OGT

Summary

OGT (O-linked N-acetylglucosamine (GlcNAc) transferase, HGNC:8127) is a protein-coding gene on chromosome Xq13.1, encoding UDP-N-acetylglucosamine–peptide N-acetylglucosaminyltransferase 110 kDa subunit (O15294). Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc). It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

This gene encodes a glycosyltransferase that catalyzes the addition of a single N-acetylglucosamine in O-glycosidic linkage to serine or threonine residues. Since both phosphorylation and glycosylation compete for similar serine or threonine residues, the two processes may compete for sites, or they may alter the substrate specificity of nearby sites by steric or electrostatic effects. The protein contains multiple tetratricopeptide repeats that are required for optimal recognition of substrates. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 8473 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, X-linked 106 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 393 total — 6 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_181672

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8127
Approved symbol	OGT
Name	O-linked N-acetylglucosamine (GlcNAc) transferase
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Aliases	O-GLCNAC, HRNT1, MGC22921, FLJ23071, OGT1
Ensembl gene	ENSG00000147162
Ensembl biotype	protein_coding
OMIM	300255
Entrez	8473

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 19 protein_coding, 6 retained_intron, 5 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000373701, ENST00000373719, ENST00000444774, ENST00000455587, ENST00000459760, ENST00000462638, ENST00000466181, ENST00000472270, ENST00000474633, ENST00000488174, ENST00000498566, ENST00000699749, ENST00000699750, ENST00000699751, ENST00000699779, ENST00000699780, ENST00000699781, ENST00000699782, ENST00000699783, ENST00000699784, ENST00000699785, ENST00000899812, ENST00000899814, ENST00000899815, ENST00000899816, ENST00000899817, ENST00000899818, ENST00000899819, ENST00000899820, ENST00000899821, ENST00000925316, ENST00000925317, ENST00000925318

RefSeq mRNA: 2 — MANE Select: NM_181672 NM_181672, NM_181673

CCDS: CCDS14414, CCDS35502

Canonical transcript exons

ENST00000373719 — 22 exons

Exon	Start	End
ENSE00003666408	71544567	71544635
ENSE00003689648	71536178	71536358
ENSE00003977568	71561775	71561900
ENSE00003977570	71564601	71564753
ENSE00003977571	71547907	71548023
ENSE00003977572	71563130	71563246
ENSE00003977573	71554513	71554592
ENSE00003977574	71556952	71557105
ENSE00003977575	71573620	71575892
ENSE00003977577	71533104	71533336
ENSE00003977578	71557493	71557672
ENSE00003977581	71537829	71538072
ENSE00003977586	71567993	71568116
ENSE00003977589	71562847	71563017
ENSE00003977590	71559588	71559677
ENSE00003977591	71563329	71563499
ENSE00003977592	71556680	71556780
ENSE00003977594	71555954	71556094
ENSE00003977595	71559267	71559425
ENSE00003977597	71555190	71555385
ENSE00003977598	71557195	71557296
ENSE00003977600	71567500	71567752

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 104.1224 / max 2252.1047, expressed in 1824 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196689	79.3646	1819
196688	14.5188	1753
196705	3.4522	1356
196701	2.2467	794
196703	1.3014	590
209726	0.9908	554
196704	0.8003	424
196697	0.5243	300
196691	0.3039	120
196690	0.2694	120

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.65	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.56	gold quality
skin of hip	UBERON:0001554	99.28	gold quality
right uterine tube	UBERON:0001302	99.20	gold quality
tibia	UBERON:0000979	99.12	gold quality
visceral pleura	UBERON:0002401	99.04	gold quality
epithelium of nasopharynx	UBERON:0001951	99.02	gold quality
upper leg skin	UBERON:0004262	99.01	gold quality
parietal pleura	UBERON:0002400	98.95	gold quality
trabecular bone tissue	UBERON:0002483	98.95	gold quality
pleura	UBERON:0000977	98.94	gold quality
pylorus	UBERON:0001166	98.89	gold quality
cardia of stomach	UBERON:0001162	98.86	gold quality
body of pancreas	UBERON:0001150	98.78	gold quality
germinal epithelium of ovary	UBERON:0001304	98.69	gold quality
endothelial cell	CL:0000115	98.60	gold quality
renal medulla	UBERON:0000362	98.58	gold quality
seminal vesicle	UBERON:0000998	98.50	gold quality
left ovary	UBERON:0002119	98.39	gold quality
corpus epididymis	UBERON:0004359	98.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.33	gold quality
superficial temporal artery	UBERON:0001614	98.29	gold quality
right ovary	UBERON:0002118	98.29	gold quality
tonsil	UBERON:0002372	98.25	gold quality
caput epididymis	UBERON:0004358	98.24	gold quality
medial globus pallidus	UBERON:0002477	98.23	gold quality
mucosa of stomach	UBERON:0001199	98.22	gold quality
spleen	UBERON:0002106	98.20	gold quality
fundus of stomach	UBERON:0001160	98.16	gold quality
lymph node	UBERON:0000029	98.14	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	15.80
E-MTAB-8498	yes	12.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, PDX1, TET1

miRNA regulators (miRDB)

