MAG

Summary

MAG (myelin associated glycoprotein, HGNC:6783) is a protein-coding gene on chromosome 19q13.1, encoding Myelin-associated glycoprotein (P20916). Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2.

The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene.

Source: NCBI Gene 4099 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex hereditary spastic paraplegia (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 371 total — 8 pathogenic, 7 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6783
Approved symbol	MAG
Name	myelin associated glycoprotein
Location	19q13.1
Locus type	gene with protein product
Status	Approved
Aliases	SIGLEC4A, SIGLEC-4A, S-MAG, SIGLEC4
Ensembl gene	ENSG00000105695
Ensembl biotype	protein_coding
OMIM	159460
Entrez	4099

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000361922, ENST00000392213, ENST00000537831, ENST00000593348, ENST00000595791, ENST00000597035, ENST00000597162, ENST00000600291, ENST00000872031, ENST00000872032, ENST00000872033, ENST00000872034, ENST00000872035, ENST00000872036, ENST00000918346, ENST00000946899

RefSeq mRNA: 3 — MANE Select: NM_002361 NM_001199216, NM_002361, NM_080600

CCDS: CCDS12455, CCDS12456, CCDS56090

Canonical transcript exons

ENST00000392213 — 11 exons

Exon	Start	End
ENSE00000700261	35309874	35310161
ENSE00000700264	35302448	35302708
ENSE00000700266	35300147	35300404
ENSE00000700268	35299554	35299850
ENSE00002306928	35292161	35292204
ENSE00002447006	35295386	35295454
ENSE00002469293	35294235	35294290
ENSE00003514513	35295613	35295981
ENSE00003619273	35311918	35312017
ENSE00003628719	35310547	35310643
ENSE00003849685	35313290	35313807

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 15.3725 / max 1845.3212, expressed in 291 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175279	14.1447	117
175299	0.3009	110
175303	0.2584	80
175301	0.2547	81
175277	0.1424	55
175300	0.1041	40
175302	0.0823	23
175280	0.0521	25
175278	0.0330	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.50	gold quality
spinal cord	UBERON:0002240	99.36	gold quality
inferior vagus X ganglion	UBERON:0005363	99.25	gold quality
middle frontal gyrus	UBERON:0002702	99.19	gold quality
corpus callosum	UBERON:0002336	98.71	gold quality
pons	UBERON:0000988	98.26	gold quality
superior vestibular nucleus	UBERON:0007227	97.99	gold quality
subthalamic nucleus	UBERON:0001906	97.97	gold quality
lateral globus pallidus	UBERON:0002476	97.91	gold quality
medulla oblongata	UBERON:0001896	97.35	gold quality
ventral tegmental area	UBERON:0002691	97.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.96	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.61	gold quality
putamen	UBERON:0001874	96.29	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.19	gold quality
substantia nigra pars compacta	UBERON:0001965	95.64	gold quality
amygdala	UBERON:0001876	95.21	gold quality
midbrain	UBERON:0001891	95.10	gold quality
substantia nigra	UBERON:0002038	94.81	gold quality
inferior olivary complex	UBERON:0002127	94.73	gold quality
caudate nucleus	UBERON:0001873	94.69	gold quality
Ammon’s horn	UBERON:0001954	94.15	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.01	gold quality
hypothalamus	UBERON:0001898	93.20	gold quality
parietal lobe	UBERON:0001872	92.89	gold quality
cranial nerve II	UBERON:0000941	92.87	gold quality
frontal pole	UBERON:0002795	92.79	gold quality
postcentral gyrus	UBERON:0002581	92.58	gold quality
left ovary	UBERON:0002119	92.13	gold quality
nucleus accumbens	UBERON:0001882	92.11	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	279.31
E-HCAD-25	yes	62.24
E-GEOD-84465	yes	13.24
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting MAG, 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-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4447	99.85	67.81	2900
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1324	99.46	66.57	1302

Literature-anchored findings (GeneRIF, showing 23)

