SLC1A5

Summary

SLC1A5 (solute carrier family 1 member 5, HGNC:10943) is a protein-coding gene on chromosome 19q13.32, encoding Neutral amino acid transporter B(0) (Q15758). Sodium-coupled antiporter of neutral amino acids. It is a selective cancer dependency (DepMap: 10.2% of cell lines).

The SLC1A5 gene encodes a sodium-dependent neutral amino acid transporter that can act as a receptor for RD114/type D retrovirus (Larriba et al., 2001 [PubMed 11781704]).

Source: NCBI Gene 6510 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 79 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.2% of screened cell lines
• MANE Select transcript: NM_005628

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10943
Approved symbol	SLC1A5
Name	solute carrier family 1 member 5
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	AAAT, ASCT2
Ensembl gene	ENSG00000105281
Ensembl biotype	protein_coding
OMIM	109190
Entrez	6510

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000412532, ENST00000434726, ENST00000542575, ENST00000593713, ENST00000594991, ENST00000598022, ENST00000713951, ENST00000891610, ENST00000891611, ENST00000926641, ENST00000926642, ENST00000926643

RefSeq mRNA: 3 — MANE Select: NM_005628 NM_001145144, NM_001145145, NM_005628

CCDS: CCDS12692, CCDS46125, CCDS46126

Canonical transcript exons

ENST00000542575 — 8 exons

Exon	Start	End
ENSE00000714262	46778675	46778908
ENSE00002281807	46787400	46788594
ENSE00003785679	46777211	46777405
ENSE00004021865	46784517	46784559
ENSE00004021866	46782383	46782549
ENSE00004021867	46776975	46777109
ENSE00004021868	46784097	46784144
ENSE00004021871	46774883	46775747

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 161.5635 / max 2458.2958, expressed in 1821 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181698	152.6252	1819
181692	4.7993	1058
181697	1.9578	921
181695	1.0624	713
181693	0.3151	131
181691	0.3028	175
181696	0.2214	85
181689	0.1840	91
181690	0.0954	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.98	gold quality
endometrium epithelium	UBERON:0004811	97.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.50	gold quality
minor salivary gland	UBERON:0001830	97.27	gold quality
saliva-secreting gland	UBERON:0001044	96.10	gold quality
mucosa of transverse colon	UBERON:0004991	95.69	gold quality
upper lobe of left lung	UBERON:0008952	95.69	gold quality
left uterine tube	UBERON:0001303	95.36	gold quality
esophagus mucosa	UBERON:0002469	95.26	gold quality
upper lobe of lung	UBERON:0008948	95.21	gold quality
right lung	UBERON:0002167	95.13	gold quality
mouth mucosa	UBERON:0003729	94.98	gold quality
omental fat pad	UBERON:0010414	94.96	gold quality
peritoneum	UBERON:0002358	94.94	gold quality
right coronary artery	UBERON:0001625	94.69	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.65	gold quality
left coronary artery	UBERON:0001626	94.20	gold quality
lower esophagus mucosa	UBERON:0035834	94.04	gold quality
right ovary	UBERON:0002118	94.00	gold quality
monocyte	CL:0000576	93.67	gold quality
coronary artery	UBERON:0001621	93.64	gold quality
gall bladder	UBERON:0002110	93.56	gold quality
body of stomach	UBERON:0001161	93.53	gold quality
transverse colon	UBERON:0001157	93.40	gold quality
skin of leg	UBERON:0001511	93.18	gold quality
mononuclear cell	CL:0000842	93.10	gold quality
popliteal artery	UBERON:0002250	93.06	gold quality
tibial artery	UBERON:0007610	93.05	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.01	gold quality
leukocyte	CL:0000738	92.95	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	67.96
E-GEOD-124858	no	309.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, E2F3, NR1H4, SP1

miRNA regulators (miRDB)

31 targeting SLC1A5, 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-8485	100.00	77.57	4731
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-4652-5P	96.46	64.22	553

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• used as receptor by HERV-W Env glycoprotein (PMID:12050356)
• level of amino acid transporter B(0)(ACST2) mRNA expression was lower in forskolin treated BeWo cells (PMID:12175968)
• in the six unrelated Hartnup pedigrees studied, examination of linkage at 19q13.3, polymorphisms in the coding sequence and quantitation of expression of SLC1A5 did not suffice to explain the defect in neutral amino acid transport (PMID:12555937)
• results strongly suggest that combinations of amino acid sequence changes and N-linked oligosaccharides in a critical carboxyl-terminal region of extracellular loop 2 (ECL2) control retroviral utilization of both the ASCT1 and ASCT2 receptors (PMID:12584318)
• Hypoxia alters expression and function of syncytin and its receptor (amino acid transport system B(0)) during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia. (PMID:12757936)
• ASCT2 messenger RNA was not altered significantly in hypoxia in cytotrophoblasts or in perfused placental cotyledons. (PMID:14520239)
• up-regulation of ASCT2 by S-nitroso-N-acetyl-DL-penicillamine might be partially associated with an increase in the density of transporter protein via de novo synthesis (PMID:15848195)
• These results show that the stimulation of ASCT2 expression in response to glutamine in part involves binding of FXR/RXR to the ASCT2 promoter. (PMID:16197915)
• analysis of SLC1A5 mutations on 19q13 in cystinuria patients (PMID:16435221)
• the activity of glutamate transporter GLAST/EAAT1 can effectively regulate the cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes (PMID:16516348)
• evaluation of the interaction of the HERV-W envelope with the hASCT2 receptor; a region consisting of the N-terminal 124 amino acids of the mature glycoprotein surface subunit was determined as the minimal receptor-binding domain (PMID:16820059)
• ASCT2 silencing inhibits mTORC1 (mTOR/raptor) signaling and leads to growth repression, followed by enhanced survival signaling via mTORC2 (mTOR/rictor comples) and apoptosis of hepatoma cells. (PMID:17329400)
• Localisation and distribution of RDR/ASCT2 in human placental villi suggests that the fusion of placental trophoblast cells is not regulated by local or temporal variations of RDR/ASCT2 expression in villous cytotrophoblast cells. (PMID:17676482)
• In human entrocytes, glutamine transport and ASCT2 surface expression induced by short-term EGF are MAPK, PI3K, and Rho-dependent. (PMID:18157695)
• SLC1A5 gene is associated with schizophrenia. (PMID:18638388)
• In primary term human trophoblasts, ASCT2 mRNA levels were preserved at normoxia and downregulated at 1% O(2) after 48 h. (PMID:19321927)
• Cx43-mediated GJIC and SLC1A5 interaction play important functional roles in trophoblast cell fusion. (PMID:22238282)
• These data suggest that intracellular replication of Francisella tularensis depends on the function of host cell SLC1A5. (PMID:22804921)
• SLC1A5 plays a key role in Gln transport controlling lung cancer cells’ metabolism, growth, and survival. (PMID:23213057)
• HER2- type breast cancer had the highest expression of stromal GLS1, tumoral GDH, stromal GDH, and tumoral ASCT, while TNBC had the lowest tumoral GDH expression. (PMID:23507704)
• stromal expression of the glutamine-metabolism-related proteins GLS1, GDH, ASCT2 increases with worsening histological phyllodes tumor grade. (PMID:23636801)
• the expression of LAT1 and ASCT2 is significantly increased in human melanoma. The importance of ASCT2 expression in melanoma was confirmed by shRNA knockdown, which inhibited glutamine uptake, mTORC1 signaling and cell proliferation. (PMID:24531984)
• ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery. (PMID:24603303)
• ASCT-2 is expressed in human oocytes.ASCT-2 is localized at the acrosomal region and equatorial segment of the spermatozoa. (PMID:24687878)
• ASCT2 expression plays an important role in tumour cell growth, and is a promising pathological marker for predicting a worse outcome in pancreatic cancer. (PMID:24845232)
• analysis of the kinetic mechanism of the transport catalyzed by the human glutamine/neutral amino acid transporter hASCT2 (PMID:25052780)
• ASCT2 expression, which correlates with that of N-Myc and ATF4, is markedly elevated in high-stage neuroblastoma (PMID:25142020)
• Report the differential expression of SLC1A5 in human colorectal cancer and normal tissues, and a functional link between SLC1A5 expression and growth and survival of colorectal cancer. (PMID:25337245)
• ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth. (PMID:25693838)
• The results demonstrate that N-glycosylation of SLC1A5 is critical for trafficking. (PMID:25862406)
• Genetic Variants in ASCT2 Gene are Associated with response to therapy in Hepatocelluar Carcinoma (PMID:25987094)
• LAT1, 4F2hc and ASCT2 were highly expressed in patients with advanced laryngeal cancer. (PMID:26024742)
• Both stable and inducible shRNA-mediated ASCT2 knockdown confirmed that inhibiting ASCT2 function was sufficient to prevent cellular proliferation and induce rapid cell death in TN basal-like breast cancer cells, but not in luminal cells. (PMID:26455325)
• Cys is a potent competitive inhibitor of hASCT2 but is not a substrate (PMID:26492990)
• High expression of LAT1 and ASCT2 correlates with metastasis and invasion in esophageal squamous cell carcinoma. (PMID:26936531)
• In the absence of SLC1A5 there is a crucial role of SNAT1 in supplying glutamine for glutaminolysis with SNAT2 acting as a “backup” for glutamine transport. (PMID:27129276)
• Data show that SERT associates with ASCT2 (alanine-serine-cysteine-threonine 2), a member of the solute carrier 1 family co-expressed with SERT in serotonergic neurons and involved in the transport of small neutral amino acids across the plasma membrane. (PMID:27143784)
• ASCT2 is an EGFR-associated protein that can be co-targeted by cetuximab, leading to sensitization of cetuximab-treated cells to ROS-induced apoptosis. (PMID:27450723)
• The tumor metabolism status determined by expression of GLUT1 and ASCT2. (PMID:28036362)
• we found that PPARdelta directly regulated neutral amino acid transporter SLC1-A5 (solute carrier family 1 member 5) and glucose transporter-1 (Glut1) gene transcription, leading to uptake of glucose and amino acid, activation of mTOR signaling, and tumor progression. In contrast, silence of PPARdelta or its antagonist inhibited this event. (PMID:28419191)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc1a5	ENSDARG00000099186
mus_musculus	Slc1a5	ENSMUSG00000001918
rattus_norvegicus	Slc1a5	ENSRNOG00000015948

Paralogs (6): SLC1A3 (ENSG00000079215), SLC1A6 (ENSG00000105143), SLC1A1 (ENSG00000106688), SLC1A2 (ENSG00000110436), SLC1A4 (ENSG00000115902), SLC1A7 (ENSG00000162383)

Protein

Protein identifiers

Neutral amino acid transporter B(0) — Q15758 (reviewed: Q15758)

Alternative names: Baboon M7 virus receptor, RD114/simian type D retrovirus receptor, Sodium-dependent neutral amino acid transporter type 2, Solute carrier family 1 member 5

All UniProt accessions (4): Q15758, M0QX44, M0QXM4, M0R144

UniProt curated annotations — full annotation on UniProt →

Function. Sodium-coupled antiporter of neutral amino acids. In a tri-substrate transport cycle, exchanges neutral amino acids between the extracellular and intracellular compartments, coupled to the inward cotransport of at least one sodium ion. The preferred substrate is the essential amino acid L-glutamine, a precursor for biosynthesis of proteins, nucleotides and amine sugars as well as an alternative fuel for mitochondrial oxidative phosphorylation. Exchanges L-glutamine with other neutral amino acids such as L-serine, L-threonine and L-asparagine in a bidirectional way. Provides L-glutamine to proliferating stem and activated cells driving the metabolic switch toward cell differentiation. The transport cycle is usually pH-independent, with the exception of L-glutamate. Transports extracellular L-glutamate coupled to the cotransport of one proton and one sodium ion in exchange for intracellular L-glutamine counter-ion. May provide for L-glutamate uptake in glial cells regulating glutamine/glutamate cycle in the nervous system. Can transport D-amino acids. Mediates D-serine release from the retinal glia potentially affecting NMDA receptor function in retinal neurons. Displays sodium- and amino acid-dependent but uncoupled channel-like anion conductance with a preference SCN(-) » NO3(-) > I(-) > Cl(-). Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development. (Microbial infection) Acts as a cell surface receptor for Feline endogenous virus RD114. (Microbial infection) Acts as a cell surface receptor for Baboon M7 endogenous virus. (Microbial infection) Acts as a cell surface receptor for type D simian retroviruses.

Subunit / interactions. Homotrimer. Interacts with secreted ERVH48-1/suppressyn (via RBD domain); this interaction decreases SLC1A5 transport rate and may negatively regulate syncytialization. Interacts with ERVW-1/syncytin (via RBD domain); this interaction decreases SLC1A5 transport rate.

Subcellular location. Cell membrane. Melanosome.

Tissue specificity. Placenta, lung, skeletal muscle, kidney, pancreas, and intestine. Expressed in CD34-positive hematopoietic progenitors (at protein level).

Activity regulation. Regulated by L-cysteine, which can either inhibit substrate influx or trigger substrate efflux without being transported itself.

Domain organisation. The transport domain consists of four transmembrane regions 3, 6, 7 and 8 and two helical hairpins HP1 and HP2. According to the one-gate elevator transport model, substrate binding and release is controlled by HP2 which acts as a gate for the transport domain. HP2 gate opening enables substrate binding or release. The gate closes once one amino acid and up to three sodium ions bind to the transport domain, which subsequently triggers transmembrane elevator-like motion of the transporter across the plasma membrane. The beta-hairpin (aa 204-224) located between the helical segments of TM4 protrudes in the extracellular space and forms a docking platform for proteins of retroviral origin.