185 targeting OGT, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• We have delineated the complete genomic structure of human OGT spanning approx 43 kb of genomic DNA in Xq13.1 (PMID:11773972)
• homology between O-linked GlcNAc transferases and proteins of the glycogen phosphorylase superfamily (PMID:11846551)
• O-linked GlcNAc transferase participates in a hexosamine-dependent signaling pathway that is linked to insulin resistance and leptin production (PMID:12136128)
• a novel HLA-A0201-restricted cytotoxic T lymphocyte (CTL)-epitope (28-SLYKFSPFPL; FSP06) derived from a mutant OGT-protein (PMID:14601650)
• OGT can respond rapidly to heat stress through the enhancement of nucleocytoplasmic protein O-GlcNAcylation. (PMID:15336570)
• Staining of OGT in streptozotocin diabetic rat liver is clearly diminished, but it was substantially restored after 6 days of insulin treatment (PMID:15561949)
• By using a series of 4-methylumbelliferyl 2-deoxy-2-N-fluoroacetyl-beta-D-glucopyranoside substrates, Taft-like linear free energy analyses of these enzymes indicates that O-GlcNAcase uses a catalytic mechanism involving anchimeric assistance (PMID:15795231)
• Thus, stably transfected HeLa cells provide an abundant source of enzyme that can be used to study the structure, function, and regulation of OGT. (PMID:15896326)
• analysis of the catalytic domain of O-linked N-acetylglucosaminyl transferase (PMID:16105839)
• Overall, transcriptional inhibition is related to the integrated effect of O-GlcNAc by direct modification of critical elements of the transcriptome and indirectly through O-GlcNAc modification of the proteasome. (PMID:16966374)
• O-GlcNAc modification stimulated by glucose deprivation results from increased OGT and decreased O-GlcNAcase levels and that these changes affect cell metabolism, thus inactivating glycogen synthase. (PMID:18174169)
• The structure of an intact OGT homolog and kinetic analysis of human OGT variants reveal a contiguous superhelical groove that directs substrates to the active site. (PMID:18536723)
• the O-GlcNAc cycling enzymes associate with kinases and phosphatases at M phase to regulate the posttranslational status of vimentin (PMID:18653473)
• Up-regulation of O-GlcNAc transferase with glucose deprivation in HepG2 cells is mediated by decreased hexosamine pathway flux. (PMID:19073609)
• Data show that forced overexpression of OGT increased the inhibitory phosphorylation of CDK1 and reduced the phosphorylation of CDK1 target proteins. (PMID:20068230)
• OGT regulates breast cancer tumorignenesis and cancer growth through targeting FixM1. (PMID:20190804)
• THAP1 was found to bind HCF-1 in vitro and to associate with HCF-1 and OGT in vivo. (PMID:20200153)
• OGT could be a co-regulatory subunit shared by functionally distinct complexes supporting epigenetic regulation of MIP-1alpha gene promoter. (PMID:20206135)
• regulating the amount of OGT during mitosis is important in ensuring correct chromosomal segregation during mitosis. (PMID:20805223)
• Enhanced OGT expression efficiently triggered programmed cell death. (PMID:20824293)
• OGT deletion in infarcted mice significantly exacerbated cardiac dysfunction. (PMID:20876116)
• two crystal structures of human OGT, as a binary complex with UDP (2.8 A resolution) and as a ternary complex with UDP and a peptide substrate (1.95 A). (PMID:21240259)
• Data identify Tau as potential substrates for the O-beta-N-acetylglucosaminyltransferase (OGT). (PMID:21327254)
• Decrease in MGEA5 and increase in O-GlcNAc transferease expression in higher grade tumors suggests that increased O-GlcNAc modification may be implicated in breast tumor progression and metastasis. (PMID:21567137)
• as prostate cancer cells alter glucose and glutamine levels, O-GlcNAc modifications and OGT levels become elevated and are required for regulation of malignant properties (PMID:22275356)
• a 154-amino acid region of MIBP1 was necessary for its O-GlcNAc transferase binding and O-GlcNAcylation. (PMID:22294689)
• Data show that the interplay between O-GlcNAc and phosphorylation on proteins and indicate that these effects can be mediated by changes in hOGT and hOGA kinetic activity. (PMID:22311971)
• These studies identify a molecular mechanism of GR transrepression, and highlight the function of O-GlcNAc in hormone signaling. (PMID:22371499)
• O-GlcNAcylation may be an important regulatory modification involved in endometrial cancer pathogenesis but the actual significance of this modification for endometrial cancer progression needs to be investigated further. (PMID:22384635)
• Hsp90 is involved in the regulation of OGT and O-GlcNAc modification and that Hsp90 inhibitors might be used to modulate O-GlcNAc modification and reverse its adverse effects in human diseases. (PMID:22496241)
• Analysis of urinary content of MGEA5 and OGT may be useful for bladder cancer diagnostics. (PMID:22783592)
• O-GlcNAc transferase/host cell factor C1 complex regulates gluconeogenesis by modulating PGC-1alpha stability. (PMID:22883232)
• we describe structural snapshots of all species along the kinetic pathway for human O-linked beta-N-acetylglucosamine transferase (O-GlcNAc transferase), an intracellular enzyme that catalyzes installation of a dynamic post-translational modification (PMID:23103939)
• we define how human OGT recognizes the sugar donor and acceptor peptide and uses a new catalytic mechanism of glycosyl transfer, involving the sugar donor alpha-phosphate as the catalytic base as well as an essential lysine (PMID:23103942)
• The human respiratory syncytial virus-induced sequestration of p38-P in IBs resulted in a substantial reduction in the accumulation of a downstream signaling substrate, MAPK-activated protein kinase 2 (MK2). (PMID:23152511)
• The double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription. (PMID:23222540)
• These studies identified OGT as a promising placental biomarker of maternal stress exposure that may relate to sex-biased outcomes in neurodevelopment. (PMID:23487789)
• Data suggest that changes in OGT (O-linked N-acetylglucosamine transferase) and OGA (peptide O-linked N-acetylglucosamine-beta-N-acetylglucosaminidase) expression are correlated with cancer prognosis. [REVIEW] (PMID:23642195)
• The backbone carbonyl oxygen of Leu653 and the hydroxyl group of Thr560 in OGT contribute to the recognition of sugar moieties via hydrogen bonds. (PMID:23700425)
• Expression of c-MYC and OGT was tightly correlated in human prostate cancer samples. (PMID:23720054)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ogt.2	ENSDARG00000099455
danio_rerio	ogt.1	ENSDARG00000105243
mus_musculus	Ogt	ENSMUSG00000034160
rattus_norvegicus	Ogt	ENSRNOG00000003359
drosophila_melanogaster	sxc	FBGN0261403
caenorhabditis_elegans		WBGENE00003858

Paralogs (14): IFT88 (ENSG00000032742), TTC7A (ENSG00000068724), TMTC4 (ENSG00000125247), TMTC1 (ENSG00000133687), TMTC3 (ENSG00000139324), TTC6 (ENSG00000139865), BBS4 (ENSG00000140463), TTC13 (ENSG00000143643), CFAP70 (ENSG00000156042), TTC8 (ENSG00000165533), TTC7B (ENSG00000165914), TTC16 (ENSG00000167094), TMTC2 (ENSG00000179104), TTC34 (ENSG00000215912)

Protein

Protein identifiers

UDP-N-acetylglucosamine–peptide N-acetylglucosaminyltransferase 110 kDa subunit — O15294 (reviewed: O15294)

Alternative names: O-GlcNAc transferase subunit p110, O-linked N-acetylglucosamine transferase 110 kDa subunit

All UniProt accessions (11): O15294, A0A8V8TNT2, A0A8V8TP17, A0A8V8TP98, A0A8V8TPA3, A0A8V8TQ37, A0A8V8TQ64, A0A8V8TQJ1, B4DTL6, C9JZL3, Q9H5T3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, AMPK, ATG4B, CAPRIN1, EZH2, FNIP1, GSDMD, KRT7, LMNA, LMNB1, LMNB2, RPTOR, HOXA1, PFKL, KMT2E/MLL5, MAPT/TAU, TET2, RBL2, RET, NOD2 and HCFC1. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing. Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the ‘Thr-308’ phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling. Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity. Plays a key role in chromatin structure by mediating O-GlcNAcylation of ‘Ser-112’ of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues. O-GlcNAcylation of ‘Ser-75’ of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex. Stabilizes KMT2E/MLL5 by mediating its glycosylation, thereby preventing KMT2E/MLL5 ubiquitination. Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. Promotes the CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2. O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1. Promotes autophagy by mediating O-glycosylation of ATG4B. Acts as a regulator of mTORC1 signaling by mediating O-glycosylation of RPTOR and FNIP1: O-GlcNAcylation of RPTOR in response to glucose sufficiency promotes activation of the mTORC1 complex. The mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line. Has N-acetylglucosaminyltransferase activity: glycosylates proteins, such as HNRNPU, NEUROD1, NUP62 and PDCD6IP. Displays specific substrate selectivity compared to other isoforms.

Subunit / interactions. Monomer; may exist in different oligomerization states in cells. Homotrimer, oligomerizes via TPR repeats 6 and 7. Trimerization is not necessary for activity in vitro, however it increases affinity for UDP-GlcNAc. Component of a THAP1/THAP3-HCFC1-OGT complex. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Found in a complex with KIF5B, RHOT1, RHOT2 and TRAK1. Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Component of a complex composed of KMT2E/MLL5 (isoform 3), OGT (isoform 1) and USP7; the complex stabilizes KMT2E/MLL5, preventing KMT2E/MLL5 ubiquitination and proteasomal-mediated degradation. Interacts (via TPRs 1-6) with SIN3A; the interaction mediates transcriptional repression in parallel with histone deacetylase. Interacts (via TPR 5-6) with TET1, TET2 and TET3. Interacts (via TPR repeats 6 and 7) with ATXN10. Interacts with NSD2. Interacts with PROSER1; this interaction mediates TET2 O-GlcNAcylation and stability by promoting the interaction between OGT and TET2. Interacts with USP7. (Microbial infection) Interacts with human T-cell leukemia virus 1/HTLV-1 protein Tax; this interaction increases Tax interacting partner CREB1 O-GlcNAcylation.

Subcellular location. Nucleus. Cytoplasm Mitochondrion. Membrane Cytoplasm. Cell membrane. Mitochondrion membrane. Cell projection Cytoplasm.

Tissue specificity. Highly expressed in pancreas and to a lesser extent in skeletal muscle, heart, brain and placenta. Present in trace amounts in lung and liver.

Post-translational modifications. Ubiquitinated by the SCF(FBXO31) complex, leading to its proteasomal degradation. Phosphorylation on Ser-3 or Ser-4 by GSK3-beta positively regulates its activity. Phosphorylation at Thr-454 by AMPK promotes nuclear localization. Glycosylated via autocatalysis; O-GlcNAcylation at Ser-399 promotes nuclear localization. Glycosylated via autocatalysis; does not affect the enzyme activity but regulates substrate selectivity.

Disease relevance. Regulation of OGT activity and altered O-GlcNAcylations are implicated in diabetes and Alzheimer disease. O-GlcNAcylation of AKT1 affects insulin signaling and, possibly diabetes. Reduced O-GlcNAcylations and resulting increased phosphorylations of MAPT/TAU are observed in Alzheimer disease (AD) brain cerebrum. Intellectual developmental disorder, X-linked 106 (XLID106) [MIM:300997] A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Subject to product inhibition by UDP.

Domain organisation. The TPR repeat domain is required for substrate binding and oligomerization.

Induction. Induction of the nucleocytoplasmic OGT (ncOGT) isoform in the liver on glucose deprivation is mediated by the decreased hexosamine biosynthesis pathway (HBP) flux.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
O15294-1	3, Nucleocytoplasmic isoform, ncOGT	yes
O15294-2	2, Mitochondrial isoform, mOGT
O15294-3	1
O15294-4	4, Short isoform, sOGT

RefSeq proteins (2): NP_858058, NP_858059 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR029489	OGT/SEC/SPY_C	Domain
IPR037919	OGT	Family

Pfam: PF00515, PF13181, PF13414, PF13424, PF13844

Enzyme classification (BRENDA):

• EC 2.4.1.255 — protein O-GlcNAc transferase (BRENDA: 18 organisms, 176 substrates, 88 inhibitors, 47 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GLCNAC	0.0005–11.8	25
[FULL-LENGTH O-GLCNACASE/D175N PROTEIN]-L-SERINE	0.0244–0.134	6
NUP62	—	2
PGGSTPVSSANMM	0.107–0.215	2
UDP-N-ACETYL-ALPHA-D-GLUCOSAMINE	0.1757–0.1805	2
UDP-N-AZIDOACETYLGLUCOSAMINE	0.0047–0.0085	2
NUP 62 PROTEIN	0.0012	1
OIP106 PROTEIN	0.0034	1
UDP-4-DEOXY-GALNAC	0.3695	1
UDP-6-DEOXY-GLCNAC	0.1418	1
UDP-GLCNPR	0.2821	1
YSDSPSTST	0.16	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl)-L-seryl-[protein] + UDP + H(+) (RHEA:48904)
• L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl)-L-threonyl-[protein] + UDP + H(+) (RHEA:48908)

UniProt features (162 total): helix 61, strand 28, mutagenesis site 20, repeat 13, glycosylation site 9, binding site 6, modified residue 6, turn 4, sequence variant 4, splice variant 3, short sequence motif 2, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

44 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5NPS	X-RAY DIFFRACTION	1.68
4GYW	X-RAY DIFFRACTION	1.7
6EOU	X-RAY DIFFRACTION	1.75
4N39	X-RAY DIFFRACTION	1.76
4GYY	X-RAY DIFFRACTION	1.85
5NPR	X-RAY DIFFRACTION	1.85
3TAX	X-RAY DIFFRACTION	1.88
4N3A	X-RAY DIFFRACTION	1.88
4GZ3	X-RAY DIFFRACTION	1.9
5LWV	X-RAY DIFFRACTION	1.9
6TKA	X-RAY DIFFRACTION	1.91
3PE4	X-RAY DIFFRACTION	1.95
6MA3	X-RAY DIFFRACTION	2
6MA4	X-RAY DIFFRACTION	2
6MA5	X-RAY DIFFRACTION	2
5C1D	X-RAY DIFFRACTION	2.05
5HGV	X-RAY DIFFRACTION	2.05
6MA2	X-RAY DIFFRACTION	2.1
4N3B	X-RAY DIFFRACTION	2.17
6IBO	X-RAY DIFFRACTION	2.17
6Q4M	X-RAY DIFFRACTION	2.2
5VIF	X-RAY DIFFRACTION	2.25
5BNW	X-RAY DIFFRACTION	2.4
6E37	X-RAY DIFFRACTION	2.53
5LVV	X-RAY DIFFRACTION	2.54
4N3C	X-RAY DIFFRACTION	2.55
5VIE	X-RAY DIFFRACTION	2.6
6MA1	X-RAY DIFFRACTION	2.75
3PE3	X-RAY DIFFRACTION	2.78
8CM9	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15294-F1	93.41	0.90

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 (1): 508 (proton acceptor)

Ligand- & substrate-binding residues (6): 849; 852; 906–908; 911–914; 930–932; 935

Post-translational modifications (6): 2, 3, 4, 20, 454, 989

Glycosylation sites (9): 10, 12, 18, 38, 52, 56, 3, 4, 399

Mutagenesis-validated functional residues (20):

Position	Phenotype
10	does not affect global auto-o-glcnacylation.
12	decreased auto-o-glcnacylation.
18	does not affect global auto-o-glcnacylation.
38	does not affect global auto-o-glcnacylation.
52	does not affect global auto-o-glcnacylation.
56	increased auto-o-glcnacylation.
127	loss of enzyme activity.
208–211	abolished homooligomerization.
208	abolishes homodimerization of the tpr domain. slightly reduced enzyme activity; when associated with d-211.
211	abolishes homodimerization of the tpr domain. slightly reduced enzyme activity; when associated with e-208.
391	reduced autoglycosylation.
393	reduced autoglycosylation.
399	reduced autoglycosylation. reduced localization to the nucleus.
404	reduced autoglycosylation.
454	abolished phosphorylation by ampk. does not affect ability to regulate mtorc1.
454	affects substrate selectivity. mimics phosphorylation; does not affect ability to regulate mtorc1.
461–463	impaired localization to the nucleus.
508	loss of enzyme activity. moderate increase in kmt2e ubiquitination. moderate increase in kmt2e ubiquitination; when asso
568	reduces enzyme activity by about 95%. moderate increase in kmt2e ubiquitination; when associated with a-508.
911	reduces enzyme activity by over 90%.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-5213460	RIPK1-mediated regulated necrosis
R-HSA-5675482	Regulation of necroptotic cell death
R-HSA-5689603	UCH proteinases
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes

MSigDB gene sets: 659 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, AGGAAGC_MIR5163P, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, AAGCAAT_MIR137, TAATAAT_MIR126, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, FISCHER_G1_S_CELL_CYCLE, TGCACTT_MIR519C_MIR519B_MIR519A

GO Biological Process (48): negative regulation of transcription by RNA polymerase II (GO:0000122), mitophagy (GO:0000423), positive regulation of transcription from RNA polymerase II promoter by glucose (GO:0000432), regulation of glycolytic process (GO:0006110), regulation of gluconeogenesis (GO:0006111), chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), protein O-linked glycosylation (GO:0006493), apoptotic process (GO:0006915), signal transduction (GO:0007165), response to nutrient (GO:0007584), protein processing (GO:0016485), hemopoiesis (GO:0030097), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of protein ubiquitination (GO:0031397), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), response to insulin (GO:0032868), circadian regulation of gene expression (GO:0032922), regulation of Rac protein signal transduction (GO:0035020), positive regulation of translation (GO:0045727), positive regulation of proteolysis (GO:0045862), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of insulin receptor signaling pathway (GO:0046626), positive regulation of lipid biosynthetic process (GO:0046889), regulation of synapse assembly (GO:0051963), regulation of necroptotic process (GO:0060544), cellular response to glucose stimulus (GO:0071333), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696), positive regulation of cold-induced thermogenesis (GO:0120162), negative regulation of non-canonical inflammasome complex assembly (GO:0160076), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), positive regulation of TORC1 signaling (GO:1904263), cytoplasmic translation (GO:0002181), obsolete protein glycosylation (GO:0006486), negative regulation of translation (GO:0017148), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202)

GO Molecular Function (8): phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), acetylglucosaminyltransferase activity (GO:0008375), chromatin DNA binding (GO:0031490), protein O-acetylglucosaminyltransferase activity (GO:0097363), protein binding (GO:0005515), lipid binding (GO:0008289), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (16): histone acetyltransferase complex (GO:0000123), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), protein N-acetylglucosaminyltransferase complex (GO:0017122), mitochondrial membrane (GO:0031966), protein-containing complex (GO:0032991), cell projection (GO:0042995), NSL complex (GO:0044545), Sin3-type complex (GO:0070822), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), mitochondrion (GO:0005739), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Regulated Necrosis	1
RIPK1-mediated regulated necrosis	1
Deubiquitination	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
transcription by RNA polymerase II	2
binding	2
chromatin	2
intracellular membrane-bounded organelle	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
autophagy of mitochondrion	1
macroautophagy	1
regulation of transcription from RNA polymerase II promoter by glucose	1
carbon catabolite activation of transcription from RNA polymerase II promoter	1
positive regulation of transcription by glucose	1
glycolytic process	1
regulation of purine nucleotide catabolic process	1
regulation of generation of precursor metabolites and energy	1
regulation of carbohydrate catabolic process	1
regulation of ATP metabolic process	1
gluconeogenesis	1
regulation of glucose metabolic process	1
regulation of carbohydrate biosynthetic process	1
cellular component organization	1
regulation of DNA-templated transcription	1
glycoprotein biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to nutrient levels	1
response to chemical	1
proteolysis	1
protein maturation	1
cell development	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1

Protein interactions and networks

STRING

2422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OGT	HCFC1	P51610	982
OGT	OGA	O60502	952
OGT	TET3	O43151	951
OGT	MCRS1	Q96EZ8	948
OGT	FOXK1	P85037	943
OGT	TET2	Q6N021	927
OGT	ASXL1	Q8IXJ9	919
OGT	KANSL3	Q9P2N6	912
OGT	TRAK1	Q9UPV9	911
OGT	KANSL2	Q9H9L4	882
OGT	WDR5	P61964	857
OGT	Q08EI0	Q08EI0	845
OGT	SIN3A	Q96ST3	828
OGT	PHF20	Q9BVI0	789
OGT	TRAK2	O60296	782

IntAct

260 interactions, top by confidence:

A	B	Type	Score
GSK3B	AXIN1	psi-mi:“MI:0914”(association)	0.980
GSK3A	AXIN1	psi-mi:“MI:0914”(association)	0.800
OGT	HCFC1	psi-mi:“MI:0915”(physical association)	0.760
HCFC1	OGT	psi-mi:“MI:0570”(protein cleavage)	0.760
OGT	HCFC1	psi-mi:“MI:0570”(protein cleavage)	0.760
HCFC1	OGT	psi-mi:“MI:0915”(physical association)	0.760
OGT	NUP62CL	psi-mi:“MI:0915”(physical association)	0.740
NUP62CL	OGT	psi-mi:“MI:0915”(physical association)	0.740
OGT	TET3	psi-mi:“MI:0915”(physical association)	0.740
TET3	OGT	psi-mi:“MI:0915”(physical association)	0.740
NUP62CL	OGT	psi-mi:“MI:0914”(association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
BAP1	OGT	psi-mi:“MI:0914”(association)	0.730
URI1	OGT	psi-mi:“MI:0914”(association)	0.670
OGT	URI1	psi-mi:“MI:0914”(association)	0.670
URI1	OGT	psi-mi:“MI:0915”(physical association)	0.670
OGT	URI1	psi-mi:“MI:0559”(glycosylation reaction)	0.670
OGT	URI1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (1159): OGT (Affinity Capture-MS), OGT (Affinity Capture-MS), OGT (Two-hybrid), TET2 (Two-hybrid), NUP62CL (Two-hybrid), PHC3 (Two-hybrid), OGT (Affinity Capture-RNA), OGT (Affinity Capture-MS), OGT (Affinity Capture-MS), OGT (Affinity Capture-MS), OGT (Affinity Capture-MS), OGT (Affinity Capture-MS), OGT (Affinity Capture-MS), NUP62CL (Two-hybrid), OGT (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8F5J9, A0JN27, F1LTR1, F1NBL0, O15294, P35438, P35439, P56558, P61201, P61202, P61203, P61599, P61600, P63138, P79101, P81436, Q03555, Q05586, Q13888, Q15303, Q27HV0, Q2PFM2, Q2TBV5, Q4L208, Q58ED9, Q5R1P0, Q5SP67, Q5ZJ75, Q61527, Q62956, Q6IQT4, Q6IR75, Q6P1K8, Q6P632, Q7ZXR3, Q8BUV3, Q8C6G8, Q8CGY8, Q8R4D1, Q91854

Diamond homologs: O15294, O18158, P56558, P81436, Q27HV0, Q8CGY8, Q9M8Y0, Q8LP10

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
TET2	up-regulates	OGT	binding
TET3	up-regulates	OGT	binding
OGT	“up-regulates activity”	TET1	glycosylation
OGT	“form complex”	“NSL histone acetyltransferase”	binding
OGT	“up-regulates activity”	G6PD	glycosylation
OGT	“down-regulates activity”	PFKP	glycosylation
OGT	“down-regulates activity”	PFKM	glycosylation
OGT	“down-regulates activity”	PFKL	glycosylation
OGT	“down-regulates activity”	PFK	glycosylation
OGT	“up-regulates activity”	PYGL	glycosylation
XIAP	“down-regulates quantity”	OGT	ubiquitination
GSK3B	“up-regulates activity”	OGT	phosphorylation
EIF2AK3	“up-regulates activity”	OGT	phosphorylation
OGT	“up-regulates activity”	YAP1	glycosylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 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
Activation of BAD and translocation to mitochondria	5	35.9×	8e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	31.7×	1e-05
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	31.7×	1e-05
Signaling by RAS mutants	7	27.9×	4e-07
Activation of BH3-only proteins	5	23.4×	5e-05
RAF activation	7	22.2×	2e-06
Oncogenic MAPK signaling	9	21.1×	9e-08
Regulation of MECP2 expression and activity	6	20.9×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
vesicle transport along microtubule	5	32.6×	4e-04
regulation of protein localization to plasma membrane	5	23.8×	8e-04
protein targeting	6	16.2×	8e-04
long-term synaptic potentiation	5	10.3×	8e-03
MAPK cascade	8	9.0×	1e-03
intracellular protein localization	8	6.2×	5e-03
Wnt signaling pathway	8	5.9×	6e-03
protein phosphorylation	11	5.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	10
Uncertain significance	135
Likely benign	38
Benign	18

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
428570	NM_181672.3(OGT):c.762G>T (p.Leu254Phe)	Pathogenic
428571	NM_181672.3(OGT):c.851G>C (p.Arg284Pro)	Pathogenic
428572	NM_181672.3(OGT):c.463-6T>G	Pathogenic
691611	NM_181672.3(OGT):c.1942A>T (p.Asn648Tyr)	Pathogenic
804282	NM_181672.3(OGT):c.762G>C (p.Leu254Phe)	Pathogenic
804284	NM_181672.3(OGT):c.1016A>G (p.Glu339Gly)	Pathogenic
1186977	NM_181672.3(OGT):c.1769G>T (p.Cys590Phe)	Likely pathogenic
1301100	NM_181672.3(OGT):c.1603A>G (p.Ile535Val)	Likely pathogenic
1313143	NM_181672.3(OGT):c.1361C>T (p.Thr454Met)	Likely pathogenic
1319673	NM_181672.3(OGT):c.563C>T (p.Pro188Leu)	Likely pathogenic
1804018	NM_181672.3(OGT):c.3139T>C (p.Ter1047Gln)	Likely pathogenic
2577949	NM_181672.3(OGT):c.1412A>T (p.His471Leu)	Likely pathogenic
2582590	NM_181672.3(OGT):c.1529G>A (p.Ser510Asn)	Likely pathogenic
3766444	NM_181672.3(OGT):c.1211C>T (p.Thr404Ile)	Likely pathogenic
4531346	NM_181672.3(OGT):c.1711T>C (p.Ser571Pro)	Likely pathogenic
689775	NM_181672.3(OGT):c.2795C>T (p.Thr932Ile)	Likely pathogenic

SpliceAI

2881 predictions. Top by Δscore:

Variant	Effect	Δscore
X:71536156:A:AG	acceptor_gain	1.0000
X:71536156:AAAT:A	acceptor_gain	1.0000
X:71536157:A:G	acceptor_gain	1.0000
X:71536159:T:G	acceptor_gain	1.0000
X:71536164:T:TA	acceptor_gain	1.0000
X:71536167:T:TA	acceptor_gain	1.0000
X:71538068:ATCCT:A	donor_gain	1.0000
X:71538069:TCCT:T	donor_gain	1.0000
X:71538070:CCT:C	donor_gain	1.0000
X:71538071:CT:C	donor_gain	1.0000
X:71538072:TG:T	donor_loss	1.0000
X:71538073:G:GA	donor_loss	1.0000
X:71538073:G:GG	donor_gain	1.0000
X:71538074:TG:T	donor_loss	1.0000
X:71538075:GAGTA:G	donor_loss	1.0000
X:71538076:AGT:A	donor_loss	1.0000
X:71538077:G:C	donor_loss	1.0000
X:71554507:TTTTA:T	acceptor_loss	1.0000
X:71554508:TTTA:T	acceptor_loss	1.0000
X:71554509:TTAG:T	acceptor_loss	1.0000
X:71554511:A:AG	acceptor_gain	1.0000
X:71554512:G:GG	acceptor_gain	1.0000
X:71554512:GGCT:G	acceptor_gain	1.0000
X:71555384:GT:G	donor_gain	1.0000
X:71555948:TTCTA:T	acceptor_loss	1.0000
X:71555949:TCTA:T	acceptor_loss	1.0000
X:71555950:CTA:C	acceptor_loss	1.0000
X:71555951:TAGG:T	acceptor_loss	1.0000
X:71555952:A:AG	acceptor_gain	1.0000
X:71555952:AGGT:A	acceptor_loss	1.0000

AlphaMissense

6939 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:71536234:T:C	Y32H	1.000
X:71536258:G:C	A40P	1.000
X:71536259:C:A	A40D	1.000
X:71536272:C:G	C44W	1.000
X:71536280:T:C	L47P	1.000
X:71536313:T:C	L58P	1.000
X:71536316:T:C	L59S	1.000
X:71536322:T:C	L61P	1.000
X:71536331:T:A	I64K	1.000
X:71536336:T:C	F66L	1.000
X:71536337:T:C	F66S	1.000
X:71536338:C:A	F66L	1.000
X:71536338:C:G	F66L	1.000
X:71537831:C:T	S74F	1.000
X:71537842:A:C	S78R	1.000
X:71537844:C:A	S78R	1.000
X:71537844:C:G	S78R	1.000
X:71537852:C:A	A81E	1.000
X:71537882:C:A	A91D	1.000
X:71537890:A:G	N94D	1.000
X:71537892:T:A	N94K	1.000
X:71537892:T:G	N94K	1.000
X:71537896:G:A	G96R	1.000
X:71537896:G:C	G96R	1.000
X:71537896:G:T	G96W	1.000
X:71537897:G:A	G96E	1.000
X:71537897:G:T	G96V	1.000
X:71537901:T:A	N97K	1.000
X:71537901:T:G	N97K	1.000
X:71537910:G:C	K100N	1.000

dbSNP variants (sampled 300 via entrez): RS1000054185 (X:71539327 G>A,T), RS1000304613 (X:71571458 T>G), RS1000343273 (X:71538891 A>C,G), RS1000382020 (X:71560061 C>A), RS1000384398 (X:71549278 A>G), RS1000493199 (X:71560901 A>G), RS1000529370 (X:71565414 A>G), RS1000665362 (X:71565024 TGGTA>T), RS1000850625 (X:71551760 A>G,T), RS1001002853 (X:71538713 CAT>C), RS1001180077 (X:71539802 T>A,C,G), RS1001211413 (X:71574662 C>G,T), RS1001504295 (X:71561073 G>A), RS1001625675 (X:71532033 G>T), RS1001660044 (X:71561500 T>A)

Disease associations

OMIM: gene MIM:300255 | disease phenotypes: MIM:300997

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked 106	Strong	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual disability, X-linked 106	Moderate	XL

Mondo (2): intellectual disability, X-linked 106 (MONDO:0030907), intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000194	Open mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000369	Low-set ears
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000664	Synophrys
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0001647	Bicuspid aortic valve
HP:0002236	Frontal upsweep of hair
HP:0004209	Clinodactyly of the 5th finger
HP:0008499	High hypermetropia
HP:0008734	Decreased testicular size
HP:0012471	Thick vermilion border
HP:0030084	Clinodactyly

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002404_422	Red cell distribution width	8.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5955 (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: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

Binding affinities (BindingDB)

26 measured of 26 human assays (26 total across all organisms); most potent 26 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(furan-2-ylmethyl)-2-[(2-oxo-3,4,4a,5,6,7,8,8a-octahydro-1H-quinolin-6-yl)sulfonylamino]-2-phenyl-N-(thiophen-2-ylmethyl)acetamide	KD	400 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(furan-2-ylmethyl)-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenyl-N-(1-thiophen-2-ylethyl)acetamide	KD	1600 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-[2-(4-benzylpiperidin-1-yl)-2-oxo-1-phenylethyl]-2-oxo-3,4-dihydro-1H-quinoline-6-sulfonamide	KD	2000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-[2-[3-methyl-4-(4-methylphenyl)piperazin-1-yl]-2-oxo-1-phenylethyl]-2-oxo-3,4-dihydro-1H-quinoline-6-sulfonamide	KD	3200 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(furan-2-ylmethyl)-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenyl-N-(thiophen-2-ylmethyl)acetamide	KD	4000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(2-ethoxyphenyl)-N-methyl-2-oxo-3,4,4a,5,6,7,8,8a-octahydro-1H-quinoline-6-sulfonamide	KD	4100 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(2-ethoxyphenyl)-2-oxo-3,4,4a,5,6,7,8,8a-octahydro-1H-quinoline-6-sulfonamide	KD	4700 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenyl-N-(2,4,6-trimethylphenyl)acetamide	KD	5600 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-benzyl-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenyl-N-propan-2-ylacetamide	KD	5700 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-[2-[4-(3-methoxyphenyl)piperazin-1-yl]-2-oxo-1-phenylethyl]-2-oxo-3,4-dihydro-1H-quinoline-6-sulfonamide	KD	6300 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-[(4-chlorophenyl)methyl]-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenylacetamide	KD	6600 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(3,4-dimethoxyphenyl)-2-oxo-3,4,4a,5,6,7,8,8a-octahydro-1H-quinoline-6-sulfonamide	KD	7200 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-methyl-N-(3-methylphenyl)-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenylacetamide	KD	7400 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-[2-[4-(4-methylphenyl)piperazin-1-yl]-2-oxo-1-phenylethyl]-2-oxo-3,4-dihydro-1H-quinoline-6-sulfonamide	KD	9000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-[2-[4-(furan-2-carbonyl)piperazin-1-yl]-2-oxo-1-phenylethyl]-2-oxo-3,4-dihydro-1H-quinoline-6-sulfonamide	KD	11000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(furan-2-ylmethyl)-N-methyl-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-3-phenylpropanamide	KD	13000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
3-(3-chlorophenyl)-3-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]propanoic acid	KD	15000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-[2-(4-cyclohexylpiperazin-1-yl)-2-oxo-1-phenylethyl]-2-oxo-3,4-dihydro-1H-quinoline-6-sulfonamide	KD	20000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N,N-diethyl-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenylacetamide	KD	21000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(2,6-dimethylphenyl)-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenylacetamide	KD	37000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
6-[(6,7-dimethoxy-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)sulfonyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-quinolin-2-one	KD	50000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(2-bromo-4-methylphenyl)-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenylacetamide	KD	52000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
2-keto-N-[2-keto-1-phenyl-2-[4-(2-pyridyl)piperazino]ethyl]-3,4-dihydro-1H-quinoline-6-sulfonamide	IC50	53000 nM
N-(6-chloro-1,3-benzothiazol-2-yl)-2-[methyl-[(2-oxo-3,4,4a,5,6,7,8,8a-octahydro-1H-quinolin-6-yl)sulfonyl]amino]acetamide	KD	60000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-(2-ethyl-6-methylphenyl)-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenylacetamide	KD	97000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof
N-benzyl-2-[(2-oxo-3,4-dihydro-1H-quinolin-6-yl)sulfonylamino]-2-phenylacetamide	KD	125000 nM	US-8957075: O-GlcNAc transferase inhibitors and uses thereof

ChEMBL bioactivities

25 potent at pChembl≥5 of 51 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.65	Kd	223	nM	MOLIBRESIB
6.40	Kd	400	nM	CHEMBL3695712
6.32	IC50	480	nM	MOLIBRESIB
5.80	Kd	1600	nM	CHEMBL3695701
5.75	IC50	1800	nM	URIDINE_DIPHOSPHATE
5.70	Kd	2000	nM	CHEMBL3691687
5.57	IC50	2700	nM	CHEMBL5559419
5.50	Kd	3200	nM	CHEMBL3691691
5.40	Kd	4000	nM	CHEMBL3695711
5.39	Kd	4100	nM	CHEMBL3695706
5.38	Kd	4200	nM	CHEMBL1713994
5.33	Kd	4700	nM	CHEMBL1480934
5.25	Kd	5600	nM	CHEMBL3695702
5.24	Kd	5700	nM	CHEMBL3695703
5.20	Kd	6300	nM	CHEMBL3691685
5.18	Kd	6600	nM	CHEMBL3691686
5.16	Kd	7000	nM	CHEMBL3695703
5.14	Kd	7200	nM	CHEMBL1611819
5.13	Kd	7400	nM	CHEMBL3639905
5.10	Ki	8000	nM	CHEMBL3596221
5.05	Kd	9000	nM	CHEMBL3695707
5.00	IC50	1e+04	nM	CHEMBL3596222

PubChem BioAssay actives

4 with measured affinity, of 128 total; 3 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179173: Binding affinity against OGT (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.2230	uM
[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	568345: Inhibition of human OGT	ic50	1.8000	uM
(2R)-N-(furan-2-ylmethyl)-2-(2-methoxyphenyl)-2-[(2-oxo-1H-quinolin-6-yl)sulfonylamino]-N-(thiophen-2-ylmethyl)acetamide	2073762: Inhibition of OGT (unknown origin)	ic50	2.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	5
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
cobaltous chloride	decreases expression	2
Cisplatin	affects reaction, decreases expression, decreases response to substance, increases expression	2
Progesterone	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
beauvericin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
hexamethylene bisacetamide	affects binding, affects cotreatment, decreases reaction	1
beta-lapachone	increases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric oxide	increases expression	1
cadmium sulfate	decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
arsenic disulfide	decreases expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
K 7174	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

37 unique, capped per target: 37 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1670863	Binding	Activity at human OGT by Western blot analysis	6’’-Azido-6’’-deoxy-UDP-N-acetylglucosamine as a glycosyltransferase substrate. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B9NY	Abcam A-549 OGT KO	Cancer cell line	Male
CVCL_D7WA	Ubigene A-549 OGT KO	Cancer cell line	Male

Clinical trials (associated diseases)

197 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
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
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
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders