Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	916	10q24.32	OGA	O-GlcNAcase
Mouse	-	916	19 38.75 cM	Oga	O-GlcNAcase
Rat	-	916	1q54	Oga	O-GlcNAcase

Previous and Unofficial Names

MEA5 | MGEA5 | NCOAT | glycoside hydrolase O-GlcNAcase | O-GlcNAc hydrolase

Database Links
Alphafold	O60502 (Hs), Q9EQQ9 (Mm), Q8VIJ5 (Rn)
BRENDA	3.2.1.169
ChEMBL Target	CHEMBL5921 (Hs), CHEMBL4523449 (Mm), CHEMBL3351213 (Rn)
Ensembl Gene	ENSG00000198408 (Hs), ENSMUSG00000025220 (Mm), ENSRNOG00000017822 (Rn)
Entrez Gene	10724 (Hs), 76055 (Mm), 154968 (Rn)
Human Protein Atlas	ENSG00000198408 (Hs)
KEGG Enzyme	3.2.1.169
KEGG Gene	hsa:10724 (Hs), mmu:76055 (Mm), rno:154968 (Rn)
OMIM	604039 (Hs)
Pharos	O60502 (Hs)
RefSeq Nucleotide	NM_012215 (Hs), NM_023799 (Mm), NM_131904 (Rn)
RefSeq Protein	NP_036347 (Hs), NP_076288 (Mm), NP_571979 (Rn)
UniProtKB	O60502 (Hs), Q9EQQ9 (Mm), Q8VIJ5 (Rn)
Wikipedia	OGA (Hs)

Enzyme Reaction
EC Number: 3.2.1.169

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference MK-8719 Hs Inhibition 8.1 pKi 3 ⤷ pKi 8.1 (Ki 7.9x10-9 M) [3] Description: In vitro enzyme inhibition assay. thiamet-G Hs Inhibition 7.7 pKi 4 ⤷ pKi 7.7 (Ki 2.1x10-8 M) [4] MK-8719 Rn Inhibition 7.3 pEC50 3 ⤷ pEC50 7.3 (EC50 5.27x10-8 M) [3] Description: Determined in an ELISA-based assay with rat PC12 cells to measure EC50 values for elevation of all protein O-GlcNAc levels in the presence of test compound. LY3372689 Hs Inhibition 8.6 pIC50 1 ⤷ pIC50 8.6 (IC50 2.36x10-9 M) [1] Description: Inhibition of OGA enzyme activity in vitro
View species-specific inhibitor tables
Inhibitor Comments
Asceneuron have developed ASN120290 (previously ASN-561; structure not yet disclosed) as a brain-permeable and orally active small-molecule O-GlcNAcase enzyme inhibitor. It is reported in a 2018 review of in-development tau-based therapeutics that ASN120290 is being progressed to Phase 2 clinical trial, but there are no records for this agent (or ASN-561) on ClinicalTrials.gov, or any citable data in PubMed articles (as far as we can ascertain). Asceneuron's patent WO2017144639A1 claims glycosidase inhibitors for the treatment of tauopathies [2].

General Comments

Post-translational O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins is a widely used mechanism that is crucial for regulating various cellular processes. The modifications are dynamic, with O-linked GlcNAc transferase (OGT) adding the O-GlcNAc modifications to protein serine and threonine residues, and O-GlcNAcase (OGA) removing them. The absence of O-GlcNAc chains leaves the serines and threonines available for phosphorylation. Two variants of the protein are produced from the human OGA gene. Both retain O-GlcNAcase enzymatic function. Multiple lines of evidence indicate that aberrant phosphorylation of the tau protein drives its aggregation and the accumulation of toxic neurofibrillary tangles. Pharmacological blockade of O-GlcNAcase (i.e. to prevent O-GlcNAc removal and decrease phosphorylation) is being investigated as a novel mechanism to reduce tau hyperphosphorylation. Selective small-molecule O-GlcNAcase inhibitors are therefore being scrutinised for clinical utility in the treatment/prevention of neurodegenerative tauopathies, including Alzheimer's disease. To date, clinical progress has focussed on disease modification in patients with progressive supranuclear palsy, which is a rapidly progressing neurodegenerative disorder for which no current effective therapy exists..