DDOST

dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit, the group of Oligosaccharyltransferase complex subunits

Basic information

Region (hg38): 1:20651766-20661544

Links

ENSG00000244038 ∙ NCBI:1650 ∙ OMIM:602202 ∙ HGNC:2728 ∙ Uniprot:P39656 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• DDOST-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• DDOST-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• DDOST-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• DDOST-congenital disorder of glycosylation (Limited), mode of inheritance: AR
• DDOST-congenital disorder of glycosylation (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ir	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Gastrointestinal; Neurologic	22305527
Hepatic-metabolized agents should be avoided

ClinVar

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

• Congenital disorder of glycosylation type Ir (149 variants)
• not provided (51 variants)
• not specified (33 variants)
• Inborn genetic diseases (22 variants)
• Congenital disorder of glycosylation (17 variants)
• Parkinson Disease, Recessive (7 variants)
• Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDOST 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			5	41	4	50
missense	1	1	73	2	2	79
nonsense						0
start loss						0
frameshift	1					1
inframe indel			5			5
splice donor/acceptor (+/-2bp)			2			2
splice region			5	4		9
non coding			11	37	30	78
Total	2	1	96	80	36

Variants in DDOST

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

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

Position	Type	Phenotype	Significance	ClinVar
1-20651799-A-AT		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-TTTTA-T		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-TTTTATTTATTTA-T		Congenital disorder of glycosylation • Parkinson Disease, Recessive	Benign/Likely benign (Jun 14, 2016)
1-20651801-T-TTTTA		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-T-TTTTATTTA		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-T-TTTTTTTTTTTTATTTATTTATTTA		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-T-TTTTTTTTATTTATTTATTTA		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-T-TTTTATTTATTTATTTA		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-T-TTTTATTTATTTATTTATTTA		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-T-TTTTTTTTTTTTATTTATTTA		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651801-T-TTTTATTTATTTA		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
1-20651917-T-C		Parkinson Disease, Recessive	Likely benign (Jun 14, 2016)
1-20651922-T-G		Parkinson Disease, Recessive	Likely benign (Jun 14, 2016)
1-20652002-C-CTT		Parkinson Disease, Recessive • Congenital disorder of glycosylation	Likely benign (Jun 14, 2016)
1-20652339-T-C		Parkinson Disease, Recessive • Congenital disorder of glycosylation • Congenital disorder of glycosylation type Ir	Benign (Jul 30, 2021)
1-20652362-G-A		not specified	Likely benign (Nov 08, 2016)
1-20652369-C-T		DDOST-related disorder	Likely benign (Feb 17, 2021)
1-20652374-G-GCC		DDOST-related disorder	Likely benign (Mar 20, 2019)
1-20652385-G-A		Congenital disorder of glycosylation type Ir	Likely benign (Dec 31, 2019)
1-20652394-C-T		Congenital disorder of glycosylation type Ir	Likely benign (Jun 05, 2022)
1-20652406-G-A		not specified • Congenital disorder of glycosylation type Ir	Benign/Likely benign (Oct 27, 2023)
1-20652409-CAAG-C		Congenital disorder of glycosylation type Ir	Uncertain significance (Dec 18, 2023)
1-20652412-G-T		Congenital disorder of glycosylation type Ir	Uncertain significance (Jul 05, 2023)
1-20652418-G-A		Congenital disorder of glycosylation type Ir	Likely benign (Oct 04, 2018)
1-20652425-A-T		Congenital disorder of glycosylation type Ir	not provided (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDOST	protein_coding	protein_coding	ENST00000375048	11	9731

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000614	0.995	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.787	239	276	0.867	0.0000156	2958
Missense in Polyphen		52	81.735	0.6362		860
Synonymous	-0.939	133	120	1.11	0.00000760	920
Loss of Function	2.49	9	21.5	0.419	0.00000104	240

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000311	0.000308
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000969	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential subunit of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Required for the assembly of both SST3A- and SS3B-containing OST complexes. Required for efficient N-glycosylation. {ECO:0000250|UniProtKB:Q05052, ECO:0000269|PubMed:22467853, ECO:0000305}.
• Disease: DISEASE: Congenital disorder of glycosylation 1R (CDG1R) [MIM:614507]: 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:22305527}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);N-Glycan biosynthesis - Homo sapiens (human);AGE-RAGE pathway;Neutrophil degranulation;SRP-dependent cotranslational protein targeting to membrane;Translation;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Asparagine N-linked glycosylation;Advanced glycosylation endproduct receptor signaling;N-Glycan biosynthesis (Consensus)

Recessive Scores

• pRec: 0.250

Intolerance Scores

• loftool: 0.387
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.85

Haploinsufficiency Scores

• pHI: 0.196
• hipred: Y
• hipred_score: 0.736
• ghis: 0.593

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.834

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ddost
• Phenotype: immune system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: protein glycosylation;protein N-linked glycosylation;protein N-linked glycosylation via asparagine;response to cytokine;T cell activation;neutrophil degranulation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;oligosaccharyltransferase complex;membrane;integral component of membrane;protein-containing complex;azurophil granule membrane;intracellular membrane-bounded organelle
• Molecular function: oligosaccharyl transferase activity;dolichyl-diphosphooligosaccharide-protein glycotransferase activity;protein binding