GLB1

Summary

GLB1 (galactosidase beta 1, HGNC:4298) is a protein-coding gene on chromosome 3p22.3, encoding Beta-galactosidase (P16278). Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the glycosyl hydrolase 35 family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature lysosomal enzyme. This enzyme catalyzes the hydrolysis of a terminal beta-linked galactose residue from ganglioside substrates and other glycoconjugates. Mutations in this gene may result in GM1-gangliosidosis and Morquio B syndrome.

Source: NCBI Gene 2720 — RefSeq curated summary.

At a glance

• Gene–disease (curated): GM1 gangliosidosis (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 28
• Clinical variants (ClinVar): 1,585 total — 174 pathogenic, 154 likely-pathogenic
• Phenotypes (HPO): 152
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000404

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4298
Approved symbol	GLB1
Name	galactosidase beta 1
Location	3p22.3
Locus type	gene with protein product
Status	Approved
Aliases	EBP
Ensembl gene	ENSG00000170266
Ensembl biotype	protein_coding
OMIM	611458
Entrez	2720

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding_CDS_not_defined, 7 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000307363, ENST00000307377, ENST00000399402, ENST00000415454, ENST00000436768, ENST00000438227, ENST00000440656, ENST00000446732, ENST00000450835, ENST00000461475, ENST00000464355, ENST00000467571, ENST00000473477, ENST00000481581, ENST00000482097, ENST00000485698, ENST00000490658, ENST00000497796, ENST00000498537

RefSeq mRNA: 5 — MANE Select: NM_000404 NM_000404, NM_001079811, NM_001135602, NM_001317040, NM_001393580

CCDS: CCDS43061, CCDS43062, CCDS46785

Canonical transcript exons

ENST00000307363 — 16 exons

Exon	Start	End
ENSE00001141416	33014056	33014310
ENSE00003227813	32996617	32997344
ENSE00003465859	33024251	33024325
ENSE00003480475	33051758	33051798
ENSE00003525222	33097011	33097146
ENSE00003538618	33072544	33072713
ENSE00003546201	33046120	33046232
ENSE00003563481	33053491	33053549
ENSE00003567674	33021566	33021655
ENSE00003568734	33065463	33065557
ENSE00003591549	33068230	33068290
ENSE00003622525	33058089	33058269
ENSE00003630294	33068820	33068970
ENSE00003639907	33018448	33018561
ENSE00003645452	33016709	33016840
ENSE00003659771	33051883	33052004

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 96.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.0831 / max 177.3677, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41614	27.8495	1820
41613	19.3298	1812
41611	2.3816	1453
41610	2.3716	1337

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.82	gold quality
mononuclear cell	CL:0000842	96.62	gold quality
stromal cell of endometrium	CL:0002255	96.61	gold quality
adrenal tissue	UBERON:0018303	96.54	gold quality
leukocyte	CL:0000738	96.53	gold quality
secondary oocyte	CL:0000655	96.23	gold quality
islet of Langerhans	UBERON:0000006	96.12	gold quality
oocyte	CL:0000023	95.49	gold quality
corpus epididymis	UBERON:0004359	95.28	gold quality
granulocyte	CL:0000094	95.12	gold quality
rectum	UBERON:0001052	94.68	gold quality
colonic epithelium	UBERON:0000397	94.27	gold quality
gall bladder	UBERON:0002110	94.18	gold quality
tibia	UBERON:0000979	94.13	gold quality
decidua	UBERON:0002450	93.67	gold quality
right adrenal gland cortex	UBERON:0035827	93.64	gold quality
bone marrow cell	CL:0002092	93.56	gold quality
right adrenal gland	UBERON:0001233	93.48	gold quality
adrenal gland	UBERON:0002369	93.35	gold quality
left adrenal gland	UBERON:0001234	93.34	gold quality
palpebral conjunctiva	UBERON:0001812	93.07	gold quality
left adrenal gland cortex	UBERON:0035825	93.04	gold quality
duodenum	UBERON:0002114	92.97	gold quality
adrenal cortex	UBERON:0001235	92.86	gold quality
mucosa of transverse colon	UBERON:0004991	92.79	gold quality
smooth muscle tissue	UBERON:0001135	92.77	gold quality
metanephros cortex	UBERON:0010533	92.60	gold quality
adult mammalian kidney	UBERON:0000082	92.44	gold quality
left lobe of thyroid gland	UBERON:0001120	92.44	gold quality
thyroid gland	UBERON:0002046	92.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.89
E-MTAB-9388	yes	7.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2, EGR1, ESR1, FOXA2, FOXN1, GATA6, HIF1A, HOXA10, LHX3, MYC, NKX2-1, NR0B1, NR5A1, PDX1, POU2F1, TCF3, TP53, YBX3

miRNA regulators (miRDB)

31 targeting GLB1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-921	97.09	66.45	562
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-4690-3P	97.02	64.72	981

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Three new mutations in three Morquio B patients where the Trp 273 Leu mutation is absent (PMID:12393180)
• This protein was expressed locally in the media and adventitia at injected arterial segments without any significant dissemination to remote areas. (PMID:12515396)
• polymorphisms in beta 1 galactosidase is associted with type-II GM1 gangliosidosis (PMID:12644936)
• the 67-kDa elastin receptor was specifically expressed in the epithelioid or multinucleated giant cells in giant cell granuloma (PMID:14987258)
• 4 new GLB1 mutations were found: a premature stop codon in exon 2 (c.171C>G); a splicing error in intron 2 (c.245+1G>A); missense mutation in exon 4 (c.451G>T); & a splicing mutation in intron 8 (c.914+4A>G). (PMID:15365997)
• 4 new and 10 known GLB1 mutations were studied. The c.1445G>A (p.Arg482His), c.175C>T (p.Arg59Cys), c.733+2T>C, c.1736G>A (p.Gly579Asp), & c.1051C>T (p.Arg351X) mutations, affect the stabilization of PPCA by hampering the interaction of GLB1/EBP & PPCA. (PMID:15714521)
• expression and number of El-R on white blood cells using a specific 67 kDa El-R antibody, and presence of mRNA corresponding to the gene coding for El-R (PMID:15907791)
• Infantile impaired elastogenesis arose from a primary elatin binding protein (ELNR1) defectin gangliosidosis, according to molecular analysis. (PMID:16314480)
• effects of GLB1, PPCA and NEU1 gene mutations on elastogenesis in skin fibroblasts (PMID:16538002)
• Senescence Associated-beta-gal activity is expressed from GLB1, the gene encoding lysosomal beta-D-galactosidase, the activity of which is typically measured at acidic pH 4.5. (PMID:16626397)
• Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients suggesting common origin for the prevalent p.R59H mutation among gypsies. (PMID:16941474)
• 14 novel mutations in the GLB1 gene were identified in patients with GM1 gangliosidosis from Argentina (PMID:17309651)
• Senescence-associated beta-galactosidase activity in human melanocytic nevi is absent in vivo. (PMID:17522702)
• Here we report the new variant p.Arg595Trp in the GLB1 gene, which markedly reduces beta-galactosidase activity when expressed in COS-1 cells. The variant was identified in the healthy father of a girl with GM1 gangliosidosis (PMID:17661814)
• GLB1 mutant alleles have roles in GM1-gangliosidosis and Morquio B patients (PMID:17664528)
• canine model is an appropriate animal model for the human late infantile form and represents a versatile system to test gene therapeutic approaches for human and canine G(M1)-gangliosidosis (PMID:18088383)
• 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)
• Mutation responsible for feline G(M1) gangliosidosis was identified in beta-galactosidase resulting in an amino acid substitution at arginine 483, known to cause G(M1) gangliosidosis in humans. (PMID:18353697)
• 102 mutations distributed along the beta-galactosidase gene have been reported in GM1 gangliosidosis patients. (PMID:18524657)
• Report deregulation of versican and elastin binding protein in solar elastosis. (PMID:18704747)
• Neuraminidase caused the desialylation of both PDGF and IGF-1 receptors and diminished the intracellular signals induced by the mitogenic ligands PDGF-BB and IGF-2. (PMID:18772331)
• Elastin receptor-mediated monocyte chemoattraction induced by polysaccharide from Candida and seaweed. (PMID:18976701)
• GLB1 mutation caused Morquio type B disease with mental regression in two siblings. (PMID:19091613)
• missense mutations affecting the catalytic site of acid beta-galactosidase in Morquio B disease (PMID:19472408)
• in skin, the activation of the S-Gal/Cath-A/Neu-1 “elastin receptor” complex might dictate cell survival and skin tissue repair (PMID:19769716)
• Data show that four mutations of GLB1 could be correlated to a distinct GM1 gangliosidosis phenotype. (PMID:20175788)
• luciferase-based assay is a reliable and convenient method for screening and evaluation of chaperone effects on human beta-gal mutants (PMID:20826101)
• Results describe four mutations in Han Chinese patients that induce significant suppression of beta-galactosidase activity, correlating with severity of GM1 gangliosidosis and presence of cardiomyopathy. (PMID:20920281)
• The hyperthermia-enhanced association between tropoelastin and its 67-kDa chaperone results in better deposition of elastic fibers. (PMID:20947500)
• Plasma beta-galactosidase and beta-hexosaminidase levels are higher in patients with Alzheimer’s disease-type 2 diabetes mellitus (T2DM) compared to those with T2DM alone. (PMID:21321400)
• 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)
• We show here that mouse GLB1 has greater stability when compared to human GLB1, and that human GLB1 activity is temperature and protective-dependent on protein cathepsin A, while that of mouse GLB1 is not (PMID:22001501)
• GLB alleles have a role in GM1-gangliosidosis and Morquio B disease, and fluorous iminoalditols act as effective pharmacological chaperones against their gene products (PMID:22033734)
• Crystal structure of human beta-galactosidase: structural basis of Gm1 gangliosidosis and morquio B diseases. (PMID:22128166)
• Elastin derived peptides may play a role in neovascular age-related macular degeneration by binding to and inducing neovascular phenotypes in choroidal endothelial cells through their receptor, GLB1. (PMID:22178079)
• In a Turkish population, mutations in GLB1 gene leads to severely deficient enzyme activity and result in infantile phenotype of the GM1 gangliosidosis. (PMID:22234367)
• In the serum of patients with Lyme disease, GAL activity significantly increased (p = 0.029), and the activity of FUC had a tendency to increase (p = 0.153), compared to the control group. (PMID:22763966)
• beta-galactosidase, considered as a senescence marker, is over-expressed only in specific subtypes of pituitary adenomas, but is also present in carcinomas considered as a group (PMID:22908062)
• We observed significant lower values of beta-galactosidase, FUC and tendency to decrease of MAN and GLU concentration in nasal polyps (PMID:23911047)
• The activity of serum GAL was significantly higher in colon cancer patients with a history of alcohol and nicotine dependence. (PMID:24018455)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	glb1	ENSDARG00000036415
mus_musculus	Glb1	ENSMUSG00000045594
rattus_norvegicus	Glb1	ENSRNOG00000010196
drosophila_melanogaster	Gal	FBGN0001089
drosophila_melanogaster	Ect3	FBGN0260746
caenorhabditis_elegans		WBGENE00011832
caenorhabditis_elegans		WBGENE00019225

Paralogs (3): GLB1L2 (ENSG00000149328), GLB1L (ENSG00000163521), GLB1L3 (ENSG00000166105)

Protein

Protein identifiers

Beta-galactosidase — P16278 (reviewed: P16278)

Alternative names: Acid beta-galactosidase, Elastin receptor 1

All UniProt accessions (8): P16278, C9J4G9, C9J539, C9JF15, C9JWX1, E7EQ29, F8WEN1, F8WF40

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans. Has no beta-galactosidase catalytic activity, but plays functional roles in the formation of extracellular elastic fibers (elastogenesis) and in the development of connective tissue. Seems to be identical to the elastin-binding protein (EBP), a major component of the non-integrin cell surface receptor expressed on fibroblasts, smooth muscle cells, chondroblasts, leukocytes, and certain cancer cell types. In elastin producing cells, associates with tropoelastin intracellularly and functions as a recycling molecular chaperone which facilitates the secretions of tropoelastin and its assembly into elastic fibers.

Subunit / interactions. Homodimer. May form higher multimers.

Subcellular location. Lysosome Cytoplasm. Perinuclear region.

Tissue specificity. Detected in placenta (at protein level). Detected in fibroblasts and testis.

Disease relevance. GM1-gangliosidosis 1 (GM1G1) [MIM:230500] An autosomal recessive lysosomal storage disease marked by the accumulation of GM1 gangliosides, glycoproteins and keratan sulfate primarily in neurons of the central nervous system. GM1-gangliosidosis type 1 is characterized by onset within the first three months of life, central nervous system degeneration, coarse facial features, hepatosplenomegaly, skeletal dysmorphology reminiscent of Hurler syndrome, and rapidly progressive psychomotor deterioration. Urinary oligosaccharide levels are high. It leads to death usually between the first and second year of life. The disease is caused by variants affecting the gene represented in this entry. GM1-gangliosidosis 2 (GM1G2) [MIM:230600] A gangliosidosis characterized by onset between ages 1 and 5. The main symptom is locomotor ataxia, ultimately leading to a state of decerebration with epileptic seizures. Patients do not display the skeletal changes associated with the infantile form, but they nonetheless excrete elevated amounts of beta-linked galactose-terminal oligosaccharides. Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. GM1-gangliosidosis 3 (GM1G3) [MIM:230650] A gangliosidosis with a variable phenotype. Patients show mild skeletal abnormalities, dysarthria, gait disturbance, dystonia and visual impairment. Visceromegaly is absent. Intellectual deficit can initially be mild or absent but progresses over time. Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Mucopolysaccharidosis 4B (MPS4B) [MIM:253010] A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. The sequence shown in this entry differs from the translation of the reference genome assembly (GRCh38/hg38) due to a polymorphic change creating a Cys at position 521 in the reference genome. The sequence shown in this entry is that of variant p.Cys521Arg, which has a frequency of about 99% in the human population according to the Genome Aggregation Database (gnomAD v4.1.0), and gives rise to a fully active beta-galactosidase.

Similarity. Belongs to the glycosyl hydrolase 35 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P16278-1	1	yes
P16278-2	2, Beta-galactosidase-related protein, Beta-galactosidase-like protein, S-Gal, Elastin-binding protein, EBP
P16278-3	3

RefSeq proteins (5): NP_000395, NP_001073279, NP_001129074, NP_001303969, NP_001380509 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001944	Glycoside_Hdrlase_35	Family
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR019801	Glyco_hydro_35_CS	Conserved_site
IPR026283	B-gal_1-like	Family
IPR031330	Gly_Hdrlase_35_cat	Domain
IPR048912	BetaGal1-like_ABD1	Domain
IPR048913	BetaGal_gal-bd	Domain

Pfam: PF01301, PF21317, PF21467

UniProt features (190 total): sequence variant 102, strand 33, helix 23, glycosylation site 7, turn 7, binding site 4, sequence conflict 2, disulfide bond 2, splice variant 2, compositionally biased region 2, active site 2, signal peptide 1, propeptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3THD	X-RAY DIFFRACTION	1.79
3THC	X-RAY DIFFRACTION	1.8
3WF1	X-RAY DIFFRACTION	2
3WEZ	X-RAY DIFFRACTION	2.11
3WF3	X-RAY DIFFRACTION	2.15
3WF0	X-RAY DIFFRACTION	2.2
3WF2	X-RAY DIFFRACTION	2.3
3WF4	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16278-F1	90.19	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): 188 (proton donor); 268 (nucleophile)

Ligand- & substrate-binding residues (4): 187; 333; 83; 129

Disulfide bonds (2): 195–230, 626–634

Glycosylation sites (7): 26, 247, 464, 498, 542, 545, 555

Function

Pathways and Gene Ontology

Reactome pathways

30 pathways

ID	Pathway
R-HSA-2022857	Keratan sulfate degradation
R-HSA-2024101	CS/DS degradation
R-HSA-2206308	MPS IV - Morquio syndrome B (Keratin metabolism)
R-HSA-4085001	Sialic acid metabolism
R-HSA-4341670	Defective NEU1 causes sialidosis
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-9953111	MPS IV - Morquio syndrome B (CS/DS degradation)
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638074	Keratan sulfate/keratin metabolism
R-HSA-1638091	Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1643685	Disease
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2024096	HS-GAG degradation
R-HSA-2206281	Mucopolysaccharidoses
R-HSA-3781860	Diseases associated with N-glycosylation of proteins
R-HSA-3781865	Diseases of glycosylation
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis
R-HSA-556833	Metabolism of lipids
R-HSA-5663084	Diseases of carbohydrate metabolism
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 1036 (showing top): GOBP_CERAMIDE_CATABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, JI_RESPONSE_TO_FSH_UP, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_162, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOCC_SECRETORY_GRANULE, GOBP_RESPONSE_TO_CORTICOSTEROID, MORF_UBE2I, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, MORF_CDK2, KEGG_LYSOSOME, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS

GO Biological Process (9): carbohydrate metabolic process (GO:0005975), glycoprotein catabolic process (GO:0006516), ganglioside catabolic process (GO:0006689), galactose catabolic process (GO:0019388), keratan sulfate proteoglycan catabolic process (GO:0042340), response to cortisone (GO:0051413), response to Thyroglobulin triiodothyronine (GO:1904016), heparan sulfate proteoglycan catabolic process (GO:0030200), glycosphingolipid catabolic process (GO:0046479)

GO Molecular Function (7): beta-galactosidase activity (GO:0004565), galactoside binding (GO:0016936), protein homodimerization activity (GO:0042803), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (12): extracellular region (GO:0005576), cytoplasm (GO:0005737), lysosome (GO:0005764), vacuole (GO:0005773), Golgi apparatus (GO:0005794), membrane (GO:0016020), azurophil granule lumen (GO:0035578), lysosomal lumen (GO:0043202), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Mucopolysaccharidoses	2
Glycosaminoglycan metabolism	2
Keratan sulfate/keratin metabolism	1
Chondroitin sulfate/dermatan sulfate metabolism	1
Synthesis of substrates in N-glycan biosythesis	1
Diseases associated with N-glycosylation of proteins	1
Innate Immune System	1
Glycosphingolipid metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Sphingolipid metabolism	1
Immune System	1
Heparan sulfate/heparin (HS-GAG) metabolism	1
Diseases of carbohydrate metabolism	1
Diseases of glycosylation	1
Diseases of metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
proteoglycan catabolic process	2
intracellular membrane-bounded organelle	2
vacuolar lumen	2
primary metabolic process	1
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
galactose metabolic process	1
hexose catabolic process	1
keratan sulfate proteoglycan metabolic process	1
response to glucocorticoid	1
response to alcohol	1
response to ketone	1
response to chemical	1
heparan sulfate proteoglycan metabolic process	1
glycosphingolipid metabolic process	1
glycolipid catabolic process	1
sphingolipid catabolic process	1
galactosidase activity	1
carbohydrate derivative binding	1
identical protein binding	1
protein dimerization activity	1
hydrolase activity, acting on glycosyl bonds	1
binding	1
catalytic activity	1
hydrolase activity	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1
secretory granule lumen	1
azurophil granule	1
lysosome	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

1312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLB1	CTSA	P10619	999
GLB1	NEU1	Q99519	997
GLB1	ELN	P15502	987
GLB1	GALNS	P34059	970
GLB1	LCT	P09848	901
GLB1	GALC	P54803	821
GLB1	GLA	P06280	801
GLB1	ACY1	Q03154	777
GLB1	SI	P14410	776
GLB1	PISD	Q9UG56	773
GLB1	ASAH1	Q13510	733
GLB1	GBA1	P04062	711
GLB1	APEH	P13798	695
GLB1	ARSA	P15289	689
GLB1	FUCA1	P04066	661

IntAct

98 interactions, top by confidence:

A	B	Type	Score
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
VIM	NEFL	psi-mi:“MI:0914”(association)	0.840
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
TP63	TP73	psi-mi:“MI:0914”(association)	0.770
RHOA	CTSA	psi-mi:“MI:0914”(association)	0.730
DNAJB4	DNAJB5	psi-mi:“MI:0914”(association)	0.730
SFXN5	CTSA	psi-mi:“MI:0914”(association)	0.640
GLB1	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
GLB1	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
GLB1	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
GLB1	GOLM1	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC1	TRAPPC13	psi-mi:“MI:0914”(association)	0.530
RHOC	ARHGEF11	psi-mi:“MI:0914”(association)	0.530
MAD2L1BP	KIF20A	psi-mi:“MI:0914”(association)	0.530
SFXN5	TOMM40	psi-mi:“MI:0914”(association)	0.530
FZR1	TK1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LAGE3	CTSA	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
YPEL5	SYNCRIP	psi-mi:“MI:0914”(association)	0.510
KHK	GLB1	psi-mi:“MI:0915”(physical association)	0.400
GLB1	FOS	psi-mi:“MI:0915”(physical association)	0.370
GLB1	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
PLK1	GLB1	psi-mi:“MI:0915”(physical association)	0.370
GLB1	TK1	psi-mi:“MI:0915”(physical association)	0.370
GLB1	NEU1	psi-mi:“MI:0403”(colocalization)	0.370

BioGRID (168): GLB1 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), C7orf43 (Affinity Capture-MS), TRAPPC10 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC6B (Affinity Capture-MS), GLB1 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), TRAPPC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A060S684, A0A075TXZ3, A0A084B9Z4, A0A0B4GDU5, A0A1L9WN42, A0A455ZJM4, A1CE56, A1CFK9, A1CTM5, B0Y7S2, B6DZC8, B6DZD1, B6DZD2, C0HLA0, D4AQ54, D4AR77, D4ASH1, D4AV38, D4AZ78, D4AZG9, H2DF87, I1RIF1, O19015, P07140, P14000, P14217, P16278, P34724, P37274, P50473, P51688, P54793, P56161, P92916, Q0INM3, Q0IZZ8, Q10723, Q10B67, Q21376, Q4WMS9

Diamond homologs: A1CE56, A1D199, A1D1Z9, A1DJ58, A1DM65, A2QA64, A2QAN3, A2QL84, A2RSQ1, A6RPN7, A7EBU5, A7EZS5, B0XMP7, B0XNY2, B0XXE7, B0Y752, B2W791, B6GW04, B6H5X9, B6QHA9, B6QLF0, B8N2I5, B8N6V7, B8NKI4, B8QGZ3, I0AIT9, O19015, P16278, P23780, P29853, P48982, Q0CMF3, Q0DGD7, Q2U6P1, Q2UCU3, Q2UMD5, Q3UPY5, Q4WG05, Q4WNE4, Q4WRD3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
Cyclin A/B1/B2 associated events during G2/M transition	5	17.3×	6e-03
Maturation of DENV proteins	5	11.9×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
response to unfolded protein	5	13.4×	5e-03
regulation of mitotic cell cycle	5	10.8×	1e-02
protein folding	9	8.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1585 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	174
Likely pathogenic	154
Uncertain significance	392
Likely benign	557
Benign	79

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100725	NM_000404.4(GLB1):c.1188dup (p.Pro397fs)	Pathogenic
100726	NM_000404.2:c.672_673delAT	Pathogenic
100727	NM_000404.4(GLB1):c.922T>C (p.Phe308Leu)	Pathogenic
1057305	NM_000404.4(GLB1):c.1388T>C (p.Leu463Pro)	Pathogenic
1069093	NM_006579.3(EBP):c.387G>A (p.Trp129Ter)	Pathogenic
1069437	NM_000404.4(GLB1):c.473del (p.Val158fs)	Pathogenic
1076248	NM_000404.4(GLB1):c.1580G>A (p.Trp527Ter)	Pathogenic
1077168	NM_000404.4(GLB1):c.75+2T>G	Pathogenic
11483	NM_006579.3(EBP):c.87G>A (p.Trp29Ter)	Pathogenic
11484	NM_006579.3(EBP):c.187C>T (p.Arg63Ter)	Pathogenic
11486	NM_006579.3(EBP):c.338+1G>T	Pathogenic
11487	NM_006579.3(EBP):c.390del (p.Pro131fs)	Pathogenic
11488	NM_006579.3(EBP):c.586_587insA (p.Trp196Ter)	Pathogenic
11489	NM_006579.3(EBP):c.386G>A (p.Trp129Ter)	Pathogenic
11490	NM_006579.3(EBP):c.523C>T (p.Gln175Ter)	Pathogenic
11491	NM_006579.3(EBP):c.587G>A (p.Trp196Ter)	Pathogenic
11492	NM_006579.3(EBP):c.440G>A (p.Arg147His)	Pathogenic
11493	NM_006579.3(EBP):c.53T>C (p.Leu18Pro)	Pathogenic
1322814	NM_006579.3(EBP):c.301+1G>A	Pathogenic
1323014	NM_000404.4(GLB1):c.1617G>A (p.Trp539Ter)	Pathogenic
1332777	NM_000404.4(GLB1):c.425_428del (p.Lys142fs)	Pathogenic
1332778	NM_000404.4(GLB1):c.266A>T (p.His89Leu)	Pathogenic
1332869	NM_000404.4(GLB1):c.75+4dup	Pathogenic
1352397	NM_006579.3(EBP):c.36G>A (p.Trp12Ter)	Pathogenic
1364568	NM_000404.4(GLB1):c.1479+1G>C	Pathogenic
1372550	NM_000404.4(GLB1):c.1276T>G (p.Cys426Gly)	Pathogenic
1378674	NM_000404.4(GLB1):c.1576_1583dup (p.His529fs)	Pathogenic
1382131	NM_000404.4(GLB1):c.1616G>A (p.Trp539Ter)	Pathogenic
1395005	NM_000404.4(GLB1):c.424A>T (p.Lys142Ter)	Pathogenic
1419594	NM_000404.4(GLB1):c.246-2A>G	Pathogenic

SpliceAI

3315 predictions. Top by Δscore:

Variant	Effect	Δscore
3:33014051:CGTA:C	donor_loss	1.0000
3:33014052:GTACC:G	donor_loss	1.0000
3:33014053:TA:T	donor_loss	1.0000
3:33014054:A:AC	donor_gain	1.0000
3:33014054:ACCTT:A	donor_loss	1.0000
3:33014055:C:CC	donor_gain	1.0000
3:33014306:AAACC:A	acceptor_gain	1.0000
3:33014307:AACC:A	acceptor_gain	1.0000
3:33014308:ACC:A	acceptor_gain	1.0000
3:33014308:ACCC:A	acceptor_loss	1.0000
3:33014309:CC:C	acceptor_gain	1.0000
3:33014309:CCC:C	acceptor_gain	1.0000
3:33014309:CCCTG:C	acceptor_loss	1.0000
3:33014310:CC:C	acceptor_gain	1.0000
3:33014311:C:CC	acceptor_gain	1.0000
3:33014312:T:A	acceptor_loss	1.0000
3:33016703:TCCTA:T	donor_loss	1.0000
3:33016704:CCTA:C	donor_loss	1.0000
3:33016705:CTACC:C	donor_loss	1.0000
3:33016706:TA:T	donor_loss	1.0000
3:33016708:C:CT	donor_loss	1.0000
3:33018445:TA:T	donor_loss	1.0000
3:33018446:A:AC	donor_gain	1.0000
3:33018446:ACC:A	donor_gain	1.0000
3:33018447:C:CC	donor_gain	1.0000
3:33018447:C:CT	donor_loss	1.0000
3:33018447:CCC:C	donor_gain	1.0000
3:33018557:TAATG:T	acceptor_gain	1.0000
3:33018559:ATG:A	acceptor_gain	1.0000
3:33018559:ATGC:A	acceptor_loss	1.0000

AlphaMissense

4417 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:33046198:G:C	S330R	0.997
3:33046198:G:T	S330R	0.997
3:33046200:T:G	S330R	0.997
3:33058261:A:C	N187K	0.997
3:33058261:A:T	N187K	0.997
3:33068960:A:G	W86R	0.997
3:33068960:A:T	W86R	0.997
3:33051758:C:A	G319W	0.996
3:33051774:A:C	N313K	0.996
3:33051774:A:T	N313K	0.996
3:33058262:T:A	N187I	0.996
3:33068830:T:A	E129V	0.996
3:33058259:T:A	E188V	0.995
3:33018470:C:G	R442P	0.994
3:33051966:C:A	W277C	0.994
3:33051966:C:G	W277C	0.994
3:33068958:C:A	W86C	0.994
3:33068958:C:G	W86C	0.994
3:33051968:A:G	W277R	0.993
3:33051968:A:T	W277R	0.993
3:33065534:A:G	W161R	0.993
3:33065534:A:T	W161R	0.993
3:33068854:C:G	R121T	0.993
3:33072613:C:G	R59P	0.993
3:33046230:C:G	A320P	0.992
3:33058265:T:A	E186V	0.992
3:33014064:A:G	W576R	0.991
3:33014064:A:T	W576R	0.991
3:33068854:C:A	R121M	0.991
3:33014056:C:A	K578N	0.990

dbSNP variants (sampled 300 via entrez): RS1000018947 (3:32970440 A>G), RS1000019778 (3:33013063 G>T), RS1000032916 (3:33079162 A>G), RS1000040456 (3:33053064 A>C), RS1000058320 (3:33035494 T>C), RS1000078930 (3:33019924 A>C), RS1000079625 (3:32993523 T>A,C), RS1000084885 (3:33066653 T>C), RS1000099060 (3:33062919 T>A,C), RS1000103371 (3:33056135 G>A), RS1000135531 (3:33041194 T>C), RS1000136348 (3:33086016 T>C,G), RS1000155871 (3:32970161 T>A,C), RS1000163528 (3:32981242 A>T), RS1000194089 (3:33050447 C>T)

Disease associations

OMIM: gene MIM:611458 | disease phenotypes: MIM:253010, MIM:230650, MIM:230500, MIM:230600, MIM:302960, MIM:300960, MIM:181500, MIM:211600, MIM:108600

GenCC curated gene-disease

Disease	Classification	Inheritance
GM1 gangliosidosis type 3	Definitive	Autosomal recessive
chondrodysplasia punctata 2, X-linked dominant	Definitive	X-linked
X-linked chondrodysplasia punctata 2	Definitive	X-linked
GM1 gangliosidosis	Definitive	Autosomal recessive
MEND syndrome	Strong	X-linked
GM1 gangliosidosis type 1	Strong	Autosomal recessive
GM1 gangliosidosis type 2	Strong	Autosomal recessive
mucopolysaccharidosis type 4B	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
GM1 gangliosidosis	Definitive	AR
MEND syndrome	Definitive	XL
mucopolysaccharidosis type 4B	Definitive	AR

Mondo (17): mucopolysaccharidosis type 4B (MONDO:0009660), GM1 gangliosidosis (MONDO:0018149), GM1 gangliosidosis type 3 (MONDO:0009262), GM1 gangliosidosis type 1 (MONDO:0009260), GM1 gangliosidosis type 2 (MONDO:0009261), lysosomal storage disease (MONDO:0002561), intellectual disability (MONDO:0001071), connective tissue disorder (MONDO:0003900), X-linked chondrodysplasia punctata 2 (MONDO:0020603), MEND syndrome (MONDO:0010498), schizophrenia (MONDO:0005090), cleft palate (MONDO:0016064), ependymoma (MONDO:0016698), progressive familial intrahepatic cholestasis (MONDO:0015762), spondyloepiphyseal dysplasia (MONDO:0016761)

Orphanet (17): Mucopolysaccharidosis type 4B (Orphanet:309310), GM1 gangliosidosis (Orphanet:354), Mucopolysaccharidosis type 4 (Orphanet:582), GM1 gangliosidosis type 3 (Orphanet:79257), GM1 gangliosidosis type 1 (Orphanet:79255), GM1 gangliosidosis type 2 (Orphanet:79256), Lysosomal disease (Orphanet:68366), X-linked dominant chondrodysplasia punctata (Orphanet:35173), MEND syndrome (Orphanet:401973), Cleft palate (Orphanet:2014), Ependymoma (Orphanet:251636), Progressive familial intrahepatic cholestasis (Orphanet:172), Spondyloepiphyseal dysplasia and spondyloepimetaphyseal dysplasia (Orphanet:253), Spastic ataxia (Orphanet:316226), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

152 total (30 of 152 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000079	Abnormality of the urinary system
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000160	Narrow mouth
HP:0000212	Gingival overgrowth
HP:0000280	Coarse facial features
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000455	Broad nasal tip
HP:0000457	Depressed nasal ridge
HP:0000470	Short neck
HP:0000618	Blindness
HP:0000648	Optic atrophy
HP:0000670	Carious teeth
HP:0000683	Grayish enamel
HP:0000687	Widely spaced teeth
HP:0000707	Abnormality of the nervous system
HP:0000750	Delayed speech and language development
HP:0000768	Pectus carinatum
HP:0000884	Prominent sternum
HP:0000900	Thickened ribs
HP:0000904	Flaring of rib cage
HP:0000924	Abnormality of the skeletal system
HP:0000926	Platyspondyly

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000902_2	Hepatocellular carcinoma	2.000000e-07
GCST001709_10	Atopic dermatitis	6.000000e-21
GCST004600_186	Eosinophil percentage of white cells	6.000000e-14
GCST004606_109	Eosinophil count	3.000000e-13
GCST004617_80	Eosinophil percentage of granulocytes	6.000000e-14
GCST004623_137	Neutrophil percentage of granulocytes	3.000000e-15
GCST004624_42	Sum eosinophil basophil counts	2.000000e-14
GCST005038_1	Allergic disease (asthma, hay fever or eczema)	3.000000e-10
GCST005523_13	Celiac disease	2.000000e-07
GCST005975_9	Eosinophil count	4.000000e-12
GCST007798_53	Asthma	3.000000e-20
GCST007798_54	Asthma	3.000000e-19
GCST007799_42	Asthma (adult onset)	4.000000e-13
GCST007800_101	Asthma (childhood onset)	4.000000e-14
GCST007941_21	Medication use (adrenergics, inhalants)	3.000000e-09
GCST007942_13	Medication use (glucocorticoids)	1.000000e-09
GCST007995_15	Asthma (childhood onset)	3.000000e-10
GCST008916_125	Asthma	3.000000e-15
GCST008916_8	Asthma	5.000000e-09
GCST009720_94	Asthma	1.000000e-15
GCST009798_68	Asthma	3.000000e-12
GCST010042_120	Asthma	2.000000e-21
GCST010043_108	Asthma	3.000000e-22
GCST010396_202	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06
GCST90002381_143	Eosinophil count	4.000000e-31
GCST90002382_559	Eosinophil percentage of white cells	4.000000e-29
GCST90011899_136	Aspartate aminotransferase levels	8.000000e-12
GCST90014325_39	Asthma	3.000000e-14

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:1002011	adult onset asthma
EFO:0009941	Inhalant adrenergic use measurement
EFO:0009942	Glucocorticoid use measurement
EFO:0007874	gut microbiome measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D003240	Connective Tissue Diseases	C17.300
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290
D016537	Gangliosidosis, GM1	C10.228.140.163.100.435.825.300.400; C16.320.565.189.435.825.300.400; C16.320.565.398.641.803.350.360; C16.320.565.595.554.825.300.400; C18.452.132.100.435.825.300.400; C18.452.584.563.641.803.350.360; C18.452.648.189.435.825.300.400; C18.452.648.398.641.803.350.360; C18.452.648.595.554.825.300.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016464	Lysosomal Storage Diseases	C16.320.565.595; C18.452.648.595
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2522 (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: 430 (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
CHEMBL110458	MIGALASTAT	4	430

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

ChEMBL bioactivities

29 potent at pChembl≥5 of 55 total, top 29 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.40	IC50	0.4	nM	CHEMBL4288931
8.10	IC50	8	nM	CHEMBL4085739
8.00	IC50	10	nM	CHEMBL4085739
8.00	IC50	10	nM	CHEMBL4284436
8.00	ED50	10	nM	CHEMBL4288931
6.90	IC50	125	nM	CHEMBL1922581
6.75	IC50	180	nM	CHEMBL4085739
6.68	IC50	210	nM	CHEMBL3771185
6.62	IC50	240	nM	CHEMBL1818433
6.60	IC50	250	nM	CHEMBL4281031
6.54	Ki	290	nM	CHEMBL4069909
6.52	Ki	300	nM	CHEMBL1922581
6.52	Ki	300	nM	CHEMBL205982
6.30	ED50	500	nM	CHEMBL4085739
6.30	ED50	500	nM	CHEMBL4284436
6.29	Ki	510	nM	CHEMBL1922581
6.22	Ki	600	nM	CHEMBL505422
6.16	Ki	700	nM	CHEMBL461161
6.16	Ki	700	nM	CHEMBL1911831
5.77	IC50	1700	nM	CHEMBL1922579
5.62	IC50	2420	nM	CHEMBL3770764
5.52	IC50	3000	nM	CHEMBL4438366
5.19	Ki	6400	nM	CHEMBL2114148
5.18	Ki	6600	nM	CHEMBL2114148
5.12	Ki	7500	nM	CHEMBL165192
5.11	IC50	7800	nM	CHEMBL505422
5.04	Ki	9200	nM	CHEMBL4090899
5.03	IC50	9400	nM	CHEMBL165192
5.00	ED50	1e+04	nM	CHEMBL4281031

PubChem BioAssay actives

27 with measured affinity, of 311 total; 18 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
(3R,4S,5R,6R)-5-(hydroxymethyl)-6-nonylpiperidine-3,4-diol	1408922: Inhibition of beta-galactosidase derived from human peripheral blood mononuclear cell lysate using 4-methylumbelliferyl beta-D-galactopyranoside as substrate after 2 hrs by fluorescence analysis	ic50	0.0004	uM
(3R,4S,5R,6R)-5-(hydroxymethyl)-6-pentylpiperidine-3,4-diol	1440002: Inhibition of beta-galactosidase in human PBMC using 4-methylumbelliferyl beta-D-galactopyranoside as substrate at pH 7.3 after 2 hrs by fluorescence assay	ic50	0.0080	uM
(3R,4S,5R,6R)-5-(hydroxymethyl)-6-(2-phenylethyl)piperidine-3,4-diol	1408922: Inhibition of beta-galactosidase derived from human peripheral blood mononuclear cell lysate using 4-methylumbelliferyl beta-D-galactopyranoside as substrate after 2 hrs by fluorescence analysis	ic50	0.0100	uM
(1S,2S,3S,6R)-4-(hydroxymethyl)-6-(octylamino)cyclohex-4-ene-1,2,3-triol	1281327: Inhibition of human lysosomal beta-galactosidase using 4-MU beta-gal as substrate incubated for 96 hrs by fluorescence assay	ic50	0.1250	uM
N-[4-[(2R,3R,4S,5R)-4,5-dihydroxy-3-(hydroxymethyl)piperidin-2-yl]butyl]-5-(dimethylamino)naphthalene-1-sulfonamide	1281327: Inhibition of human lysosomal beta-galactosidase using 4-MU beta-gal as substrate incubated for 96 hrs by fluorescence assay	ic50	0.2100	uM
(3R,4S,5R)-5-(hydroxymethyl)piperidine-3,4-diol	1440002: Inhibition of beta-galactosidase in human PBMC using 4-methylumbelliferyl beta-D-galactopyranoside as substrate at pH 7.3 after 2 hrs by fluorescence assay	ic50	0.2400	uM
(3R,4S,5R,6R)-5-(hydroxymethyl)-6-methylpiperidine-3,4-diol	1408922: Inhibition of beta-galactosidase derived from human peripheral blood mononuclear cell lysate using 4-methylumbelliferyl beta-D-galactopyranoside as substrate after 2 hrs by fluorescence analysis	ic50	0.2500	uM
5-(dimethylamino)-N-[6-[[(1R,2S,3S,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)cyclopentyl]amino]hexyl]naphthalene-1-sulfonamide	1454197: Competitive inhibition of human fibroblast lysosomal beta-galactosidase using 4-methylumbelliferyl-beta-D-galactopyranoside as substrate pre-incubated for up to 5 mins before substrate addition and measured after 30 mins	ki	0.2900	uM
5-(dimethylamino)-N-[6-[(2R,3S,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]hexyl]naphthalene-1-sulfonamide	626416: Inhibition of human lysosomal beta-galactosidase assessed as inhibition of hydrolyzed 4-methylumbelliferone production after 30 mins by luminescence spectrophotometry	ki	0.3000	uM
methyl 6-[[(2S)-2-[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]-6-[(2R,3S,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]hexanoyl]amino]hexanoate	626416: Inhibition of human lysosomal beta-galactosidase assessed as inhibition of hydrolyzed 4-methylumbelliferone production after 30 mins by luminescence spectrophotometry	ki	0.6000	uM
methyl (2S)-2-[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]-6-[(2R,3S,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]hexanoate	626416: Inhibition of human lysosomal beta-galactosidase assessed as inhibition of hydrolyzed 4-methylumbelliferone production after 30 mins by luminescence spectrophotometry	ki	0.7000	uM
N-[6-[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]hexyl]-6-[(2R,3S,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]hexanamide	626416: Inhibition of human lysosomal beta-galactosidase assessed as inhibition of hydrolyzed 4-methylumbelliferone production after 30 mins by luminescence spectrophotometry	ki	0.7000	uM
(1S,2S,3R,6S)-4-(hydroxymethyl)-6-(octylamino)cyclohex-4-ene-1,2,3-triol	1802833: β-Gal Inhibitory Assay from Article 10.1074/jbc.M113.529529: “Structural basis of pharmacological chaperoning for human ß-galactosidase.”	ki	0.9400	uM
(3R,4S,5R,6R)-6-(2-hydroxyethyl)-5-(hydroxymethyl)piperidine-3,4-diol	1281327: Inhibition of human lysosomal beta-galactosidase using 4-MU beta-gal as substrate incubated for 96 hrs by fluorescence assay	ic50	2.4200	uM
(3S,4R,5R,7R)-7-butylazepane-3,4,5-triol	1585817: Inhibition of beta-galactosidase (unknown origin)	ic50	3.0000	uM
ethyl 5-[(2S,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]-2-methylfuran-3-carboxylate	40138: Inhibition constant against Beta-galactosidase from Jack beans; Mixed (Non competitive and competitive)	ki	6.4000	uM
N-[(3R,4R,5S)-5-(1,2-dihydroxyethyl)-2-hydroxy-4-[[(2R,3S,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]methyl]oxolan-3-yl]acetamide;N-[(3S,4R,5R,6R)-2,5-dihydroxy-6-(hydroxymethyl)-4-[[(2R,3S,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]methyl]oxan-3-yl]acetamide	218553: Inhibition constant against beta-galactosidase enzyme of jack bean was reported	ki	7.5000	uM
(1S,2S,3S,4R,5R)-4-(6-aminohexylamino)-5-(hydroxymethyl)cyclopentane-1,2,3-triol	1454197: Competitive inhibition of human fibroblast lysosomal beta-galactosidase using 4-methylumbelliferyl-beta-D-galactopyranoside as substrate pre-incubated for up to 5 mins before substrate addition and measured after 30 mins	ki	9.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Hydrogen Peroxide	decreases reaction, increases expression, affects expression, increases activity	6
Glucose	affects reaction, decreases reaction, increases expression, increases activity	5
bisphenol A	increases expression, decreases expression	4
Particulate Matter	affects cotreatment, increases expression, decreases reaction, increases abundance, increases activity (+1 more)	4
Cisplatin	decreases expression, increases activity, increases expression	3
Rotenone	affects expression, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Cyclosporine	affects expression, affects cotreatment, increases expression, decreases expression	3
cobaltiprotoporphyrin	decreases reaction, increases expression	2
sodium arsenite	increases expression	2
Arsenic Trioxide	decreases reaction, increases reaction, increases activity	2
Microplastics	increases abundance, increases expression, increases activity	2
Acetylcysteine	increases abundance, decreases reaction, increases activity	2
Vehicle Emissions	increases activity, affects reaction, decreases reaction, increases abundance	2
Cannabidiol	increases expression, increases activity	2
Estradiol	decreases reaction, increases expression, decreases expression	2
Etoposide	increases activity, increases expression	2
Polystyrenes	increases abundance, increases expression, increases activity	2
Valproic Acid	increases expression	2
N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide	decreases reaction, increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
protocatechualdehyde	decreases reaction, increases expression	1
baicalein	decreases reaction, increases activity	1
4-biphenylamine	decreases expression	1
deoxynivalenol	decreases expression	1
nuciferine	decreases reaction, increases activity	1
cannabichromene	increases expression	1
ferric ammonium citrate	increases expression	1
beta-lapachone	increases expression	1

ChEMBL screening assays

124 unique, capped per target: 123 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1010084	Binding	Inhibition of human lysosomal beta galactosidase	1-Deoxygalactonojirimycin-lysine hybrids as potent D-galactosidase inhibitors. — Bioorg Med Chem
CHEMBL3994059	ADMET	Prodrug activation in PBS buffer assessed as beta-galactosidase (unknown origin) mediated CA4 formation at 0.2 mM after 1 hr by HPLC analysis	Combretastatin A4-β-Galactosyl Conjugates for Ovarian Cancer Prodrug Monotherapy. — ACS Med Chem Lett

Cellosaurus cell lines

21 cell lines: 7 cancer cell line, 6 induced pluripotent stem cell, 5 finite cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5510	GP8 [Mouse]	Transformed cell line
CVCL_5530	I51T	Transformed cell line
CVCL_6540	R201C	Transformed cell line
CVCL_9W82	GM01602	Finite cell line	Female
CVCL_9W84	GM02455	Finite cell line	Female
CVCL_9W94	GM03251	Finite cell line	Female
CVCL_B5K6	HAP1 GLB1 (-) 2	Cancer cell line	Male
CVCL_B7XH	Abcam Raji GLB1 KO	Cancer cell line	Male
CVCL_B9Y6	Abcam THP-1 GLB1 KO	Cancer cell line	Male
CVCL_C7A0	Abcam PC-3 GLB1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT07054515	PHASE3	RECRUITING	A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease, GM1 Gangliosidosis or GM2 Gangliosidosis
NCT00654433	PHASE3	TERMINATED	ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases
NCT04283227	PHASE3	ACTIVE_NOT_RECRUITING	OTL-200 in Patients With Late Juvenile Metachromatic Leukodystrophy (MLD)
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00383448	PHASE2	COMPLETED	HSCT for High Risk Inherited Inborn Errors
NCT03392987	PHASE2	COMPLETED	A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD)
NCT06130228	PHASE2	UNKNOWN	Nutritional Therapy in Late-onset Pompe Disease
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)