ARSI

Summary

ARSI (arylsulfatase family member I, HGNC:32521) is a protein-coding gene on chromosome 5q32, encoding Arylsulfatase I (Q5FYB1). Displays arylsulfatase activity at neutral pH, when co-expressed with SUMF1; arylsulfatase activity is measured in the secretion medium of retinal cell line, but no activity is recorded when measured in cell extracts.

This gene encodes a protein that belongs to a large family of sulfatases that hydrolyze sulfate esters and sulfamates. Members of this family play a role in several cellular processes, including hormone synthesis, cell signaling in development and degradation of macromolecules. The protein encoded by this gene is thought to be secreted, and to function in extracellular space.

Source: NCBI Gene 340075 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive spastic paraplegia type 66 (Supportive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 194 total
• Phenotypes (HPO): 14
• MANE Select transcript: NM_001012301

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32521
Approved symbol	ARSI
Name	arylsulfatase family member I
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16069, SPG66
Ensembl gene	ENSG00000183876
Ensembl biotype	protein_coding
OMIM	610009
Entrez	340075

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000328668, ENST00000509146, ENST00000515301

RefSeq mRNA: 1 — MANE Select: NM_001012301 NM_001012301

CCDS: CCDS34275

Canonical transcript exons

ENST00000328668 — 2 exons

Exon	Start	End
ENSE00001310797	150302063	150302905
ENSE00001328397	150296343	150298612

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 80.25.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7807 / max 205.3345, expressed in 687 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64211	1.8188	594
64210	0.4174	214
64209	0.2251	78
203739	0.1862	113
64208	0.1332	76

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	80.25	gold quality
tibia	UBERON:0000979	79.46	gold quality
palpebral conjunctiva	UBERON:0001812	75.11	gold quality
cartilage tissue	UBERON:0002418	74.19	gold quality
gingival epithelium	UBERON:0001949	73.19	silver quality
gingiva	UBERON:0001828	71.45	silver quality
endothelial cell	CL:0000115	70.89	gold quality
placenta	UBERON:0001987	70.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	69.46	gold quality
smooth muscle tissue	UBERON:0001135	69.29	gold quality
left uterine tube	UBERON:0001303	68.50	gold quality
upper lobe of left lung	UBERON:0008952	68.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	68.35	gold quality
lower esophagus	UBERON:0013473	68.33	gold quality
vermiform appendix	UBERON:0001154	67.64	gold quality
ectocervix	UBERON:0012249	67.36	gold quality
spinal cord	UBERON:0002240	66.82	gold quality
upper lobe of lung	UBERON:0008948	66.64	gold quality
tibial nerve	UBERON:0001323	66.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	64.96	gold quality
body of uterus	UBERON:0009853	64.95	gold quality
esophagus	UBERON:0001043	64.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.21	gold quality
lower esophagus mucosa	UBERON:0035834	63.45	gold quality
urinary bladder	UBERON:0001255	63.20	gold quality
islet of Langerhans	UBERON:0000006	62.63	gold quality
parotid gland	UBERON:0001831	62.41	gold quality
esophagus mucosa	UBERON:0002469	62.27	gold quality
lung	UBERON:0002048	62.10	gold quality
vagina	UBERON:0000996	62.02	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

26 targeting ARSI, 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-4673	100.00	66.64	1490
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-6861-5P	96.23	67.19	800
HSA-MIR-4509	96.19	65.80	900
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-2114-3P	95.45	66.11	579
HSA-MIR-6823-3P	95.45	66.14	704

Literature-anchored findings (GeneRIF, showing 2)

• The identification, molecular cloning and initial characterization of three new members of this human gene family is reported. (PMID:16500042)
• No mutation was found in the ARSI gene locus of the retinitis pigmentosa patients examined. (PMID:19262745)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	arsia	ENSDARG00000077606
mus_musculus	Arsi	ENSMUSG00000036412
rattus_norvegicus	Arsi	ENSRNOG00000026060
drosophila_melanogaster	CG18278	FBGN0033836
drosophila_melanogaster	CG7408	FBGN0036765
drosophila_melanogaster	CG7402	FBGN0036768
drosophila_melanogaster	Sulf1	FBGN0040271
drosophila_melanogaster	CG32191	FBGN0052191
drosophila_melanogaster	CG30059	FBGN0260475
caenorhabditis_elegans		WBGENE00006308
caenorhabditis_elegans		WBGENE00006309

Paralogs (16): ARSD (ENSG00000006756), IDS (ENSG00000010404), ARSF (ENSG00000062096), ARSA (ENSG00000100299), STS (ENSG00000101846), ARSB (ENSG00000113273), GNS (ENSG00000135677), SULF1 (ENSG00000137573), GALNS (ENSG00000141012), ARSG (ENSG00000141337), ARSL (ENSG00000157399), ARSK (ENSG00000164291), ARSJ (ENSG00000180801), SGSH (ENSG00000181523), SULF2 (ENSG00000196562), ARSH (ENSG00000205667)

Protein

Protein identifiers

Arylsulfatase I — Q5FYB1 (reviewed: Q5FYB1)

All UniProt accessions (2): Q5FYB1, D6RDH0

UniProt curated annotations — full annotation on UniProt →

Function. Displays arylsulfatase activity at neutral pH, when co-expressed with SUMF1; arylsulfatase activity is measured in the secretion medium of retinal cell line, but no activity is recorded when measured in cell extracts. Lacks arylsulfatase activity.

Subcellular location. Secreted. Endoplasmic reticulum.

Tissue specificity. Expressed in placenta, in embryonic stem cells, fetal eyes and lens.

Post-translational modifications. The oxidation of Cys-93 residue to 3-oxoalanine (also known as C(alpha)-formylglycine) by SUMF1/Sulfatase-modifying factor 1, seems critical for catalytic activity.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Similarity. Belongs to the sulfatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5FYB1-1	1	yes
Q5FYB1-2	2

RefSeq proteins (1): NP_001012301* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000917	Sulfatase_N	Domain
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR024607	Sulfatase_CS	Conserved_site
IPR047115	ARSB	Family

Pfam: PF00884

UniProt features (22 total): binding site 8, glycosylation site 4, sequence conflict 2, active site 2, signal peptide 1, chain 1, modified residue 1, splice variant 1, mutagenesis site 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5FYB1-F1	87.35	0.77

Functional residue map

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

Catalytic / active sites (2): 93 (nucleophile); 149

Ligand- & substrate-binding residues (8): 297; 298; 315; 55; 56; 93 (via 3-oxoalanine); 147; 239

Post-translational modifications (1): 93

Glycosylation sites (4): 276, 288, 466, 496

Mutagenesis-validated functional residues (1):

Position	Phenotype
93	no arylsulfatase activity in the media of retinal epithelium cell.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1663150	The activation of arylsulfatases
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 92 (showing top): REACTOME_SPHINGOLIPID_METABOLISM, chr5q32, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_SULFURIC_ESTER_HYDROLASE_ACTIVITY, GOMF_ARYLSULFATASE_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MARTENS_TRETINOIN_RESPONSE_UP, LIM_MAMMARY_STEM_CELL_UP, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, REACTOME_GAMMA_CARBOXYLATION_HYPUSINYLATION_HYDROXYLATION_AND_ARYLSULFATASE_ACTIVATION, REACTOME_METABOLISM_OF_LIPIDS, ZNF92_TARGET_GENES, MIR6780B_5P

GO Biological Process (0):

GO Molecular Function (5): arylsulfatase activity (GO:0004065), sulfuric ester hydrolase activity (GO:0008484), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Glycosphingolipid metabolism	1
Post-translational protein modification	1
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sulfuric ester hydrolase activity	1
hydrolase activity, acting on ester bonds	1
cation binding	1
binding	1
catalytic activity	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARSI	ARSK	Q6UWY0	728
ARSI	SPG21	Q9NZD8	478
ARSI	AP4B1	Q9Y6B7	478
ARSI	AP5Z1	O43299	461
ARSI	AP4S1	Q9Y587	450
ARSI	AR	P10275	448
ARSI	AP4E1	Q9UPM8	435
ARSI	VPS37A	Q8NEZ2	435
ARSI	C19orf12	Q9NSK7	434
ARSI	REEP2	Q9BRK0	430
ARSI	ARL6IP1	Q15041	426
ARSI	MTRFR	Q9H3J6	422
ARSI	PGAP1	Q75T13	419
ARSI	TECPR2	O15040	418
ARSI	AP4M1	O00189	416
ARSI	DDHD2	O94830	416

IntAct

6 interactions, top by confidence:

A	B	Type	Score
KRT40	ARSI	psi-mi:“MI:0915”(physical association)	0.560
ARSI	KRT40	psi-mi:“MI:0915”(physical association)	0.560
ARSI	HSPA5	psi-mi:“MI:0914”(association)	0.530
ARSI	FBXO21	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): ARSI (Two-hybrid), NOL11 (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), FBXO21 (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), NOL11 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS)

ESM2 similar proteins: A2AIR5, A5PK45, F1PZV2, O00222, O09009, O15303, O15399, O60391, O97583, P31423, P35349, P52849, P52850, P70579, Q00961, Q01098, Q03391, Q13467, Q14833, Q14957, Q1ZZH0, Q32KH7, Q32KI9, Q32KJ8, Q3U481, Q5FYB1, Q5NCH9, Q5RDQ8, Q61088, Q62645, Q68EF4, Q6PCB7, Q863I4, Q8CHL0, Q8K078, Q8K297, Q8NBJ5, Q8TCU5, Q8VHN2, Q91ZU9

Diamond homologs: P08842, P14000, P15289, P15589, P20713, P22304, P31447, P34059, P50427, P50428, P50473, P51689, P51690, P54793, Q08890, Q08DD1, Q32KH5, Q32KH8, Q32KH9, Q32KI9, Q32KJ6, Q32KJ8, Q32KJ9, Q3TYD4, Q571E4, Q5FYA8, Q5FYB1, Q60HH5, Q8WNQ7, Q96EG1, Q9X759, T2KMG4, P15586, P50426, Q5FYB0, Q8A2F6, Q8A2H2, Q8BFR4, Q8BM89, Q8IWU6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	139
Likely benign	35
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

223 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150298610:TAC:T	acceptor_gain	1.0000
5:150298611:AC:A	acceptor_gain	1.0000
5:150298612:CCTGG:C	acceptor_gain	1.0000
5:150298613:C:CC	acceptor_gain	1.0000
5:150298613:CT:C	acceptor_loss	1.0000
5:150298616:G:GC	acceptor_gain	1.0000
5:150302057:GCCTA:G	donor_loss	1.0000
5:150302058:CCTA:C	donor_loss	1.0000
5:150302059:CTA:C	donor_loss	1.0000
5:150302060:TAC:T	donor_loss	1.0000
5:150302061:ACC:A	donor_loss	1.0000
5:150298608:GGTAC:G	acceptor_gain	0.9900
5:150298609:GTAC:G	acceptor_gain	0.9900
5:150302065:G:A	donor_gain	0.9900
5:150302127:TG:T	donor_gain	0.9900
5:150298616:G:C	acceptor_gain	0.9800
5:150298609:GTACC:G	acceptor_gain	0.9700
5:150298610:TACCT:T	acceptor_gain	0.9700
5:150298611:ACC:A	acceptor_gain	0.9700
5:150298612:CCT:C	acceptor_gain	0.9700
5:150298613:CTGGT:C	acceptor_gain	0.9700
5:150302061:A:AC	donor_gain	0.9700
5:150302061:ACCTG:A	donor_gain	0.9700
5:150302062:C:CC	donor_gain	0.9700
5:150302062:CCTG:C	donor_gain	0.9700
5:150302062:CCTGC:C	donor_gain	0.9700
5:150298614:T:A	acceptor_gain	0.9600
5:150300468:AGGGC:A	donor_gain	0.9600
5:150298223:GCCAC:G	acceptor_gain	0.8800
5:150298613:C:T	acceptor_gain	0.8800

AlphaMissense

3695 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150298482:A:G	W148R	1.000
5:150298482:A:T	W148R	1.000
5:150297979:C:A	K315N	0.999
5:150297979:C:G	K315N	0.999
5:150298028:C:T	G299D	0.999
5:150298480:C:A	W148C	0.999
5:150298480:C:G	W148C	0.999
5:150302210:T:A	D55V	0.999
5:150297364:C:A	W520C	0.998
5:150297364:C:G	W520C	0.998
5:150297647:A:G	L426P	0.998
5:150297876:A:G	W350R	0.998
5:150297876:A:T	W350R	0.998
5:150297938:A:T	V329D	0.998
5:150298000:G:C	N308K	0.998
5:150298000:G:T	N308K	0.998
5:150298028:C:A	G299V	0.998
5:150298034:T:A	D297V	0.998
5:150298209:G:C	H239D	0.998
5:150298432:G:C	F164L	0.998
5:150298432:G:T	F164L	0.998
5:150298434:A:G	F164L	0.998
5:150298448:G:T	P159H	0.998
5:150298483:C:A	K147N	0.998
5:150298483:C:G	K147N	0.998
5:150298487:C:A	G146V	0.998
5:150298592:A:G	L111P	0.998
5:150302087:G:C	S96W	0.998
5:150302095:G:C	C93W	0.998
5:150302096:C:T	C93Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000655947 (5:150303054 G>A), RS1001246916 (5:150299051 A>T), RS1001418211 (5:150303574 C>T), RS1001491420 (5:150303189 T>C), RS1001650603 (5:150297179 G>C,T), RS1002908904 (5:150296057 C>A,T), RS1002973254 (5:150302288 G>A,T), RS1003404920 (5:150300985 T>C), RS1004570882 (5:150296247 C>T), RS1004664009 (5:150296489 C>T), RS1005023360 (5:150302897 A>G), RS1005328145 (5:150298918 C>G), RS1006033244 (5:150303664 A>C,G), RS1007405064 (5:150297728 G>C,T), RS1007427800 (5:150298223 G>A,C,T)

Disease associations

OMIM: gene MIM:610009 | disease phenotypes: MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive spastic paraplegia type 66	Supportive	Autosomal recessive

Mondo (2): hereditary spastic paraplegia (MONDO:0019064), autosomal recessive spastic paraplegia type 66 (MONDO:0018418)

Orphanet (1): Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0001249	Intellectual disability
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001301	Chronic sensorineural polyneuropathy
HP:0001321	Cerebellar hypoplasia
HP:0001762	Talipes equinovarus
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002079	Hypoplasia of the corpus callosum
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002509	Limb hypertonia
HP:0007020	Progressive spastic paraplegia
HP:0007210	Lower limb amyotrophy
HP:0030048	Colpocephaly

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004735_15	Epstein-Barr virus copy number in lymphoblastoid cell lines	7.000000e-06
GCST009391_1519	Metabolite levels	9.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010418	triacylglycerol 52:6 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
dicrotophos	decreases expression	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	increases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Arsenicals	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Endosulfan	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Silicon Dioxide	increases expression	1
Silver	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
NCT06572046	Not specified	RECRUITING	STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies
NCT06573866	Not specified	RECRUITING	Enhancement of Quality of Work And Life
NCT06680063	Not specified	COMPLETED	Correlation Between Clinical Assessment and Neurophysiological Assessment in Spinal Cord Injury