DPAGT1

Chr 11AR

dolichyl-phosphate N-acetylglucosaminephosphotransferase 1

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

NCBI Gene: 1798 ENSG00000172269 UniProt: Q9H3H5 OMIM: 191350

The encoded enzyme catalyzes the first step in the dolichol-linked oligosaccharide pathway for glycoprotein biosynthesis as an integral endoplasmic reticulum membrane protein. Autosomal recessive mutations cause congenital disorder of glycosylation type Ij and congenital myasthenic syndrome 13 with tubular aggregates. The pathogenic mechanism appears to be dominant-negative, where mutant proteins interfere with normal glycosylation processes.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.082 OMIM phenotypes

Clinical Summary— DPAGT1

🧬

Gene-Disease Validity (ClinGen)

DPAGT1-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

44 unique Pathogenic / Likely Pathogenic· 157 VUS of 373 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — DPAGT1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

1.43Z-score

OE missense 0.73 (0.64–0.83)

156 obs / 214.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.39–1.08)

0≤0.351.4

Missense OE?0.73 (0.64–0.83)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 10 / 15.7Missense obs/exp: 156 / 214.8Syn Z: 1.14

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveDPAGT1-related congenital disorder of glycosylationOTHERAR

definitiveDPAGT1-related myasthenic syndrome, congenital, with tubular aggregatesLOFAR

This gene — mechanism propensity

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

0.83top 10%

GOF

0.6540th %ile

LOF

0.1796th %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

373 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic27

VUS157

Likely Benign127

Benign12

Conflicting26

Pathogenic

Likely Pathogenic

157

VUS

127

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	5	1	1	17
Likely Pathogenic	9	17	1	0	27
VUS	2	132	22	1	157
Likely Benign	0	1	65	61	127
Benign	0	1	11	0	12
Conflicting	—				26
Total	21	156	100	63	366

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap DPAGT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →