Spinocerebellar ataxia 50

Summary

Spinocerebellar ataxia 50 (MONDO:0859334) is a disease caused by NPTX1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: NPTX1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia 50
Mondo ID	MONDO:0859334
OMIM	620158
UMLS	C5774272
MedGen	1824045
GARD	0026703
Is cancer (heuristic)	no

Data availability: 8 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 dominant disease › autosomal dominant cerebellar ataxia › spinocerebellar ataxia 50

Related subtypes (15): GRID2-related autosomal dominant spinocerebellar ataxia, spinocerebellar ataxia 27A, spinocerebellar ataxia 9, spinocerebellar ataxia 43, spinocerebellar ataxia 7, autosomal dominant cerebellar ataxia type I, autosomal dominant cerebellar ataxia type III, autosomal dominant cerebellar ataxia type IV, spinocerebellar ataxia 49, spinocerebellar ataxia 48, spinocerebellar ataxia 44, spinocerebellar ataxia 47, spinocerebellar ataxia 27B, late-onset, spinocerebellar ataxia 51, spinocerebellar ataxia 52

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

8 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184956	NM_002522.4(NPTX1):c.1165G>A (p.Gly389Arg)	NPTX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1806388	NM_002522.4(NPTX1):c.980A>G (p.Glu327Gly)	NPTX1	Pathogenic	no assertion criteria provided
1806389	NM_002522.4(NPTX1):c.428G>T (p.Arg143Leu)	NPTX1	Likely pathogenic	criteria provided, single submitter
1806390	NM_002522.4(NPTX1):c.1109A>G (p.Gln370Arg)	NPTX1	Likely pathogenic	criteria provided, single submitter
2692519	NM_002522.4(NPTX1):c.539G>T (p.Arg180Leu)	NPTX1	Likely pathogenic	criteria provided, single submitter
3358966	NM_002522.4(NPTX1):c.1261_1287del (p.Thr421_Arg429del)	NPTX1	Likely pathogenic	criteria provided, single submitter
3899846	Single allele	SPG21	Likely pathogenic	criteria provided, single submitter
3067920	NM_002522.4(NPTX1):c.396A>C (p.Gln132His)	NPTX1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
NPTX1	Strong	Autosomal dominant	spinocerebellar ataxia 50	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPG21	Orphanet:101001	Autosomal recessive spastic paraplegia type 21

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NPTX1	HGNC:7952	ENSG00000171246	Q15818	Neuronal pentraxin-1	gencc,clinvar
SPG21	HGNC:20373	ENSG00000090487	Q9NZD8	Maspardin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NPTX1	Neuronal pentraxin-1	May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses.
SPG21	Maspardin	May play a role as a negative regulatory factor in CD4-dependent T-cell activation.

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)
NPTX1	Other/Unknown	no		PTX_dom, ConA-like_dom_sf, Pentaxin_CS
SPG21	Other/Unknown	no		AB_hydrolase_1, Maspardin, AB_hydrolase_fold

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
cerebellar vermis	1
middle temporal gyrus	1
paraflocculus	1
corpus epididymis	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NPTX1	210	broad	marker	cerebellar vermis, paraflocculus, middle temporal gyrus
SPG21	286	ubiquitous	marker	corpus epididymis, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPG21	1,776
NPTX1	1,648

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NPTX1	Q15818	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SPG21	Q9NZD8	93.02

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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to epidermal growth factor	1	1685.2×	0.004	SPG21
antigen receptor-mediated signaling pathway	1	1404.3×	0.004	SPG21
postsynaptic density assembly	1	936.2×	0.004	NPTX1
axonogenesis involved in innervation	1	842.6×	0.004	NPTX1
mitochondrial fragmentation involved in apoptotic process	1	702.2×	0.004	NPTX1
mitochondrial transport	1	601.9×	0.004	NPTX1
collateral sprouting	1	601.9×	0.004	SPG21
cellular response to potassium ion	1	526.6×	0.004	NPTX1
neuron maturation	1	401.2×	0.004	SPG21
neurotransmitter receptor localization to postsynaptic specialization membrane	1	401.2×	0.004	NPTX1
neuromuscular process	1	263.3×	0.006	SPG21
limb development	1	205.5×	0.007	SPG21
cellular response to glucose stimulus	1	133.8×	0.010	NPTX1
epidermal growth factor receptor signaling pathway	1	123.9×	0.010	SPG21
locomotory behavior	1	89.6×	0.013	SPG21
central nervous system development	1	57.7×	0.019	NPTX1
gene expression	1	39.9×	0.026	SPG21
chemical synaptic transmission	1	38.6×	0.026	NPTX1

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
NPTX1	0	0
SPG21	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	NPTX1, SPG21

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)
NPTX1	0	—
SPG21	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.