• Myelin destruction with preferential loss of MAG is found in autopsy brains with acute white matter ischemia as well as in HSV- and CMV-encephalitis. (PMID:12528815)
• Possible association of MAG and schizophrenia in a Chinese Han cohort of family trios (PMID:15820319)
• Our findings of a significant associations between schizophrenia and the MAG gene suggest that this gene may be involved in susceptibility to schizophrenia in the Chinese Han population. (PMID:16039057)
• Expression of MAG, CNP and OLIG2 did not differ between patients with schizophrenia and controls in the grey or white matter (PMID:17964117)
• These results support the hypothesis that the adhesive interactions between MUC1 and MAG are of biological significance in pancreatic cancer perineural invasion. (PMID:17974963)
• Twenty of 46 patients with IgM amyloidosis (7 with and 13 without polyneuropathy) had elevation of anti-MAG or SGPG by enzyme-linked immunosorbent assay (PMID:18236455)
• This finding provides support for potential association of the CNP gene but not the MAG gene in schizophrenia in a Caucasian population. (PMID:18496213)
• In our patient, propriospinal myoclonus was associated with anti-MAG polyneuropathy, but the causal relationship remains unclear. (PMID:18816614)
• RNF10 is a trans-acting protein regulating MAG expression and is required for myelin formation. (PMID:18941509)
• Taken together, these findings suggest that in anti-MAG neuropathy patients, IgM deposits are entrapped within cutaneous perineurium-ensheathed nerve bundles where they accumulate in the endoneurial space. (PMID:19151627)
• ELISA is more sensitive than Western blot to diagnose anti-myelin-associated glycoprotein related polyneuropathy, although a positive serology may be found in other forms of polyneuropathy as well. (PMID:19720975)
• polysialylated NCAM persistence, up-regulated polysialyltransferase-1 mRNA and previously uncovered defective myelin-associated glycoprotein may be early pathogenetic events in adult-onset autosomal-dominant leukodystrophy (PMID:19725832)
• Distal acquired demyelinating symmetric neuropathy without anti-MAG antibodies is more likely to be considered a variant of chronic inflammatory demyelinating polyradiculoneuropathy, including a hematological or immunological condition. (PMID:21199182)
• Primary mitochondrial respiratory chain defects affecting the white matter, and unrelated to inflammation, are associated with MAG loss and central nervous system demyelination. (PMID:22491194)
• Results show that MAG is important for axon-glia contact in a model for Charcot-Marie-Tooth disease type 1A, and suggest that its increased expression in patients has a compensatory role in the disease pathology (PMID:22940629)
• Increased serum levels of MAG (and MBP) were found in autistic patients with allergic manifestations compared to those without these manifestations. (PMID:23726766)
• LRP1 assembles unique co-receptor systems to initiate cell signaling in response to tissue-type plasminogen activator and myelin-associated glycoprotein. (PMID:24129569)
• polyneuropathy associated with anti-MAG antibodies is less homogeneous. (PMID:26065001)
• This study identify involvement of myelin-associated glycoprotein in this family with a disorder affecting the central and peripheral nervous system, and suggest that loss of the protein function is responsible for the unique clinical phenotype (PMID:26179919)
• we observed two-way correlations between the MOG and MAG levels and the fractional anisotropy and mean diffusivity values in the white matter of the left middle frontal lobe, right inferior parietal lobe, and right supplementary motor area in major depressive disorder patients (PMID:29477585)
• Clinical and laboratory features of anti-MAG neuropathy without monoclonal gammopathy. (PMID:30992531)
• Recessive null-allele variants in MAG associated with spastic ataxia, nystagmus, neuropathy, and dystonia. (PMID:32629324)
• Myelin-associated proteins are potential diagnostic markers in patients with primary brain tumour. (PMID:34601991)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mag	ENSDARG00000104023
mus_musculus	Mag	ENSMUSG00000036634
rattus_norvegicus	Mag	ENSRNOG00000021023

Paralogs (16): CD22 (ENSG00000012124), SIGLEC1 (ENSG00000088827), SIGLEC8 (ENSG00000105366), CD33 (ENSG00000105383), SIGLEC6 (ENSG00000105492), SIGLEC9 (ENSG00000129450), SIGLEC10 (ENSG00000142512), TMEM25 (ENSG00000149582), SIGLEC11 (ENSG00000161640), SIGLEC16 (ENSG00000161643), SIGLEC7 (ENSG00000168995), SIGLECL1 (ENSG00000179213), SIGLEC15 (ENSG00000197046), SIGLEC14 (ENSG00000254415), SIGLEC12 (ENSG00000254521), SIGLEC5 (ENSG00000268500)

Protein

Protein identifiers

Myelin-associated glycoprotein — P20916 (reviewed: P20916)

