DPAGT1

dolichyl-phosphate N-acetylglucosaminephosphotransferase 1

Basic information

Region (hg38): 11:119096024-119108331

Previous symbols: [ "DPAGT2", "DPAGT" ]

Links

ENSG00000172269 ∙ NCBI:1798 ∙ OMIM:191350 ∙ HGNC:2995 ∙ Uniprot:Q9H3H5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 13 (Definitive), mode of inheritance: AR
• hematopoietic stem cell kinetics, control of (Definitive), mode of inheritance: AR
• congenital myasthenic syndrome 13 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 13 (Strong), mode of inheritance: AR
• DPAGT1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• DPAGT1-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• congenital myasthenic syndromes with glycosylation defect (Supportive), mode of inheritance: AR
• DPAGT1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 13 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 13; Congenital disorder of glycosylation, type Ij	AR	Hematologic; Neurologic	Depending on the age of onset, individuals may present with findings such as hypotonia, gait problems, or falls, and medical treatment (eg, with anticholinesterases or agents that increase nerve terminal acetylcholine release) have been described as beneficial; In CDG, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Genitourinary	12872255; 16870884; 22742743; 23249953; 23278575
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPAGT1 gene.

• DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13 (121 variants)
• Congenital myasthenic syndrome 13;DPAGT1-congenital disorder of glycosylation (82 variants)
• not provided (46 variants)
• DPAGT1-congenital disorder of glycosylation (46 variants)
• Congenital myasthenic syndrome 13 (15 variants)
• not specified (12 variants)
• Congenital disorder of glycosylation (11 variants)
• Inborn genetic diseases (10 variants)
• Acute intermittent porphyria (7 variants)
• Abnormality of metabolism/homeostasis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPAGT1 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	1		1	43		45
missense	1	12	88		1	102
nonsense	2	1	2			5
start loss		1				1
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			10	13		23
non coding			13	27	8	48
Total	7	16	104	70	9

Highest pathogenic variant AF is 0.0000263

Variants in DPAGT1

This is a list of pathogenic ClinVar variants found in the DPAGT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-119096514-A-G		DPAGT1-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
11-119096571-A-C		Acute intermittent porphyria • Congenital disorder of glycosylation • DPAGT1-congenital disorder of glycosylation	Conflicting classifications of pathogenicity (May 24, 2021)
11-119096581-A-G		Congenital disorder of glycosylation • Acute intermittent porphyria • DPAGT1-congenital disorder of glycosylation	Benign (May 11, 2021)
11-119096608-T-C		DPAGT1-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
11-119096612-C-T		DPAGT1-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
11-119096619-C-A		DPAGT1-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
11-119096629-T-C		DPAGT1-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
11-119096733-T-C		Congenital disorder of glycosylation • Acute intermittent porphyria • DPAGT1-congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-119096757-A-G		DPAGT1-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
11-119096814-C-T		Acute intermittent porphyria • DPAGT1-congenital disorder of glycosylation • Congenital disorder of glycosylation	Benign (Jun 29, 2018)
11-119096839-C-T		Acute intermittent porphyria • DPAGT1-congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-119097001-G-A		Congenital myasthenic syndrome 13;DPAGT1-congenital disorder of glycosylation	Likely benign (Jan 15, 2023)
11-119097004-A-G		DPAGT1-congenital disorder of glycosylation • DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13	Conflicting classifications of pathogenicity (Apr 08, 2022)
11-119097006-C-T		Congenital myasthenic syndrome 13;DPAGT1-congenital disorder of glycosylation	Uncertain significance (Aug 23, 2022)
11-119097015-G-A		DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13	Uncertain significance (Mar 18, 2022)
11-119097017-C-T		DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13 • Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
11-119097018-G-A		DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13	Uncertain significance (May 15, 2023)
11-119097021-C-T		Congenital myasthenic syndrome 13;DPAGT1-congenital disorder of glycosylation • DPAGT1-congenital disorder of glycosylation	Uncertain significance (Sep 01, 2021)
11-119097022-G-A		DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13	Likely benign (Jan 20, 2024)
11-119097024-G-A		DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13 • Inborn genetic diseases	Uncertain significance (Aug 15, 2022)
11-119097025-C-A		DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13	Uncertain significance (Jan 11, 2022)
11-119097028-A-T		Congenital disorder of glycosylation	Likely pathogenic (-)
11-119097032-C-T		DPAGT1-congenital disorder of glycosylation;Congenital myasthenic syndrome 13 • DPAGT1-congenital disorder of glycosylation	Uncertain significance (Jul 19, 2023)
11-119097033-G-A		Congenital myasthenic syndrome 13;DPAGT1-congenital disorder of glycosylation	Uncertain significance (Aug 12, 2021)
11-119097037-G-A		Congenital myasthenic syndrome 13;DPAGT1-congenital disorder of glycosylation	Likely benign (Dec 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPAGT1	protein_coding	protein_coding	ENST00000409993	9	11829

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000112	0.824	125707	0	41	125748	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	156	215	0.726	0.0000115	2663
Missense in Polyphen		61	92.444	0.65986		1161
Synonymous	1.14	75	88.7	0.846	0.00000450	853
Loss of Function	1.33	10	15.7	0.638	6.94e-7	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000474	0.000474
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the initial step of dolichol-linked oligosaccharide biosynthesis in N-linked protein glycosylation pathway: transfers GlcNAc-1-P from UDP-GlcNAc onto the carrier lipid dolichyl phosphate (P-dolichol), yielding GlcNAc-P-P- dolichol. {ECO:0000269|PubMed:29459785}.
• Disease: DISEASE: Congenital disorder of glycosylation 1J (CDG1J) [MIM:608093]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:12872255}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 13 (CMS13) [MIM:614750]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS13 is characterized by muscle weakness mostly affecting proximal limb muscles, minimal involvement of facial, ocular and bulbar muscles, and tubular aggregates present on muscle biopsy. Symptoms include difficulty walking and frequent falls. Younger patients show hypotonia and poor head control. Neurophysiological features indicate a disorder of neuromuscular transmission on electromyography. {ECO:0000269|PubMed:22742743}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;dolichyl-diphosphooligosaccharide biosynthesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;N-Glycan biosynthesis (Consensus)

Recessive Scores

• pRec: 0.218

Intolerance Scores

• loftool: 0.383
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.53

Haploinsufficiency Scores

• pHI: 0.188
• hipred: Y
• hipred_score: 0.501
• ghis: 0.508

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.541

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dpagt1
• Phenotype: embryo 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)

Gene ontology

• Biological process: UDP-N-acetylglucosamine metabolic process;protein N-linked glycosylation;dolichol-linked oligosaccharide biosynthetic process;dolichyl diphosphate biosynthetic process;dolichol metabolic process;protein complex oligomerization
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of membrane;integral component of endoplasmic reticulum membrane;intracellular membrane-bounded organelle
• Molecular function: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity;UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity;phospho-N-acetylmuramoyl-pentapeptide-transferase activity;transferase activity, transferring glycosyl groups