MPDU1

Chr 17AR

mannose-P-dolichol utilization defect 1

Also known as: CDGIF, HBEBP2BPA, Lec35, My008, PP3958, PQLC5, SL15, SLC66A5

NCBI Gene: 9526ENSG00000129255UniProt: O75352

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]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IfMIM #609180
AR
151
ClinVar variants
34
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MPDU1
🧬
Gene-Disease Validity (ClinGen)
MPDU1-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 69 VUS of 151 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.31LOEUF
pLI 0.000
Z-score 0.79
OE 0.75 (0.45–1.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.44Z-score
OE missense 0.89 (0.76–1.04)
112 obs / 125.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.75 (0.45–1.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.76–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 9 / 11.9Missense obs/exp: 112 / 125.9Syn Z: 0.20

ClinVar Variant Classifications

151 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic12
VUS69
Likely Benign33
Benign7
Conflicting8
22
Pathogenic
12
Likely Pathogenic
69
VUS
33
Likely Benign
7
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
19
0
22
Likely Pathogenic
6
2
3
1
12
VUS
3
42
21
3
69
Likely Benign
1
8
13
11
33
Benign
0
3
4
0
7
Conflicting
—8
Total10586015151

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MPDU1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MPDU1-related congenital disorder of glycosylation

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type If

MIM #609180

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MPDU1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
MPDU1 regulates CEACAM1 and cell adhesion in vitro and in vivo.
Bennett DC et al.·Glycoconj J
2018
Severe Ciliopathy-Like Phenotype in an Infant With a Novel MPDU1 Missense Variant.
Darouich S et al.·Pediatr Dev Pathol
2023
Severe ichthyosis in MPDU1-CDG.
Thiel C et al.·J Inherit Metab Dis
2018Case report
A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If).
Kranz C et al.·J Clin Invest
2001Case report
Synergistic use of glycomics and single-molecule molecular inversion probes for identification of congenital disorders of glycosylation type-1.
Abu Bakar N et al.·J Inherit Metab Dis
2022
Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II.
Al Teneiji A et al.·Mol Genet Metab
2017
MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If.
Schenk B et al.·J Clin Invest
2001
Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs.
Bastaki F et al.·Ann Hum Genet
2018Cohort
Inherited Retinal Degeneration Caused by Dehydrodolichyl Diphosphate Synthase Mutation-Effect of an ALG6 Modifier Variant.
Monson E et al.·Int J Mol Sci
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools