HEXB

Summary

HEXB (hexosaminidase subunit beta, HGNC:4879) is a protein-coding gene on chromosome 5q13.3, encoding Beta-hexosaminidase subunit beta (P07686). Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides.

Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3074 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Sandhoff disease (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 951 total — 108 pathogenic, 95 likely-pathogenic
• Phenotypes (HPO): 82
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000521

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4879
Approved symbol	HEXB
Name	hexosaminidase subunit beta
Location	5q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000049860
Ensembl biotype	protein_coding
OMIM	606873
Entrez	3074

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 retained_intron, 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261416, ENST00000503312, ENST00000504459, ENST00000505859, ENST00000509579, ENST00000510820, ENST00000511181, ENST00000511621, ENST00000513079, ENST00000513336, ENST00000513539, ENST00000513867, ENST00000515528

RefSeq mRNA: 2 — MANE Select: NM_000521 NM_000521, NM_001292004

CCDS: CCDS4022, CCDS78021

Canonical transcript exons

ENST00000261416 — 14 exons

Exon	Start	End
ENSE00001031135	74713506	74713635
ENSE00001083771	74685233	74685559
ENSE00001171600	74721118	74721288
ENSE00003463471	74696693	74696739
ENSE00003472112	74689328	74689473
ENSE00003487626	74693639	74693704
ENSE00003504641	74715510	74715690
ENSE00003512042	74720428	74720518
ENSE00003549476	74716587	74716673
ENSE00003602471	74718797	74718971
ENSE00003615845	74718291	74718363
ENSE00003673440	74696996	74697106
ENSE00003680120	74720643	74720747
ENSE00003682143	74705219	74705320

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.1349 / max 1890.7255, expressed in 1823 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57065	32.6427	1812
57062	19.0914	1803
57064	15.1228	1786
57061	1.3959	947
57063	0.5155	268
57066	0.3666	177

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	99.26	gold quality
stromal cell of endometrium	CL:0002255	99.20	gold quality
calcaneal tendon	UBERON:0003701	99.01	gold quality
decidua	UBERON:0002450	98.86	gold quality
monocyte	CL:0000576	98.83	gold quality
islet of Langerhans	UBERON:0000006	98.81	gold quality
type B pancreatic cell	CL:0000169	98.77	gold quality
mononuclear cell	CL:0000842	98.71	gold quality
corpus epididymis	UBERON:0004359	98.67	gold quality
tendon of biceps brachii	UBERON:0008188	98.67	gold quality
leukocyte	CL:0000738	98.63	gold quality
synovial joint	UBERON:0002217	98.62	gold quality
tendon	UBERON:0000043	98.57	gold quality
gall bladder	UBERON:0002110	98.50	gold quality
visceral pleura	UBERON:0002401	98.47	gold quality
mucosa of transverse colon	UBERON:0004991	98.47	gold quality
rectum	UBERON:0001052	98.45	gold quality
endocervix	UBERON:0000458	98.42	gold quality
oocyte	CL:0000023	98.39	gold quality
layer of synovial tissue	UBERON:0007616	98.36	gold quality
body of pancreas	UBERON:0001150	98.34	gold quality
descending thoracic aorta	UBERON:0002345	98.34	gold quality
right lung	UBERON:0002167	98.32	gold quality
ascending aorta	UBERON:0001496	98.17	gold quality
thoracic aorta	UBERON:0001515	98.17	gold quality
minor salivary gland	UBERON:0001830	98.17	gold quality
secondary oocyte	CL:0000655	98.16	gold quality
upper lobe of left lung	UBERON:0008952	98.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.12	gold quality
upper lobe of lung	UBERON:0008948	98.10	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	68.98
E-MTAB-6678	yes	17.77
E-CURD-112	yes	15.61
E-GEOD-93593	yes	8.85
E-MTAB-6075	no	1065.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CCL3	Activation

miRNA regulators (miRDB)

7 targeting HEXB, 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-3613-3P	100.00	76.36	7965
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-508-3P	98.66	69.62	887

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• plasma activity of total Hex does not appear to be a reliable marker of erosion and cartilage degradation in rheumatoid arthritis patients; liver function appears to be the major determinant for the plasma Hex activity in these patients (PMID:12413610)
• The X-ray crystal structure of beta-hexosaminidase B provides new insights into mutations that cause Sandhoff disease. (PMID:12706724)
• alpha-subunit loop structure is required for GM2 activator protein binding by beta-hexosaminidase A (PMID:15485660)
• Therefore, our bicistronic lentivector supplying both alpha- and beta-subunits of beta-hexosaminidases may provide a potential therapeutic tool for the treatment of Sandhoff disease. (PMID:15953731)
• The highest activities of exoglycosidases were observed in high-grade gliomas, and a positive correlation of enzyme activities and degree of malignancy was noted. (PMID:16710745)
• novel c.1556A>G transition in exon 12 of the HEXB gene associated with chronic Sandhoff’s disease (PMID:17251047)
• Beta-hexosaminidase is a peptidoglycan hydrolase that surprisingly exerts its mycobactericidal effect at the macrophage plasma membrane during mycobacteria-induced secretion of lysosomes (PMID:18180457)
• Elevated activity of beta-hexosaminidase observed in subjects with asthma suggests that the beta-hex isozyme could take part in airway inflammation and remodeling in asthma. (PMID:18204279)
• following HIV infection, there is an increased rate of catabolism of glycoconjugates in saliva resulting from changes in the proportions of the activity of isoenzymes A and B of N-acetyl-beta-hexosaminidase, beta-galactosidase and alpha-fucosidase (PMID:18217416)
• Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED. (PMID:18552385)
• These results reveal a new aspect of beta-hexosaminidase biology and suggest that a fully processed membrane-associated form of Hex is translocated from the lysosomal membrane to the PM by an as yet unknown mechanism. W (PMID:18588514)
• Results describe the molecular genetics of Sandhoff disease in Italy and provide new insights into the molecular basis of the disease through HEXB mutation. (PMID:18758829)
• A new D459A missense HEXB mutation was discovered in six juvenile patients with Sandhoff disease. (PMID:18930675)
• Gene therapy reduced GM(2) storage and ameliorated neuroinflammation in the brain of HexB(-/-) mice, as well as attenuated behavioral deficits. (PMID:19278737)
• Data suggest that cigarette smoking can inhibit, by the influence on N-acetyl-beta-hexosaminidase activity, catabolism of oligosaccharide chains in cancer tissues. (PMID:19615986)
• Urinary NAG (ninefold), NGAL (1.5-fold), and H-FABP (3.5-fold) were significantly elevated in normoalbuminuric diabetic patients compared with nondiabetic control subjects. (PMID:21307379)
• Plasma beta-hexosaminidase and beta-galactosidase) levels are higher in patients with Alzheimer’s disease-type 2 diabetes mellitus (T2DM) compared to those with T2DM alone. (PMID:21321400)
• Down-regulation of beta-N-acetyl-D-glucosaminidase increases Akt1 activity in thyroid anaplastic cancer cells (PMID:21637923)
• The non-random distribution of plasma membrane-associated beta-hexosaminidase and beta-galactosidase and their localization within lipid microdomains, suggest a role of these enzymes in the local reorganization of glycosphingolipid-based signalling units. (PMID:21978926)
• The absence of beta-N-acetyl-hexosaminidase activity does not alter the differentiation of i-DCs from HSCs, but it is critical for the activation of CD4(+)T cells because knock-down of HEXA or HEXB gene causes a loss of function of i-DCs. (PMID:21997228)
• We describe a novel HEXB mutation that is shared among 4 patients with Sandhoff disease. (PMID:22191674)
• identified 27 different mutations, 14 of which were novel, in the HEXA gene and 14 different mutations, 8 of which unreported until now, in the HEXB gene, and attempted to correlate these mutations with the clinical presentation of the patients (PMID:22789865)
• minigene studies revealed the presence of a novel alternative spliced HEXB mRNA variant also present in normal cells (PMID:22848519)
• Expression of beta-hexosaminidase in the neurons of Sandhoff disease patients rescues transgenic mice from neurodegeneration. (PMID:22863301)
• Characterization of seven novel mutations on the HEXB gene in French Sandhoff patients. (PMID:23046579)
• GM2 gangliosidosis is caused by the gene mutation. (review) (PMID:23370522)
• A patient with Sandhoff disease also is found to have a compound macro-deletion in HEXB. (PMID:23886397)
• A highly significant correlation of HEX-7 and %CDT has been found. Because of exclusion of the P isoform, HEX-7 could be a useful supplementary marker for detecting chronic alcohol abuse. (PMID:23906468)
• Concentration and specific activity of N-acetyl-B-hexosaminidase in palatine tonsils in patients with tonsillar hypertrophy and chronic tonsillitis both in childhood and adulthood significantly increase in comparison to healthy individuals. (PMID:23911049)
• A total of 19 HEXB variants were found in the 1092 genomes of which 5 are suspected of having a deleterious effect on hexosaminidase activity. (PMID:24461908)
• DNA from Iranian Tay-Sachs patients reveals a novel mutation in HEXB predicting a termination codon or nonsense mutation. (PMID:24518553)
• report on the heterogeneity of the mutational spectrum of the HEXB gene in Indian patients with Sandhoff disease (PMID:26582265)
• a modified human hexosaminidase subunit beta (HexB), which we have termed mod2B, composed of homodimeric beta subunits that contain amino acid sequences from the alpha subunit that confer GM2 ganglioside-degrading activity and protease resistance. (PMID:27018595)
• Mutations of the HEXB gene is associated with maple syrup urine disease or Sandhoff disease. (PMID:27682710)
• Reported data present, for the first time, reference values for urinary activities of HEX and its isoenzymes HEX A and HEX B in children and adolescent. (PMID:28846871)
• Direct sequencing of HEXA and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and c.850C>T (p.Arg284Ter) in gangliosidosis, respectively (PMID:29448188)
• Novel bicistronic lentiviral vectors correct beta-Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis. (PMID:31682993)
• identified a homozygous splice site variant (NM_000521:c.445 + 1G > T) in the hexosaminidase B (HEXB) gene confirming a diagnosis of Sandhoff disease (SD; type II GM2-gangliosidosis), an autosomal recessive lysosomal storage disorder caused by deficiency of hexosaminidases in a single family (PMID:31852446)
• Clinical and Molecular Characteristics of Two Chinese Children with Infantile Sandhoff Disease and Review of the Literature. (PMID:31919734)
• Infantile onset Sandhoff disease: clinical manifestation and a novel common mutation in Thai patients. (PMID:33407268)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hexb	ENSDARG00000034368
mus_musculus	Hexb	ENSMUSG00000021665
rattus_norvegicus	Hexb	ENSRNOG00000025274
drosophila_melanogaster	Hexo2	FBGN0041629
drosophila_melanogaster	Hexo1	FBGN0041630
drosophila_melanogaster	fdl	FBGN0045063
caenorhabditis_elegans		WBGENE00020509

Paralogs (1): HEXA (ENSG00000213614)

Protein

Protein identifiers

Beta-hexosaminidase subunit beta — P07686 (reviewed: P07686)

Alternative names: Beta-N-acetylhexosaminidase subunit beta, Cervical cancer proto-oncogene 7 protein, N-acetyl-beta-glucosaminidase subunit beta

All UniProt accessions (6): D6REQ8, P07686, H0Y9B6, H0Y9M3, H0YA83, Q5URX0

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides. The isozyme B does not hydrolyze each of these substrates, however hydrolyzes efficiently neutral oligosaccharide. Only the isozyme A is responsible for the degradation of GM2 gangliosides in the presence of GM2A. During fertilization is responsible, at least in part, for the zona block to polyspermy. Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and inactivates the sperm galactosyltransferase-binding site, accounting for the block in sperm binding to the zona pellucida.

Subunit / interactions. There are 3 forms of beta-hexosaminidase: hexosaminidase A is a heterodimer composed of one subunit alpha and one subunit beta (chain A and B); hexosaminidase B is a homodimer of two beta subunits (two chains A and B); hexosaminidase S is a homodimer of two alpha subunits. The composition of the dimer (isozyme A versus isozyme S) has a significant effect on the substrate specificity of the alpha subunit active site.

Subcellular location. Lysosome. Cytoplasmic vesicle. Secretory vesicle. Cortical granule.

Post-translational modifications. N-linked glycans at Asn-142 and Asn-190 consist of Man(3)-GlcNAc(2) and Man(5 to 7)-GlcNAc(2), respectively. The beta-A and beta-B chains are produced by proteolytic processing of the precursor beta chain.

Disease relevance. GM2-gangliosidosis 2 (GM2G2) [MIM:268800] An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. Clinically indistinguishable from GM2-gangliosidosis type 1, presenting startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Addition of GM2A stimulates the hydrolysis of sulfated glycosphingolipid SM2 and the ganglioside GM2.

Similarity. Belongs to the glycosyl hydrolase 20 family.

RefSeq proteins (2): NP_000512, NP_001278933 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015883	GH20_cat	Domain
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR025705	GH20	Family
IPR029018	Hex-like_dom2	Homologous_superfamily
IPR029019	HEX_eukaryotic_N	Domain

Pfam: PF00728, PF14845

Enzyme classification (BRENDA):

• EC 3.2.1.52 — beta-N-acetylhexosaminidase (BRENDA: 145 organisms, 466 substrates, 704 inhibitors, 351 Km, 150 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
P-NITROPHENYL-BETA-2-ACETAMIDO-2-DEOXY-D-GLUCOPY	0.04–18.8	59
P-NITROPHENYL-BETA-2-ACETAMIDO-2-DEOXY-D-GALACTO	0.04–7.8	47
4-NITROPHENYL N-ACETYL-BETA-D-GLUCOSAMINE	0.026–101.1	35
4-NITROPHENYL N-ACETYL-BETA-D-GLUCOSAMINIDE	0.04–4.15	31
4-METHYLUMBELLIFERYL N-ACETYL-BETA-D-GLUCOSAMINI	0.07–1.22	10
4-NITROPHENYL N-ACETYL-BETA-D-GALACTOSAMINIDE	0.0525–3.29	10
4-METHYLUMBELLIFERYL-2-ACETAMIDO-2-DEOXY-BETA-D-	0.11–1	9
(N-ACETYL-BETA-D-GLUCOSAMINE)3	0.05–8	6
4-NITROPHENYL BETA-N-ACETYL-D-GLUCOSAMINIDE	0.0027–4.15	6
4-NITROPHENYL N-ACETYL-BETA-D-GALACTOSAMINE	0.124–0.975	6
N-ACETYLGLUCOSAMINYL-BETA-1,2-MAN	0.98–1.51	6
P-NITROPHENYL-N-ACETYL-BETA-D-GLUCOSAMINIDE	0.0846–3	6
(N-ACETYL-BETA-D-GLUCOSAMINE)2	0.117–4.1	5
4-NITROPHENYL BETA-N-ACETYL-D-GALACTOSAMINIDE	0.25–11.1	5
4-NITROPHENYL-N-ACETYL-BETA-D-GLUCOSAMINIDE	0.025–8.57	5

Catalyzed reactions (Rhea), 5 shown:

• a ganglioside GM2 (d18:1(4E)) + H2O = a ganglioside GM3 (d18:1(4E)) + N-acetyl-beta-D-galactosamine (RHEA:47940)
• a ganglioside GM2 + H2O = a ganglioside GM3 + N-acetyl-beta-D-galactosamine (RHEA:47968)
• N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-3-sulfogalactosyl-(1->4)-beta-D-glucosyl-(1<->1’)-ceramide + H2O = a beta-D-3-sulfogalactosyl-(1->4)-beta-D-glucosyl-(1<->1’)-ceramide + N-acetyl-beta-D-galactosamine (RHEA:48276)
• beta-D-GalNAc-(1->4)-alpha-L-IdoA-(1->3)-beta-D-GalNAc-4-sulfate-(1->4)-alpha-L-IdoA-(1->3)-D-GalNAc-4-sulfate + H2O = alpha-L-IdoA-(1->3)-beta-D-GalNAc-4-sulfate-(1->4)-alpha-L-IdoA-(1->3)-D-GalNAc-4-sulfate + N-acetyl-D-galactosamine (RHEA:64372)
• N-acetyl-beta-D-6-sulfogalactosaminyl-(1->4)-alpha-L-iduronyl-(1->3)-N-acetyl-D-6-sulfogalactosamine + H2O = alpha-L-iduronyl-(1->3)-N-acetyl-D-6-sulfogalactosamine + N-acetyl-D-6-sulfogalactosamine (RHEA:64384)

UniProt features (73 total): strand 22, helix 20, sequence variant 11, mutagenesis site 5, glycosylation site 4, disulfide bond 3, chain 3, signal peptide 1, propeptide 1, active site 1, site 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
1NOW	X-RAY DIFFRACTION	2.2
1O7A	X-RAY DIFFRACTION	2.25
1NOU	X-RAY DIFFRACTION	2.4
5BRO	X-RAY DIFFRACTION	2.4
1NP0	X-RAY DIFFRACTION	2.5
2GJX	X-RAY DIFFRACTION	2.8
3LMY	X-RAY DIFFRACTION	2.8
2GK1	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07686-F1	93.12	0.85

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 (2): 355 (proton donor); 497 (not glycosylated)

Disulfide bonds (3): 91–137, 309–360, 534–551

Glycosylation sites (4): 327, 84, 142, 190

Mutagenesis-validated functional residues (5):

Position	Phenotype
211	does not affect the native conformation of the isozyme a. does not affect hydrolysis of gm2 ganglioside by the isozyme a
241	2.7-fold reduction in substrate affinity. 39-fold reduction in catalytic efficiency.
354	no effect on substrate affinity. 1750-fold reduction in catalytic efficiency.
355	1.5-fold increase in substrate affinity. 2300-fold reduction in catalytic efficiency. reduces optimal ph to 3-3.5.
491	no effect on substrate affinity and on catalytic efficiency.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-2022857	Keratan sulfate degradation
R-HSA-2024101	CS/DS degradation
R-HSA-2160916	Hyaluronan degradation
R-HSA-3656248	Defective HEXB causes GM2G2 (Hyaluronan metabolism)
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism

MSigDB gene sets: 505 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_SINGLE_FERTILIZATION, GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_N_GLYCAN_PROCESSING, ZHAN_LATE_DIFFERENTIATION_GENES_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_VACUOLE_ORGANIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_SECRETORY_GRANULE, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION

GO Biological Process (30): skeletal system development (GO:0001501), N-acetylglucosamine metabolic process (GO:0006044), N-glycan processing (GO:0006491), ganglioside catabolic process (GO:0006689), intracellular calcium ion homeostasis (GO:0006874), lysosome organization (GO:0007040), single fertilization (GO:0007338), penetration of zona pellucida (GO:0007341), sensory perception of sound (GO:0007605), locomotory behavior (GO:0007626), male courtship behavior (GO:0008049), regulation of cell shape (GO:0008360), phospholipid biosynthetic process (GO:0008654), oligosaccharide catabolic process (GO:0009313), lipid storage (GO:0019915), glycosaminoglycan metabolic process (GO:0030203), chondroitin sulfate proteoglycan catabolic process (GO:0030207), dermatan sulfate proteoglycan catabolic process (GO:0030209), hyaluronan catabolic process (GO:0030214), myelination (GO:0042552), astrocyte cell migration (GO:0043615), positive regulation of transcription by RNA polymerase II (GO:0045944), oogenesis (GO:0048477), neuromuscular process controlling balance (GO:0050885), neuron cellular homeostasis (GO:0070050), carbohydrate metabolic process (GO:0005975), lipid metabolic process (GO:0006629), glycosphingolipid metabolic process (GO:0006687), neuromuscular process (GO:0050905), carbohydrate derivative metabolic process (GO:1901135)

GO Molecular Function (11): beta-N-acetylhexosaminidase activity (GO:0004563), acetylglucosaminyltransferase activity (GO:0008375), beta-N-acetylglucosaminidase activity (GO:0016231), carbohydrate binding (GO:0030246), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), protein binding (GO:0005515), hexosaminidase activity (GO:0015929), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (12): acrosomal vesicle (GO:0001669), extracellular region (GO:0005576), lysosome (GO:0005764), membrane (GO:0016020), azurophil granule lumen (GO:0035578), azurophil granule (GO:0042582), lysosomal lumen (GO:0043202), cortical granule (GO:0060473), extracellular exosome (GO:0070062), beta-N-acetylhexosaminidase complex (GO:1905379), obsolete extracellular space (GO:0005615), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Keratan sulfate/keratin metabolism	1
Chondroitin sulfate/dermatan sulfate metabolism	1
Hyaluronan metabolism	1
Diseases associated with glycosaminoglycan metabolism	1
Innate Immune System	1
Glycosphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
secretory granule	3
proteoglycan catabolic process	2
cellular anatomical structure	2
vacuolar lumen	2
system development	1
amino sugar metabolic process	1
protein N-linked glycosylation	1
glycoprotein biosynthetic process	1
ganglioside metabolic process	1
glycosphingolipid catabolic process	1
ceramide catabolic process	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
lytic vacuole organization	1
fertilization	1
single fertilization	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
sensory perception of mechanical stimulus	1
behavior	1
courtship behavior	1
male mating behavior	1
regulation of cell morphogenesis	1
regulation of biological quality	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
oligosaccharide metabolic process	1
carbohydrate catabolic process	1
nutrient storage	1
aminoglycan metabolic process	1
chondroitin sulfate proteoglycan metabolic process	1
dermatan sulfate proteoglycan metabolic process	1
glycosaminoglycan catabolic process	1
hyaluronan metabolic process	1
axon ensheathment	1
hexosaminidase activity	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEXB	ENC1	O14682	912
HEXB	OGA	O60502	814
HEXB	GM2A	P17900	813
HEXB	LARS1	Q9P2J5	492
HEXB	GLB1	P16278	430
HEXB	TMEM119	Q4V9L6	418
HEXB	KIAA1191	Q96A73	412
HEXB	RPS14	P06366	399
HEXB	NAGA	P17050	399
HEXB	NEU1	Q99519	390
HEXB	MRPL3	P09001	373
HEXB	FUCA1	P04066	363
HEXB	ARSI	Q5FYB1	349
HEXB	ARSK	Q6UWY0	348
HEXB	GNPTAB	Q3T906	347
HEXB	FUT8	Q9BYC5	347

IntAct

113 interactions, top by confidence:

A	B	Type	Score
HEXB	HEXA	psi-mi:“MI:0407”(direct interaction)	0.730
HEXA	HEXB	psi-mi:“MI:0407”(direct interaction)	0.730
HEXA	HEXB	psi-mi:“MI:0914”(association)	0.730
HEXA	HEXB	psi-mi:“MI:0915”(physical association)	0.730
HEXB	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
HEXB	FAM210B	psi-mi:“MI:0915”(physical association)	0.560
HEXB	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
XIAP	HEXB	psi-mi:“MI:0915”(physical association)	0.560
UBL3	HEXB	psi-mi:“MI:0915”(physical association)	0.560
HEXB	CAPN15	psi-mi:“MI:0915”(physical association)	0.560
HEXB	TLE1	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	HEXB	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	HEXB	psi-mi:“MI:0915”(physical association)	0.560
HEXB	ZBTB16	psi-mi:“MI:0915”(physical association)	0.560
COPS3	HEXB	psi-mi:“MI:0915”(physical association)	0.560
HEXB	PIAS1	psi-mi:“MI:0915”(physical association)	0.560
NAE1	HEXB	psi-mi:“MI:0915”(physical association)	0.560
WWP2	HEXB	psi-mi:“MI:0915”(physical association)	0.560
RCHY1	HEXB	psi-mi:“MI:0915”(physical association)	0.560
HEXB	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
HEXB	UBQLN3	psi-mi:“MI:0915”(physical association)	0.560
ASB3	HEXB	psi-mi:“MI:0915”(physical association)	0.560
OTUB1	HEXB	psi-mi:“MI:0915”(physical association)	0.560
NXF2B	HEXB	psi-mi:“MI:0915”(physical association)	0.560
HEXB	KLHL36	psi-mi:“MI:0915”(physical association)	0.560
HEXB	LNX1	psi-mi:“MI:0915”(physical association)	0.560
HEXB	RNF183	psi-mi:“MI:0915”(physical association)	0.560
HEXB	UBQLNL	psi-mi:“MI:0915”(physical association)	0.560
UBR1	HEXB	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1396): HEXB (Affinity Capture-MS), HEXB (Co-fractionation), STIM1 (Co-fractionation), STIM2 (Co-fractionation), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Affinity Capture-MS), HEXB (Co-crystal Structure)

ESM2 similar proteins: A5D6U8, O23244, O48840, O97860, P06865, P07686, P08236, P09889, P13686, P20060, P29240, P29288, P29416, P49614, P80366, Q05117, Q0V8R6, Q38924, Q53F39, Q5MAU8, Q5R5N6, Q5RC84, Q5RET5, Q5RFI5, Q641X3, Q641Z7, Q687E1, Q6AYS4, Q6TPH1, Q6ZNF0, Q8BX37, Q8H1R2, Q8S340, Q8S341, Q8VYU7, Q8VYZ2, Q93WP4, Q949Y3, Q99KR8, Q9BTY2

Diamond homologs: A7WM73, E9DFH0, P06865, P07686, P13670, P13723, P20060, P29416, P49009, P49010, P49614, Q06GJ0, Q0V8R6, Q22492, Q29548, Q54K55, Q54K56, Q54SC9, Q5RC84, Q619W7, Q641X3, Q6AXR4, Q86M34, Q8J2T0, Q8L7S6, Q8WSF3, Q9HGI3, Q9SYK0, D4AYT4, P43077, B2UPR7, H2A0L6, P86956, Q54468, B2UQG6, P96155, D4AUH6, P53915

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of DNA damage response and repair proteins	5	17.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
ubiquitin-dependent protein catabolic process	7	9.1×	3e-03
protein ubiquitination	10	7.3×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	108
Likely pathogenic	95
Uncertain significance	229
Likely benign	386
Benign	41

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012509	NM_000521.4(HEXB):c.876del (p.His294fs)	Pathogenic
1012510	NM_000521.4(HEXB):c.1165dup (p.Gln389fs)	Pathogenic
1069640	NM_000521.4(HEXB):c.1144A>T (p.Lys382Ter)	Pathogenic
1070002	NM_000521.4(HEXB):c.1156_1159del (p.Phe386fs)	Pathogenic
1070441	NM_000521.4(HEXB):c.1017_1018del (p.Glu339fs)	Pathogenic
1070612	NC_000005.9:g.(?73981066)(74017020_?)del	Pathogenic
1070645	NM_000521.4(HEXB):c.782_785del (p.Ser261fs)	Pathogenic
1071217	NM_000521.4(HEXB):c.1578T>G (p.Tyr526Ter)	Pathogenic
1073343	NM_000521.4(HEXB):c.1299_1303del (p.Arg435fs)	Pathogenic
1074051	NM_000521.4(HEXB):c.1389_1393del (p.Tyr463_Lys465delinsTer)	Pathogenic
1074772	NM_000521.4(HEXB):c.1586_1589del (p.Leu529fs)	Pathogenic
1379520	NM_000521.4(HEXB):c.1264dup (p.Glu422fs)	Pathogenic
1398058	NM_000521.4(HEXB):c.916_917del (p.Leu306fs)	Pathogenic
1405131	NC_000005.9:g.(?74011325)(74017010_?)del	Pathogenic
1415401	NM_000521.4(HEXB):c.1278_1279del (p.Asp426fs)	Pathogenic
1442270	NM_000521.4(HEXB):c.731del (p.Phe244fs)	Pathogenic
1450108	NM_000521.4(HEXB):c.1159_1160insTTTTTTTTTTTTTTTTTTTNNNNNNNNNNTTTTTCTTTTCCTTTTATTTTATTTTTTGAGACGGAGTCTTGCTCTGTTGTCTGGGTGGAGTGCAGTGGTGCAATCTCGGCTCACTGCAACCTCTTCCTCCCAGGTTGAAGCGGAAACTAGAATCTTTCT (p.Tyr387delinsPhePhePhePhePhePheXaaXaaXaaXaaPhePhePheSerPheTyrPheIlePheTer)	Pathogenic
1454030	NM_000521.4(HEXB):c.1024del (p.Glu342fs)	Pathogenic
1455054	NC_000005.9:g.(?73985143)(74014806_?)del	Pathogenic
1458290	NM_000521.4(HEXB):c.1303_1304insT (p.Arg435fs)	Pathogenic
1459374	NM_000521.4(HEXB):c.992_993insAGTATGTA (p.Ser331fs)	Pathogenic
1704505	NC_000005.9:g.(?73980968)(73992932_74001043)del	Pathogenic
1878340	NM_000521.4(HEXB):c.1640dup (p.Tyr547Ter)	Pathogenic
1916265	NM_000521.4(HEXB):c.1431_1432del (p.Lys478fs)	Pathogenic
1951242	NM_000521.4(HEXB):c.1469del (p.Gly490fs)	Pathogenic
1971246	NM_000521.4(HEXB):c.1216C>T (p.Gln406Ter)	Pathogenic
1999812	NM_000521.4(HEXB):c.894G>A (p.Trp298Ter)	Pathogenic
2022764	NM_000521.4(HEXB):c.937C>T (p.Gln313Ter)	Pathogenic
2026408	NM_000521.4(HEXB):c.875dup (p.Gly293fs)	Pathogenic
2089991	NM_000521.4(HEXB):c.758del (p.Glu253fs)	Pathogenic

SpliceAI

2079 predictions. Top by Δscore:

Variant	Effect	Δscore
5:74685546:G:GT	donor_gain	1.0000
5:74689469:GTCTT:G	donor_gain	1.0000
5:74696740:G:GG	donor_gain	1.0000
5:74696991:CATA:C	acceptor_loss	1.0000
5:74696992:ATAGT:A	acceptor_loss	1.0000
5:74696993:T:G	acceptor_gain	1.0000
5:74696994:A:AG	acceptor_gain	1.0000
5:74696994:A:T	acceptor_loss	1.0000
5:74696995:G:GG	acceptor_gain	1.0000
5:74696995:GTT:G	acceptor_gain	1.0000
5:74696995:GTTC:G	acceptor_gain	1.0000
5:74696995:GTTCA:G	acceptor_gain	1.0000
5:74697102:CTCTG:C	donor_gain	1.0000
5:74697103:TCTG:T	donor_gain	1.0000
5:74697105:TGGTA:T	donor_loss	1.0000
5:74697106:GGT:G	donor_loss	1.0000
5:74697107:G:GA	donor_loss	1.0000
5:74697107:G:GG	donor_gain	1.0000
5:74697108:T:A	donor_loss	1.0000
5:74705321:G:GG	donor_gain	1.0000
5:74713505:GGGAA:G	acceptor_gain	1.0000
5:74713631:AAAAG:A	donor_loss	1.0000
5:74713633:AAGGT:A	donor_loss	1.0000
5:74713635:GGTA:G	donor_loss	1.0000
5:74713636:G:A	donor_loss	1.0000
5:74713637:T:A	donor_loss	1.0000
5:74715505:TCTA:T	acceptor_loss	1.0000
5:74715507:TA:T	acceptor_loss	1.0000
5:74715508:A:AG	acceptor_gain	1.0000
5:74715508:A:AT	acceptor_loss	1.0000

AlphaMissense

3633 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:74705255:T:A	W236R	0.997
5:74705255:T:C	W236R	0.997
5:74718932:T:A	W460R	0.996
5:74718932:T:C	W460R	0.996
5:74718934:G:C	W460C	0.996
5:74718934:G:T	W460C	0.996
5:74720517:T:A	W503R	0.996
5:74720517:T:C	W503R	0.996
5:74716587:G:C	W361C	0.995
5:74716587:G:T	W361C	0.995
5:74720653:A:C	S507R	0.995
5:74720655:T:A	S507R	0.995
5:74720655:T:G	S507R	0.995
5:74713567:C:A	A278D	0.994
5:74720674:T:A	W514R	0.994
5:74720674:T:C	W514R	0.994
5:74705259:A:C	H237P	0.993
5:74713626:T:A	W298R	0.993
5:74713626:T:C	W298R	0.993
5:74718334:T:A	W405R	0.993
5:74718334:T:C	W405R	0.993
5:74718899:T:A	W449R	0.993
5:74718899:T:C	W449R	0.993
5:74697046:A:C	R203S	0.992
5:74697046:A:T	R203S	0.992
5:74697059:G:C	D208H	0.992
5:74705258:C:G	H237D	0.992
5:74705291:A:C	S248R	0.992
5:74705293:C:A	S248R	0.992
5:74705293:C:G	S248R	0.992

dbSNP variants (sampled 300 via entrez): RS1000018886 (5:74677867 T>C), RS1000085521 (5:74641939 A>C), RS1000120743 (5:74702289 G>A), RS1000206773 (5:74660018 A>G), RS1000228495 (5:74668971 C>T), RS1000229104 (5:74653223 C>T), RS1000242486 (5:74675109 G>A), RS1000262421 (5:74675449 T>C), RS1000285063 (5:74708919 A>G), RS1000342868 (5:74704849 T>A,C), RS1000385010 (5:74663067 T>C), RS1000394207 (5:74638351 A>G), RS1000472669 (5:74699103 G>A,T), RS1000505114 (5:74699288 T>C), RS1000537965 (5:74681745 A>C)

Disease associations

OMIM: gene MIM:606873 | disease phenotypes: MIM:268800

GenCC curated gene-disease

Disease	Classification	Inheritance
Sandhoff disease	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Sandhoff disease	Definitive	AR

Mondo (4): Sandhoff disease (MONDO:0010006), Sandhoff disease, juvenile form (MONDO:0017722), Sandhoff disease, adult form (MONDO:0017723), Sandhoff disease, infantile form (MONDO:0017721)

Orphanet (4): Sandhoff disease (Orphanet:796), Sandhoff disease, juvenile form (Orphanet:309162), Sandhoff disease, adult form (Orphanet:309169), Sandhoff disease, infantile form (Orphanet:309155)

HPO phenotypes

82 total (30 of 82 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000158	Macroglossia
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000618	Blindness
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000802	Impotence
HP:0000966	Hypohidrosis
HP:0000975	Hyperhidrosis
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001262	Excessive daytime somnolence
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001278	Orthostatic hypotension
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001634	Mitral valve prolapse

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003542_148	Night sleep phenotypes	8.000000e-06
GCST009391_497	Metabolite levels	3.000000e-07
GCST009391_608	Metabolite levels	8.000000e-06
GCST90007004_2	Gut microbiota relative abundance (unassigned genus belonging to family Clostridiales)	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010521	phosphocreatine measurement
EFO:0010505	isocitrate measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D012497	Sandhoff Disease	C10.228.140.163.100.435.825.300.300.249; C16.320.565.189.435.825.300.300.249; C16.320.565.398.641.803.350.300.700; C16.320.565.595.554.825.300.300.800; C18.452.132.100.435.825.300.300.249; C18.452.584.563.641.803.350.300.700; C18.452.648.189.435.825.300.300.249; C18.452.648.398.641.803.350.300.700; C18.452.648.595.554.825.300.300.800

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3038485 (PROTEIN FAMILY), CHEMBL5877 (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: 19,344 (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
CHEMBL36	PYRIMETHAMINE	4	19,344

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

Binding affinities (BindingDB)

18 measured of 19 human assays (19 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[1-(7-{bis[(4-methoxyphenyl)methyl]amino}heptyl)-4,5-dihydroxy-6-(hydroxymethyl)piperidin-3-yl]acetamide, 4	KI	0.69 nM
N-[4,5-dihydroxy-6-(hydroxymethyl)-1-(7-{[(4-methoxyphenyl)methyl]amino}heptyl)piperidin-3-yl]acetamide, 3	KI	1.2 nM
N-[1-(7-aminoheptyl)-4,5-dihydroxy-6-(hydroxymethyl)piperidin-3-yl]acetamide, 2	KI	2.1 nM
Iminocyclitol, 4	KI	24 nM
N-{7-[5-acetamido-3,4-dihydroxy-2-(hydroxymethyl)piperidin-1-yl]heptyl}-5-{2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl}pentanamide, 6	KI	26.7 nM
Iminocyclitol, 3	KI	40 nM
Iminocyclitol, 2	KI	65 nM
Iminocyclitol, 8	KI	100 nM
Iminocyclitol, 1	KI	240 nM
Iminocyclitol, 6	KI	860 nM
2-ACETAMIDO-1,2-DIDEOXYNOJIRMYCIN	KI	1200 nM
[2-[2,3-dihydroxypropyl(methyl)amino]-2-oxoethyl]-dimethyl-tetradecylazanium	IC50	3100 nM	US-10143668: Hydroxy-substituted amino and ammonium derivatives and their medical use
dimethyl-[2-[methyl-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]-2-oxoethyl]-tetradecylazanium	IC50	3800 nM	US-10143668: Hydroxy-substituted amino and ammonium derivatives and their medical use
n-hexadecylphosphocholine	IC50	4200 nM	US-10143668: Hydroxy-substituted amino and ammonium derivatives and their medical use
N-methyl-2-[methyl(tetradecyl)amino]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide	IC50	4900 nM	US-10143668: Hydroxy-substituted amino and ammonium derivatives and their medical use
Iminocyclitol, 10	KI	10000 nM
Iminocyclitol, 9	KI	11000 nM
2-[dodecyl(methyl)amino]-N-methyl-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide	IC50	12300 nM	US-10143668: Hydroxy-substituted amino and ammonium derivatives and their medical use

ChEMBL bioactivities

42 potent at pChembl≥5 of 66 total, top 42 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.26	Kd	54.7	nM	CHEMBL5653589
7.24	ED50	57.12	nM	CHEMBL5653589
7.16	Ki	70	nM	CHEMBL4527453
6.72	Ki	190	nM	CHEMBL257158
6.54	Ki	290	nM	CHEMBL257158
6.20	Ki	630	nM	CHEMBL2385922
6.16	Ki	690	nM	CHEMBL2385089
6.10	Ki	790	nM	CHEMBL4108795
6.03	Ki	930	nM	CHEMBL2385933
5.98	Ki	1040	nM	CHEMBL2385932
5.97	Ki	1080	nM	CHEMBL2385919
5.95	Ki	1130	nM	CHEMBL2385935
5.92	Ki	1200	nM	CHEMBL4448965
5.91	Ki	1230	nM	CHEMBL2385936
5.89	Ki	1300	nM	CHEMBL4443587
5.87	Ki	1350	nM	CHEMBL2385934
5.80	Ki	1600	nM	CHEMBL4452208
5.80	Ki	1600	nM	CHEMBL4435797
5.80	Ki	1600	nM	CHEMBL4473252
5.75	Ki	1800	nM	CHEMBL4454357
5.75	Ki	1800	nM	CHEMBL4548064
5.68	Ki	2090	nM	CHEMBL42904
5.58	Ki	2600	nM	CHEMBL4548738
5.55	Ki	2810	nM	CHEMBL20330
5.52	Ki	3000	nM	CHEMBL2385939
5.51	IC50	3100	nM	CHEMBL2333316
5.51	IC50	3100	nM	PYRIMETHAMINE
5.49	Ki	3220	nM	CHEMBL2333316
5.44	Ki	3600	nM	CHEMBL4483089
5.41	Ki	3900	nM	CHEMBL4113501
5.38	Ki	4200	nM	CHEMBL2385941
5.36	Ki	4390	nM	CHEMBL2385937
5.36	Ki	4400	nM	CHEMBL4555514
5.35	IC50	4500	nM	PYRIMETHAMINE
5.35	Ki	4500	nM	CHEMBL3681909
5.33	Ki	4630	nM	CHEMBL2385921
5.30	Ki	4990	nM	CHEMBL2385924
5.29	Ki	5100	nM	CHEMBL4540913
5.21	Ki	6220	nM	CHEMBL2385923
5.09	Ki	8100	nM	CHEMBL4112447
5.05	IC50	8900	nM	PYRIMETHAMINE
5.04	IC50	9100	nM	PYRIMETHAMINE

PubChem BioAssay actives

54 with measured affinity, of 218 total; 48 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
N-[1-[7-[bis[(4-methoxyphenyl)methyl]amino]heptyl]-4,5-dihydroxy-6-(hydroxymethyl)piperidin-3-yl]acetamide	1799431: Enzyme Inhibition Assay from Article 10.1021/cb100011u: “Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors.”	ki	0.0007	uM
N-[4,5-dihydroxy-6-(hydroxymethyl)-1-[7-[(4-methoxyphenyl)methylamino]heptyl]piperidin-3-yl]acetamide	1799431: Enzyme Inhibition Assay from Article 10.1021/cb100011u: “Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors.”	ki	0.0012	uM
N-[1-(7-aminoheptyl)-4,5-dihydroxy-6-(hydroxymethyl)piperidin-3-yl]acetamide	1799431: Enzyme Inhibition Assay from Article 10.1021/cb100011u: “Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors.”	ki	0.0021	uM
N-[(2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-methylpyrrolidin-2-yl]acetamide	1799473: Inhibition Assay from Article 10.1016/S1074-5521(01)00045-X: “Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis.”	ki	0.0240	uM
N-[7-[5-acetamido-3,4-dihydroxy-2-(hydroxymethyl)piperidin-1-yl]heptyl]-5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanamide	1799431: Enzyme Inhibition Assay from Article 10.1021/cb100011u: “Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors.”	ki	0.0267	uM
N-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]acetamide	1799473: Inhibition Assay from Article 10.1016/S1074-5521(01)00045-X: “Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis.”	ki	0.0400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148502: Binding affinity to human HEXB incubated for 45 mins by Kinobead based pull down assay	kd	0.0547	uM
N-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-methylpyrrolidin-2-yl]acetamide	1799473: Inhibition Assay from Article 10.1016/S1074-5521(01)00045-X: “Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis.”	ki	0.0650	uM
(3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol	1558056: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl 2-acetamido-2-deoxy-beta-D-glucopyranoside as substrate incubated for 30 mins by fluorescence spectrophotometry	ki	0.0700	uM
(3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol	1533277: Inhibition of human HexB	ki	0.1900	uM
N-[(2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]acetamide	1799473: Inhibition Assay from Article 10.1016/S1074-5521(01)00045-X: “Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis.”	ki	0.2400	uM
N-[(3S,4R,5R,6R)-4,5-dihydroxy-6-(hydroxymethyl)piperidin-3-yl]acetamide	1799431: Enzyme Inhibition Assay from Article 10.1021/cb100011u: “Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors.”	ki	0.5400	uM
2-[2-[(4-methoxyphenyl)methylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	0.6300	uM
2-[2-[2-(3,4-dimethoxyphenoxy)ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	0.6900	uM
(3aR,5S,6S,7R,7aR)-5-(fluoromethyl)-2-methylimino-1,3a,5,6,7,7a-hexahydropyrano[3,2-d][1,3]thiazole-6,7-diol	1558064: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide dihydrate as substrate measured every 60 sec for 45 mins by fluorescence spectrophotometry	ki	0.7900	uM
N-[4,5-dihydroxy-6-(hydroxymethyl)-1-methylpiperidin-3-yl]acetamide	1799473: Inhibition Assay from Article 10.1016/S1074-5521(01)00045-X: “Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis.”	ki	0.8600	uM
2-[2-[2-(3-methoxyphenoxy)ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	0.9300	uM
2-[2-[2-(4-methoxyphenoxy)ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	1.0400	uM
2-[2-[2-(4-methoxyanilino)ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	1.0800	uM
2-[2-[2-(4-methoxyphenyl)sulfanylethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	1.1300	uM
N-[(2S,3R,4R,5S,6R)-2-[2-[2-(6-chloro-1,3-dioxobenzo[de]isoquinolin-2-yl)ethylamino]ethylsulfanyl]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	1533272: Inhibition of recombinant human His6-tagged HexB expressed in Pichia pastoris using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis	ki	1.2000	uM
2-[2-[3-(4-methoxyphenoxy)propylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	1.2300	uM
(3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol	1558064: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide dihydrate as substrate measured every 60 sec for 45 mins by fluorescence spectrophotometry	ki	1.3000	uM
2-[2-[2-(2-methoxyphenoxy)ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	1.3500	uM
N-[(2S,3R,4R,5S,6R)-2-[2-[3-(6-chloro-1,3-dioxobenzo[de]isoquinolin-2-yl)propylamino]ethylsulfanyl]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	1533272: Inhibition of recombinant human His6-tagged HexB expressed in Pichia pastoris using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis	ki	1.6000	uM
N-[(2S,3R,4R,5S,6R)-2-[3-[2-(6-chloro-1,3-dioxobenzo[de]isoquinolin-2-yl)ethylamino]propylsulfanyl]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	1533272: Inhibition of recombinant human His6-tagged HexB expressed in Pichia pastoris using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis	ki	1.6000	uM
(3aR,5S,6S,7R,7aR)-2-(dimethylamino)-5-(fluoromethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol	1558064: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide dihydrate as substrate measured every 60 sec for 45 mins by fluorescence spectrophotometry	ki	1.6000	uM
N-[1-(7-azidoheptyl)-4,5-dihydroxy-6-(hydroxymethyl)piperidin-3-yl]acetamide	1799431: Enzyme Inhibition Assay from Article 10.1021/cb100011u: “Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors.”	ki	1.7000	uM
N-[(2S,3R,4R,5S,6R)-2-[3-[3-(6-chloro-1,3-dioxobenzo[de]isoquinolin-2-yl)propylamino]propylsulfanyl]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	1533272: Inhibition of recombinant human His6-tagged HexB expressed in Pichia pastoris using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis	ki	1.8000	uM
N-[(2S,3R,4R,5S,6R)-2-[2-[3-(6-bromo-1,3-dioxobenzo[de]isoquinolin-2-yl)propylamino]ethylsulfanyl]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	1533272: Inhibition of recombinant human His6-tagged HexB expressed in Pichia pastoris using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis	ki	1.8000	uM
2-(2-aminoethyl)benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	2.0900	uM
N-[(2S,3R,4R,5S,6R)-2-[2-[2-(6-bromo-1,3-dioxobenzo[de]isoquinolin-2-yl)ethylamino]ethylsulfanyl]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	1533272: Inhibition of recombinant human His6-tagged HexB expressed in Pichia pastoris using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis	ki	2.6000	uM
2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	2.8100	uM
2-[2-[2-(1,3-benzodioxol-5-yloxy)ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	3.0000	uM
2-[2-[2-(1,3-dioxobenzo[de]isoquinolin-2-yl)ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748368: Competitive inhibition of human beta-N-acetyl-D-hexosaminidase-B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate assessed as release of 4-Methylumbelliferyl fluorophore measured for 7 mins	ic50	3.1000	uM
Pyrimethamine	1227098: Inhibition of human placental HexA using MUGS substrate incubated for 1 to 2 hrs at pH 7.0 by spectrofluorometry	ic50	3.1000	uM
(3aR,5R,6S,7R,7aR)-2-[ethyl(methyl)amino]-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol	1558064: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide dihydrate as substrate measured every 60 sec for 45 mins by fluorescence spectrophotometry	ki	3.6000	uM
(3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol	1558064: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide dihydrate as substrate measured every 60 sec for 45 mins by fluorescence spectrophotometry	ki	3.9000	uM
methyl 4-[2-[2-(1,3-dioxobenzo[de]isoquinolin-2-yl)ethylamino]ethoxy]benzoate	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	4.2000	uM
2-[2-[3-(3-methoxyphenoxy)propylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	4.3900	uM
N-[(2S,3R,4R,5S,6R)-2-[3-[3-(6-bromo-1,3-dioxobenzo[de]isoquinolin-2-yl)propylamino]propylsulfanyl]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	1533272: Inhibition of recombinant human His6-tagged HexB expressed in Pichia pastoris using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis	ki	4.4000	uM
(3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-2-[methyl(prop-2-enyl)amino]-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol	1558064: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide dihydrate as substrate measured every 60 sec for 45 mins by fluorescence spectrophotometry	ki	4.5000	uM
2-[2-[2-(2,4-dimethoxyanilino)ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	4.6300	uM
2-[2-[(3,4-dimethoxyphenyl)methylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	4.9900	uM
[(2R,3S,4R,5S)-5-acetamido-3,4-dihydroxy-1-methylpyrrolidin-2-yl] sulfate	1799473: Inhibition Assay from Article 10.1016/S1074-5521(01)00045-X: “Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis.”	ki	5.0000	uM
N-[(2S,3R,4R,5S,6R)-2-[3-[2-(6-bromo-1,3-dioxobenzo[de]isoquinolin-2-yl)ethylamino]propylsulfanyl]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	1533272: Inhibition of recombinant human His6-tagged HexB expressed in Pichia pastoris using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis	ki	5.1000	uM
2-[2-[(3-methoxyphenyl)methylamino]ethyl]benzo[de]isoquinoline-1,3-dione	748372: Inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate incubated for 10 mins prior to substrate addition by spectrofluorometric analysis	ki	6.2200	uM
(3aR,5R,6R,7R,7aR)-7-fluoro-5-(hydroxymethyl)-2-methylimino-1,3a,5,6,7,7a-hexahydropyrano[3,2-d][1,3]thiazol-6-ol	1558064: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide dihydrate as substrate measured every 60 sec for 45 mins by fluorescence spectrophotometry	ki	8.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression, decreases reaction	5
bisphenol F	increases expression, affects cotreatment	2
sodium arsenite	increases expression, increases abundance	2
bisphenol S	affects expression, affects cotreatment, increases expression	2
Cisplatin	affects expression, increases expression	2
Quercetin	affects cotreatment, affects secretion, increases expression	2
Rotenone	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
dicrotophos	decreases expression	1
beauvericin	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
trigonelline	increases secretion, decreases reaction	1
iopromide	increases secretion	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
iodixanol	increases secretion, decreases reaction	1
ioversol	increases secretion	1
dinitrophenyl-human serum albumin conjugate	affects cotreatment, affects secretion	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
alpha-curcumene	increases secretion	1
enniatins	affects cotreatment, decreases expression	1
deguelin	increases expression	1
entinostat	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

