DPM2

Chr 9AR

dolichyl-phosphate mannosyltransferase subunit 2, regulatory

Also known as: CDG1U

NCBI Gene: 8818ENSG00000136908UniProt: O94777

Dolichol-phosphate mannose (Dol-P-Man) serves as a donor of mannosyl residues on the lumenal side of the endoplasmic reticulum (ER). Lack of Dol-P-Man results in defective surface expression of GPI-anchored proteins. Dol-P-Man is synthesized from GDP-mannose and dolichol-phosphate on the cytosolic side of the ER by the enzyme dolichyl-phosphate mannosyltransferase. The protein encoded by this gene is a hydrophobic protein that contains 2 predicted transmembrane domains and a putative ER localization signal near the C terminus. This protein associates with DPM1 in vivo and is required for the ER localization and stable expression of DPM1 and also enhances the binding of dolichol-phosphate to DPM1. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IuMIM #615042
AR
181
ClinVar variants
50
Pathogenic / LP
0.32
pLI score
0
Active trials
Clinical Summary— DPM2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 61 VUS of 181 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.
1.12LOEUF
pLI 0.318
Z-score 1.44
OE 0.24 (0.08–1.12)
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.
0.60Z-score
OE missense 0.74 (0.55–0.99)
31 obs / 42.0 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.0.24 (0.08–1.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.55–0.99)
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.0.82
0≤1.21.6
LoF obs/exp: 1 / 4.2Missense obs/exp: 31 / 42.0Syn Z: 0.61

ClinVar Variant Classifications

181 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic3
VUS61
Likely Benign58
Benign6
Conflicting1
47
Pathogenic
3
Likely Pathogenic
61
VUS
58
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
42
0
47
Likely Pathogenic
0
1
2
0
3
VUS
2
28
31
0
61
Likely Benign
0
1
38
19
58
Benign
0
1
4
1
6
Conflicting
—1
Total53311720176

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

View in ClinVar →

Protein Context — Lollipop Plot

DPM2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type Iu

MIM #615042

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation.
Radenkovic S et al.·Mol Genet Metab
2021Case report
Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.
Chestnykh D et al.·Mol Psychiatry
2025
Clinical and genetic characterization of congenital disorders of glycosylation in 20 Chinese patients.
Zhao P et al.·Orphanet J Rare Dis
2025Cohort
A recurrent homozygous missense DPM3 variant leads to muscle and brain disease.
Nagy S et al.·Clin Genet
2022
A single point mutation resulting in an adversely reduced expression of DPM2 in the Lec15.1 cells.
Pu L et al.·Biochem Biophys Res Commun
2003
DPM2-CDG: a muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy.
Barone R et al.·Ann Neurol
2012
Yil102c-A is a Functional Homologue of the DPMII Subunit of Dolichyl Phosphate Mannose Synthase in Saccharomyces cerevisiae.
Piłsyk S et al.·Int J Mol Sci
2020Functional
Molecular hypotheses to explain the shared pathways and underlying pathobiological causes in catatonia and in catatonic presentations in neuropsychiatric disorders.
Peter-Ross EM·Med Hypotheses
2018
Evaluation of the association between five genetic variants and primary open-angle glaucoma in a Han Chinese population.
Li K et al.·Ophthalmic Genet
2020
A new intronic mutation in the DPM1 gene is associated with a milder form of CDG Ie in two French siblings.
Dancourt J et al.·Pediatr Res
2006Case report
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