NEU1

Summary

NEU1 (neuraminidase 1, HGNC:7758) is a protein-coding gene on chromosome 6p21.33, encoding Sialidase-1 (Q99519). Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids.

The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as ‘protective protein’). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity.

Source: NCBI Gene 4758 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sialidosis (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 30
• Clinical variants (ClinVar): 357 total — 43 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 96
• Druggable target: yes
• MANE Select transcript: NM_000434

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7758
Approved symbol	NEU1
Name	neuraminidase 1
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204386
Ensembl biotype	protein_coding
OMIM	608272
Entrez	4758

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 retained_intron, 4 protein_coding, 3 nonsense_mediated_decay

ENST00000375631, ENST00000480384, ENST00000491768, ENST00000495807, ENST00000677054, ENST00000677512, ENST00000678869, ENST00000850553, ENST00000850554, ENST00000850555, ENST00000877813, ENST00000951252

RefSeq mRNA: 1 — MANE Select: NM_000434 NM_000434

CCDS: CCDS4723

Canonical transcript exons

ENST00000229725 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 96.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.7948 / max 348.5504, expressed in 1804 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72848	25.6415	1804
72849	1.2097	799
72850	0.5788	323
72847	0.3012	100
72846	0.0637	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	96.69	gold quality
right adrenal gland cortex	UBERON:0035827	95.57	gold quality
right adrenal gland	UBERON:0001233	95.30	gold quality
bone marrow cell	CL:0002092	95.08	gold quality
left adrenal gland	UBERON:0001234	94.82	gold quality
placenta	UBERON:0001987	94.42	gold quality
left adrenal gland cortex	UBERON:0035825	94.35	gold quality
adrenal gland	UBERON:0002369	93.61	gold quality
gall bladder	UBERON:0002110	93.44	gold quality
pancreas	UBERON:0001264	92.85	gold quality
adult mammalian kidney	UBERON:0000082	92.58	gold quality
duodenum	UBERON:0002114	92.29	gold quality
cortex of kidney	UBERON:0001225	91.71	gold quality
stromal cell of endometrium	CL:0002255	91.62	gold quality
pituitary gland	UBERON:0000007	91.58	gold quality
adenohypophysis	UBERON:0002196	91.53	gold quality
mucosa of transverse colon	UBERON:0004991	91.33	gold quality
kidney	UBERON:0002113	91.19	gold quality
body of pancreas	UBERON:0001150	91.05	gold quality
granulocyte	CL:0000094	90.93	gold quality
bone marrow	UBERON:0002371	90.88	gold quality
saliva-secreting gland	UBERON:0001044	90.87	gold quality
minor salivary gland	UBERON:0001830	90.82	gold quality
body of stomach	UBERON:0001161	90.68	gold quality
blood	UBERON:0000178	90.65	gold quality
left lobe of thyroid gland	UBERON:0001120	90.57	gold quality
right lobe of thyroid gland	UBERON:0001119	90.56	gold quality
thyroid gland	UBERON:0002046	90.52	gold quality
leukocyte	CL:0000738	90.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.63
E-MTAB-10137	no	190.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, MYF5, MYOD1, SP1

miRNA regulators (miRDB)

32 targeting NEU1, 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-4682	100.00	68.89	1258
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-4509	96.19	65.80	900
HSA-MIR-8083	95.93	67.55	694

Literature-anchored findings (GeneRIF, showing 40)

• Summary of NEU1 mutations found in sialidosis patients. (PMID:14517945)
• type II sialidosis associated mutations in NEU1 affect lysosomal sialidase activity. (PMID:14695530)
• Data show that the differentiation of monocytes into macrophages is associated with regulation of the expression of at least three distinct cellular sialidases, Neu1, 3, and 4, with specific up-regulation of the enzyme activity of only Neu1. (PMID:15885103)
• Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface to facilitate elastic fiber assembly (PMID:16314420)
• effects of GLB1, PPCA and NEU1 gene mutations on elastogenesis in skin fibroblasts (PMID:16538002)
• upregulation of the Neu1 expression is important for the primary function of macrophages and there is a link between Neu1 and the cellular immune response (PMID:16835219)
• Activation of lymphocytes resulted in a ninefold increase in Neu1-specific activity after growth of cells in culture for 5 days.Cell surface Neu1 was found tightly associated with a subunit of protective protein/cathepsin A (PPCA). (PMID:17028199)
• Female cervical mucus contains an endogenous menstrual cycle-related sialidase that could be involved in modifying the rheologic properties of mucus to favor sperm progression at fertilization. (PMID:17562335)
• NEU1 is a negative regulator of lysosomal exocytosis. (PMID:18606142)
• related to malignancy and may be potential targets for cancer diagnosis and therapy (PMID:18651674)
• Neuraminidase caused the desialylation of both PDGF and IGF-1 receptors and diminished the intracellular signals induced by the mitogenic ligands PDGF-BB and IGF-2. (PMID:18772331)
• results suggest that NEU1 is important in regulation of integrin beta4-mediated signaling, leading to suppression of metastasis (PMID:19151752)
• findings show homozygous mutations of NEU1 544A–>G (Ser182Gly substitution) play a major role of the genotype and phenotype of Sialidosis type 1 (PMID:19473359)
• The genetic characterization of the two patients showed one known [c. 679G > A (p.G227R)] NEU1 missense mutation (detected in P2), and the new c.807 + 1G > A splicing defect (PMID:19568825)
• Results describe the hydrodynamic properties of PPCA, NEU1, and a complex of the two proteins and identified multiple binding sites on both proteins. (PMID:19666471)
• occurrence of Neu3 in the inner membrane and Neu1 in the outer membrane of the nuclear envelope (PMID:19686243)
• Data show that Neu-1 siRNA blocks the process of GM(3)/LacCer conversion. (PMID:21103358)
• colocalized with CD18 in PMNs; could be a physiologic source of the enzymatic activity that removes sialyl residues on beta2 integrin and ICAM-1, resulting in their enhanced interaction (PMID:21551251)
• a novel Neu1 and MMP9 cross-talk in alliance with TLR4 on the cell surface that is essential for ligand activation of TLRs and subsequent cellular signaling. (PMID:21873432)
• Neuraminidase 1 as a modulator of cell receptors. (Review) (PMID:21928149)
• human airway epithelia express catalytically active NEU1 sialidase that regulates EGFR- and MUC1-dependent signaling and bacterial adhesion. (PMID:22247545)
• Data show that NEU1 was immunolocalized to both the plasma membrane and the perinuclear region, and NEU3 was detected both in the cytosol and nucleus. (PMID:22403397)
• Weak anchorage of NEU1 and NEU3 to the plasma membrane and their loss during erythrocyte life could be a tool to preserve the cellular sialic acid content to avoid early aging of erythrocyte and processes of cell aggregation in the capillaries. (PMID:22903576)
• Data indicate that sialidases Neu1 and Neu3 are present on sperm, and their activity is required for capacitation and zona pellucida binding. (PMID:22989879)
• NEU1 gene missense mutation was found in a patient diagnosed with type I sialoidosis. (PMID:23291686)
• Three novel mutations in the NEU1 gene in two Indian patients of sialidosis, one with the type I form and the other with the infantile type II form are reported here. (PMID:23391804)
• catalytically active NEU1 inhibits in vitro angiogenesis through desialylation of its substrate, CD31 (PMID:24550400)
• Insulin-induced phosphorylation of the insulin receptor is dependent on Neu1 sialidase activity. (PMID:24583283)
• Sialidosis should be suspected and the NEU1 gene analyzed in patients with isolated action myoclonus presenting in adulthood in the absence of other typical clinical and laboratory findings. (PMID:24808020)
• The lymphocyte levels of NEU1 and ST6GAL1 mRNA expression are significantly increased in erythremia. (PMID:25566667)
• This study analyzed patient cells with GM1 gangliosidosis and sialidosis. A novel mutation p.R347Q is identified in NEU1 gene. (PMID:25600812)
• Muc1 clearly plays a significant role in enhancing the hypoxia-inducible transcription factors protective pathway during ischemic insult and recovery in kidney epithelia (PMID:25925251)
• Flagellin drives NEU1 to desialylate MUC1, thereby increasing its adhesiveness for Pseudomonas aeruginosa and its shedding (PMID:25963144)
• Basal Neu-1 catalytic activity is strongly increased in aged cells. (PMID:26086247)
• Neu1 desialylation is a mechanism of Fc-independent platelet clearance in immune thrombocytopenia. (PMID:26185093)
• How the point mutations of the neuraminidase sequences affected the susceptibility of H9N2 virus to oseltamivir is still to be determined and deserve further investigations (PMID:26455375)
• NEU1 siRNA can effectively inhibit proliferation, apoptosis, and invasion of human ovarian cancer cells by targeting lysosome and oxidative phosphorylation signaling, which can serve as a new target ovarian cancer treatment (PMID:26463994)
• Our study shows that the 340-cavity is not an occasional or atypical domain in NA subtypes, and it has potential to function as a new hotspot for influenza drug binding. (PMID:26768362)
• Elevated NEU1 expression alters functional activities of distinct lung cell types in vitro and recapitulates lymphocytic infiltration and collagen accumulation in vivo, consistent with mechanisms implicated in lung fibrosis. (PMID:26993524)
• neuraminidase-1 (Neu1) in complex with matrix metalloproteinase-9 and G protein-coupled receptor tethered to RTKs and TLRs is identified as a major target in multistage tumorigenesis [review] (PMID:27029067)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	neu1	ENSDARG00000008832
mus_musculus	Neu1	ENSMUSG00000007038
rattus_norvegicus	Neu1	ENSRNOG00000032942

Paralogs (3): NEU2 (ENSG00000115488), NEU3 (ENSG00000162139), NEU4 (ENSG00000204099)

Protein

Protein identifiers

Sialidase-1 — Q99519 (reviewed: Q99519)

Alternative names: Acetylneuraminyl hydrolase, G9 sialidase, Lysosomal sialidase, N-acetyl-alpha-neuraminidase 1

All UniProt accessions (3): Q99519, E9PIF4, Q5JQI0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.

Subunit / interactions. Interacts with cathepsin A (protective protein), beta-galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a multienzyme complex.

Subcellular location. Lysosome membrane. Lysosome lumen. Cell membrane. Cytoplasmic vesicle. Lysosome.

Tissue specificity. Highly expressed in pancreas, followed by skeletal muscle, kidney, placenta, heart, lung and liver. Weakly expressed in brain.

Post-translational modifications. N-glycosylated. Phosphorylation of tyrosine within the internalization signal results in inhibition of sialidase internalization and blockage on the plasma membrane.

Disease relevance. Sialidosis (SIALIDOSIS) [MIM:256550] Lysosomal storage disease occurring as two types with various manifestations. Type 1 sialidosis (cherry red spot-myoclonus syndrome or normosomatic type) is late-onset and it is characterized by the formation of cherry red macular spots in childhood, progressive debilitating myoclonus, insiduous visual loss and rarely ataxia. The diagnosis can be confirmed by the screening of the urine for sialyloligosaccharides. Type 2 sialidosis (also known as dysmorphic type) occurs as several variants of increasing severity with earlier age of onset. It is characterized by the presence of abnormal somatic features including coarse facies and dysostosis multiplex, vertebral deformities, intellectual disability, cherry-red spot/myoclonus, sialuria, cytoplasmic vacuolation of peripheral lymphocytes, bone marrow cells and conjunctival epithelial cells. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. A C-terminal internalization signal (YGTL) appears to allow the targeting of plasma membrane proteins to endosomes.

Similarity. Belongs to the glycosyl hydrolase 33 family.

RefSeq proteins (1): NP_000425* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011040	Sialidase	Domain
IPR026856	Sialidase_fam	Family
IPR036278	Sialidase_sf	Homologous_superfamily

Pfam: PF13088

Enzyme classification (BRENDA):

• EC 3.2.1.18 — exo-alpha-sialidase (BRENDA: 87 organisms, 524 substrates, 467 inhibitors, 232 Km, 45 kcat entries)

Substrate kinetics (BRENDA)

90 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-METHYLUMBELLIFERYL ALPHA-D-N-ACETYLNEURAMINIC	0.018–3.3	22
4-METHYLUMBELLIFERYL-ALPHA-D-N-ACETYLNEURAMINIC	0.0002–4.9	22
FETUIN	0.0005–6.7	11
4-METHYLUMBELLIFERYL N-ACETYLNEURAMINIC ACID	0.0103–0.5652	9
SIALYL-ALPHA-2,6-LACTOSE	0.13–3.5	9
2-(4-METHYLUMBELLIFERYL)-ALPHA-D-N-ACETYLNEURAMI	0.0063–0.16	8
SIALYL-ALPHA-2,3-LACTOSE	0.1–4.9	8
ALPHA-SIALYLLACTOSE	0.5–3.3	5
SIALYLLACTOSE	0.52–2.38	5
5-BROMO-4-CHLORO-INDOLYL BETA-D-GALACTOPYRANOSYL	0.08–0.121	4
GANGLIOSIDE GD1B	0.1–0.59	4
GD1A	0.02–1.75	4
N-ACETYLNEURAMINYLLACTOSE	0.78–3	4
2’-(4-METHYLUMBELLIFERYL)-ALPHA-D-N-ACETYLNEURAM	0.028–1.4	3
4-METHYLUMBELLIFERYL N-ACETYL-ALPHA-D-NEURAMINIC	0.06–1.508	3

UniProt features (59 total): sequence variant 37, binding site 5, repeat 4, active site 3, glycosylation site 3, mutagenesis site 3, short sequence motif 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99519-F1	89.12	0.81

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 (3): 394; 103 (proton acceptor); 370 (nucleophile)

Ligand- & substrate-binding residues (5): 78; 97; 264; 280; 341

Glycosylation sites (3): 186, 343, 352

Mutagenesis-validated functional residues (3):

Position	Phenotype
412	correct sorting to the plasma membrane but no endocytosis and internalization.
413	correct sorting to the plasma membrane but no endocytosis and internalization.
415	correct sorting to the plasma membrane but no endocytosis and internalization.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-4085001	Sialic acid metabolism
R-HSA-4341670	Defective NEU1 causes sialidosis
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-3781860	Diseases associated with N-glycosylation of proteins
R-HSA-3781865	Diseases of glycosylation
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis
R-HSA-556833	Metabolism of lipids
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 436 (showing top): GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_OLIGOSACCHARIDE_CATABOLIC_PROCESS, KEGG_LYSOSOME, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PATIL_LIVER_CANCER

GO Biological Process (4): ganglioside catabolic process (GO:0006689), oligosaccharide catabolic process (GO:0009313), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042)

GO Molecular Function (5): exo-alpha-sialidase activity (GO:0004308), alpha-sialidase activity (GO:0016997), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (11): extracellular region (GO:0005576), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), membrane (GO:0016020), cell junction (GO:0030054), specific granule lumen (GO:0035580), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1
Diseases associated with N-glycosylation of proteins	1
Innate Immune System	1
Glycosphingolipid metabolism	1
Sphingolipid metabolism	1
Immune System	1
Diseases of glycosylation	1
Diseases of metabolism	1
Metabolism of lipids	1
Asparagine N-linked glycosylation	1
Post-translational protein modification	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Metabolism	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
lysosome	2
ganglioside metabolic process	1
glycosphingolipid catabolic process	1
ceramide catabolic process	1
oligosaccharide metabolic process	1
carbohydrate catabolic process	1
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
alpha-sialidase activity	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
binding	1
catalytic activity	1
hydrolase activity	1
intracellular anatomical structure	1
lytic vacuole	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
secretory granule lumen	1
specific granule	1
vacuolar lumen	1
extracellular vesicle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEU1	CTSA	P10619	999
NEU1	GLB1	P16278	997
NEU1	LAMP1	P11279	800
NEU1	GALNS	P34059	770
NEU1	NANP	Q8TBE9	769
NEU1	CTSS	P25774	653
NEU1	NMB	P08949	653
NEU1	ELN	P15502	644
NEU1	NEU2	Q9Y3R4	630
NEU1	TBC1D24	Q9ULP9	616
NEU1	MMP9	P14780	536
NEU1	HEXA	P06865	528
NEU1	GNE	Q9Y223	523
NEU1	ST3GAL2	Q16842	507
NEU1	NEU3	Q9UQ49	488

IntAct

92 interactions, top by confidence:

A	B	Type	Score
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
NEU1	CREB3	psi-mi:“MI:0915”(physical association)	0.560
NEU1	GOLM1	psi-mi:“MI:0915”(physical association)	0.560
NEU1	CERS3	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	NEU1	psi-mi:“MI:0915”(physical association)	0.560
EBP	NEU1	psi-mi:“MI:0915”(physical association)	0.560
AQP6	NEU1	psi-mi:“MI:0915”(physical association)	0.560
NEU1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
NEU1	CERS4	psi-mi:“MI:0915”(physical association)	0.560
MUC1	NEU1	psi-mi:“MI:0915”(physical association)	0.560
NEU1	SLC39A9	psi-mi:“MI:0915”(physical association)	0.560
GPX8	NEU1	psi-mi:“MI:0915”(physical association)	0.560
NEU1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
GOLM1	NEU1	psi-mi:“MI:0915”(physical association)	0.560
SLC18A1	NEU1	psi-mi:“MI:0915”(physical association)	0.560
HSD17B11	NEU1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	NEU1	psi-mi:“MI:0915”(physical association)	0.560
CD79A	NEU1	psi-mi:“MI:0915”(physical association)	0.560
MGST3	NEU1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	NEU1	psi-mi:“MI:0915”(physical association)	0.560
CERS3	NEU1	psi-mi:“MI:0915”(physical association)	0.560
GPR152	NEU1	psi-mi:“MI:0915”(physical association)	0.560
	PLOD2	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530
NEU1	CCR9	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (78): NEU1 (Affinity Capture-MS), NEU1 (Affinity Capture-MS), NEU1 (Two-hybrid), CREB3 (Two-hybrid), NEU1 (Two-hybrid), NEU1 (Affinity Capture-MS), NEU1 (Affinity Capture-RNA), NEU1 (Affinity Capture-MS), NEU1 (Two-hybrid), NEU1 (Two-hybrid), EEF1A1 (Two-hybrid), NEU1 (Two-hybrid), NEU1 (Two-hybrid), NEU1 (Two-hybrid), NEU1 (Two-hybrid)

ESM2 similar proteins: A0A0A7LRQ7, A0A291P0C1, A0A2U8U2M1, A0A348HAY2, A0A4P8GEA3, A1DAU0, A3DFA0, A5F7A4, A5PF10, A6BMK7, B6H711, C6HAY7, C7YS44, D4AR77, D4B4P1, E1ACQ5, G0KYA7, L7WU85, O35657, P0C6E9, P41402, P84193, P84908, P94127, Q01940, Q4P3I9, Q4WGU1, Q4WQS0, Q50420, Q5AS50, Q5B5P1, Q5BA89, Q5BD38, Q5JS37, Q5LKW0, Q5R9V0, Q5RAF4, Q5UPJ1, Q70DK5, Q754Q4

Diamond homologs: A5PF10, A6BMK7, O35657, P62575, P62576, Q02834, Q5RAF4, Q8BZL1, Q8WWR8, Q99519, Q99PW3, P29768, P10481, P15698, P18269, P31206, Q27701, P29767, Q2MGH6, Q8DR60, Q9UQ49, I1S2N3, P0CS93, P0DTR4, Q0TR53, Q8XL08, O97859, Q64393, Q64627, Q99PW5, Q9JMH3, Q9JMH7, Q9Y3R4

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
NEU1	“down-regulates activity”	ITGB4
NEU1	“down-regulates activity”	ERK1/2
NEU1	up-regulates	Apoptosis
NEU1	“down-regulates activity”	“A5/b1 integrin”	binding
NEU1	“down-regulates activity”	AKT
TFEB	“up-regulates quantity by expression”	NEU1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	43
Likely pathogenic	14
Uncertain significance	96
Likely benign	156
Benign	5

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1331449	NM_000434.4(NEU1):c.982G>A (p.Gly328Ser)	Pathogenic
1695155	NM_000434.4(NEU1):c.725_727del (p.Tyr242_Gly243delinsTer)	Pathogenic
2000058	NM_000434.4(NEU1):c.1021+1G>T	Pathogenic
2008260	NM_000434.4(NEU1):c.43dup (p.Trp15fs)	Pathogenic
218331	NM_000434.4(NEU1):c.353-2A>G	Pathogenic
218332	NM_000434.4(NEU1):c.1170C>G (p.Tyr390Ter)	Pathogenic
2443	NM_000434.4(NEU1):c.1129G>T (p.Glu377Ter)	Pathogenic
2444	NM_000434.4(NEU1):c.272T>G (p.Leu91Arg)	Pathogenic
2445	NM_000434.4(NEU1):c.1208del (p.Ser403fs)	Pathogenic
2448	NM_000434.4(NEU1):c.625del (p.Glu209fs)	Pathogenic
2451	NM_000434.4(NEU1):c.87G>A (p.Trp29Ter)	Pathogenic
2452	NM_000434.4(NEU1):c.239C>T (p.Pro80Leu)	Pathogenic
2453	NM_000434.4(NEU1):c.718T>C (p.Trp240Arg)	Pathogenic
2454	NM_000434.4(NEU1):c.946C>T (p.Pro316Ser)	Pathogenic
2455	NM_000434.4(NEU1):c.1021+1G>C	Pathogenic
2456	NM_000434.4(NEU1):c.674G>C (p.Arg225Pro)	Pathogenic
2458	NM_000434.4(NEU1):c.69G>A (p.Trp23Ter)	Pathogenic
2693471	NM_000434.4(NEU1):c.48del (p.Pro17fs)	Pathogenic
2697868	NM_000434.4(NEU1):c.192_193insCATGGTCAGCCGCTGGTGACCA (p.Trp65fs)	Pathogenic
2708625	NM_000434.4(NEU1):c.880C>T (p.Arg294Cys)	Pathogenic
2734832	NM_000434.4(NEU1):c.1039C>T (p.Arg347Ter)	Pathogenic
2742954	NM_000434.4(NEU1):c.421dup (p.Ala141fs)	Pathogenic
2791873	NM_000434.4(NEU1):c.93dup (p.Ala32fs)	Pathogenic
2807373	NM_000434.4(NEU1):c.1084C>T (p.Gln362Ter)	Pathogenic
2864480	NM_000434.4(NEU1):c.362G>A (p.Trp121Ter)	Pathogenic
2967133	NM_000434.4(NEU1):c.913del (p.Arg305fs)	Pathogenic
2983112	NM_000434.4(NEU1):c.986_987del (p.Ile329fs)	Pathogenic
2994026	NM_000434.4(NEU1):c.1021+1G>A	Pathogenic
3010917	NM_000434.4(NEU1):c.868C>T (p.Arg290Ter)	Pathogenic
3026737	NM_000434.4(NEU1):c.300del (p.Ser101fs)	Pathogenic

SpliceAI

995 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31859943:CTC:C	acceptor_gain	1.0000
6:31859946:C:CC	acceptor_gain	1.0000
6:31860035:CACT:C	donor_loss	1.0000
6:31860036:ACTC:A	donor_loss	1.0000
6:31860038:TCA:T	donor_loss	1.0000
6:31860039:C:CG	donor_loss	1.0000
6:31860040:A:AC	donor_gain	1.0000
6:31860041:C:CG	donor_gain	1.0000
6:31860041:CGG:C	donor_gain	1.0000
6:31860041:CGGA:C	donor_gain	1.0000
6:31860041:CGGAA:C	donor_gain	1.0000
6:31860045:A:C	donor_gain	1.0000
6:31860260:TAGGG:T	acceptor_gain	1.0000
6:31860261:AGGG:A	acceptor_gain	1.0000
6:31860265:C:CC	acceptor_gain	1.0000
6:31860434:CTGAC:C	donor_loss	1.0000
6:31860435:TGACC:T	donor_loss	1.0000
6:31860436:GAC:G	donor_loss	1.0000
6:31860437:ACC:A	donor_loss	1.0000
6:31860438:C:CT	donor_loss	1.0000
6:31860463:ATTTT:A	donor_gain	1.0000
6:31860467:T:A	donor_gain	1.0000
6:31860508:T:TA	donor_gain	1.0000
6:31860617:TGTTT:T	acceptor_gain	1.0000
6:31860618:GTTT:G	acceptor_gain	1.0000
6:31860619:TTT:T	acceptor_gain	1.0000
6:31860620:TT:T	acceptor_gain	1.0000
6:31860622:C:CC	acceptor_gain	1.0000
6:31860624:G:C	acceptor_gain	1.0000
6:31861357:C:CA	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000048216 (6:31859828 A>G), RS1000150045 (6:31861554 C>A,G,T), RS1002213609 (6:31859137 G>A,C), RS1002514526 (6:31857951 C>G,T), RS1003189303 (6:31864557 G>T), RS1003414779 (6:31861999 CCTGGTCCATGGA>C), RS1003483337 (6:31858237 A>G), RS1003800186 (6:31863492 T>C), RS1004157639 (6:31860701 A>G), RS1004162394 (6:31857458 G>A), RS1005022255 (6:31863797 C>T), RS1006128914 (6:31857491 C>T), RS1006244669 (6:31858955 G>A), RS1006253074 (6:31859126 A>G), RS1007118120 (6:31858084 C>A,G)

Disease associations

OMIM: gene MIM:608272 | disease phenotypes: MIM:256150, MIM:256550, MIM:236750

GenCC curated gene-disease

Disease	Classification	Inheritance
sialidosis type 2	Definitive	Autosomal recessive
sialidosis type 1	Supportive	Autosomal recessive
juvenile sialidosis type 2	Supportive	Autosomal recessive
congenital sialidosis type 2	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
sialidosis	Definitive	AR

Mondo (7): sialidosis type 2 (MONDO:0009738), sialidosis (MONDO:0017734), non-immune hydrops fetalis (MONDO:0009369), sialidosis type 1 (MONDO:0019346), lysosomal storage disease (MONDO:0002561), juvenile sialidosis type 2 (MONDO:0019681), congenital sialidosis type 2 (MONDO:0019682)

Orphanet (5): Sialidosis type 1 (Orphanet:812), Sialidosis type 2 (Orphanet:87876), Sialidosis (Orphanet:309294), Non-immune hydrops fetalis (Orphanet:363999), Lysosomal disease (Orphanet:68366)

HPO phenotypes

96 total (30 of 96 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000077	Abnormality of the kidney
HP:0000093	Proteinuria
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000282	Facial edema
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000529	Progressive visual loss
HP:0000572	Visual loss
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000762	Decreased nerve conduction velocity
HP:0000768	Pectus carinatum
HP:0000943	Dysostosis multiplex
HP:0000962	Hyperkeratosis
HP:0000967	Petechiae
HP:0000969	Edema

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST003726_30	Basal cell carcinoma	1.000000e-08
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_162	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST004746_10	Small cell lung carcinoma	5.000000e-06
GCST004750_58	Squamous cell lung carcinoma	3.000000e-17
GCST008058_188	Estimated glomerular filtration rate	3.000000e-14
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST90002399_286	Neutrophil percentage of white cells	4.000000e-11
GCST90002401_40	Platelet distribution width	3.000000e-16
GCST90020024_1048	A body shape index	1.000000e-09
GCST90020027_714	Waist-hip index	6.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007984	platelet component distribution width
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016464	Lysosomal Storage Diseases	C16.320.565.595; C18.452.648.595
C562606	Nephrosialidosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2726 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 22 [PMID: 30457869]	Inhibition	4.85	pIC50

Binding affinities (BindingDB)

3 measured of 7 human assays (7 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(3R,4S)-3-acetamido-2-[(1S,2S)-3-(4-ethoxytriazol-1-yl)-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	IC50	170000 nM	US-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE
(3R,4S)-3-acetamido-2-[(1S,2S)-1,2-dihydroxy-3-(4-phenyltriazol-1-yl)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	IC50	200000 nM	US-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE
(3R,4S)-3-acetamido-2-[(1S,2S)-1,2-dihydroxy-3-[4-(3-hydroxypropyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	IC50	660000 nM	US-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE

ChEMBL bioactivities

63 potent at pChembl≥5 of 111 total, top 39 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.28	Ki	53	nM	CHEMBL4278858
6.85	IC50	140	nM	CHEMBL4290253
6.75	Ki	180	nM	CHEMBL4291908
6.62	Ki	240	nM	CHEMBL4281290
6.46	IC50	350	nM	CHEMBL4279593
6.40	IC50	400	nM	CHEMBL4283057
6.38	IC50	420	nM	CHEMBL4291908
6.38	IC50	420	nM	CHEMBL4453020
6.26	IC50	550	nM	CHEMBL4472555
6.24	IC50	580	nM	CHEMBL4566262
6.08	Ki	830	nM	CHEMBL4076483
6.00	IC50	990	nM	CHEMBL4281290
6.00	IC50	990	nM	CHEMBL4440333
5.92	IC50	1200	nM	CHEMBL4293651
5.85	IC50	1400	nM	CHEMBL4286830
5.82	IC50	1500	nM	CHEMBL4283482
5.80	IC50	1600	nM	CHEMBL4294730
5.77	IC50	1700	nM	CHEMBL4284515
5.75	IC50	1800	nM	CHEMBL4558105
5.72	IC50	1900	nM	CHEMBL4279510
5.68	IC50	2100	nM	CHEMBL4289583
5.60	IC50	2500	nM	CHEMBL1289198
5.60	IC50	2500	nM	CHEMBL4280607
5.54	IC50	2900	nM	CHEMBL4294428
5.50	IC50	3200	nM	CHEMBL4294661
5.47	IC50	3400	nM	CHEMBL4076483
5.43	IC50	3740	nM	CHEMBL4076483
5.40	IC50	4000	nM	CHEMBL4289116
5.37	IC50	4300	nM	CHEMBL4291325
5.32	IC50	4820	nM	CHEMBL4076483
5.30	IC50	5000	nM	CHEMBL4294428
5.28	IC50	5300	nM	CHEMBL3558288
5.19	IC50	6500	nM	CHEMBL4290845
5.19	IC50	6500	nM	CHEMBL4277321
5.16	IC50	6900	nM	CHEMBL4291733
5.12	IC50	7500	nM	CHEMBL4277321
5.08	IC50	8400	nM	CHEMBL4288490
5.00	IC50	1e+04	nM	CHEMBL252264
5.00	IC50	9900	nM	CHEMBL4286541

PubChem BioAssay actives

33 with measured affinity, of 171 total; 27 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
(2R,3R,4S)-3-[[2-[4-(4-aminophenyl)triazol-1-yl]acetyl]amino]-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415005: Competitive inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated with substrate for 15 mins and measured every min for 30 mins by Lineweaver-Burk plot analysis	ki	0.0530	uM
(2R,3R,4S)-2-[(1R,2R)-3-acetamido-1,2-dihydroxypropyl]-3-(hexanoylamino)-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	0.1400	uM
(2R,3R,4S)-3-(hexanoylamino)-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415005: Competitive inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated with substrate for 15 mins and measured every min for 30 mins by Lineweaver-Burk plot analysis	ki	0.1800	uM
(2R,3R,4S)-4-hydroxy-3-(pentanoylamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415005: Competitive inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated with substrate for 15 mins and measured every min for 30 mins by Lineweaver-Burk plot analysis	ki	0.2400	uM
(2R,3R,4S)-2-[(1R,2R)-3-acetamido-1,2-dihydroxypropyl]-4-hydroxy-3-(pentanoylamino)-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	0.3500	uM
(2R,3R,4S)-2-[(1R,2R)-1,2-dihydroxy-3-(propanoylamino)propyl]-3-(hexanoylamino)-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	0.4000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(pentanoylamino)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415006: Non-competitive inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated with substrate for 15 mins and measured every min for 30 mins by Lineweaver-Burk plot analysis	ki	0.8300	uM
(2R,3R,4S)-2-[(1R,2R)-3-(butanoylamino)-1,2-dihydroxypropyl]-3-(hexanoylamino)-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	1.2000	uM
(2R,3R,4S)-2-[(1R,2R)-3-(hexanoylamino)-1,2-dihydroxypropyl]-4-hydroxy-3-(propanoylamino)-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	1.4000	uM
(2R,3R,4S)-2-[(1R,2R)-1,2-dihydroxy-3-(pentanoylamino)propyl]-4-hydroxy-3-(pentanoylamino)-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	1.5000	uM
(2R,3R,4S)-2-[(1R,2R)-1,2-dihydroxy-3-(pentanoylamino)propyl]-4-hydroxy-3-(propanoylamino)-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	1.6000	uM
(2R,3R,4S)-4-hydroxy-3-(4-methylpentanoylamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	1.7000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[(4-acetamidobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	1.9000	uM
(2R,3R,4S)-3-(heptanoylamino)-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	2.1000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(3-methylbutanoylamino)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	2.5000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-benzamido-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	2.5000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-(hexanoylamino)-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	2.9000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(4-methylpentanoylamino)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	3.2000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-(butanoylamino)-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	4.0000	uM
(2R,3R,4S)-3-(hexanoylamino)-2-[(1R,2R)-3-(hexanoylamino)-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	4.3000	uM
(2R,3R,4S)-4-hydroxy-3-(2-methylpropanoylamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	5.3000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[(3-aminobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	6.5000	uM
(2R,3R,4S)-3-(cyclopropanecarbonylamino)-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	6.9000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[(3-acetamidobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	7.5000	uM
(2R,3R,4S)-3-(butanoylamino)-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	8.4000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-(heptanoylamino)-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415001: Inhibition of human His6-tagged NEU1 expressed in HEK293 cells using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	9.9000	uM
(2R,3R,4S)-3-acetamido-2-[(1S,2S)-1,2-dihydroxy-3-(pentanoylamino)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	313828: Inhibition of human NEU1 expressed in HEK293 cells	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	4
Valproic Acid	affects expression, increases expression	4
bisphenol A	affects expression, increases expression	3
sodium arsenite	affects expression, increases expression	3
trichostatin A	affects expression, increases expression	2
Acetaminophen	increases expression	2
Arsenic	increases abundance, increases expression, affects methylation	2
Formaldehyde	increases expression	2
Silicon Dioxide	increases expression	2
Cyclosporine	increases expression	2
Asbestos, Crocidolite	increases expression	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
tremortin	decreases expression	1
bufotalin	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
sodium arsenate	increases abundance, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects expression	1
perfluorooctanoic acid	decreases expression	1
4-hydroxy-2-nonenal	increases expression	1
Trimeresurus venoms	increases expression	1
cupric chloride	decreases expression	1
nickel sulfate	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
yessotoxin	increases expression	1
tacedinaline	decreases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1060572	Binding	Inhibition of human NEU1 transiently transfected in HEK293 cells at 1 mM by fluorimetric analysis	Human sialidase inhibitors: design, synthesis, and biological evaluation of 4-acetamido-5-acylamido-2-fluoro benzoic acids. — Bioorg Med Chem

Cellosaurus cell lines

18 cell lines: 10 cancer cell line, 4 finite cell line, 4 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_9R63	GM01718	Finite cell line	Female
CVCL_9R64	GM01719	Finite cell line	Female
CVCL_9R65	GM01720	Finite cell line	Male
CVCL_9R94	GM11604	Finite cell line	Male
CVCL_D1XQ	Abcam A-549 NEU1 KO	Cancer cell line	Male
CVCL_D5FA	HeLa::TMEM192-3xHA NEU1 partial KO	Cancer cell line	Female
CVCL_D7VN	Ubigene A-549 NEU1 KO	Cancer cell line	Male
CVCL_E1KU	HyCyte HeLa KO-hNEU1	Cancer cell line	Female
CVCL_E2DP	HAP1 NEU1 (-) 1	Cancer cell line	Male
CVCL_E2DQ	HAP1 NEU1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00654433	PHASE3	TERMINATED	ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases
NCT04283227	PHASE3	ACTIVE_NOT_RECRUITING	OTL-200 in Patients With Late Juvenile Metachromatic Leukodystrophy (MLD)
NCT03392987	PHASE2	COMPLETED	A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD)
NCT06130228	PHASE2	UNKNOWN	Nutritional Therapy in Late-onset Pompe Disease
NCT00215527	PHASE1	TERMINATED	Intrathecal Enzyme Replacement Therapy for Spinal Cord Compression in Mucopolysaccharidosis (MPS) I
NCT00744692	PHASE1	COMPLETED	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
NCT00786968	PHASE1	TERMINATED	Extension Study of Intrathecal Enzyme Replacement Therapy for MPS I
NCT01003912	PHASE1	WITHDRAWN	Fetal Umbilical Cord Blood (UCB) Transplant for Lysosomal Storage Diseases
NCT01891422	Not specified	COMPLETED	Longitudinal Studies of the Glycoproteinoses
NCT04624789	Not specified	UNKNOWN	Registry Gangliosidoses
NCT04308603	Not specified	COMPLETED	Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
NCT05528796	Not specified	ENROLLING_BY_INVITATION	Uncovering the Etiologies of Non-immune Hydrops Fetalis
NCT01560182	PHASE1/PHASE2	COMPLETED	Gene Therapy for Metachromatic Leukodystrophy (MLD)
NCT03897361	PHASE1/PHASE2	COMPLETED	Stem Cell Gene Therapy for Cystinosis
NCT03952637	PHASE1/PHASE2	RECRUITING	A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis
NCT04040049	PHASE1/PHASE2	TERMINATED	A Fabry Disease Gene Therapy Study
NCT04093349	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
NCT04455230	PHASE1/PHASE2	COMPLETED	A Long Term Follow-Up Study of Fabry Disease Subjects Treated With FLT190
NCT00001215	Not specified	ENROLLING_BY_INVITATION	Genetic Studies of Lysosomal Storage Disorders
NCT00001671	Not specified	COMPLETED	The Classification and Cause of Leukodystrophies of Unknown Cause
NCT00001780	Not specified	COMPLETED	Magnetic Stimulation of the Human Nervous System
NCT00046202	Not specified	COMPLETED	Study of Inborn Errors of Cholesterol Synthesis and Related Disorders
NCT00852358	Not specified	COMPLETED	A Study of Intrathecal Enzyme Therapy for Cognitive Decline in MPS I
NCT01458613	Not specified	WITHDRAWN	Biomarker for Maroteaux-Lamy Disease (BioMaroteaux)
NCT01626092	Not specified	COMPLETED	Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders
NCT01963650	Not specified	TERMINATED	Natural History Study of Children With Metachromatic Leukodystrophy
NCT02000310	Not specified	UNKNOWN	Molecular and Cellular Mechanisms of Lysosomal Storage Diseases
NCT02120235	Not specified	UNKNOWN	Investigating Lysosomal Storage Diseases in Minority Groups
NCT02363153	Not specified	COMPLETED	Diet and Exercise in Pompe Disease
NCT02416661	Not specified	COMPLETED	Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT03639844	Not specified	NO_LONGER_AVAILABLE	BPX-501 T Cells Infused Post Stem Cell Transplant in Pediatrics With Non-Malignant Disorders Ineligible for BPU004 Study
NCT03812042	Not specified	UNKNOWN	Screening of Lysosomal Storage Disorders Diseases in Minority Groups
NCT03812055	Not specified	UNKNOWN	Cellular Pharmacodynamics of Small Molecules in Lysosomal Storage Disorders
NCT03853876	Not specified	TERMINATED	A Natural History Study of Aspartylglucosaminuria
NCT03893240	Not specified	COMPLETED	Neutralizing Antibody Seroprevalence Study With a Retrospective Component in Participants With Late-Onset Pompe Disease
NCT04189601	Not specified	WITHDRAWN	Complement Activation in the Lysosomal Storage Disorders
NCT04393701	Not specified	RECRUITING	A Pilot Study for Systematic Neonatal Screening for Lysosomal Storage Diseases Using Tandem Mass Spectrometry
NCT04399694	Not specified	COMPLETED	Identification and Characterization of Novel Non-Coding Variants That Contribute to Genetic Disorders
NCT04943991	Not specified	ACTIVE_NOT_RECRUITING	Fabry Disease in High-risk Patients With Left Ventricular Hypertrophy: Prevalence and Implementation of a Clinical Score