DPM1

Chr 20AR

dolichyl-phosphate mannosyltransferase subunit 1, catalytic

Also known as: CDGIE, MPDS

NCBI Gene: 8813ENSG00000000419UniProt: O60762

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. Human DPM1 lacks a carboxy-terminal transmembrane domain and signal sequence and is regulated by DPM2. Mutations in this gene are associated with congenital disorder of glycosylation type Ie. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IeMIM #608799
AR
331
ClinVar variants
40
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— DPM1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 136 VUS of 331 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.87LOEUF
pLI 0.000
Z-score 1.96
OE 0.50 (0.30–0.87)
Tolerant

Typical tolerance to LoF variation

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.
0.38Z-score
OE missense 0.91 (0.79–1.05)
129 obs / 141.7 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.0.50 (0.30–0.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.79–1.05)
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.1.32
0≤1.21.6
LoF obs/exp: 9 / 18.0Missense obs/exp: 129 / 141.7Syn Z: -1.76

ClinVar Variant Classifications

331 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic13
VUS136
Likely Benign120
Benign9
Conflicting14
27
Pathogenic
13
Likely Pathogenic
136
VUS
120
Likely Benign
9
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
19
0
27
Likely Pathogenic
3
4
6
0
13
VUS
1
116
16
3
136
Likely Benign
1
2
65
52
120
Benign
0
0
9
0
9
Conflicting
—14
Total1212311555319

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

View in ClinVar →

Protein Context — Lollipop Plot

DPM1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DPM1-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 Ie

MIM #608799

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Unique clinical presentations and follow-up outcomes from experience with congenital disorders of glycosylation: PMM2-PGM1-DPAGT1-MPI-POMT2-B3GALNT2-DPM1-SRD5A3-CDG.
Yoldas Celik M et al.·J Pediatr Endocrinol Metab
2023Natural history
The expression of genes KRAS, DPM1, ACRV1, and MBD3L2 in the saliva as potential tumor markers in the detection of pancreatic cancer.
Ciosek J et al.·Pol Przegl Chir
2025
A recurrent homozygous missense DPM3 variant leads to muscle and brain disease.
Nagy S et al.·Clin Genet
2022
Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation.
Zemet R et al.·Mol Genet Metab
2024Natural history
Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.
Medrano C et al.·Clin Genet
2019
Congenital disorder of glycosylation due to DPM1 mutations presenting with dystroglycanopathy-type congenital muscular dystrophy.
Yang AC et al.·Mol Genet Metab
2013Case report
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
Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of glycosylation type Ie.
Imbach T et al.·J Clin Invest
2000
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
Ethanol-induced impairment in the biosynthesis of N-linked glycosylation.
Welti M et al.·J Cell Biochem
2014
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
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools