NEU4

Summary

NEU4 (neuraminidase 4, HGNC:21328) is a protein-coding gene on chromosome 2q37.3, encoding Sialidase-4 (Q8WWR8). Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides.

The protein encoded by this gene belongs to a family of glycohydrolytic enzymes, which remove terminal sialic acid residues from various sialo derivatives, such as glycoproteins, glycolipids, oligosaccharides, and gangliosides. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.

Source: NCBI Gene 129807 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 143 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001167600

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21328
Approved symbol	NEU4
Name	neuraminidase 4
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204099
Ensembl biotype	protein_coding
OMIM	608527
Entrez	129807

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 24 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000325935, ENST00000391969, ENST00000404257, ENST00000405370, ENST00000407683, ENST00000415936, ENST00000420288, ENST00000423583, ENST00000426032, ENST00000428592, ENST00000435855, ENST00000435894, ENST00000435934, ENST00000476542, ENST00000488997, ENST00000494678, ENST00000618597, ENST00000859313, ENST00000859314, ENST00000859315, ENST00000859316, ENST00000859317, ENST00000859318, ENST00000859319, ENST00000859320, ENST00000859321, ENST00000859322, ENST00000859323, ENST00000966408

RefSeq mRNA: 5 — MANE Select: NM_001167600 NM_001167599, NM_001167600, NM_001167601, NM_001167602, NM_080741

CCDS: CCDS2553, CCDS54441, CCDS54442

Canonical transcript exons

ENST00000407683 — 4 exons

Exon	Start	End
ENSE00001318258	241814892	241815147
ENSE00001548171	241816051	241817413
ENSE00002692537	241809193	241809274
ENSE00003487727	241814482	241814685

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 95.33.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4922 / max 120.9200, expressed in 227 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26575	0.8266	109
26572	0.2939	29
26574	0.2718	88
26573	0.0720	17
26571	0.0279	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.33	gold quality
right lobe of liver	UBERON:0001114	94.05	gold quality
liver	UBERON:0002107	91.22	gold quality
substantia nigra	UBERON:0002038	84.61	gold quality
duodenum	UBERON:0002114	84.38	gold quality
temporal lobe	UBERON:0001871	83.93	gold quality
amygdala	UBERON:0001876	83.89	gold quality
Ammon’s horn	UBERON:0001954	83.80	gold quality
hypothalamus	UBERON:0001898	83.10	gold quality
transverse colon	UBERON:0001157	82.62	gold quality
putamen	UBERON:0001874	81.50	gold quality
anterior cingulate cortex	UBERON:0009835	80.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.28	gold quality
right frontal lobe	UBERON:0002810	79.64	gold quality
nucleus accumbens	UBERON:0001882	79.14	gold quality
caudate nucleus	UBERON:0001873	78.32	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.31	gold quality
cerebral cortex	UBERON:0000956	77.23	gold quality
primary visual cortex	UBERON:0002436	76.30	gold quality
rectum	UBERON:0001052	76.08	gold quality
superior frontal gyrus	UBERON:0002661	75.82	gold quality
brain	UBERON:0000955	75.80	gold quality
frontal cortex	UBERON:0001870	74.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.01	gold quality
small intestine	UBERON:0002108	73.19	gold quality
cerebellum	UBERON:0002037	72.97	gold quality
cerebellar hemisphere	UBERON:0002245	72.91	gold quality
cerebellar cortex	UBERON:0002129	72.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	15.18
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 14)

• The NEU4 gene, identified by searching sequence databases for entries showing homologies to the human cytosolic sialidase NEU2, maps in 2q37 and encodes a 484-residue protein. (PMID:14962670)
• Neu4 is a novel human lysosomal lumen sialidase (PMID:15213228)
• 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)
• related to malignancy and may be potential targets for cancer diagnosis and therapy (PMID:18651674)
• The NEU4 long form localizes in mitochondria, while the short form is also associated with the endoplasmic reticulum. (PMID:19797320)
• NEU4 plays an important role in control of sialyl Lewis antigen expression and its impairment in colon cancer (PMID:21521691)
• Overexpression of NEU4 is associated with neuroblastoma. (PMID:22287118)
• NEU4 is involved in regulation of neuronal function by polySia degradation in mammals. (PMID:22393058)
• The results demonstrate that the proline-rich region can also enhance cell proliferation and retinoic acid (RA)-induced neuronal differentiation and it is also involved in NEU4 interaction with Akt. (PMID:24030392)
• The silencing or chemical inhibition of NEU4 changes the entire glycosylation pattern of proteins and lipids, making it more similar to that of differentiated GBM cells and drastically reduces GSCs survival. (PMID:25144716)
• The most potent compound tested targeted the human Neu4 isoenzyme, and was able to substantially reduce the rate of cell migration. We found that the lateral mobility of integrins was reduced by treatment of cells with Neu3, suggesting that Neu3 enzyme activity resulted in changes to integrin-co-receptor or integrin-cytoskeleton interactions (PMID:27344026)
• Synergistic activation of the NEU4 promoter by p73 and AP2 in colon cancer cells. (PMID:30700826)
• Neuraminidase 4 (NEU4): new biological and physiological player. (PMID:36728702)
• Biomarkers of ulcerative colitis disease activity CXCL1, CYP2R1, LPCAT1, and NEU4 and their relationship to immune infiltrates. (PMID:37495756)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	neu4	ENSDARG00000057677
mus_musculus	Neu4	ENSMUSG00000034000
rattus_norvegicus	Neu4	ENSRNOG00000019031

Paralogs (3): NEU2 (ENSG00000115488), NEU3 (ENSG00000162139), NEU1 (ENSG00000204386)

Protein

Protein identifiers

Sialidase-4 — Q8WWR8 (reviewed: Q8WWR8)

Alternative names: N-acetyl-alpha-neuraminidase 4

All UniProt accessions (10): B3KR54, C9IZG9, C9J295, C9J2R4, C9J2V4, Q8WWR8, C9J5X2, C9JEA3, C9JRN9, F8WE58

UniProt curated annotations — full annotation on UniProt →

Function. Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides. Efficiently hydrolyzes gangliosides including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3. Hydrolyzes poly-alpha-(2->8)-sialylated neural cell adhesion molecule NCAM1 likely at growth cones, suppressing neurite outgrowth in hippocampal neurons. May desialylate sialyl Lewis A and X antigens at the cell surface, down-regulating these glycan epitopes recognized by SELE/E selectin in the initiation of cell adhesion and extravasation. Has sialidase activity toward mucin, fetuin and sialyllactose.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Microsome membrane. Mitochondrion membrane. Cell projection. Neuron projection Mitochondrion inner membrane. Mitochondrion outer membrane. Lysosome lumen.

Tissue specificity. Predominant form in liver. Also expressed in brain, kidney and colon. Highly expressed in brain and at lower levels in kidney and liver.

Post-translational modifications. N-glycosylated.

Induction. Down-regulated during monocyte to macrophage differentiation.

Similarity. Belongs to the glycosyl hydrolase 33 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WWR8-1	1	yes
Q8WWR8-2	2
Q8WWR8-3	3

RefSeq proteins (5): NP_001161071, NP_001161072, NP_001161073, NP_001161074, NP_542779 (=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

Catalyzed reactions (Rhea), 8 shown:

• a ganglioside GD1a + H2O = a ganglioside GM1 + N-acetylneuraminate (RHEA:47832)
• a ganglioside GD1a (d18:1(4E)) + H2O = a ganglioside GM1 (d18:1(4E)) + N-acetylneuraminate (RHEA:47856)
• a ganglioside GM3 (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + N-acetylneuraminate (RHEA:47900)
• a ganglioside GM2 (d18:1(4E)) + H2O = a ganglioside GA2 (d18:1(4E)) + N-acetylneuraminate (RHEA:48068)
• a ganglioside GD3 + H2O = a ganglioside GM3 + N-acetylneuraminate (RHEA:48120)
• a ganglioside GD3 (d18:1(4E)) + H2O = a ganglioside GM3 (d18:1(4E)) + N-acetylneuraminate (RHEA:48124)
• a ganglioside GM3 + H2O = a beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + N-acetylneuraminate (RHEA:48136)
• a ganglioside GM2 + H2O = a ganglioside GA2 + N-acetylneuraminate (RHEA:48172)

UniProt features (23 total): binding site 7, active site 4, repeat 3, splice variant 2, chain 1, sequence variant 1, mutagenesis site 1, sequence conflict 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWR8-F1	83.42	0.71

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 (4): 440; 47 (proton acceptor); 48 (proton acceptor); 419 (nucleophile)

Ligand- & substrate-binding residues (7): 23; 43; 177; 179; 222; 242; 389

Mutagenesis-validated functional residues (1):

Position	Phenotype
5	impairs mitochondrial targeting.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-4085001	Sialic acid metabolism
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-392499	Metabolism of proteins
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-597592	Post-translational protein modification

MSigDB gene sets: 93 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_GLYCOLIPID_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (6): glycoprotein catabolic process (GO:0006516), ganglioside catabolic process (GO:0006689), oligosaccharide catabolic process (GO:0009313), negative regulation of neuron projection development (GO:0010977), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042)

GO Molecular Function (4): exo-alpha-sialidase activity (GO:0004308), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (14): cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), mitochondrial inner membrane (GO:0005743), lysosome (GO:0005764), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), organelle inner membrane (GO:0019866), neuron projection (GO:0043005), lysosomal lumen (GO:0043202), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), mitochondrial membrane (GO:0031966), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1
Glycosphingolipid metabolism	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 of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
organelle membrane	3
mitochondrial membrane	2
cytoplasm	2
intracellular membrane-bounded organelle	2
glycoprotein metabolic process	1
protein catabolic process	1
carbohydrate derivative catabolic process	1
ganglioside metabolic process	1
glycosphingolipid catabolic process	1
ceramide catabolic process	1
oligosaccharide metabolic process	1
carbohydrate catabolic process	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
alpha-sialidase activity	1
binding	1
catalytic activity	1
hydrolase activity	1
intracellular anatomical structure	1
organelle outer membrane	1
organelle inner membrane	1
lytic vacuole	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
organelle envelope	1
plasma membrane bounded cell projection	1
lysosome	1
vacuolar lumen	1
endomembrane system	1
mitochondrion	1
mitochondrial envelope	1

Protein interactions and networks

STRING

944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEU4	GAL3ST2	Q9H3Q3	892
NEU4	DTYMK	P23919	890
NEU4	CTSA	P10619	689
NEU4	ST3GAL1	Q11201	630
NEU4	ST3GAL2	Q16842	594
NEU4	CASD1	Q96PB1	568
NEU4	ST3GAL3	Q11203	547
NEU4	ST8SIA1	Q92185	513
NEU4	ST6GAL1	P15907	500
NEU4	ST3GAL4	Q11206	498
NEU4	ST6GAL2	Q96JF0	495
NEU4	ST3GAL6	Q9Y274	478
NEU4	ST3GAL5	Q9UNP4	473
NEU4	NEU1	Q99519	458
NEU4	CMAS	Q8NFW8	457

IntAct

13 interactions, top by confidence:

A	B	Type	Score
MDFI	NEU4	psi-mi:“MI:0915”(physical association)	0.710
NEU4	MDFI	psi-mi:“MI:0915”(physical association)	0.710
RHOXF2	NEU4	psi-mi:“MI:0915”(physical association)	0.550
PLSCR1	NEU4	psi-mi:“MI:0915”(physical association)	0.510
NEU4	PLSCR1	psi-mi:“MI:0915”(physical association)	0.510
Dlg4	NEU4	psi-mi:“MI:0407”(direct interaction)	0.440
CFTR	NEU4	psi-mi:“MI:0915”(physical association)	0.370
RBPMS	NEU4	psi-mi:“MI:0915”(physical association)	0.370
NEU4	AIP	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Two-hybrid), NEU4 (Affinity Capture-Western), MDFI (Two-hybrid), TRIP6 (Two-hybrid), RPUSD2 (Affinity Capture-MS), ZPR1 (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A5PJN5, A6NFQ2, A6QLU7, A6QQ07, A6QQV6, A7Z052, O95479, O97859, P16452, P49753, P56201, Q32N48, Q32PY6, Q3U3W5, Q3UY23, Q5HZW3, Q5R8R3, Q5RJG7, Q5S6T3, Q5U4E8, Q5XFW6, Q5XIA3, Q64393, Q64627, Q68G58, Q865R1, Q8BZL1, Q8BZW8, Q8C0L6, Q8CAE2, Q8CFX1, Q8NFF5, Q8VDG7, Q8WWR8, Q921K8, Q922X9, Q99ME2, Q99MI9, Q99PW5

Diamond homologs: A5PF10, A6BMK7, O35657, P62575, P62576, Q02834, Q5RAF4, Q8BZL1, Q8WWR8, Q99519, Q99PW3, D4B4P1, O97859, Q4WQS0, Q64393, Q64627, Q99PW5, Q9JMH3, Q9JMH7, Q9UQ49, Q9Y3R4, P29768, P31206

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1261 predictions. Top by Δscore:

Variant	Effect	Δscore
2:241813867:G:GT	donor_gain	1.0000
2:241813926:G:GT	donor_gain	1.0000
2:241815146:GG:G	donor_gain	1.0000
2:241815147:GG:G	donor_gain	1.0000
2:241816049:A:AG	acceptor_gain	1.0000
2:241816050:G:GG	acceptor_gain	1.0000
2:241816050:GACT:G	acceptor_gain	1.0000
2:241813867:G:T	donor_gain	0.9900
2:241813926:G:T	donor_gain	0.9900
2:241813932:G:GT	donor_gain	0.9900
2:241814686:G:GG	donor_gain	0.9900
2:241814885:T:TA	acceptor_gain	0.9900
2:241814890:AGTGG:A	acceptor_gain	0.9900
2:241814891:GTGGG:G	acceptor_gain	0.9900
2:241814997:ATCGC:A	acceptor_gain	0.9900
2:241815001:C:CA	acceptor_gain	0.9900
2:241815123:G:GT	donor_gain	0.9900
2:241815134:T:TA	donor_gain	0.9900
2:241815135:G:GA	donor_gain	0.9900
2:241815148:G:T	donor_gain	0.9900
2:241816049:A:AT	acceptor_loss	0.9900
2:241816049:AGACT:A	acceptor_gain	0.9900
2:241816050:G:GA	acceptor_loss	0.9900
2:241816050:GACTG:G	acceptor_gain	0.9900
2:241813866:GGAA:G	donor_gain	0.9800
2:241813873:G:GT	donor_gain	0.9800
2:241813925:GGAA:G	donor_gain	0.9800
2:241813927:A:T	donor_gain	0.9800
2:241814655:G:GT	donor_gain	0.9800
2:241814682:GCGG:G	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000377147 (2:241817512 A>T), RS1000453104 (2:241809587 G>A), RS1000825328 (2:241814559 C>G,T), RS1000858144 (2:241810018 C>T), RS1000905827 (2:241809774 A>G), RS1001386039 (2:241810350 C>A,T), RS1001732303 (2:241813074 C>G), RS1001858683 (2:241809291 TAG>T), RS1001990576 (2:241811209 T>A), RS1002108318 (2:241808188 A>C,G), RS1002192863 (2:241812956 G>C), RS1002466182 (2:241811355 G>A,C,T), RS1002922341 (2:241808520 T>C), RS1003063548 (2:241812290 T>C), RS1003148275 (2:241811934 G>A,T)

Disease associations

OMIM: gene MIM:608527 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009798_13	Asthma	5.000000e-36

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4174 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 42,528 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL222813	ZANAMIVIR	4	42,528

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

ChEMBL bioactivities

54 potent at pChembl≥5 of 105 total, top 31 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.52	Ki	30	nM	CHEMBL1289650
7.22	Ki	60	nM	CHEMBL1289754
6.80	IC50	160	nM	CHEMBL1289650
6.58	Ki	260	nM	CHEMBL4076203
6.28	IC50	520	nM	CHEMBL4076203
6.13	IC50	740	nM	CHEMBL1289650
6.09	IC50	810	nM	CHEMBL1289754
6.01	IC50	970	nM	CHEMBL4062382
6.00	Ki	1000	nM	NEU5AC2EN
5.96	IC50	1100	nM	CHEMBL4454277
5.89	IC50	1300	nM	CHEMBL4096864
5.77	IC50	1700	nM	CHEMBL1289649
5.68	IC50	2100	nM	CHEMBL1289755
5.64	IC50	2300	nM	CHEMBL1289428
5.58	IC50	2600	nM	CHEMBL4060974
5.58	IC50	2600	nM	CHEMBL4285561
5.52	IC50	3000	nM	CHEMBL4071732
5.44	IC50	3600	nM	CHEMBL1289540
5.43	IC50	3700	nM	CHEMBL4076203
5.43	IC50	3700	nM	CHEMBL4454422
5.41	IC50	3900	nM	CHEMBL4089157
5.40	IC50	4000	nM	CHEMBL1289861
5.35	IC50	4500	nM	CHEMBL1289862
5.30	IC50	5000	nM	CHEMBL4069646
5.30	Ki	5000	nM	CHEMBL4099818
5.25	IC50	5600	nM	CHEMBL1289862
5.25	IC50	5600	nM	CHEMBL4467946
5.24	Ki	5800	nM	NEU5AC2EN
5.23	IC50	5900	nM	CHEMBL4099818
5.08	IC50	8300	nM	NEU5AC2EN
5.08	IC50	8400	nM	CHEMBL4288490

PubChem BioAssay actives

33 with measured affinity, of 182 total; 19 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-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(hydroxymethyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	748616: Inhibition of human NEU4 using 4-MU-NANA as substrate measured every 30 seconds for 60 mins by fluorescence plate reader analysis	ki	0.0300	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(2-hydroxyethyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	748616: Inhibition of human NEU4 using 4-MU-NANA as substrate measured every 30 seconds for 60 mins by fluorescence plate reader analysis	ki	0.0600	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-phenylphenyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1490011: Inhibition of human N-terminal MBP-fused NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured every minute for 30 mins by fluorescence based assay	ki	0.2600	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-phenoxyphenyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1490015: Inhibition of human N-terminal MBP-fused NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assay	ic50	0.9700	uM
(2R,3R,4S)-3-acetamido-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	728980: Inhibition of human neuraminidase 4 using 4MU-NANA as substrate measured for every 30 seconds for 60 mins by fluorescence assay	ki	1.0000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[4-(4-fluorophenyl)triazol-1-yl]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1490015: Inhibition of human N-terminal MBP-fused NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assay	ic50	1.3000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(phenoxymethyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	748619: Inhibition of human NEU4 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysis	ic50	1.7000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(3-hydroxypropyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	748619: Inhibition of human NEU4 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysis	ic50	2.1000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(4-phenyltriazol-1-yl)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	748619: Inhibition of human NEU4 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysis	ic50	2.3000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-methoxyphenyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1490015: Inhibition of human N-terminal MBP-fused NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assay	ic50	2.6000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(4-pentyltriazol-1-yl)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1415004: Inhibition of MBP-fused human NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	2.6000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[4-(4-carboxyphenyl)triazol-1-yl]-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1490015: Inhibition of human N-terminal MBP-fused NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assay	ic50	3.0000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-(4-ethoxytriazol-1-yl)-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	748619: Inhibition of human NEU4 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysis	ic50	3.6000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-methylphenyl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1490015: Inhibition of human N-terminal MBP-fused NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assay	ic50	3.9000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-(2-hydroxypropan-2-yl)triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	748619: Inhibition of human NEU4 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysis	ic50	4.0000	uM
(2R,3R,4S)-3-[(2-azidoacetyl)amino]-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	748619: Inhibition of human NEU4 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysis	ic50	4.5000	uM
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-[4-[4-(trifluoromethyl)phenyl]triazol-1-yl]propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	1490015: Inhibition of human N-terminal MBP-fused NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by fluorescence based assay	ic50	5.0000	uM
(2R,3R,4S)-3-acetamido-4-(diaminomethylideneamino)-2-[(1R,2R)-1,2-dihydroxy-3-[4-(4-phenylphenyl)triazol-1-yl]propyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1490011: Inhibition of human N-terminal MBP-fused NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition measured every minute for 30 mins by fluorescence based assay	ki	5.0000	uM
(2R,3R,4S)-3-(butanoylamino)-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415004: Inhibition of MBP-fused human NEU4 expressed in Escherichia coli 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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	3
Cyclosporine	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
TL8-506	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
licochalcone B	decreases expression	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arbutin	increases expression	1
Lipopolysaccharides	affects response to substance, affects cotreatment, increases expression	1
Malathion	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

31 unique, capped per target: 31 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1060577	Binding	Inhibition of human NEU4 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

Clinical trials (associated diseases)

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