OGT

O-linked N-acetylglucosamine (GlcNAc) transferase, the group of NSL histone acetyltransferase complex|O-linked N-acetylglucosaminyltransferases|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): X:71533087-71575892

Links

ENSG00000147162 ∙ NCBI:8473 ∙ OMIM:300255 ∙ HGNC:8127 ∙ Uniprot:O15294 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, X-linked 106 (Moderate), mode of inheritance: XL
• intellectual disability, X-linked 106 (Strong), mode of inheritance: XL
• intellectual disability, X-linked 106 (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 106	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	28302723; 28584052

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OGT gene.

• Intellectual disability, X-linked 106 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OGT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	14	6	23
missense	1	6	62	2		71
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	4	2	7
non coding				3	7	10
Total	1	6	66	19	13

Variants in OGT

This is a list of pathogenic ClinVar variants found in the OGT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-71533302-G-A			Uncertain significance (Oct 12, 2020)
X-71533318-A-C			Uncertain significance (Nov 27, 2023)
X-71533327-G-A			Uncertain significance (Nov 10, 2019)
X-71536191-T-C			Uncertain significance (Sep 19, 2022)
X-71536206-A-G			Uncertain significance (Sep 19, 2022)
X-71536225-C-T			Uncertain significance (Mar 31, 2023)
X-71536280-T-G		Intellectual disability, X-linked 106	Uncertain significance (Jan 12, 2021)
X-71536301-A-G			Uncertain significance (Jul 01, 2023)
X-71536350-G-T		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
X-71536370-TG-T			Benign (Jul 06, 2022)
X-71537851-G-A			Uncertain significance (Nov 21, 2022)
X-71537869-C-G		Inborn genetic diseases	Uncertain significance (Oct 13, 2023)
X-71537917-G-A		Inborn genetic diseases • Intellectual disability, X-linked 106	Conflicting classifications of pathogenicity (Dec 28, 2016)
X-71537923-T-C			Likely benign (Apr 26, 2023)
X-71537955-A-C			Likely benign (Aug 16, 2022)
X-71537959-C-T		Intellectual disability, X-linked 106	Uncertain significance (Dec 18, 2019)
X-71537962-C-T			Uncertain significance (Dec 23, 2022)
X-71538022-G-A			Uncertain significance (Feb 28, 2022)
X-71538030-A-T		Intellectual disability, X-linked 106	Uncertain significance (Oct 18, 2023)
X-71538037-G-A			Uncertain significance (Jan 01, 2024)
X-71538068-A-G			Uncertain significance (May 26, 2022)
X-71544561-T-G		Intellectual disability, X-linked 106	Pathogenic (Aug 19, 2021)
X-71544568-A-T			Uncertain significance (Jun 29, 2020)
X-71544626-A-C		OGT-related disorder	Uncertain significance (Feb 09, 2024)
X-71544641-T-C		not specified	Uncertain significance (May 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OGT	protein_coding	protein_coding	ENST00000373719	22	42815

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000174	102448	0	1	102449	0.00000488

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.67	82	402	0.204	0.0000309	6930
Missense in Polyphen		12	152.98	0.078443		2558
Synonymous	1.30	121	141	0.861	0.0000107	2007
Loss of Function	5.64	0	37.0	0.00	0.00000299	619

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000150	0.0000114
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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) (PubMed:26678539, PubMed:23103939, PubMed:21240259, PubMed:21285374, PubMed:15361863). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374). Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (PubMed:26678539). 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 (By similarity). Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity (PubMed:22923583). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. 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) (PubMed:22121020, PubMed:23353889). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex (PubMed:24474760). Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins ARNTL/BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. Promotes the CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2 (PubMed:12150998, PubMed:19451179, PubMed:20018868, PubMed:20200153, PubMed:21285374, PubMed:15361863). O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (PubMed:21285374, PubMed:28584052, PubMed:28302723). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Glycosylates HOXA1 (By similarity). {ECO:0000250|UniProtKB:P56558, ECO:0000250|UniProtKB:Q8CGY8, ECO:0000269|PubMed:12150998, ECO:0000269|PubMed:15361863, ECO:0000269|PubMed:19451179, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20018868, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:21285374, ECO:0000269|PubMed:22121020, ECO:0000269|PubMed:22923583, ECO:0000269|PubMed:23103939, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24474760, ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:28302723, ECO:0000269|PubMed:28584052}.
• Disease: DISEASE: Note=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.; DISEASE: Mental retardation, X-linked 106 (MRX106) [MIM:300997]: A form of mental retardation, 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 mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:26273451, ECO:0000269|PubMed:28302723, ECO:0000269|PubMed:28584052}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Insulin resistance - Homo sapiens (human);Other types of O-glycan biosynthesis - Homo sapiens (human);Ectoderm Differentiation;Post-translational protein modification;Metabolism of proteins;Chromatin modifying enzymes;protein <i>O</i>-[<i>N</i>-acetyl]-glucosylation;HATs acetylate histones;UCH proteinases;Deubiquitination;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.326

Intolerance Scores

• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.359
• hipred: Y
• hipred_score: 0.783
• ghis: 0.628

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.853

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ogt
• Phenotype: reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: ogt.2
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: regulation of glycolytic process;regulation of gluconeogenesis;regulation of transcription by RNA polymerase II;protein O-linked glycosylation;apoptotic process;signal transduction;response to nutrient;viral process;protein processing;protein deubiquitination;negative regulation of protein ubiquitination;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;response to insulin;circadian regulation of gene expression;regulation of Rac protein signal transduction;histone H4-K5 acetylation;histone H4-K8 acetylation;histone H4-K16 acetylation;positive regulation of proteolysis;positive regulation of transcription by RNA polymerase II;regulation of insulin receptor signaling pathway;phosphatidylinositol-mediated signaling;positive regulation of histone H3-K27 methylation;histone H3-K4 trimethylation;positive regulation of cold-induced thermogenesis
• Cellular component: histone acetyltransferase complex;nucleus;nucleoplasm;cytosol;plasma membrane;mitochondrial membrane;protein-containing complex;cell projection
• Molecular function: protein binding;phosphatidylinositol-3,4,5-trisphosphate binding;acetylglucosaminyltransferase activity;protein N-acetylglucosaminyltransferase activity;histone acetyltransferase activity (H4-K5 specific);histone acetyltransferase activity (H4-K8 specific);histone acetyltransferase activity (H4-K16 specific);protein O-GlcNAc transferase activity