Alternative names: Siglec-4a

All UniProt accessions (4): P20916, M0QZU4, M0R3B9, M0R3I4

UniProt curated annotations — full annotation on UniProt →

Function. Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2. Not required for initial myelination, but seems to play a role in the maintenance of normal axon myelination. Protects motoneurons against apoptosis, also after injury; protection against apoptosis is probably mediated via interaction with neuronal RTN4R and RTN4RL2. Required to prevent degeneration of myelinated axons in adults; this probably depends on binding to gangliosides on the axon cell membrane. Negative regulator of neurite outgrowth; in dorsal root ganglion neurons the inhibition is mediated primarily via binding to neuronal RTN4R or RTN4RL2 and to a lesser degree via binding to neuronal gangliosides. In cerebellar granule cells the inhibition is mediated primarily via binding to neuronal gangliosides. In sensory neurons, inhibition of neurite extension depends only partially on RTN4R, RTN4RL2 and gangliosides. Inhibits axon longitudinal growth. Inhibits axon outgrowth by binding to RTN4R. Preferentially binds to alpha-2,3-linked sialic acid. Binds ganglioside Gt1b.

Subunit / interactions. Monomer and homodimer. Interacts (via the first three N-terminal Ig-like domains) with RTN4R and RTN4RL2. Interacts with RTN4R. Interacts with isoform 2 of BSG.

Subcellular location. Cell membrane. Membrane raft.

Tissue specificity. Both isoform 1 and isoform 2 are detected in myelinated structures in the central and peripheral nervous system, in periaxonal myelin and at Schmidt-Lanterman incisures. Detected in optic nerve, in oligodendroglia and in periaxonal myelin sheaths. Detected in compact myelin (at protein level). Both isoform 1 and isoform 2 are detected in the central and peripheral nervous system.

Post-translational modifications. N-glycosylated. Phosphorylated on tyrosine residues. Ubiquitinated, leading to proteasomal degradation.

Disease relevance. Spastic paraplegia 75, autosomal recessive (SPG75) [MIM:616680] 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. SPG75 is characterized by onset in early childhood and is associated with mild to moderate cognitive impairment. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.

Isoforms (3)

UniProt ID	Names	Canonical?
P20916-1	1, L-MAG	yes
P20916-2	2, S-MAG
P20916-3	3

RefSeq proteins (3): NP_001186145, NP_002352, NP_542167 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051036	SIGLEC	Family

Pfam: PF08205, PF13927

UniProt features (43 total): glycosylation site 8, disulfide bond 7, domain 5, sequence variant 4, region of interest 3, binding site 3, modified residue 3, topological domain 2, splice variant 2, signal peptide 1, chain 1, site 1, lipid moiety-binding region 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20916-F1	80.53	0.61

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 (1): 332 (not glycosylated)

Ligand- & substrate-binding residues (3): 65–67; 118; 124–128

Post-translational modifications (4): 545, 547, 549, 531

Disulfide bonds (7): 37–165, 42–100, 159–217, 261–305, 347–392, 421–430, 432–488

Glycosylation sites (8): 99, 106, 223, 246, 315, 406, 450, 454

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-193634	Axonal growth inhibition (RHOA activation)
R-HSA-210991	Basigin interactions
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-193697	p75NTR regulates axonogenesis
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-73887	Death Receptor Signaling
R-HSA-9675108	Nervous system development

MSigDB gene sets: 310 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_GROWTH, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_MYELINATION

GO Biological Process (16): cell adhesion (GO:0007155), negative regulation of neuron projection development (GO:0010977), transmission of nerve impulse (GO:0019226), substantia nigra development (GO:0021762), negative regulation of axon extension (GO:0030517), axon regeneration (GO:0031103), positive regulation of myelination (GO:0031643), central nervous system myelin formation (GO:0032289), negative regulation of neuron apoptotic process (GO:0043524), negative regulation of neuron differentiation (GO:0045665), positive regulation of astrocyte differentiation (GO:0048711), cellular response to mechanical stimulus (GO:0071260), obsolete cell-cell adhesion via plasma-membrane adhesion molecules (GO:0098742), nervous system development (GO:0007399), central nervous system myelination (GO:0022010), myelination (GO:0042552)

GO Molecular Function (7): signaling receptor binding (GO:0005102), protein kinase binding (GO:0019901), carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), protein homodimerization activity (GO:0042803), ganglioside GT1b binding (GO:1905576), lipid binding (GO:0008289)

