DPAGT1

Chr 11AR

dolichyl-phosphate N-acetylglucosaminephosphotransferase 1

Also known as: ALG7, CDG-Ij, CDG1J, CMS13, CMSTA2, D11S366, DGPT, DPAGT

NCBI Gene: 1798ENSG00000172269UniProt: Q9H3H5

The protein encoded by this gene is an enzyme that catalyzes the first step in the dolichol-linked oligosaccharide pathway for glycoprotein biosynthesis. This enzyme belongs to the glycosyltransferase family 4. This protein is an integral membrane protein of the endoplasmic reticulum. The congenital disorder of glycosylation type Ij is caused by mutation in the gene encoding this enzyme. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IjMIM #608093
AR
Myasthenic syndrome, congenital, 13, with tubular aggregatesMIM #614750
AR
415
ClinVar variants
72
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DPAGT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
72 Pathogenic / Likely Pathogenic· 169 VUS of 415 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.
1.08LOEUF
pLI 0.000
Z-score 1.33
OE 0.64 (0.39–1.08)
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.
1.43Z-score
OE missense 0.73 (0.64–0.83)
156 obs / 214.8 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.0.64 (0.39–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.64–0.83)
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.0.85
0≤1.21.6
LoF obs/exp: 10 / 15.7Missense obs/exp: 156 / 214.8Syn Z: 1.14

ClinVar Variant Classifications

415 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic28
VUS169
Likely Benign129
Benign12
Conflicting26
44
Pathogenic
28
Likely Pathogenic
169
VUS
129
Likely Benign
12
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
5
33
1
44
Likely Pathogenic
6
16
6
0
28
VUS
0
133
35
1
169
Likely Benign
0
2
66
61
129
Benign
0
1
11
0
12
Conflicting
—26
Total1115715163408

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

View in ClinVar →

Protein Context — Lollipop Plot

DPAGT1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DPAGT1-related congenital disorder of glycosylation

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

DPAGT1-related myasthenic syndrome, congenital, with tubular aggregates

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type Ij

MIM #608093

Molecular basis of disorder known

Autosomal recessive

Myasthenic syndrome, congenital, 13, with tubular aggregates

MIM #614750

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
Ohno K et al.·Int J Mol Sci
2023Review
Inhibition of DPAGT1 suppresses HER2 shedding and trastuzumab resistance in human breast cancer.
Yang M et al.·J Clin Invest
2023
Clinical and genetic characterisation of a large Indian congenital myasthenic syndrome cohort.
Polavarapu K et al.·Brain
2024Cohort
A drug repurposing screen reveals dopamine signaling as a critical pathway underlying potential therapeutics for the rare disease DPAGT1-CDG.
Dalton HM et al.·PLoS Genet
2024
DPAGT1-CDG: Functional analysis of disease-causing pathogenic mutations and role of endoplasmic reticulum stress.
Yuste-Checa P et al.·PLoS One
2017Functional
Novel DPAGT1 Gene Mutation in Two Twins with Congenital Myasthenic Syndrome and a Review of the Literature.
Cheli M et al.·J Neuromuscul Dis
2023Review
Aberrant protein glycosylation: Implications on diagnosis and Immunotherapy.
Bangarh R et al.·Biotechnol Adv
2023Review
Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.
Dong YY et al.·Cell
2018Functional
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
Trouble at the junction: When myopathy and myasthenia overlap.
Nicolau S et al.·Muscle Nerve
2019Review
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