DPM1

dolichyl-phosphate mannosyltransferase subunit 1, catalytic, the group of Dolichyl-phosphate mannosyltransferase subunits|Glycosyltransferase family 2

Basic information

Region (hg38): 20:50934867-50959140

Links

ENSG00000000419 ∙ NCBI:8813 ∙ OMIM:603503 ∙ HGNC:3005 ∙ Uniprot:O60762 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital disorder of glycosylation type 1E (Strong), mode of inheritance: AR
• congenital disorder of glycosylation type 1E (Strong), mode of inheritance: AR
• congenital disorder of glycosylation type 1E (Supportive), mode of inheritance: AR
• congenital disorder of glycosylation type 1E (Moderate), mode of inheritance: AR
• congenital disorder of glycosylation type 1E (Definitive), mode of inheritance: AR
• congenital disorder of glycosylation type 1E (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ie	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Craniofacial; Neurologic; Ophthalmologic	642602; 10642597; 15669674; 16641202
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPM1 gene.

• Congenital_disorder_of_glycosylation_type_1E (224 variants)
• not_provided (41 variants)
• Inborn_genetic_diseases (40 variants)
• not_specified (12 variants)
• DPM1-related_disorder (8 variants)
• Congenital_disorder_of_glycosylation (2 variants)
• Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPM1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003859.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	51		54
missense	1	5	113	4		123
nonsense	3	2				5
start loss		2				2
frameshift	7	1				8
splice donor/acceptor (+/-2bp)	1	3	1			5
Total	12	13	117	55	0

Highest pathogenic variant AF is 0.000102932

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPM1	protein_coding	protein_coding	ENST00000371588	9	23689

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000162	0.972	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.378	129	142	0.911	0.00000714	1671
Missense in Polyphen		24	38.175	0.62868		461
Synonymous	-1.76	65	49.3	1.32	0.00000236	495
Loss of Function	1.96	9	18.0	0.501	9.53e-7	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O- mannosylation of proteins; catalytic subunit of the dolichol- phosphate mannose (DPM) synthase complex.
• Disease: DISEASE: Congenital disorder of glycosylation 1E (CDG1E) [MIM:608799]: 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. Some CDG1E patients have features consistent with a dystroglycanopathy and congenital muscular dystrophy, including O-mannosylation defect, camptodactyly, elevated creatine kinase, motor delay and dystrophic changes on muscel biopsy. {ECO:0000269|PubMed:10642597, ECO:0000269|PubMed:10642602, ECO:0000269|PubMed:15669674, ECO:0000269|PubMed:23856421}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins;dolichyl-diphosphooligosaccharide biosynthesis;Synthesis of dolichyl-phosphate mannose;Synthesis of substrates in N-glycan biosythesis;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: 0.466

Intolerance Scores

• loftool: 0.443
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.64

Haploinsufficiency Scores

• pHI: 0.481
• hipred: N
• hipred_score: 0.413
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Mouse Genome Informatics

• Gene name: Dpm1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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)

Zebrafish Information Network

• Gene name: dpm1
• Affected structure: vasculature
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: GPI anchor biosynthetic process;dolichol metabolic process;protein mannosylation;protein O-linked mannosylation
• Cellular component: nucleus;endoplasmic reticulum;endoplasmic reticulum membrane;membrane;dolichol-phosphate-mannose synthase complex
• Molecular function: dolichyl-phosphate-mannose-protein mannosyltransferase activity;dolichyl-phosphate beta-D-mannosyltransferase activity;protein binding