Similarity. Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A5 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15758-1	1	yes
Q15758-2	2
Q15758-3	3

RefSeq proteins (3): NP_001138616, NP_001138617, NP_005619* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001991	Na-dicarboxylate_symporter	Family
IPR018107	Na-dicarboxylate_symporter_CS	Conserved_site
IPR036458	Na:dicarbo_symporter_sf	Homologous_superfamily
IPR050746	DAACS	Family

Pfam: PF00375

Catalyzed reactions (Rhea), 12 shown:

• nitrate(in) = nitrate(out) (RHEA:34923)
• iodide(out) = iodide(in) (RHEA:66324)
• L-glutamine(out) + L-serine(in) + Na(+)(out) = L-glutamine(in) + L-serine(out) + Na(+)(in) (RHEA:70855)
• L-asparagine(in) + L-glutamine(out) + Na(+)(out) = L-asparagine(out) + L-glutamine(in) + Na(+)(in) (RHEA:70859)
• L-threonine(in) + L-glutamine(out) + Na(+)(out) = L-threonine(out) + L-glutamine(in) + Na(+)(in) (RHEA:70863)
• L-glutamine(in) + L-alanine(out) + Na(+)(out) = L-glutamine(out) + L-alanine(in) + Na(+)(in) (RHEA:70867)
• L-valine(out) + L-glutamine(in) + Na(+)(out) = L-valine(in) + L-glutamine(out) + Na(+)(in) (RHEA:70871)
• L-glutamine(in) + L-methionine(out) + Na(+)(out) = L-glutamine(out) + L-methionine(in) + Na(+)(in) (RHEA:70875)
• L-threonine(out) + L-glutamine(in) + Na(+)(out) = L-threonine(in) + L-glutamine(out) + Na(+)(in) (RHEA:70879)
• L-glutamine(in) + L-glutamate(out) + Na(+)(out) + H(+)(out) = L-glutamine(out) + L-glutamate(in) + Na(+)(in) + H(+)(in) (RHEA:70883)
• L-glutamine(in) + L-serine(out) + Na(+)(out) = L-glutamine(out) + L-serine(in) + Na(+)(in) (RHEA:70887)
• L-asparagine(out) + L-glutamine(in) + Na(+)(out) = L-asparagine(in) + L-glutamine(out) + Na(+)(in) (RHEA:70891)

UniProt features (101 total): binding site 25, helix 23, topological domain 11, transmembrane region 8, sequence conflict 8, modified residue 6, strand 4, turn 4, intramembrane region 2, region of interest 2, glycosylation site 2, splice variant 2, sequence variant 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
8OUD	ELECTRON MICROSCOPY	2.31
8QRO	ELECTRON MICROSCOPY	2.6
8OUH	ELECTRON MICROSCOPY	2.62
8QRP	ELECTRON MICROSCOPY	2.7
8QRQ	ELECTRON MICROSCOPY	2.74
8QRR	ELECTRON MICROSCOPY	2.78
8QRS	ELECTRON MICROSCOPY	2.86
8QRU	ELECTRON MICROSCOPY	2.9
8QRV	ELECTRON MICROSCOPY	2.9
8QRW	ELECTRON MICROSCOPY	3
5LM4	X-RAY DIFFRACTION	3.1
5LLM	X-RAY DIFFRACTION	3.25
7AWM	X-RAY DIFFRACTION	3.25
5LLU	X-RAY DIFFRACTION	3.32
7BCT	ELECTRON MICROSCOPY	3.37
7BCQ	ELECTRON MICROSCOPY	3.43
7BCS	ELECTRON MICROSCOPY	3.43
8OUJ	ELECTRON MICROSCOPY	3.5
6MP6	ELECTRON MICROSCOPY	3.54
6RVX	ELECTRON MICROSCOPY	3.61
7AWQ	X-RAY DIFFRACTION	3.65
5MJU	X-RAY DIFFRACTION	3.71
6MPB	ELECTRON MICROSCOPY	3.84
6GCT	ELECTRON MICROSCOPY	3.85
7AWP	X-RAY DIFFRACTION	3.91
7AWN	X-RAY DIFFRACTION	3.92
6RVY	ELECTRON MICROSCOPY	4.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15758-F1	78.91	0.50

Antibody-complex structures (SAbDab): 1 — 8OUD

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 (25): 135; 138; 139; 351; 351; 353; 353; 382; 384; 386; 386; 388 …

Post-translational modifications (6): 1, 493, 494, 503, 535, 539

Glycosylation sites (2): 163, 212

Mutagenesis-validated functional residues (1):

Position	Phenotype
467	changes the substrate specificity toward negatively charged amino acids. impairs l-glutamine transport and enables l-asp

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013407	RHOH GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 358 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_CIRCULATORY_SYSTEM_PROCESS, SASAI_TARGETS_OF_CXCR6_AND_PTCH1_UP, GOBP_ERYTHROCYTE_HOMEOSTASIS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, LANG_MYB_FAMILY_TARGETS, MODULE_16, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP

GO Biological Process (13): amino acid transport (GO:0006865), L-glutamine transport (GO:0006868), L-glutamine secretion (GO:0010585), neutral amino acid transport (GO:0015804), erythrocyte differentiation (GO:0030218), protein homotrimerization (GO:0070207), L-aspartate import across plasma membrane (GO:0140009), transport across blood-brain barrier (GO:0150104), L-glutamine import across plasma membrane (GO:1903803), L-serine transport (GO:0015825), symbiont entry into host cell (GO:0046718), transmembrane transport (GO:0055085), L-alpha-amino acid transmembrane transport (GO:1902475)

GO Molecular Function (13): virus receptor activity (GO:0001618), amino acid transmembrane transporter activity (GO:0015171), neutral L-amino acid transmembrane transporter activity (GO:0015175), L-aspartate transmembrane transporter activity (GO:0015183), L-glutamine transmembrane transporter activity (GO:0015186), L-serine transmembrane transporter activity (GO:0015194), symporter activity (GO:0015293), antiporter activity (GO:0015297), ligand-gated channel activity (GO:0022834), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872), protein binding (GO:0005515), L-amino acid transmembrane transporter activity (GO:0015179)

GO Cellular Component (7): plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), melanosome (GO:0042470), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
RHO GTPase cycle	5
SLC-mediated transport of amino acids	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Transport of small molecules	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
L-amino acid transport	3
L-glutamine transport	3
L-amino acid transmembrane transporter activity	3
transport	2
neutral amino acid transport	2
L-aspartate transmembrane transport	2
amino acid import across plasma membrane	2
L-alpha-amino acid transmembrane transport	2
amino acid transmembrane transport	2
amino acid transmembrane transporter activity	2
secondary active transmembrane transporter activity	2
cellular anatomical structure	2
secretion by cell	1
amino acid transport	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
protein homooligomerization	1
protein trimerization	1
vascular transport	1
serine transport	1
viral life cycle	1
symbiont entry into host	1
cellular process	1
carboxylic acid transmembrane transport	1
symbiont entry into host cell	1
exogenous protein binding	1
transmembrane transporter activity	1
acidic amino acid transmembrane transporter activity	1
C4-dicarboxylate transmembrane transporter activity	1
neutral L-amino acid transmembrane transporter activity	1
L-serine transport	1
gated channel activity	1
molecular transducer activity	1
cation binding	1
binding	1
carboxylic acid transmembrane transporter activity	1
membrane	1
cell periphery	1
basal part of cell	1
plasma membrane region	1

Protein interactions and networks

STRING

2366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC1A5	ERVW-1	Q9UQF0	989
SLC1A5	SLC6A14	Q9UN76	944
SLC1A5	SLC6A5	Q9Y345	880
SLC1A5	SLC3A2	P08195	865
SLC1A5	SLC7A5	Q01650	834
SLC1A5	ERVFRD-1	P60508	831
SLC1A5	GLS2	Q9UI32	830
SLC1A5	GLS	O94925	800
SLC1A5	SLC38A2	Q96QD8	790
SLC1A5	SLC38A1	Q9H2H9	763
SLC1A5	SLC2A1	P11166	744
SLC1A5	SLC6A19	Q695T7	716
SLC1A5	SLC7A1	P30825	690
SLC1A5	SLC7A11	Q9UPY5	687
SLC1A5	SLC38A5	Q8WUX1	676

IntAct

304 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PTPN3	ACOT8	psi-mi:“MI:0914”(association)	0.590
PTPN3	SLC1A5	psi-mi:“MI:0407”(direct interaction)	0.590
RNF5	SLC1A5	psi-mi:“MI:0914”(association)	0.580
RNF5	SLC1A5	psi-mi:“MI:0915”(physical association)	0.580
PLP1	SLC1A5	psi-mi:“MI:0915”(physical association)	0.560
APOL3	SLC1A5	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	SLC1A5	psi-mi:“MI:0915”(physical association)	0.560
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
SLC1A5	SLC1A4	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
SERINC1	LGALS3	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	SLC1A5	psi-mi:“MI:0570”(protein cleavage)	0.440
SNX27	SLC1A5	psi-mi:“MI:0407”(direct interaction)	0.440
SLC1A5	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
SLC1A5	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC1A5	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
MAST1	SLC1A5	psi-mi:“MI:0407”(direct interaction)	0.440
SLC1A5	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
SCRIB	SLC1A5	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	SLC1A5	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (415): SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Proximity Label-MS), SLC1A5 (Proximity Label-MS), SLC1A5 (Proximity Label-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS)

ESM2 similar proteins: A0A6P3HVI0, A2VDL4, A4IHB9, D3ZJ25, E7EXX2, O00341, O19105, O35544, O35874, O35921, O43511, O54902, O57321, P24942, P31596, P31597, P43003, P43004, P43005, P43006, P43007, P46411, P48664, P49281, P49282, P51906, P51907, P51912, P55012, P56564, Q10901, Q15758, Q25605, Q4R8W8, Q5BKR2, Q5R6B8, Q5R839, Q86UD5, Q8BJA2, Q8IVJ1

Diamond homologs: A2RGC2, A2VDL4, D3ZJ25, O00341, O19105, O35544, O35874, O35921, O57321, O59010, P0DF78, P0DF79, P24942, P31596, P31597, P43003, P43004, P43005, P43006, P43007, P46411, P48664, P51906, P51907, P51912, P56564, Q10901, Q15758, Q1J8E1, Q1JDG4, Q1JII6, Q1JND7, Q21353, Q21751, Q22682, Q25605, Q48V75, Q4R8W8, Q5XDS5, Q8JZR4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SLC1A5	“up-regulates quantity”	“L-glutamine zwitterion”	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 222 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FCERI mediated MAPK activation	6	14.1×	6e-04
RHOF GTPase cycle	5	8.8×	7e-03
RHOJ GTPase cycle	6	8.2×	5e-03
Toll Like Receptor 7/8 (TLR7/8) Cascade	6	7.5×	7e-03
RHOQ GTPase cycle	6	7.4×	7e-03
Toll Like Receptor 9 (TLR9) Cascade	6	7.2×	7e-03
Infectious disease	16	2.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	6
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

870 predictions. Top by Δscore:

Variant	Effect	Δscore
19:46775743:GGTCG:G	acceptor_gain	1.0000
19:46775745:TCG:T	acceptor_gain	1.0000
19:46775746:CG:C	acceptor_gain	1.0000
19:46775746:CGC:C	acceptor_gain	1.0000
19:46775747:GC:G	acceptor_loss	1.0000
19:46775748:C:CA	acceptor_loss	1.0000
19:46775748:C:CC	acceptor_gain	1.0000
19:46776968:CA:C	donor_gain	1.0000
19:46776973:A:AC	donor_gain	1.0000
19:46776973:AC:A	donor_loss	1.0000
19:46776974:C:CA	donor_gain	1.0000
19:46776974:CA:C	donor_gain	1.0000
19:46776974:CACT:C	donor_gain	1.0000
19:46776974:CACTA:C	donor_gain	1.0000
19:46777105:TGACC:T	acceptor_gain	1.0000
19:46777106:GACC:G	acceptor_gain	1.0000
19:46777107:ACC:A	acceptor_gain	1.0000
19:46777108:CC:C	acceptor_gain	1.0000
19:46777108:CCC:C	acceptor_gain	1.0000
19:46777109:CC:C	acceptor_gain	1.0000
19:46777109:CCTGA:C	acceptor_loss	1.0000
19:46777110:C:CA	acceptor_loss	1.0000
19:46777110:C:CC	acceptor_gain	1.0000
19:46777110:C:T	acceptor_gain	1.0000
19:46777204:CA:C	donor_gain	1.0000
19:46777208:CA:C	donor_loss	1.0000
19:46777209:A:AC	donor_gain	1.0000
19:46777210:C:CT	donor_gain	1.0000
19:46777210:CA:C	donor_gain	1.0000
19:46777210:CAG:C	donor_gain	1.0000

AlphaMissense

3436 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:46777088:G:C	S425R	0.999
19:46777088:G:T	S425R	0.999
19:46777090:T:G	S425R	0.999
19:46777095:G:T	A423E	0.997
19:46777102:C:G	A421P	0.997
19:46777303:C:A	M387I	0.997
19:46777303:C:G	M387I	0.997
19:46777303:C:T	M387I	0.997
19:46777310:A:T	V385D	0.997
19:46787649:G:C	P106R	0.997
19:46775723:A:C	N471K	0.996
19:46775723:A:T	N471K	0.996
19:46777101:G:T	A421D	0.996
19:46777306:G:C	N386K	0.996
19:46777306:G:T	N386K	0.996
19:46777319:C:T	G382D	0.996
19:46787649:G:T	P106Q	0.996
19:46777264:G:C	F400L	0.995
19:46777264:G:T	F400L	0.995
19:46777266:A:G	F400L	0.995
19:46777339:G:C	S375R	0.995
19:46777339:G:T	S375R	0.995
19:46777341:T:G	S375R	0.995
19:46782482:C:T	G242D	0.995
19:46787633:G:C	S111R	0.995
19:46787633:G:T	S111R	0.995
19:46787635:T:G	S111R	0.995
19:46775709:G:T	A476D	0.994
19:46775710:C:G	A476P	0.994
19:46777394:A:G	L357P	0.994

dbSNP variants (sampled 300 via entrez): RS1000549367 (19:46783356 A>G), RS1000926159 (19:46789150 C>A,T), RS1001011647 (19:46784847 C>T), RS1001285426 (19:46784154 G>T), RS1001460321 (19:46778512 T>C), RS1001585730 (19:46778315 G>C), RS1002376312 (19:46788227 G>A), RS1002388118 (19:46790330 G>T), RS1002481647 (19:46782300 A>C), RS1002941693 (19:46774488 G>A), RS1003378245 (19:46786737 C>T), RS1003398372 (19:46788673 G>T), RS1003455006 (19:46785387 A>G,T), RS1003753251 (19:46777323 T>A,G), RS1003827385 (19:46777499 A>C)

Disease associations

OMIM: gene MIM:109190 | disease phenotypes: MIM:303350

GenCC curated gene-disease

Mondo (1): hereditary spastic paraplegia (MONDO:0019064)

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

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_278	Metabolite levels	7.000000e-06
GCST010106_1	Conjunctival UV autofluorescence (CUVAF)	3.000000e-08
GCST90000025_570	Appendicular lean mass	2.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010495	guanosine monophosphate measurement
EFO:0004731	eye measurement
EFO:0010729	sun exposure measurement
EFO:0004980	appendicular lean mass

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: yes

ChEMBL targets (1): CHEMBL3562162 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Alanine/serine/cysteine transporter subfamily

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 25e [PMID: 38217503]	Inhibition	5.29	pIC50
p-nitrophenyl glutamyl anilide	Inhibition	4.26	pKi
benzylcysteine	Inhibition	3.11	pKi
benzylserine	Inhibition	3.05	pKi

Binding affinities (BindingDB)

8 measured of 8 human assays (8 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-2-amino-5-[2-(morpholin-4-ylmethyl)anilino]-5-oxopentanoic acid	IC50	312000 nM	US-10189805: Metabolism probes for therapy and diagnosis
(2S)-2-amino-5-[2-(1,3-benzothiazol-2-yl)anilino]-5-oxopentanoic acid	IC50	436000 nM	US-10189805: Metabolism probes for therapy and diagnosis
(2S)-2-amino-5-(2-morpholin-4-ylanilino)-5-oxopentanoic acid	IC50	664000 nM	US-10189805: Metabolism probes for therapy and diagnosis
(2S)-2-amino-5-[[2-(morpholin-4-ylsulfonylmethyl)phenyl]methylamino]-5-oxopentanoic acid	IC50	677000 nM	US-10189805: Metabolism probes for therapy and diagnosis
(2S)-2-amino-5-[[2-[(4-methylpiperazin-1-yl)methyl]phenyl]methylamino]-5-oxopentanoic acid	IC50	697000 nM	US-10189805: Metabolism probes for therapy and diagnosis
(2S)-2-amino-5-oxo-5-(2-piperidin-1-ylanilino)pentanoic acid	IC50	776000 nM	US-10189805: Metabolism probes for therapy and diagnosis
(2S)-2-amino-5-oxo-5-[2-(2-pyridin-4-ylethyl)anilino]pentanoic acid	IC50	832000 nM	US-10189805: Metabolism probes for therapy and diagnosis
(2S)-2-amino-5-(4-nitroanilino)-5-oxopentanoic acid	IC50	954000 nM	US-10189805: Metabolism probes for therapy and diagnosis

ChEMBL bioactivities

14 potent at pChembl≥5 of 32 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.58	Kd	26.26	nM	CHEMBL3752910
7.58	ED50	26.26	nM	CHEMBL3752910
7.49	Kd	32.05	nM	CHEMBL5653589
7.49	ED50	32.05	nM	CHEMBL5653589
5.46	IC50	3500	nM	CHEMBL5570488
5.43	IC50	3700	nM	CHEMBL3753379
5.29	IC50	5140	nM	CHEMBL5572948
5.28	IC50	5300	nM	CHEMBL5569240
5.25	IC50	5600	nM	CHEMBL5570488
5.14	IC50	7200	nM	CHEMBL3754498
5.10	IC50	7900	nM	CHEMBL3752210
5.09	IC50	8100	nM	CHEMBL4867768
5.02	IC50	9600	nM	CHEMBL3754053

PubChem BioAssay actives

12 with measured affinity, of 101 total; 10 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149403: Binding affinity to human SLC1A5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0263	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149403: Binding affinity to human SLC1A5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0321	uM
(2S)-2-amino-4-[bis[[2-[3-(4-chlorophenyl)prop-2-ynoxy]phenyl]methyl]amino]butanoic acid	2098759: Inhibition of ASCT2 in HEK293 cells assessed as reduction in glutamine uptake preincubated for 5 mins followed by substrate addition and measured after 15 mins	ic50	3.5000	uM
5-bromo-2-[(4-chlorodithiazol-5-ylidene)amino]benzonitrile	1272488: Inhibition of ASCT2 (unknown origin)-mediated glutamine transport	ic50	3.7000	uM
(2S)-2-amino-4-[bis[[5-tert-butyl-2-(3-phenylprop-2-ynoxy)phenyl]methyl]amino]butanoic acid	2098759: Inhibition of ASCT2 in HEK293 cells assessed as reduction in glutamine uptake preincubated for 5 mins followed by substrate addition and measured after 15 mins	ic50	5.1400	uM
(2S)-2-amino-4-[bis[[2-(3-phenylprop-2-ynoxy)phenyl]methyl]amino]butanoic acid	2098759: Inhibition of ASCT2 in HEK293 cells assessed as reduction in glutamine uptake preincubated for 5 mins followed by substrate addition and measured after 15 mins	ic50	5.3000	uM
(2S)-2-amino-4-[bis[[2-[(3-methoxyphenyl)methoxy]phenyl]methyl]amino]butanoic acid	1272490: Inhibition of ASCT2-mediated glutamine transport in human HEK293 cells using [3H]-glutamine after 15 mins by scintillation counting	ic50	7.2000	uM
(2S)-2-amino-4-[bis[[2-[(2-fluorophenyl)methoxy]phenyl]methyl]amino]butanoic acid	1272490: Inhibition of ASCT2-mediated glutamine transport in human HEK293 cells using [3H]-glutamine after 15 mins by scintillation counting	ic50	7.9000	uM
4-chloro-N-[3-chloro-4-(trifluoromethoxy)phenyl]dithiazol-5-imine;ethane	1763554: Inhibition of ASCT2 (unknown origin)	ic50	8.1000	uM
(2S)-2-amino-4-[bis[[2-[(3-methylphenyl)methoxy]phenyl]methyl]amino]butanoic acid	1272490: Inhibition of ASCT2-mediated glutamine transport in human HEK293 cells using [3H]-glutamine after 15 mins by scintillation counting	ic50	9.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	5
sodium arsenite	increases expression, increases reaction, affects cotreatment, increases abundance, affects reaction (+2 more)	5
Cyclosporine	increases expression	5
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	4
Estradiol	decreases expression, increases expression	4
perfluorooctane sulfonic acid	increases expression	3
Cadmium Chloride	decreases expression, increases expression, decreases reaction, increases abundance, increases palmitoylation	3
deoxynivalenol	decreases expression	2
bisphenol S	affects expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Cadmium	increases palmitoylation, increases expression, decreases reaction, increases abundance	2
Cisplatin	decreases expression, increases expression	2
Ethinyl Estradiol	affects expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	decreases expression, increases reaction, increases methylation	2
beta-Naphthoflavone	increases expression	2
Genistein	increases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
beauvericin	affects cotreatment, increases expression	1
chloroacetaldehyde	affects expression	1
methylmercuric chloride	increases expression	1
alpha phellandrene	decreases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
o,p’-DDT	increases expression	1
sulforaphane	increases expression	1
zinc chloride	decreases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3578657	Binding	Inhibition of ASCT2-mediated [3H]glutamine uptake in HEK293 cells after 15 mins by Live-cell glutamine uptake assay	2-Substituted Nγ-glutamylanilides as novel probes of ASCT2 with improved potency. — Bioorg Med Chem Lett

Cellosaurus cell lines

11 cell lines: 5 transformed cell line, 5 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C5TT	HEK293-SLC1A5	Transformed cell line	Female
CVCL_D3PI	CHO/ASCT2	Transformed cell line	Female
CVCL_D4DW	HEK-SLC1A5-KO-c8	Transformed cell line	Female
CVCL_D4DX	HEK-SLC1A5-KO-c9	Transformed cell line	Female
CVCL_D4IQ	HCT116-SLC1A5-KO-c7	Cancer cell line	Male
CVCL_D4IR	HCT116-SLC1A5-KO-c8	Cancer cell line	Male
CVCL_D9RQ	Ubigene HEK293 SLC1A5 KO	Transformed cell line	Female
CVCL_TL86	HAP1 SLC1A5 (-) 1	Cancer cell line	Male
CVCL_TL87	HAP1 SLC1A5 (-) 2	Cancer cell line	Male
CVCL_TL88	HAP1 SLC1A5 (-) 3	Cancer cell line	Male

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
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