MPDU1

Chr 17AR

mannose-P-dolichol utilization defect 1

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

NCBI Gene: 9526 ENSG00000129255 UniProt: O75352 OMIM: 604041

The encoded endoplasmic reticulum membrane protein is required for normal utilization of mannose-dolichol phosphate in the synthesis of N-linked and O-linked oligosaccharides and GPI anchors. Mutations cause congenital disorder of glycosylation type If, which follows autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation (pLI <0.001, LOEUF 1.31).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.311 OMIM phenotype

Clinical Summary— MPDU1

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Gene-Disease Validity (ClinGen)

MPDU1-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

16 unique Pathogenic / Likely Pathogenic· 60 VUS of 138 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.44Z-score

OE missense 0.89 (0.76–1.04)

112 obs / 125.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.45–1.31)

0≤0.351.4

Missense OE?0.89 (0.76–1.04)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 9 / 11.9Missense obs/exp: 112 / 125.9Syn Z: 0.20

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMPDU1-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7131th %ile

GOF

0.7029th %ile

LOF

0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

138 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic13

VUS60

Likely Benign33

Benign7

Conflicting8

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	3	0	0	3
Likely Pathogenic	11	2	0	0	13
VUS	5	41	11	3	60
Likely Benign	1	8	13	11	33
Benign	0	3	4	0	7
Conflicting	—				8
Total	17	57	28	14	124

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap MPDU1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →