NEU2

Summary

NEU2 (neuraminidase 2, HGNC:7759) is a protein-coding gene on chromosome 2q37.1, encoding Sialidase-2 (Q9Y3R4). 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.

This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipids. Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase. Its cytosolic localization was demonstrated by cell fractionation experiments.

Source: NCBI Gene 4759 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 62 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7759
Approved symbol	NEU2
Name	neuraminidase 2
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	SIAL2
Ensembl gene	ENSG00000115488
Ensembl biotype	protein_coding
OMIM	605528
Entrez	4759

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000233840, ENST00000851001

RefSeq mRNA: 1 — MANE Select: NM_005383 NM_005383

CCDS: CCDS2501

Canonical transcript exons

ENST00000233840 — 2 exons

Exon	Start	End
ENSE00004283225	233032672	233032872
ENSE00004283226	233034116	233035057

Expression profiles

Bgee: expression breadth tissue_specific, 10 present calls, max score 85.25.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.25	silver quality
parotid gland	UBERON:0001831	61.19	gold quality
secondary oocyte	CL:0000655	58.58	gold quality
skin of leg	UBERON:0001511	57.75	gold quality
skin of abdomen	UBERON:0001416	55.96	gold quality
medial globus pallidus	UBERON:0002477	55.28	gold quality
zone of skin	UBERON:0000014	55.07	gold quality
myocardium	UBERON:0002349	54.38	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	53.32	gold quality
inferior olivary complex	UBERON:0002127	53.19	gold quality
trabecular bone tissue	UBERON:0002483	52.45	gold quality
decidua	UBERON:0002450	52.25	gold quality
tendon of biceps brachii	UBERON:0008188	52.10	gold quality
globus pallidus	UBERON:0001875	52.02	gold quality
deltoid	UBERON:0001476	50.45	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
renal glomerulus	UBERON:0000074	46.86	gold quality
middle temporal gyrus	UBERON:0002771	46.83	gold quality
metanephric glomerulus	UBERON:0004736	46.77	gold quality
nephron tubule	UBERON:0001231	46.71	gold quality
nasal cavity epithelium	UBERON:0005384	46.18	gold quality
sural nerve	UBERON:0015488	45.87	gold quality
amniotic fluid	UBERON:0000173	45.80	gold quality
vastus lateralis	UBERON:0001379	45.71	gold quality
quadriceps femoris	UBERON:0001377	45.58	gold quality
bone marrow	UBERON:0002371	43.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
oocyte	CL:0000023	43.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX2, SP3

Literature-anchored findings (GeneRIF, showing 12)

• HsNEU2 differentially recognizes the type of sialosyl linkage, the aglycone part of the substrate, and the supramolecular organization (monomer/micelle/vesicle) of gangliosides (PMID:14613940)
• the first high resolution x-ray structures of sialidase, human Neu2 (PMID:15501818)
• propose that this Asian-enriched sialidase variation caused by the SNP, likely in homozygous form, may be associated with certain severe adverse reactions to oseltamivir (PMID:17426694)
• Neu2 loss of expression might exacerbate the defective myogenic differentiation of rhabdomyosarcoma cells. (PMID:19524683)
• NEU2 appears to be activated when lysine 45 and glutamine 112 are mutated to alanine. (PMID:22228546)
• the present study demonstrated NEU2 expression to be detectable but very low in many human tissues and cells, and suggested possible functional roles in PC-3 prostate cancer cells. (PMID:23068092)
• Q136K is a novel mutation in an expressed NEU2 protein that was discovered during crystallographic analysis. (PMID:23908028)
• Circular dichroism (CD) spectra at variable temperatures have been recorded for human cytosolic sialidase NEU2 in buffered water solutions and in the presence of divalent cations. (PMID:25033330)
• cytosolic GBA3 is likely involved in the catabolism of cytosolic sialyl free N-glycans, possibly by stabilizing the activity of the NEU2 protein (PMID:26193330)
• Synchrotron radiation reflectometry was used to access the transverse structure of model membranes under the action of the human sialidase NEU2, down to the Angstrom length scale (PMID:28087363)
• The role of neuraminidase 1 and 2 in glycoprotein Ibalpha-mediated integrin alphaIIbbeta3 activation. (PMID:31273092)
• Desialylation of Sonic-Hedgehog by Neu2 Inhibits Its Association with Patched1 Reducing Stemness-Like Properties in Pancreatic Cancer Sphere-forming Cells. (PMID:32575925)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Neu2	ENSMUSG00000079434
rattus_norvegicus	Neu2	ENSRNOG00000016962

Paralogs (3): NEU3 (ENSG00000162139), NEU4 (ENSG00000204099), NEU1 (ENSG00000204386)

Protein

Protein identifiers

Sialidase-2 — Q9Y3R4 (reviewed: Q9Y3R4)

Alternative names: Cytosolic sialidase, N-acetyl-alpha-neuraminidase 2

All UniProt accessions (1): Q9Y3R4

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. Recognizes sialyl linkage positions of the glycan moiety as well as the supramolecular organization of the sialoglycoconjugate. Displays preference for alpha-(2->3)-sialylated GD1a and GT1B gangliosides over alpha-(2->8)-sialylated GD1b, in both monomeric forms and micelles. Hydrolyzes monomeric GM1 ganglioside, but has no activity toward the miscellar form. Has lower sialidase activity for glycoproteins such as fetuin and TF/transferrin that carry a mixture of alpha-(2->3) and alpha-(2->6)-sialyl linkages. Cleaves milk oligosaccharide alpha-(2->3)-sialyllactose, but is inactive toward alpha-(2->6)-sialyllactose isomer. Has no activity toward colominic acid, a homomer of alpha-(2->8)-linked Neu5Ac residues.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed in skeletal muscle, fetal liver and embryonic carcinoma cell line NT2-D1.

Similarity. Belongs to the glycosyl hydrolase 33 family.

RefSeq proteins (1): NP_005374* (*=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), 9 shown:

• a ganglioside GT1b + H2O = a ganglioside GD1b + N-acetylneuraminate (RHEA:47828)
• a ganglioside GD1a + H2O = a ganglioside GM1 + N-acetylneuraminate (RHEA:47832)
• a neolactoside IV(3)-alpha-NeuAc-nLc4Cer(d18:1(4E)) + H2O = a neolactoside nLc4Cer(d18:1(4E)) + N-acetylneuraminate (RHEA:47852)
• a ganglioside GM1 + H2O = a ganglioside GA1 + N-acetylneuraminate (RHEA:47872)
• a ganglioside GD1b + H2O = a ganglioside GM1 + N-acetylneuraminate (RHEA:47876)
• a ganglioside GD3 + H2O = a ganglioside GM3 + N-acetylneuraminate (RHEA:48120)
• 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)
• N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->4)-D-glucose + H2O = lactose + N-acetylneuraminate (RHEA:64640)

UniProt features (58 total): strand 24, binding site 7, helix 7, sequence variant 5, turn 5, mutagenesis site 3, active site 3, repeat 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
1SO7	X-RAY DIFFRACTION	1.49
2F26	X-RAY DIFFRACTION	1.58
2F28	X-RAY DIFFRACTION	1.67
1SNT	X-RAY DIFFRACTION	1.75
2F24	X-RAY DIFFRACTION	1.76
2F25	X-RAY DIFFRACTION	1.95
2F27	X-RAY DIFFRACTION	2.15
4NCS	X-RAY DIFFRACTION	2.2
2F13	X-RAY DIFFRACTION	2.26
2F12	X-RAY DIFFRACTION	2.27
4NC5	X-RAY DIFFRACTION	2.51
2F11	X-RAY DIFFRACTION	2.57
2F0Z	X-RAY DIFFRACTION	2.8
1VCU	X-RAY DIFFRACTION	2.85
2F10	X-RAY DIFFRACTION	2.9
2F29	X-RAY DIFFRACTION	2.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3R4-F1	97.20	0.95

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): 46 (proton acceptor); 334 (nucleophile); 355

Ligand- & substrate-binding residues (7): 181; 218; 237; 304; 21; 41; 179

Mutagenesis-validated functional residues (3):

Position	Phenotype
46	loss of enzyme activity.
218	loss of enzyme activity.
270	no effect on enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-4085001	Sialic acid metabolism
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
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-597592	Post-translational protein modification

MSigDB gene sets: 86 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_CATABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, GOBP_GLYCOLIPID_CATABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, PETRETTO_HEART_MASS_QTL_CIS_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (6): glycoprotein catabolic process (GO:0006516), ganglioside catabolic process (GO:0006689), oligosaccharide catabolic process (GO:0009313), glycosphingolipid catabolic process (GO:0046479), 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 (5): cytoplasm (GO:0005737), lysosome (GO:0005764), cytosol (GO:0005829), membrane (GO:0016020), catalytic complex (GO:1902494)

Reactome top-level categories

Rollup of top-9 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
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
glycosphingolipid metabolic process	1
glycolipid catabolic process	1
sphingolipid catabolic process	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
lytic vacuole	1
cytoplasm	1
protein-containing complex	1

Protein interactions and networks

STRING

602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEU2	GAL3ST2	Q9H3Q3	669
NEU2	DTYMK	P23919	648
NEU2	NEU1	Q99519	630
NEU2	ST3GAL1	Q11201	605
NEU2	ST3GAL2	Q16842	591
NEU2	CTSA	P10619	577
NEU2	ST6GALNAC1	Q9NSC7	541
NEU2	ZNF205	O95201	520
NEU2	ST6GAL2	Q96JF0	514
NEU2	ST8SIA1	Q92185	509
NEU2	RAD51AP1	Q96B01	507
NEU2	ST6GAL1	P15907	503
NEU2	NEU3	Q9UQ49	502
NEU2	NAT9	Q9BTE0	499
NEU2	SVOPL	Q8N434	488
NEU2	LRGUK	Q96M69	488

IntAct

46 interactions, top by confidence:

A	B	Type	Score
NOTCH2NLA	NEU2	psi-mi:“MI:0915”(physical association)	0.720
NEU2	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.720
ANXA9	PPL	psi-mi:“MI:0914”(association)	0.660
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
CYSRT1	NEU2	psi-mi:“MI:0915”(physical association)	0.560
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
CCDC51	TGM5	psi-mi:“MI:0914”(association)	0.530
FAM217B	NCK2	psi-mi:“MI:0914”(association)	0.530
RPN2	SMPD2	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
SYT5	SYT1	psi-mi:“MI:0914”(association)	0.530
NEU2	PEX14	psi-mi:“MI:0914”(association)	0.350
PYHIN1	DUSP14	psi-mi:“MI:0914”(association)	0.350
IL31RA	DUSP14	psi-mi:“MI:0914”(association)	0.350
ZMAT4	VSIG8	psi-mi:“MI:0914”(association)	0.350
TIFAB	DDX3X	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350
ADIPOR2	NCK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): NOTCH2NL (Two-hybrid), KIAA1671 (Affinity Capture-MS), CWF19L2 (Affinity Capture-MS), NOSIP (Affinity Capture-MS), ZWINT (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX5 (Affinity Capture-MS), NOTCH3 (Affinity Capture-MS), KEAP1 (Affinity Capture-MS), TFAP4 (Affinity Capture-MS), ALKBH3 (Affinity Capture-MS), NEU2 (Affinity Capture-MS), NEU2 (Affinity Capture-MS), NEU2 (Affinity Capture-MS), NOTCH2NL (Two-hybrid)

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: D4B4P1, O97859, Q4WQS0, Q9Y3R4, P62575, P62576, Q64393, Q64627, Q8BZL1, Q8WWR8, Q99PW5, Q9JMH3, Q9JMH7, Q9UQ49, P10481, P15698, P29768, P31206, A5PF10, A6BMK7, Q5RAF4, Q99519

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

154 predictions. Top by Δscore:

Variant	Effect	Δscore
2:233032868:TTCAG:T	donor_loss	1.0000
2:233032869:TCAGG:T	donor_loss	1.0000
2:233032870:CAGG:C	donor_loss	1.0000
2:233032871:AG:A	donor_loss	1.0000
2:233032882:G:GT	donor_gain	1.0000
2:233034110:A:AG	acceptor_gain	0.9900
2:233034111:C:G	acceptor_gain	0.9900
2:233034114:A:AG	acceptor_gain	0.9900
2:233034114:AGT:A	acceptor_gain	0.9900
2:233034115:G:GG	acceptor_gain	0.9900
2:233034115:GT:G	acceptor_gain	0.9900
2:233034115:GTG:G	acceptor_gain	0.9900
2:233032873:G:GG	donor_gain	0.9800
2:233034114:AGTG:A	acceptor_gain	0.9800
2:233034115:GTGG:G	acceptor_gain	0.9800
2:233034115:GTGGC:G	acceptor_gain	0.9800
2:233032841:GAGAC:G	donor_gain	0.9700
2:233034111:CTCA:C	acceptor_loss	0.9700
2:233034112:TCAG:T	acceptor_loss	0.9700
2:233034113:CA:C	acceptor_loss	0.9700
2:233032807:GA:G	donor_gain	0.9500
2:233032868:TTC:T	donor_gain	0.9500
2:233032869:TCA:T	donor_gain	0.9500
2:233032870:CAG:C	donor_gain	0.9500
2:233032867:GT:G	donor_gain	0.9100
2:233032871:A:G	donor_gain	0.9100
2:233032872:GG:G	donor_gain	0.9100
2:233033456:A:AG	donor_gain	0.9100
2:233032873:G:T	donor_gain	0.9000
2:233034114:AGTGG:A	acceptor_gain	0.9000

AlphaMissense

2462 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:233034118:G:C	W68C	0.993
2:233034118:G:T	W68C	0.993
2:233034116:T:A	W68R	0.990
2:233034116:T:C	W68R	0.990
2:233034875:T:A	W321R	0.988
2:233034875:T:C	W321R	0.988
2:233034877:G:C	W321C	0.987
2:233034877:G:T	W321C	0.987
2:233034737:A:C	S275R	0.986
2:233034739:C:A	S275R	0.986
2:233034739:C:G	S275R	0.986
2:233034322:G:C	W136C	0.984
2:233034322:G:T	W136C	0.984
2:233034643:G:C	R243S	0.983
2:233034643:G:T	R243S	0.983
2:233034656:A:C	S248R	0.983
2:233034658:C:A	S248R	0.983
2:233034658:C:G	S248R	0.983
2:233035014:T:C	F367S	0.983
2:233032780:T:C	F37L	0.982
2:233032782:C:A	F37L	0.982
2:233032782:C:G	F37L	0.982
2:233034320:T:A	W136R	0.982
2:233034320:T:C	W136R	0.982
2:233034642:G:T	R243M	0.982
2:233032781:T:C	F37S	0.981
2:233034374:T:A	W154R	0.981
2:233034374:T:C	W154R	0.981
2:233034532:G:C	W206C	0.981
2:233034532:G:T	W206C	0.981

dbSNP variants (sampled 300 via entrez): RS1001298329 (2:233034891 T>C,G), RS1001582504 (2:233035181 G>A,C), RS1001809355 (2:233033133 G>A), RS1003782546 (2:233031336 G>A), RS1003834867 (2:233031552 G>A), RS1005176169 (2:233034757 C>G,T), RS1006710658 (2:233031004 G>A), RS1006846364 (2:233031466 A>C), RS1006967699 (2:233032328 C>T), RS1007925119 (2:233033162 G>A), RS1008715864 (2:233033479 T>C), RS1009823868 (2:233030862 G>C), RS1010119696 (2:233031255 C>G,T), RS1011032737 (2:233034087 T>A), RS1011241019 (2:233032127 G>C)

Disease associations

OMIM: gene MIM:605528 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002238_4	Contrast sensitivity	4.000000e-06
GCST009602_38	Metabolic syndrome	8.000000e-28
GCST010658_3	High density lipoprotein cholesterol levels	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005419	contrast sensitivity measurement
EFO:0000195	metabolic syndrome
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3200 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 42,755 (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
CHEMBL139367	PERAMIVIR ANHYDROUS	4	227
CHEMBL222813	ZANAMIVIR	4	42,528

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2233385	NEU2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 22 [PMID: 30457869]	Inhibition	5.68	pIC50
compound 13c [PMID: 30457869]	Inhibition	5.36	pIC50

Binding affinities (BindingDB)

5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2,6-Anhydro-5-(2-azidoacetamido)-3,5-dideoxy-	IC50	8300 nM	US-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE
2,6-Anhydro-3,5-dideoxy-5-glycolylamido-D-	IC50	34000 nM	US-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE
(2R,3R,4S)-2-[(1R,2R)-3-azido-1,2-dihydroxypropyl]-4-hydroxy-3-[(2-hydroxyacetyl)amino]-3,4-dihydro-2H-pyran-6-carboxylic acid	IC50	190000 nM	US-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-methoxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	IC50	410000 nM	US-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE
(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1,2-dihydroxy-3-(propylamino)propyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid	IC50	2.4e+06 nM	US-20250144172: ANTI-FIBROTIC SIALIDASE INHIBITOR COMPOUNDS AND METHODS OF USE

ChEMBL bioactivities

29 potent at pChembl≥5 of 125 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.89	Ki	1300	nM	CHEMBL4277689
5.68	IC50	2100	nM	CHEMBL4277689
5.68	Ki	2100	nM	CHEMBL4278858
5.57	Ki	2700	nM	CHEMBL4280792
5.48	IC50	3300	nM	CHEMBL4280792
5.41	IC50	3900	nM	ZANAMIVIR
5.36	IC50	4400	nM	CHEMBL4278858
5.35	IC50	4500	nM	CHEMBL4277391
5.34	IC50	4600	nM	CHEMBL4277391
5.30	Ki	5000	nM	NEU5AC2EN
5.28	IC50	5300	nM	ZANAMIVIR
5.24	Ki	5700	nM	ZANAMIVIR
5.23	IC50	5900	nM	CHEMBL4099818
5.16	IC50	7000	nM	CHEMBL4284515
5.14	IC50	7300	nM	CHEMBL4284515
5.11	IC50	7800	nM	ZANAMIVIR
5.08	IC50	8300	nM	CHEMBL1289862
5.05	IC50	9000	nM	CHEMBL1289979

PubChem BioAssay actives

19 with measured affinity, of 297 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
(2R,3R,4S)-4-(diaminomethylideneamino)-3-(4-methylpentanoylamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415007: Competitive inhibition of N-terminal MBP-fused human NEU2 expressed in Escherichia coli using 4MU-NANA as substrate preincubated with substrate for 15 mins and measured every min for 30 mins by Lineweaver-Burk plot analysis	ki	1.3000	uM
(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	1415008: Non-competitive inhibition of N-terminal MBP-fused human NEU2 expressed in Escherichia coli using 4MU-NANA as substrate preincubated with substrate for 15 mins and measured every min for 30 mins by Lineweaver-Burk plot analysis	ki	2.1000	uM
(2R,3R,4S)-4-hydroxy-3-[[2-[4-(4-methylphenyl)triazol-1-yl]acetyl]amino]-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415008: Non-competitive inhibition of N-terminal MBP-fused human NEU2 expressed in Escherichia coli using 4MU-NANA as substrate preincubated with substrate for 15 mins and measured every min for 30 mins by Lineweaver-Burk plot analysis	ki	2.7000	uM
Zanamivir	1889675: Inhibition of NEU2 (unknown origin) using Neu5Acalpha2-6GalbetapNP as substrate incubated for 30 mins	ic50	3.9000	uM
(2R,3R,4S)-3-[[2-[4-(4-fluorophenyl)triazol-1-yl]acetyl]amino]-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415002: Inhibition of N-terminal MBP-fused human NEU2 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	4.5000	uM
(2R,3R,4S)-3-acetamido-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	728982: Inhibition of human neuraminidase 2 expressed in Escherichia coli using 4MU-NANA as substrate measured for every 30 seconds for 60 mins by fluorescence assay	ki	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	1490017: Inhibition of human N-terminal MBP-fused NEU2 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	5.9000	uM
(2R,3R,4S)-4-hydroxy-3-(4-methylpentanoylamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	1415002: Inhibition of N-terminal MBP-fused human NEU2 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	7.3000	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	1889674: Inhibition of NEU2 (unknown origin) using Neu5Acalpha2-3GalbetapNP as substrate incubated for 30 mins	ic50	8.3000	uM
(2R,3R,4S)-4-hydroxy-3-[[2-(4-phenyltriazol-1-yl)acetyl]amino]-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid	748620: Inhibition of human NEU2 using 4-MU-NANA as substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence plate reader analysis	ic50	9.0000	uM

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Valproic Acid	increases methylation	1
Lactic Acid	decreases expression	1
Particulate Matter	increases expression, increases abundance	1

ChEMBL screening assays

38 unique, capped per target: 38 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1060573	Binding	Inhibition of human NEU2 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.