SPAST-related motor disorder

Summary

SPAST-related motor disorder (MONDO:0100523) is a disease caused by SPAST (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SPAST (GenCC Strong)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	SPAST-related motor disorder
Mondo ID	MONDO:0100523
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › SPAST-related motor disorder

Related subtypes (18): autoimmune disorder of central nervous system, autonomic nervous system disorder, optic nerve disorder, spinal cord disorder, high pressure neurological syndrome, central nervous system vasculitis, encephalomyelitis, neurodegenerative disease, brain disorder, central nervous system neoplasm, palsy, trigeminal neuralgia, infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly, sporadic fetal brain disruption sequence, congenital narrowing of cervical spinal canal, central nervous system infectious disorder, cerebrospinal fluid leak, tinnitus

Subtypes (1): hereditary spastic paraplegia 4

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
SPAST	Strong	Autosomal recessive	SPAST-related motor disorder	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPAST	Orphanet:100985	Autosomal dominant spastic paraplegia type 4

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
SPAST	HGNC:11233	ENSG00000021574	Q9UBP0	Spastin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPAST	Spastin	ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPAST	Enzyme (other)	yes	5.6.1.1	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS

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
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPAST	284	ubiquitous	marker	cortical plate, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPAST	3,393

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPAST	Q9UBP0	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.012	SPAST
Nuclear Envelope (NE) Reassembly	1	292.8×	0.012	SPAST
Mitotic Metaphase and Anaphase	1	96.8×	0.018	SPAST
Mitotic Anaphase	1	96.8×	0.018	SPAST
M Phase	1	66.0×	0.021	SPAST
Cell Cycle, Mitotic	1	48.2×	0.024	SPAST
Cell Cycle	1	36.0×	0.028	SPAST

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
cytokinetic process	1	5617.3×	0.002	SPAST
mitotic spindle disassembly	1	5617.3×	0.002	SPAST
positive regulation of microtubule depolymerization	1	3370.4×	0.002	SPAST
central nervous system neuron axonogenesis	1	1872.4×	0.002	SPAST
mitotic nuclear membrane reassembly	1	1685.2×	0.002	SPAST
axonal transport of mitochondrion	1	1404.3×	0.002	SPAST
protein hexamerization	1	1404.3×	0.002	SPAST
microtubule severing	1	1296.3×	0.002	SPAST
exit from mitosis	1	1053.2×	0.002	SPAST
nuclear membrane reassembly	1	991.3×	0.002	SPAST
cytoskeleton-dependent cytokinesis	1	802.5×	0.002	SPAST
anterograde axonal transport	1	581.1×	0.003	SPAST
microtubule bundle formation	1	510.7×	0.003	SPAST
membrane fission	1	411.0×	0.003	SPAST
positive regulation of cytokinesis	1	401.2×	0.003	SPAST
mitotic cytokinesis	1	259.3×	0.004	SPAST
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.008	SPAST
protein homooligomerization	1	122.1×	0.008	SPAST

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
SPAST	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SPAST	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SPAST	5.6.1.1	microtubule-severing ATPase

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	1	SPAST
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
SPAST	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.