53 unique, capped per target: 53 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2388712	Binding	Competitive inhibition of human beta-N-acetyl-D-hexosaminidase-A/B using 4-Methylumbelliferyl N-acetyl-beta-D-glucosaminide as substrate at 0.1 mM incubated for 10 mins prior to substrate addition by Dixon plot analysis	Development of Unsymmetrical Dyads As Potent Noncarbohydrate-Based Inhibitors against Human β-N-Acetyl-d-hexosaminidase. — ACS Med Chem Lett

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D5EV	HeLa::TMEM192-3xHA HEXB KO	Cancer cell line	Female
CVCL_D7R9	Ubigene A-549 HEXB KO	Cancer cell line	Male
CVCL_F0PY	H9 AAVS1-TRE3G-NGN2 TMEM192-3xHA (heterozygous) HEXB-/-	Embryonic stem cell	Female
CVCL_SR29	HAP1 HEXB (-) 1	Cancer cell line	Male
CVCL_SR30	HAP1 HEXB (-) 2	Cancer cell line	Male
CVCL_SR31	HAP1 HEXB (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02030015	PHASE4	TERMINATED	Synergistic Enteral Regimen for Treatment of the Gangliosidoses
NCT00672022	PHASE3	COMPLETED	Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses
NCT04221451	PHASE3	TERMINATED	A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2
NCT03759665	PHASE2	COMPLETED	N-Acetyl-L-Leucine for GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease)
NCT02254863	PHASE1	RECRUITING	UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells
NCT04669535	PHASE1	TERMINATED	A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease
NCT00176904	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Inborn Errors of Metabolism
NCT01102686	PHASE1/PHASE2	COMPLETED	Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)
NCT01372228	PHASE1/PHASE2	TERMINATED	Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders
NCT00668187	Not specified	RECRUITING	A Natural History Study of the Gangliosidoses
NCT01869270	Not specified	COMPLETED	Gene Therapy for Tay-Sachs Disease
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT04470713	Not specified	COMPLETED	Natural History Study for Pediatric Patients With Early Onset of Either GM1 Gangliosidosis, GM2 Gangliosidoses, or Gaucher Disease Type 2
NCT04624789	Not specified	UNKNOWN	Registry Gangliosidoses
NCT05109793	Not specified	COMPLETED	GM1 and GM2 Gangliosidosis PROspective Neurological Disease TrajectOry Study (PRONTO)
NCT06614569	Not specified	ACTIVE_NOT_RECRUITING	Long-Term Follow-Up of Subjects Treated With AXO-AAV-GM2 for Tay-Sachs or Sandhoff Disease