SPAST

Summary

SPAST (spastin, HGNC:11233) is a protein-coding gene on chromosome 2p22.3, encoding Spastin (Q9UBP0). ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the AAA (ATPases associated with a variety of cellular activities) protein family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. The use of alternative translational initiation sites in this gene results in a single transcript variant that can produce isoforms that differ in the length of their N-terminus and which thereby differ in the efficiency of their export from the nucleus to the cytoplasm. In addition, alternative splicing results in multiple transcript variants that encode isoforms that differ in other protein regions as well. One isoform of this gene has been shown to be a microtubule-severing enzyme that regulates microtubule abundance, mobility, and plus-end distribution. Mutations in this gene cause the most frequent form of autosomal dominant spastic paraplegia 4.

Source: NCBI Gene 6683 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary spastic paraplegia 4 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,578 total — 512 pathogenic, 128 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_014946

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11233
Approved symbol	SPAST
Name	spastin
Location	2p22.3
Locus type	gene with protein product
Status	Approved
Aliases	FSP2, ADPSP, KIAA1083
Ensembl gene	ENSG00000021574
Ensembl biotype	protein_coding
OMIM	604277
Entrez	6683

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 8 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000315285, ENST00000621856, ENST00000642281, ENST00000642455, ENST00000642751, ENST00000642999, ENST00000643327, ENST00000644408, ENST00000644954, ENST00000645159, ENST00000645400, ENST00000645550, ENST00000645671, ENST00000645730, ENST00000646082, ENST00000646571, ENST00000647007, ENST00000647133, ENST00000704289, ENST00000713714, ENST00000713715, ENST00000713716, ENST00000713718, ENST00000713719, ENST00000933131, ENST00000933132, ENST00000933133

RefSeq mRNA: 5 — MANE Select: NM_014946 NM_001363823, NM_001363875, NM_001377959, NM_014946, NM_199436

CCDS: CCDS1778, CCDS1779, CCDS86830, CCDS92732

Canonical transcript exons

ENST00000315285 — 17 exons

Exon	Start	End
ENSE00001070179	32087492	32087578
ENSE00001070181	32089522	32089605
ENSE00003815281	32063556	32064246
ENSE00004020827	32154374	32157637
ENSE00004020830	32141904	32141946
ENSE00004020833	32114638	32114825
ENSE00004020836	32144937	32145007
ENSE00004020841	32136877	32136968
ENSE00004020847	32137109	32137188
ENSE00004020850	32147218	32147258
ENSE00004020853	32136563	32136638
ENSE00004020855	32143336	32143415
ENSE00004020856	32128408	32128479
ENSE00004020858	32126948	32127022
ENSE00004020860	32115702	32115835
ENSE00004020862	32098796	32098891
ENSE00004020865	32116119	32116212

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.4849 / max 266.9382, expressed in 1811 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19630	13.4775	1791
19626	2.1480	1054
19628	1.8650	945
19627	0.6924	335
19629	0.2405	126
19631	0.0616	24

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.27	gold quality
oocyte	CL:0000023	95.65	gold quality
secondary oocyte	CL:0000655	94.72	gold quality
ganglionic eminence	UBERON:0004023	94.22	gold quality
calcaneal tendon	UBERON:0003701	92.24	gold quality
palpebral conjunctiva	UBERON:0001812	91.78	gold quality
epithelium of nasopharynx	UBERON:0001951	91.39	gold quality
ventricular zone	UBERON:0003053	91.21	gold quality
germinal epithelium of ovary	UBERON:0001304	91.08	gold quality
embryo	UBERON:0000922	90.77	gold quality
endothelial cell	CL:0000115	90.51	gold quality
tibia	UBERON:0000979	90.38	gold quality
esophagus squamous epithelium	UBERON:0006920	87.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.82	gold quality
amniotic fluid	UBERON:0000173	87.80	gold quality
monocyte	CL:0000576	87.06	gold quality
mononuclear cell	CL:0000842	86.91	gold quality
leukocyte	CL:0000738	86.78	gold quality
corpus callosum	UBERON:0002336	86.67	gold quality
parietal pleura	UBERON:0002400	85.35	gold quality
jejunal mucosa	UBERON:0000399	85.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.17	gold quality
adrenal tissue	UBERON:0018303	85.12	gold quality
pleura	UBERON:0000977	84.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.53	gold quality
visceral pleura	UBERON:0002401	84.52	gold quality
spinal cord	UBERON:0002240	84.22	gold quality
islet of Langerhans	UBERON:0000006	84.20	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.64
E-MTAB-6386	no	84.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELK1, HOXA10, MYC, NRF1, SOX11

miRNA regulators (miRDB)

160 targeting SPAST, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• second leaky splice-site mutation in hereditary spastic paraplegia (PMID:11704932)
• may be involved in microtubule dynamics similarly to the highly homologous microtubule-severing protein, katanin; Impairment of fine regulation of the microtubule cytoskeleton in long axons, due to spastin mutations, may underlie pathogenesis of HSP. (PMID:11809724)
• A novel mutation in the spastin gene in a family with spastic paraplegia. (PMID:12023066)
• Novel mutations of SPG4 in patients with autosomal dominant hereditary spastic paraplegia are located mainly in the conserved AAA cassette-encoding region of the spastin gene. (PMID:12124993)
• Five spastin gene mutations have been detected in Japanese with hereditary spastic paraplegia, three of which are novel. (PMID:12161613)
• Three novel spastin (SPG4) mutations in families with autosomal dominant hereditary spastic paraplegia. (PMID:12163196)
• Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree (PMID:12471215)
• Mutations of spastin are responsible for the most common autosomal dominant form of hereditary spastic paraplegia (PMID:12490534)
• Eight SPG4 mutations, seven of which are novel, have been identified in pure autosomal dominant spastic paraplegia patients. (PMID:12552568)
• A novel insertion mutation in spastin gene is the cause of spastic paraplegia in a Chinese (PMID:12736085)
• mutation in spastin and paraplegin genes does not appear to cause motor neuron disease (PMID:14506940)
• The abnormal interaction of mutant spastin with microtubules is demonstrated to be associated with an abnormal perinuclear clustering of mitochondria and peroxisomes, suggestive of an impairment of kinesin-mediated intracellular transport. (PMID:14681884)
• The percentage of involved Chinese families with autosomal dominant hereditary spastic paraplegia with an SPG4 mutation is 18% (4/22), lower than the estimated 40% linked to this lo (PMID:14732620)
• A variant form of hereditary spastic paraplegia & congenital arachnoid cysts has an new autosomal dominant mutation, T614I, in exon 17 of SPG4. It may play a role in both focal cortical dysgenesis & corticospinal motoneuron neurodegeneration. (PMID:15159500)
• spastin phosphorylation by Cdks has a role in the neurodegeneration of the most-common form of hereditary spastic paraplegia (PMID:15248095)
• Spastin interacts with the centrosomal protein NA14, and co-fractionates with gamma-tubulin, a centrosomal marker. (PMID:15269182)
• 2 codominant mutations of different SPG4 alleles (P361L & S44L)resulted in a more severe phenotype. P361L is a new mutation near the beginning of the AAA casette. (PMID:15326248)
• This study detected two novel missense mutations, 1375A > G (R459G) and 1378C > T (R460C) in the patient with autosomal dominant hereditary spastic paraplegia (PMID:15482961)
• A novel SPG4-nonsense-mutation (p.Leu239X trancation) in a large German pedigree with pure spastic paraplegia. (PMID:15739043)
• Eleven novel mutations within the SPG4 gene are associated with autosomal dominant hereditary spastic paraplegia (AD-HSP). (PMID:15841487)
• A novel SPG4 906delT frame-shift mutation in exon 6 was identified in a large Italian family with an autosomal dominant form of hereditary spastic paraplegia (ADHSP). (PMID:15858810)
• Spastin plays a role in microtubule dynamics, with a crucial role in microtubule organization in spastic paraplegia. (PMID:15891913)
• Reduced regional cerebral blood flow in SPG4-linked hereditary spastic paraplegia. (PMID:15939438)
• We propose that sequence alterations of spastin may comprise a genetic risk factor in a greater spectrum of motor neuron disorders including clinical variants of ALS. (PMID:16009903)
• Data show that spastin function is modulated through usage of alternative translational start sites and active nuclear import and export, opening new perspectives for the pathogenesis of hereditary spastic paraplegia (PMID:16026783)
• SPG4 gene mutations in patients with sporadic spastic paraplegia suggests that gene testing should be done in individuals with pure or complicated spastic paraplegia without family histories. (PMID:16055926)
• spastin mutations are a frequent cause of apparently sporadic spastic paraparesis but not of primary lateral sclerosis (PMID:16240363)
• Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners. (PMID:16339213)
• Data demonstrate that reticulon 1 interacts specifically with spastin. (PMID:16602018)
• The frequency for SPG4 mutations detected in autosomal dominant hereditary spastic paraplegia was 44.4%. This study contributes to expand the spectrum of SPG4 mutations in Italian population. (PMID:16684598)
• These results suggest that the frequency of SPAST mutations is higher among Japanese patients with autosomal dominant Hereditary spastic paraplegia (HSP), although SPAST mutations are also observed in patients with sporadic spastic paraplegia. (PMID:16788734)
• Interaction between spastin and atlastin may define a cellular biological pathway that is important in axon maintenance, the failure of which may be pathogenetically relevant. (PMID:16815977)
• The demonstration of spastin in functionally different brain regions may provide neuroanatomical basis to explain why different brain disorders and cognitive impairment occur in patients with spastin mutation. (PMID:16828199)
• Partial SPAST deletions represent an underestimated cause of autosomal dominant hereditary spastic paraplegia. Partial SPAST deletions are likely to act via haploinsufficiency. (PMID:17035675)
• 16 different heterozygotic spg4 exon deletions were found. Exon deletions in SPG4 are as frequent as point mutations. (PMID:17098887)
• The clinical course of hereditary spastic paraplegia is related to the type of the spastin gene mutation. (PMID:17100993)
• data implies that for SPAST, in contrast to many other genes, large genomic deletions together with the long recognized alterations in or near the coding sequences represent the complete spectrum of hereditary spastic paraplegia-causing mutations (PMID:17345589)
• Given that Spastin engages the MT in two places, we propose that severing occurs by forces exerted on the C-terminal tail of tubulin, which results in a conformational change in tubulin, which releases it from the polymer. (PMID:17389232)
• The studied kindred has typical clinical manifestations of hereditary spastic paraplegia. The pathogenesis has no association with mutation of the exons of spastin gene. (PMID:17407089)
• Genotyping two sets of MS patients and controls could not provide any evidence to suggest that genes involved in the pathogenesis of Hereditary Spastic Paraplegia [including spastin] play a role in susceptibility to MS or modifying the course of MS (PMID:17420921)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	spast	ENSDARG00000024933
mus_musculus	Spast	ENSMUSG00000024068
rattus_norvegicus	Spast	ENSRNOG00000027136
drosophila_melanogaster	spas	FBGN0039141
caenorhabditis_elegans		WBGENE00016045

Paralogs (9): KATNAL1 (ENSG00000102781), VPS4B (ENSG00000119541), FIGNL1 (ENSG00000132436), VPS4A (ENSG00000132612), ATAD1 (ENSG00000138138), KATNAL2 (ENSG00000167216), FIGN (ENSG00000182263), KATNA1 (ENSG00000186625), FIGNL2 (ENSG00000261308)

Protein

Protein identifiers

Spastin — Q9UBP0 (reviewed: Q9UBP0)

Alternative names: Spastic paraplegia 4 protein

All UniProt accessions (20): A0A2R8Y481, A0A2R8Y4I8, A0A2R8Y5N9, A0A2R8Y7K2, A0A2R8Y7W6, A0A2R8YCL5, A0A2R8YEA0, A0A2R8YFC9, A0A2R8YFW8, A0A2R8YGN6, A0A2U3TZR0, A0A994J6X4, A0AAQ5BGQ0, A0AAQ5BGQ4, A0AAQ5BGR4, A0AAQ5BGS6, A0AAQ5BGU3, E5KRP5, E5KRP6, Q9UBP0

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated. Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold. Severing activity is not dependent on tubulin acetylation or detyrosination. Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex. Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex. Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling. Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing. Probably plays a role in axon growth and the formation of axonal branches. Involved in lipid metabolism by regulating the size and distribution of lipid droplets.

Subunit / interactions. Homohexamer. Mostly monomeric, but assembles into hexameric structure for short periods of time. Oligomerization seems to be a prerequisite for catalytic activity. Binding to ATP in a cleft between two adjacent subunits stabilizes the homohexameric form. Binds to microtubules at least in part via the alpha-tubulin and beta-tubulin tails. The hexamer adopts a ring conformation through which microtubules pass prior to being severed. Does not interact strongly with tubulin heterodimers. Interacts (via MIT domain) with CHMP1B; the interaction is direct. Interacts with SSNA1. Interacts with ATL1. Interacts with RTN1. Interacts with ZFYVE27. Isoform 1 but not isoform 3 interacts with RTN2. Interacts with REEP1. Interacts (via MIT domain) with IST1.

Subcellular location. Membrane. Endoplasmic reticulum. Midbody. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Perinuclear region. Nucleus. Spindle. Cell projection. Axon Endoplasmic reticulum membrane. Nucleus membrane. Lipid droplet. Endosome Cytoplasm. Endosome.

Tissue specificity. Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. The short isoforms may predominate in brain and spinal cord.

Disease relevance. Spastic paraplegia 4, autosomal dominant (SPG4) [MIM:182601] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers. Microtubule binding promotes cooperative interactions among spastin subunits. ATP-bound enzyme interacts strongly and cooperatively with microtubules; this interaction stimulates ATP hydrolysis.

Miscellaneous. Produced by alternative promoter usage. May also be produced by alternative initiation at Met-87 of isoform 1. Major isoform. Produced by alternative promoter usage and alternative splicing. May also be produced by alternative initiation at Met-87 of isoform 2.

Similarity. Belongs to the AAA ATPase family. Spastin subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UBP0-1	1, Long, Long variant 1, 68 kDa, M1	yes
Q9UBP0-2	2, Long variant 2
Q9UBP0-3	3, Short, Short variant 1, 60 kDa, M87
Q9UBP0-4	4, Short variant 2

RefSeq proteins (5): NP_001350752, NP_001350804, NP_001364888, NP_055761, NP_955468 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR003960	ATPase_AAA_CS	Conserved_site
IPR007330	MIT_dom	Domain
IPR015415	Spast_Vps4_C	Domain
IPR017179	Spastin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR035106	Spastin_chordate	Family
IPR041569	AAA_lid_3	Domain
IPR050304	MT-severing_AAA_ATPase	Family

Pfam: PF00004, PF09336, PF17862

Enzyme classification (BRENDA):

• EC 5.6.1.1 — microtubule-severing ATPase (BRENDA: 21 organisms, 29 substrates, 57 inhibitors, 16 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0003–2.94	16

UniProt features (207 total): sequence variant 127, helix 22, mutagenesis site 15, region of interest 13, strand 6, turn 6, modified residue 4, short sequence motif 3, compositionally biased region 3, topological domain 2, splice variant 2, chain 1, intramembrane region 1, binding site 1, domain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7S7J	X-RAY DIFFRACTION	1.15
3EAB	X-RAY DIFFRACTION	2.5
5Z6Q	X-RAY DIFFRACTION	3
5Z6R	X-RAY DIFFRACTION	3
3VFD	X-RAY DIFFRACTION	3.3
6PEK	ELECTRON MICROSCOPY	4.2
6PEN	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBP0-F1	77.03	0.48

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 382–389

Post-translational modifications (4): 245, 268, 306, 597

Mutagenesis-validated functional residues (15):

Position	Phenotype
1	cytoplasmic and nuclear.
65	abolishes localization to lipid droplets.
81–84	does not affect localization to lipid droplets.
87	exclusively cytoplasmic.
120	impairs binding to chmp1b. impairs midbody localization; when associated with d-124.
124	impairs binding to chmp1b.
124	impairs binding to chmp1b. impairs midbody localization; when associated with d-120.
310–312	loss of microtubule-binding.
388	abrogates atpase activity and abolishes microtubule severing.
415	abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs atpase activity and abolishes microtubule sev
442	abrogates atp hydrolysis, abolishes microtubule severing, stabilizes the homohexameric form, and promotes microtubule bi
448	abolishes atpase activity.
448	does not affect atpase activity.
451	abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs atpase activity and abolishes microtubule sev
457	abrogates binding to the tail of alpha-tubulin and beta-3-tubulin and abolishes microtubule severing.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9668328	Sealing of the nuclear envelope (NE) by ESCRT-III
R-HSA-1640170	Cell Cycle
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2995410	Nuclear Envelope (NE) Reassembly
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 390 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_MITOTIC_CYTOKINESIS, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_NUCLEAR_MEMBRANE_REASSEMBLY, TAATAAT_MIR126, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, MORF_MSH3, GOBP_MEMBRANE_BIOGENESIS, MORF_BRCA1, MORF_ATRX, GCM_ZNF198, GOBP_CELL_CYCLE_PHASE_TRANSITION, GCM_PPM1D, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN

GO Biological Process (23): mitotic cytokinesis (GO:0000281), microtubule bundle formation (GO:0001578), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), mitotic nuclear membrane reassembly (GO:0007084), anterograde axonal transport (GO:0008089), exit from mitosis (GO:0010458), axonal transport of mitochondrion (GO:0019896), central nervous system neuron axonogenesis (GO:0021955), positive regulation of microtubule depolymerization (GO:0031117), nuclear membrane reassembly (GO:0031468), positive regulation of cytokinesis (GO:0032467), cytokinetic process (GO:0032506), protein hexamerization (GO:0034214), microtubule severing (GO:0051013), mitotic spindle disassembly (GO:0051228), protein homooligomerization (GO:0051260), cytoskeleton-dependent cytokinesis (GO:0061640), membrane fission (GO:0090148), microtubule cytoskeleton organization (GO:0000226), nervous system development (GO:0007399), axonogenesis (GO:0007409), cell differentiation (GO:0030154), cell division (GO:0051301)

GO Molecular Function (11): ATP binding (GO:0005524), microtubule binding (GO:0008017), microtubule severing ATPase activity (GO:0008568), ATP hydrolysis activity (GO:0016887), alpha-tubulin binding (GO:0043014), protein-containing complex binding (GO:0044877), beta-tubulin binding (GO:0048487), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (24): spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), axon (GO:0030424), midbody (GO:0030496), cytoplasmic vesicle (GO:0031410), nuclear membrane (GO:0031965), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), endoplasmic reticulum tubular network (GO:0071782), axon cytoplasm (GO:1904115), endoplasmic reticulum (GO:0005783), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Nuclear Envelope (NE) Reassembly	1
M Phase	1
Mitotic Anaphase	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	5
mitotic cell cycle	3
microtubule cytoskeleton organization	3
cytokinesis	3
tubulin binding	3
axonal transport	2
axon cytoplasm	2
protein complex oligomerization	2
ATP-dependent activity	2
binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
organelle membrane	2
endoplasmic reticulum subcompartment	2
intracellular membraneless organelle	2
microtubule cytoskeleton	2
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
nuclear membrane reassembly	1
mitotic nuclear membrane organization	1
mitotic cell cycle phase transition	1
mitotic nuclear division	1
mitochondrion transport along microtubule	1
axonogenesis	1
central nervous system neuron development	1
microtubule depolymerization	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
positive regulation of protein depolymerization	1
positive regulation of supramolecular fiber organization	1
membrane assembly	1
nuclear membrane organization	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
cell cycle process	1

Protein interactions and networks

STRING

3242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPAST	CHMP1B	Q7LBR1	998
SPAST	ATL1	Q8WXF7	995
SPAST	IST1	P53990	987
SPAST	REEP1	Q9H902	976
SPAST	ATL2	Q8NHH9	970
SPAST	ATL3	Q6DD88	965
SPAST	ZFYVE27	Q5T4F4	950
SPAST	SPG11	Q96JI7	936
SPAST	NIPA1	Q7RTP0	933
SPAST	RTN1	Q16799	896
SPAST	ABCD1	P33897	890
SPAST	WASHC5	Q12768	888
SPAST	SSNA1	O43805	881
SPAST	KIF5A	Q12840	832
SPAST	RTN2	O75298	810

IntAct

41 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
NUP43	NUP98	psi-mi:“MI:0914”(association)	0.640
SPAST	ATL1	psi-mi:“MI:0915”(physical association)	0.590
SPAST	ATL1	psi-mi:“MI:0407”(direct interaction)	0.590
FBXL17	SPAST	psi-mi:“MI:0407”(direct interaction)	0.590
SPAST	FBXL17	psi-mi:“MI:0915”(physical association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
CHMP1B	IST1	psi-mi:“MI:0914”(association)	0.530
ZFYVE27	SPAST	psi-mi:“MI:0915”(physical association)	0.460
ZFYVE27	SPAST	psi-mi:“MI:0403”(colocalization)	0.460
DCAF8	SPAST	psi-mi:“MI:0407”(direct interaction)	0.440
USP20	SPAST	psi-mi:“MI:0407”(direct interaction)	0.440
SPAST	SVIL	psi-mi:“MI:0915”(physical association)	0.400
ZNF30	SPAST	psi-mi:“MI:0915”(physical association)	0.400
SPAST	ATL1	psi-mi:“MI:0915”(physical association)	0.370
ALB	CNOT1	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
HTRA4	ATOX1	psi-mi:“MI:0914”(association)	0.350
SPAST	SKP1	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
CLTA	CLTB	psi-mi:“MI:0914”(association)	0.350
PSPC1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
RPS16	MCRIP1	psi-mi:“MI:0914”(association)	0.350
TEX28	NBAS	psi-mi:“MI:0914”(association)	0.350
SERF2	WDR46	psi-mi:“MI:0914”(association)	0.350
SPAST	CBLIF	psi-mi:“MI:0914”(association)	0.350
PLAGL2	CRABP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (110): SPAST (Synthetic Lethality), SPAST (Affinity Capture-MS), SPAST (Affinity Capture-MS), SPAST (Affinity Capture-MS), SPAST (Affinity Capture-MS), SPAST (Affinity Capture-MS), SPAST (Affinity Capture-MS), SPAST (Affinity Capture-MS), SPAST (Affinity Capture-MS), SPAST (Affinity Capture-MS), IST1 (Affinity Capture-MS), NUP98 (Affinity Capture-MS), NUP107 (Affinity Capture-MS), WDR45 (Affinity Capture-MS), NUP43 (Affinity Capture-MS)

ESM2 similar proteins: A0A097I2B5, A0A097I2D0, A0A0D2UG83, A2VDN5, A5DBG5, A5DJJ1, B0R160, B2RYN7, O16810, O59824, O75367, O93327, P02293, P02294, P04913, P08993, P08994, P0CO02, P0CO03, P27795, P27893, P32795, P40284, Q02874, Q27490, Q54BC2, Q54WG6, Q5Y2C3, Q64524, Q6BKW7, Q6BRG2, Q6C4I6, Q6CK60, Q6CMV8, Q6CND0, Q6FM30, Q6FWM8, Q719N1, Q74ZL5, Q7M400

Diamond homologs: A0A8I6AGW3, A0LR74, A2VDN5, A4IHT0, A6NMB9, B2RYN7, B3M301, B3P8A3, B4F6J6, B4G437, B4HGG6, B4JII0, B4K799, B4M0H8, B4NBP4, B4PL32, B4QSF0, B7PXE3, D0FH76, D2VS83, E9QEA3, F4JEX5, F6QV99, J3QK54, O05209, O14114, O14325, O15381, O16299, O28972, O57940, O60058, P03974, P23787, P25694, P32794, P36966, P40340, P46462, P54609

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NRF1	“up-regulates quantity by expression”	SPAST	“transcriptional regulation”
SOX11	“up-regulates quantity by expression”	SPAST	“transcriptional regulation”
IST1	“up-regulates activity”	SPAST	relocalization
SPAST	up-regulates	Neurite_outgrowth
SPAST	up-regulates	Microtubule_polimerization	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

1578 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	512
Likely pathogenic	128
Uncertain significance	458
Likely benign	238
Benign	56

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065559	NM_014946.4(SPAST):c.1606C>T (p.Gln536Ter)	Pathogenic
1065986	NM_014946.4(SPAST):c.1724_1725insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCANNNNNNNNNNNNAAAAAAAAAAAAAAAAAAGAATATGTCTGCCAG (p.Ser575fs)	Pathogenic
1068473	NM_014946.4(SPAST):c.1350_1351del (p.Glu452fs)	Pathogenic
1070153	NC_000002.11:g.(?32288891)(32341291_?)del	Pathogenic
1070647	NM_014946.4(SPAST):c.1728+1G>T	Pathogenic
1070822	NM_014946.4(SPAST):c.1238C>A (p.Ser413Ter)	Pathogenic
1072047	NM_014946.4(SPAST):c.1539_1540del (p.Arg514fs)	Pathogenic
1072181	NM_014946.4(SPAST):c.746dup (p.Thr251fs)	Pathogenic
1072248	NC_000002.11:g.(?32361622)(32379575_?)del	Pathogenic
1072249	NC_000002.11:g.(?32366967)(32372333_?)del	Pathogenic
1072725	NM_014946.4(SPAST):c.936dup (p.Asp313fs)	Pathogenic
1074112	NC_000002.11:g.(?32339697)(32379575_?)del	Pathogenic
1074538	NM_014946.4(SPAST):c.1118del (p.Ala373fs)	Pathogenic
1075296	NM_014946.4(SPAST):c.1506del (p.Lys502fs)	Pathogenic
1076083	NM_014946.4(SPAST):c.1375del (p.Arg459fs)	Pathogenic
1076310	NM_014946.4(SPAST):c.1250G>T (p.Gly417Val)	Pathogenic
1076483	NM_014946.4(SPAST):c.1069del (p.Ile357fs)	Pathogenic
1172817	NM_014946.4(SPAST):c.1099-4371_1245+1010del	Pathogenic
1177433	NM_014946.4(SPAST):c.1537-8T>G	Pathogenic
1184950	NM_014946.4(SPAST):c.430C>T (p.Gln144Ter)	Pathogenic
1184967	NM_014946.4(SPAST):c.936del (p.Asp313fs)	Pathogenic
1191560	NM_014946.4(SPAST):c.1322-1G>A	Pathogenic
1256239	NM_014946.4(SPAST):c.1053del (p.Lys351fs)	Pathogenic
1256240	NM_014946.4(SPAST):c.1054C>T (p.Gln352Ter)	Pathogenic
1256241	NM_014946.4(SPAST):c.1322-1G>T	Pathogenic
1256242	NM_014946.4(SPAST):c.1344T>A (p.Cys448Ter)	Pathogenic
1256244	NM_014946.4(SPAST):c.1536+1G>T	Pathogenic
1256421	Single allele	Pathogenic
1256422	Single allele	Pathogenic
1256424	Single allele	Pathogenic

SpliceAI

2447 predictions. Top by Δscore:

Variant	Effect	Δscore
2:32064237:G:GT	donor_gain	1.0000
2:32064242:GAAAG:G	donor_gain	1.0000
2:32064245:AGGTA:A	donor_loss	1.0000
2:32064246:GGT:G	donor_loss	1.0000
2:32064247:G:GA	donor_loss	1.0000
2:32064248:T:A	donor_loss	1.0000
2:32087491:GCA:G	acceptor_gain	1.0000
2:32087574:ACAAG:A	donor_loss	1.0000
2:32087575:CAAG:C	donor_loss	1.0000
2:32087576:AAGGT:A	donor_loss	1.0000
2:32087577:AGGTA:A	donor_loss	1.0000
2:32087579:G:A	donor_loss	1.0000
2:32087580:T:A	donor_loss	1.0000
2:32089516:TTTCA:T	acceptor_loss	1.0000
2:32089518:TCAG:T	acceptor_loss	1.0000
2:32089519:CA:C	acceptor_loss	1.0000
2:32089520:A:AT	acceptor_loss	1.0000
2:32089521:G:GT	acceptor_loss	1.0000
2:32098770:T:A	acceptor_gain	1.0000
2:32098779:C:G	acceptor_gain	1.0000
2:32098786:T:A	acceptor_gain	1.0000
2:32098789:T:A	acceptor_gain	1.0000
2:32098793:T:G	acceptor_gain	1.0000
2:32114637:GAAA:G	acceptor_gain	1.0000
2:32115699:AAG:A	acceptor_gain	1.0000
2:32115700:A:G	acceptor_gain	1.0000
2:32115700:AG:A	acceptor_gain	1.0000
2:32115701:G:GG	acceptor_gain	1.0000
2:32115701:GG:G	acceptor_gain	1.0000
2:32115829:TGGAC:T	donor_gain	1.0000

AlphaMissense

3992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:32064220:C:A	A130D	1.000
2:32064223:T:C	L131P	1.000
2:32087530:G:C	G152R	1.000
2:32087543:T:C	L156P	1.000
2:32089591:G:C	R191P	1.000
2:32115814:T:A	I328K	1.000
2:32116187:T:A	V358D	1.000
2:32126951:T:C	F368L	1.000
2:32126953:C:A	F368L	1.000
2:32126953:C:G	F368L	1.000
2:32126985:T:C	L379S	1.000
2:32126993:G:C	G382R	1.000
2:32126994:G:A	G382D	1.000
2:32127002:G:T	G385W	1.000
2:32127003:G:A	G385E	1.000
2:32127008:G:T	G387W	1.000
2:32127009:G:A	G387E	1.000
2:32128409:C:A	A392D	1.000
2:32128414:G:C	A394P	1.000
2:32128421:C:A	A396D	1.000
2:32128457:C:A	A408D	1.000
2:32128471:T:C	S413P	1.000
2:32136590:G:C	A425P	1.000
2:32136594:T:C	L426P	1.000
2:32136606:C:A	A430D	1.000
2:32136632:T:C	F439L	1.000
2:32136634:T:A	F439L	1.000
2:32136634:T:G	F439L	1.000
2:32136879:G:A	E442K	1.000
2:32136880:A:T	E442V	1.000

dbSNP variants (sampled 300 via entrez): RS1000012880 (2:32065468 A>G), RS1000022015 (2:32108260 C>A,T), RS1000029472 (2:32116809 G>C), RS1000035597 (2:32154942 C>T), RS1000068761 (2:32072068 A>T), RS1000122585 (2:32079514 A>T), RS1000172576 (2:32096896 T>C), RS1000187000 (2:32151256 T>G), RS1000212512 (2:32120319 C>A), RS1000221065 (2:32077020 C>T), RS1000249815 (2:32082313 C>A), RS1000260010 (2:32078222 C>A), RS1000279927 (2:32102109 A>G), RS1000282333 (2:32139505 C>G,T), RS1000310951 (2:32101903 T>C)

Disease associations

OMIM: gene MIM:604277 | disease phenotypes: MIM:182601, MIM:303350, MIM:312920, MIM:108600

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 4	Definitive	Autosomal dominant
SPAST-related motor disorder	Strong	Autosomal recessive
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (9): hereditary spastic paraplegia 4 (MONDO:0008438), hereditary spastic paraplegia (MONDO:0019064), cerebral palsy (MONDO:0006497), neurodevelopmental disorder (MONDO:0700092), hereditary spastic paraplegia 2 (MONDO:0010733), spastic ataxia (MONDO:0017845), hereditary ataxia (MONDO:0100309), tic disorder (MONDO:0002420), SPAST-related motor disorder (MONDO:0100523)

Orphanet (5): Autosomal dominant spastic paraplegia type 4 (Orphanet:100985), Hereditary spastic paraplegia (Orphanet:685), Spastic paraplegia type 2 (Orphanet:99015), Spastic ataxia (Orphanet:316226), Hereditary ataxia (Orphanet:183518)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000639	Nystagmus
HP:0000713	Agitation
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000726	Dementia
HP:0000734	Disinhibition
HP:0000741	Apathy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001761	Pes cavus
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002314	Degeneration of the lateral corticospinal tracts
HP:0002354	Memory impairment
HP:0002839	Urinary bladder sphincter dysfunction
HP:0003419	Low back pain
HP:0003487	Babinski sign
HP:0003587	Insidious onset
HP:0003676	Progressive
HP:0003693	Distal amyotrophy

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002255_2	Inflammatory biomarkers	3.000000e-19
GCST006661_237	Male-pattern baldness	7.000000e-26
GCST006661_314	Male-pattern baldness	4.000000e-20
GCST008097_14	Bisphosphonate-associated atypical femoral fracture	8.000000e-07
GCST009736_2	Interleukin-18 levels	3.000000e-19
GCST010241_401	Apolipoprotein A1 levels	1.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004812	interleukin-1 beta measurement
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture
EFO:0004581	interleukin 18 measurement
EFO:0004614	apolipoprotein A 1 measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D065886	Neurodevelopmental Disorders	F03.625
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
D013981	Tic Disorders	C10.228.662.825; F03.625.992
C531684	Hereditary spinal ataxia (supp.)
C564815	Spastic Ataxia (supp.)
C536865	Spastic paraplegia 4, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169203 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	IC50	99	nM	CHEMBL5190401
5.36	IC50	4400	nM	CHEMBL5201542

PubChem BioAssay actives

2 with measured affinity, of 2 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(5-tert-butyl-1H-pyrazol-3-yl)-2-[(3R)-3-propan-2-ylpiperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1846614: Inhibition of human Spastin in presence of ATP	ic50	0.0990	uM
N-(5-tert-butyl-1H-pyrazol-3-yl)-2-[(2R)-2-methylpiperazin-1-yl]quinazolin-4-amine	1846614: Inhibition of human Spastin in presence of ATP	ic50	4.4000	uM

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	3
Particulate Matter	decreases reaction, increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
triacsin C	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Gold	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Nickel	decreases expression	1
Phthalic Acids	increases methylation	1
Quercetin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5097625	Binding	Inhibition of human Spastin in presence of ATP	AAA ATPases as therapeutic targets: Structure, functions, and small-molecule inhibitors. — Eur J Med Chem

Cellosaurus cell lines

10 cell lines: 5 induced pluripotent stem cell, 2 transformed cell line, 2 finite cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3I0	Abcam HEK293T SPAST KO	Transformed cell line	Female
CVCL_B7BR	HIHCNi006-A-1	Induced pluripotent stem cell	Male
CVCL_B7BS	HIHCNi006-A-2	Induced pluripotent stem cell	Male
CVCL_C3RJ	HIHCNi008-A-1	Induced pluripotent stem cell	Male
CVCL_C3RK	HIHCNi008-A-2	Induced pluripotent stem cell	Male
CVCL_D2ZY	GM28977	Finite cell line	Male
CVCL_D9SU	Ubigene HEK293 SPAST KO	Transformed cell line	Female
CVCL_E2KP	HAP1 SPAST (-)	Cancer cell line	Male
CVCL_F0Z3	GM29367	Finite cell line	Male
CVCL_IJ21	iPS-SPG4-splice	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

500 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	PHASE3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
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