MPDU1

protein-coding

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

Gene summary

This gene encodes an endoplasmic reticulum membrane protein that is required for utilization of the mannose donor mannose-P-dolichol in the synthesis of lipid-linked oligosaccharides and glycosylphosphatidylinositols. Mutations in this gene result in congenital disorder of glycosylation type If. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

MANE transcript

NM_004870.4

Inheritance

ClinVar variants

P:20U:58B:23

Top phenotype

Congenital disorder of glycosylation, type If

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr17:7,583,529-7,592,789

External References & Databases

Ensembl (ENSG00000129255)

Transcript & Mutation Effects

hg38 • Region Span ~9.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

MPDU1-congenital disorder of glycosylationDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012211

Submitter: G2P

MPDU1-congenital disorder of glycosylationSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012211

Submitter: Orphanet

MPDU1-congenital disorder of glycosylationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012211

Submitter: PanelApp Australia

MPDU1-congenital disorder of glycosylationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012211

Submitter: Labcorp Genetics (formerly Invitae)

MPDU1-congenital disorder of glycosylationDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012211

Submitter: ClinGen

*MPDU1* was first reported in relation to MPDU1-congenital disorder of glycosylation (synonym: congenital disorder of glycosylation, type If) in 2001 (Kranz et al, PMID: 11733556; Schenk et al, PMID: 11733564). This condition is characterized by developmental delay, intellectual disability, seizures, brain atrophy, skin disorder, cardiac defects, and a CDG type I pattern of serum transferrin glycosylation (increase in asialo- and disialotransferrin). In addition, a specific pattern of lipid-linked oligosaccharides has been observed in patient fibroblasts and Lec35 CHO cells, which have a defect in the hamster orthologue of *MPDU1*. This includes accumulation of Man9GlcNAc2 and Man5GlcNAc2 and presence of the complete Glc3Man9GlcNAc2 oligosaccharide (Kranz et al, PMID: 11733556; Schenk et al, PMID: 11733564). *MPDU1*-congenital disorder of glycosylation is currently the only disorder known to result from variants in *MPDU1*. 12 variants (7 missense, 2 small in-frame deletions, 1 nonsense, 1 frameshift, 1 initiation codon) that have been reported in 13 probands in 9 publications (Kranz et al, 2001 PMID: 11733556; Schenk et al, 2001, PMID: 11733564; Al Teneiji et al, 2017, PMID: 28122681; Bastaki et al, 2018, PMID: 28940310; Thiel et al, 2018, PMID: 29721919; van Tol et al, 2019, PMID: 31741824; Abu Bakar et al, 2022, PMID: 35279850; Darouich et al, 2023, PMID: 36755425; Wei et al, 2025, PMID: 38831602) are included in this curation. One variant, c.218G>A (p.Gly73Glu) (ClinVar Variation ID: 5867) has been identified in 4 independent probands. Additional evidence is available in the literature (e.g. PMID: 31677975, 35810431) but the maximum score for genetic evidence (12 points) has been reached. This gene-disease relationship is also supported by experimental evidence. The function of *MPDU1* in glycosylation, as a chaperone that facilitates the transport of dolichol-linked sugars - mannose-P-dolichol and glucose-P-dolichol - across the ER membrane, is consistent with the results of analysis of transferrin glycosylation and lipid linked oligosaccharides from patients. Lec35 (hamster orthologue of *MPDU1*, has been shown to be involved in all four classes of sugar-P-dolichol–dependent reactions known in mammalian cells; GPD-dependent reactions in LLO synthesis, and MPD-dependent reactions in LLO, GPI, and C-mannosyl tryptophan synthesis (Anand et al, 2001, PMID: 11179430). Glycosylation patterns in Lec35 cells are similar to those observed in patients. Human *MPDU1* cDNA rescues the glycosylation phenotype in Lec35 CHO cells (Anand et al, 2001, PMID: 11179430). In summary, there is definitive evidence supporting the relationship between *MPDU1* and *MPDU1*-congenital disorder of glycosylation (also known as congenital disorder of glycosylation, type If). This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on July 16, 2025 (SOP Version 11).

Clinical Genomic Database (CGD)

Congenital disorder of glycosylation, type IfAR

Manifestation: Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Hematologic

Rationale: At least theoretically, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery

Comments: Hepatic-metabolized agents should be avoided

Refs: 11733556; 11733564; 20301507

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MPDU1 variants in ClinVar

7 Conditions Cataloged

MPDU1-congenital disorder of glycosylationTotal: 73

not providedTotal: 26

Inborn genetic diseasesTotal: 26

not specifiedTotal: 13

MPDU1-related disorderTotal: 5

MPDU1-related disordersTotal: 1

Fetal anomalies with a likely genetic causeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004870.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	16 clinvar		19
missense	2 clinvar	3 clinvar	50 clinvar	5 clinvar	2 clinvar	62
nonsense		4 clinvar				4
start loss	1 clinvar					1
frameshift		6 clinvar	2 clinvar			8
splice donor/acceptor (+/-2bp)		4 clinvar	3 clinvar			7
Total	3	17	58	21	2	101

Highest pathogenic variant AF is 0.000027261563

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004870.4	RefSeq	NP_004861.2	7	MANE Select
ENST00000250124.11	Ensembl	ENSP00000250124.6	7	MANE Select
NM_001330073.1	RefSeq	NP_001317002.1	6	Standard
ENST00000359822.10	Ensembl	ENSP00000352876.6	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

protein folding
dolichol-linked oligosaccharide biosynthetic process
oligosaccharide biosynthetic process

Molecular Function

protein binding

Cellular Component

endoplasmic reticulum membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000250124
Coding exons: 7
Length: 9261
Individuals with no LoFs: 125684
Homozygous LoFs: 0
Heterozygous LoFs: 64
Defined: 125748
p: 0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.440	112	126	0.890	0.00000666	1563
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.00032	0.00032	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Intolerance Scores

LoFtool: 0.405
RVIS EVS: 0.44
RVIS percentile EVS: 77.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.955

Gene Damage Prediction

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