MPDU1

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

Basic information

Region (hg38): 17:7583528-7592789

Links

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

Phenotypes

GenCC

Source: genCC

• SRD5A3-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• 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

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)
• not specified (11 variants)
• Inborn genetic diseases (11 variants)
• Congenital disorder of glycosylation type I (1 variants)
• Congenital disorder of glycosylation (1 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.

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	12		15
missense		2	27	3	3	35
nonsense		2				2
start loss						0
frameshift		3	1			4
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding			10	8	4	22
Total	0	7	42	23	7

Highest pathogenic variant AF is 0.0000197

Variants in MPDU1

This is a list of pathogenic ClinVar variants found in the MPDU1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-7583681-G-C		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
17-7583724-G-A		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
17-7583755-G-A		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
17-7583790-A-G		Congenital disorder of glycosylation	Benign/Likely benign (Jun 29, 2018)
17-7583827-C-T		Congenital disorder of glycosylation • not specified	Conflicting classifications of pathogenicity (Dec 21, 2016)
17-7583829-G-A		not specified	Likely benign (Feb 11, 2016)
17-7583864-T-C		MPDU1-congenital disorder of glycosylation	Pathogenic (Dec 01, 2001)
17-7583872-G-A		MPDU1-congenital disorder of glycosylation	Uncertain significance (May 23, 2018)
17-7583874-G-A		not specified • MPDU1-congenital disorder of glycosylation	Likely benign (Jul 13, 2020)
17-7583881-G-T		MPDU1-congenital disorder of glycosylation • Inborn genetic diseases	Likely pathogenic (Mar 26, 2021)
17-7583885-C-T		Inborn genetic diseases	Likely benign (Aug 02, 2021)
17-7583886-G-C			Likely benign (Mar 29, 2018)
17-7583905-C-T		MPDU1-congenital disorder of glycosylation • not specified	Conflicting classifications of pathogenicity (Dec 13, 2023)
17-7583915-T-C		MPDU1-congenital disorder of glycosylation • Inborn genetic diseases	Uncertain significance (Aug 30, 2022)
17-7583918-C-T		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
17-7583928-C-G		MPDU1-congenital disorder of glycosylation	Uncertain significance (Oct 28, 2018)
17-7583930-AC-A		MPDU1-congenital disorder of glycosylation	Likely pathogenic (Jan 03, 2022)
17-7583946-T-C		MPDU1-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
17-7583953-G-C		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
17-7583984-C-T		MPDU1-congenital disorder of glycosylation	Likely benign (Feb 04, 2022)
17-7584067-T-C			Likely benign (May 19, 2021)
17-7585536-CCA-C			Benign (Aug 06, 2019)
17-7585742-C-G		not specified • MPDU1-related disorder	Likely benign (Jul 28, 2022)
17-7585749-C-G		MPDU1-congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Aug 07, 2020)
17-7585755-A-C		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)

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