MPDU1

mannose-P-dolichol utilization defect 1, the group of Solute carrier family 66

Basic information

Region (hg38): 17:7583529-7592789

Links

ENSG00000129255 ∙ NCBI:9526 ∙ OMIM:604041 ∙ HGNC:7207 ∙ Uniprot:O75352 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MPDU1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• MPDU1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• MPDU1-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• MPDU1-congenital disorder of glycosylation (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type If	AR	Hematologic	At least theoretically, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	11733556; 11733564; 20301507
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MPDU1 gene.

• MPDU1-congenital_disorder_of_glycosylation (64 variants)
• not_provided (23 variants)
• Inborn_genetic_diseases (23 variants)
• not_specified (9 variants)
• MPDU1-related_disorder (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MPDU1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004870.4. 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	15		18
missense	2	3	38	5	2	50
nonsense		3				3
start loss	1					1
frameshift		5	2			7
splice donor/acceptor (+/-2bp)		2	1			3
Total	3	13	44	20	2

Highest pathogenic variant AF is 0.0000272616

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MPDU1	protein_coding	protein_coding	ENST00000250124	7	9261

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000101	0.576	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.440	112	126	0.890	0.00000666	1563
Missense in Polyphen		32	29.178	1.0967		394
Synonymous	0.202	57	59.0	0.966	0.00000372	539
Loss of Function	0.789	9	11.9	0.754	6.14e-7	130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00126	0.00126
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000477	0.0000462
European (Non-Finnish)	0.000317	0.000316
Middle Eastern	0.0000544	0.0000544
South Asian	0.000132	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal utilization of mannose-dolichol phosphate (Dol-P-Man) in the synthesis of N-linked and O-linked oligosaccharides and GPI anchors. {ECO:0000250}.
• Disease: DISEASE: Congenital disorder of glycosylation 1F (CDG1F) [MIM:609180]: 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:11733556, ECO:0000269|PubMed:11733564}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;Post-translational protein modification;Metabolism of proteins;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Intolerance Scores

• loftool: 0.405
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.7

Haploinsufficiency Scores

• pHI: 0.111
• hipred: N
• hipred_score: 0.278
• ghis: 0.423

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mpdu1

Gene ontology

• Biological process: protein folding;dolichol-linked oligosaccharide biosynthetic process;oligosaccharide biosynthetic process
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: protein binding