GO Cellular Component (9): plasma membrane (GO:0005886), paranode region of axon (GO:0033270), myelin sheath adaxonal region (GO:0035749), myelin sheath (GO:0043209), compact myelin (GO:0043218), Schmidt-Lanterman incisure (GO:0043220), membrane raft (GO:0045121), mesaxon (GO:0097453), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
p75NTR regulates axonogenesis	1
Cell surface interactions at the vascular wall	1
Nervous system development	1
p75 NTR receptor-mediated signalling	1
Death Receptor Signaling	1
Hemostasis	1
Signal Transduction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
myelination	2
binding	2
carboxylic acid binding	2
myelin sheath	2
cellular process	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
action potential	1
cell communication	1
chemical synaptic transmission	1
nervous system process	1
midbrain development	1
neural nucleus development	1
negative regulation of cell growth	1
regulation of axon extension	1
negative regulation of developmental growth	1
axon extension	1
negative regulation of axonogenesis	1
neuron projection regeneration	1
response to axon injury	1
axon development	1
regulation of myelination	1
positive regulation of nervous system process	1
positive regulation of cellular process	1
central nervous system myelination	1
myelin assembly	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
neuron differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
positive regulation of glial cell differentiation	1
astrocyte differentiation	1
regulation of astrocyte differentiation	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1

Protein interactions and networks

STRING

2478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAG	RTN4R	Q9BZR6	999
MAG	MBP	P02686	986
MAG	OMG	P23515	983
MAG	RTN4	Q9NQC3	980
MAG	RTN4RL2	Q86UN3	917
MAG	LINGO1	Q96FE5	878
MAG	MOG	Q16653	867
MAG	CNP	P09543	861
MAG	PLP1	P04400	853
MAG	MUC1	P13931	853
MAG	TNFRSF19	Q9NS68	839
MAG	MPZL1	O95297	821
MAG	MYOM2	P54296	813
MAG	NGFR	P08138	749
MAG	RTN4RL1	Q86UN2	739

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CD33	MAG	psi-mi:“MI:0915”(physical association)	0.400
MAG	IL18BP	psi-mi:“MI:0915”(physical association)	0.400
IGSF10	MAG	psi-mi:“MI:0915”(physical association)	0.400
IL6R	MAG	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC15	MAG	psi-mi:“MI:0915”(physical association)	0.400
MAG	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	MAG	psi-mi:“MI:0915”(physical association)	0.400
MAG	MXRA5	psi-mi:“MI:0915”(physical association)	0.400
SCN2B	MAG	psi-mi:“MI:0915”(physical association)	0.400
MAG	gB	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
MAG	PLCB3	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): MAG (Proximity Label-MS), MAG (Affinity Capture-MS), MAG (Affinity Capture-MS), COL1A1 (Reconstituted Complex), COL2A1 (Reconstituted Complex), COL3A1 (Reconstituted Complex), COL4A1 (Reconstituted Complex), COL5A1 (Reconstituted Complex), COL6A1 (Reconstituted Complex), COL9A1 (Reconstituted Complex), PLCB3 (Affinity Capture-MS), MARS2 (Affinity Capture-MS), FYN (Reconstituted Complex), MAP1B (Affinity Capture-Western), MAG (Affinity Capture-MS)

ESM2 similar proteins: A6NMB1, D3ZQE1, E9QA28, G1T7E7, G1TR84, O75054, O75144, P05362, P07722, P09564, P11364, P15151, P16573, P20916, P20917, P32506, P32942, P33729, Q08ET2, Q1WIM1, Q1WIM3, Q28110, Q28125, Q28730, Q28806, Q2WEN9, Q5DRQ8, Q5NKU6, Q5NKV4, Q5NKV6, Q5NKV9, Q5R996, Q60625, Q64JA4, Q6BAA4, Q7TSU7, Q8N126, Q8NFZ8, Q8R464, Q8VBT3

Diamond homologs: A0A087WV53, A1KZ92, A2AJ76, A4IFW2, A4IGL7, A6NDA9, B0BNK7, B0V2N1, D2HFT7, D3YXG0, D4A1J9, D4ABX8, F1NWE3, G5EG78, O15146, O73775, O75325, O94898, P07722, P15364, P20916, P20917, P23468, P43146, P48960, P53813, P70193, P70211, Q03142, Q08761, Q08879, Q13332, Q13449, Q1ENI8, Q1RMS4, Q1WIM1, Q21038, Q24372, Q26474, Q2Q421

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FYN	“up-regulates activity”	MAG	phosphorylation
SMO	“up-regulates quantity”	MAG	“transcriptional regulation”
MAG	up-regulates	Myelination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	7
Uncertain significance	178
Likely benign	141
Benign	21

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
120188	NM_002361.4(MAG):c.1288T>G (p.Cys430Gly)	Pathogenic
1478560	NM_002361.4(MAG):c.719dup (p.Val241fs)	Pathogenic
218187	NM_002361.4(MAG):c.399C>G (p.Ser133Arg)	Pathogenic
3764543	NM_002361.4(MAG):c.337G>A (p.Gly113Arg)	Pathogenic
4703049	NM_002361.4(MAG):c.1273C>T (p.Arg425Ter)	Pathogenic
488543	NM_002361.4(MAG):c.517_521dup (p.Trp174Ter)	Pathogenic
657878	NM_002361.4(MAG):c.328G>T (p.Glu110Ter)	Pathogenic
976659	NM_002361.4(MAG):c.1126C>T (p.Gln376Ter)	Pathogenic
2585566	NM_002361.4(MAG):c.470del (p.Val157fs)	Likely pathogenic
2857234	NM_002361.4(MAG):c.1520-3_1520-2del	Likely pathogenic
3256730	NM_002361.4(MAG):c.809T>C (p.Leu270Pro)	Likely pathogenic
3643289	NM_002361.4(MAG):c.1616+1G>A	Likely pathogenic
3644099	NM_002361.4(MAG):c.1232-3_1240del	Likely pathogenic
4278447	NM_002361.4(MAG):c.1231+3G>C	Likely pathogenic
435794	NM_002361.4(MAG):c.416-6_418dup	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4045 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35299660:G:C	W174C	1.000
19:35299660:G:T	W174C	1.000
19:35302665:C:A	N396K	1.000
19:35302665:C:G	N396K	1.000
19:35310610:C:A	A528D	1.000
19:35295679:T:A	V38D	0.999
19:35295690:T:C	C42R	0.999
19:35295691:G:A	C42Y	0.999
19:35295692:C:G	C42W	0.999
19:35295741:T:A	W59R	0.999
19:35295741:T:C	W59R	0.999
19:35295743:G:C	W59C	0.999
19:35295743:G:T	W59C	0.999
19:35295866:C:G	C100W	0.999
19:35299613:T:C	C159R	0.999
19:35299658:T:A	W174R	0.999
19:35299658:T:C	W174R	0.999
19:35299787:T:A	C217S	0.999
19:35299788:G:C	C217S	0.999
19:35300253:G:C	W273C	0.999
19:35300253:G:T	W273C	0.999
19:35300361:T:A	N309K	0.999
19:35300361:T:G	N309K	0.999
19:35302516:T:A	C347S	0.999
19:35302516:T:C	C347R	0.999
19:35302517:G:C	C347S	0.999
19:35302518:C:G	C347W	0.999
19:35302528:A:C	S351R	0.999
19:35302530:C:A	S351R	0.999
19:35302530:C:G	S351R	0.999

dbSNP variants (sampled 300 via entrez): RS1000019762 (19:35294255 G>A), RS1000249539 (19:35312718 A>G), RS1000369353 (19:35290618 T>C), RS1000574456 (19:35301526 T>C), RS1000626205 (19:35312971 G>A), RS1000707153 (19:35307512 T>C), RS1000725510 (19:35294648 G>T), RS1000833312 (19:35311864 G>A,T), RS1001008879 (19:35301206 C>A), RS1001088434 (19:35294822 T>C,G), RS1001226165 (19:35311837 G>A), RS1001260158 (19:35311729 C>T), RS1001350923 (19:35300093 C>G,T), RS1001465334 (19:35306243 C>T), RS1001606918 (19:35305865 G>A)

Disease associations

OMIM: gene MIM:159460 | disease phenotypes: MIM:616680, MIM:303350, MIM:119530

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 75	Strong	Autosomal recessive
complex hereditary spastic paraplegia	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex hereditary spastic paraplegia	Definitive	AR

Mondo (4): hereditary spastic paraplegia 75 (MONDO:0014729), hereditary spastic paraplegia (MONDO:0019064), orofacial cleft 1 (MONDO:0007335), complex hereditary spastic paraplegia (MONDO:0015150)

Orphanet (2): Autosomal recessive spastic paraplegia type 75 (Orphanet:459056), Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

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
C566121	Orofacial Cleft 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5807 (SINGLE PROTEIN)

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

ChEMBL bioactivities

25 potent at pChembl≥5 of 33 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	IC50	9	nM	CHEMBL1836190
7.82	Kd	15	nM	CHEMBL1836190
7.10	IC50	79	nM	CHEMBL1836336
6.89	Kd	130	nM	CHEMBL1836336
6.52	IC50	300	nM	CHEMBL1836306
6.52	IC50	300	nM	CHEMBL1836340
6.32	Kd	480	nM	CHEMBL1836340
6.30	Kd	500	nM	CHEMBL1836312
6.21	IC50	610	nM	CHEMBL1836335
6.19	IC50	650	nM	CHEMBL1836334
6.19	IC50	640	nM	CHEMBL1836337
6.12	IC50	750	nM	CHEMBL1836339
6.00	Kd	1000	nM	CHEMBL1836334
6.00	Kd	1000	nM	CHEMBL1836335
6.00	Kd	1000	nM	CHEMBL1836337
5.96	IC50	1100	nM	CHEMBL1836338
5.92	IC50	1200	nM	CHEMBL1836310
5.92	IC50	1200	nM	CHEMBL1836313
5.92	Kd	1200	nM	CHEMBL1836339
5.75	Kd	1760	nM	CHEMBL1836338
5.72	Kd	1900	nM	CHEMBL1836313
5.55	Kd	2830	nM	CHEMBL507374
5.30	Kd	5000	nM	CHEMBL454284
5.10	IC50	7900	nM	CHEMBL1833997
5.03	IC50	9270	nM	CHEMBL1684363

PubChem BioAssay actives

25 with measured affinity, of 89 total; 16 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
disodium;(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-4-[(2R,3R,4S,5S,6R)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxylato-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxyoxan-2-yl]methoxy]-6-[(1R,2R)-3-[(4-fluorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.0090	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-[(1R,2R)-3-[(4-fluorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.0790	uM
disodium;(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-4-[(2R,3R,4S,5S,6R)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxylato-6-[(1R,2R)-3-[(4-fluorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.3000	uM
disodium;(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-4-[(2R,3R,4S,5S,6R)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxylato-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(1S,2R)-1-amino-1-carboxypropan-2-yl]oxy-3-hydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620751: Inhibition of MAG	ic50	0.3000	uM
sodium (2R,4S,5R,6R)-6-[(1R,2R)-3-benzamido-1,2-dihydroxypropyl]-2-[(2,3-difluorophenyl)methoxy]-5-[(2-fluoroacetyl)amino]-4-hydroxyoxane-2-carboxylate	620750: Binding affinity to MAG	kd	0.5000	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-[(1R,2R)-3-[(4-chlorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.6100	uM
sodium (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxy-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]-6-[(1R,2R)-3-[(4-chlorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.6400	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-[(1R,2R)-3-benzamido-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.6500	uM
disodium;(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-4-[(2R,3R,4S,5S,6R)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxylato-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.7500	uM
sodium (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxy-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]-6-[(1R,2R)-3-[(4-fluorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	1.1000	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	1.2000	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(1S,2R)-1-amino-1-carboxypropan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620751: Inhibition of MAG	ic50	1.2000	uM
sodium (2S,4S,5R,6R)-5-acetamido-6-[(1S,2R)-3-[(4-chlorobenzoyl)amino]-1,2-dihydroxypropyl]-2-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,3R,4R)-3-hydroxy-2-[(4-phenylphenoxy)methyl]oxan-4-yl]oxyoxan-4-yl]oxy-4-hydroxyoxane-2-carboxylate	346346: Binding affinity to human IgG Fc-domain tagged MAG N-terminal domain expressed in CHO cells by surface plasmon resonance	kd	2.8300	uM
sodium (2S,4S,5R,6R)-5-acetamido-6-[(1S,2R)-3-benzamido-1,2-dihydroxypropyl]-2-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,3R,4R)-3-hydroxy-2-[(4-phenylphenoxy)methyl]oxan-4-yl]oxyoxan-4-yl]oxy-4-hydroxyoxane-2-carboxylate	346346: Binding affinity to human IgG Fc-domain tagged MAG N-terminal domain expressed in CHO cells by surface plasmon resonance	kd	5.0000	uM
sodium (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxy-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	7.9000	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(4-hydroxyphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-phenylmethoxyoxane-2-carboxylic acid	578489: Inhibition of human MAG after 1 hr by competitive ELISA	ic50	9.2700	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
bisphenol S	increases expression	1
Leflunomide	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cadmium	decreases expression, increases abundance	1
Testosterone	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1686889	Binding	Inhibition of human MAG after 1 hr by competitive ELISA	CD22-antagonists with nanomolar potency: the synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold. — Bioorg Med Chem

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