474	Somatic sensory dysfunction	Frequent (30-79%)
HP:0006855	Cerebellar vermis atrophy	Frequent (30-79%)
HP:0100275	Diffuse cerebellar atrophy	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 37
Mondo ID	MONDO:0014410
OMIM	615945
Orphanet	363710
DOID	DOID:0050984
SNOMED CT	719301002
UMLS	C3889636
MedGen	855217
GARD	0012368
Is cancer (heuristic)	no

Also known as: SCA37 · spinocerebellar ataxia 37 · spinocerebellar ataxia with altered vertical eye movements

Data availability: 7 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 dominant disease › autosomal dominant cerebellar ataxia › autosomal dominant cerebellar ataxia type I › spinocerebellar ataxia type 37

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

7 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 conflicting classifications of pathogenicity, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
430691	NC_000001.10:g.57832716_57832797ins[(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90]	DAB1	Pathogenic	criteria provided, single submitter
2440675	NM_001365792.1(DAB1):c.43G>A (p.Ala15Thr)	DAB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1298313	NM_001365792.1(DAB1):c.209G>A (p.Gly70Asp)	DAB1	Uncertain significance	no assertion criteria provided
2346807	NM_001365792.1(DAB1):c.718G>C (p.Val240Leu)	DAB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2440676	NM_001365792.1(DAB1):c.122G>A (p.Arg41Gln)	DAB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3393313	NM_001365792.1(DAB1):c.319C>T (p.His107Tyr)	DAB1	Uncertain significance	criteria provided, single submitter
3068648	NM_001365792.1(DAB1):c.-136-4G>T	DAB1	Benign	criteria provided, single submitter

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
DAB1	Strong	Autosomal dominant	spinocerebellar ataxia type 37	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DAB1	Orphanet:363710	Spinocerebellar ataxia type 37

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
DAB1	HGNC:2661	ENSG00000173406	O75553	Disabled homolog 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DAB1	Disabled homolog 1	Signaling adapter of the reelin-mediated signaling pathway, which regulates the migration and differentiation of postmitotic neurons during brain development.

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)
DAB1	Other/Unknown	no		PTB/PI_dom, PH-like_dom_sf, DAB1/2_SBM

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
cortical plate	1
jejunal mucosa	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DAB1	190	broad	marker	cortical plate, jejunal mucosa, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DAB1	845

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DAB1	O75553	59.20

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
Reelin signalling pathway	1	1903.3×	5e-04	DAB1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell-cell adhesion involved in neuronal-glial interactions involved in cerebral cortex radial glia guided migration	1	16852.0×	0.001	DAB1
cerebellum structural organization	1	8426.0×	0.001	DAB1
radial glia guided migration of Purkinje cell	1	5617.3×	0.001	DAB1
lateral motor column neuron migration	1	5617.3×	0.001	DAB1
radial glia-guided pyramidal neuron migration	1	4213.0×	0.001	DAB1
Golgi localization	1	2106.5×	0.002	DAB1
ventral spinal cord development	1	1872.4×	0.002	DAB1
negative regulation of astrocyte differentiation	1	1532.0×	0.002	DAB1
negative regulation of axonogenesis	1	1296.3×	0.002	DAB1
reelin-mediated signaling pathway	1	1203.7×	0.002	DAB1
layer formation in cerebral cortex	1	1123.5×	0.002	DAB1
regulation of synapse maturation	1	936.2×	0.002	DAB1
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.002	DAB1
astrocyte differentiation	1	766.0×	0.002	DAB1
central nervous system neuron differentiation	1	601.9×	0.003	DAB1
adult walking behavior	1	495.6×	0.003	DAB1
dendrite development	1	391.9×	0.003	DAB1
negative regulation of cell adhesion	1	383.0×	0.003	DAB1
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.004	DAB1
hippocampus development	1	230.8×	0.005	DAB1
positive regulation of neuron differentiation	1	198.3×	0.006	DAB1
small GTPase-mediated signal transduction	1	183.2×	0.006	DAB1
axonogenesis	1	160.5×	0.007	DAB1
neuron migration	1	133.8×	0.007	DAB1

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
DAB1	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	DAB1

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)
DAB1	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

Cohort genes: DAB1