DPM1

Chr 20AR

dolichyl-phosphate mannosyltransferase subunit 1, catalytic

Also known as: CDGIE, MPDS

DPM1 encodes the catalytic subunit of dolichol-phosphate mannose synthase, which transfers mannose from GDP-mannose to dolichol monophosphate to produce the mannosyl donor required for N-glycosylation, GPI anchor synthesis, and O-mannosylation of proteins. Mutations cause congenital disorder of glycosylation type Ie, which is inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants (pLI 0.0002, LOEUF 0.87), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.871 OMIM phenotype
Clinical SummaryDPM1
🧬
Gene-Disease Validity (ClinGen)
congenital disorder of glycosylation type 1E · 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
7 unique Pathogenic / Likely Pathogenic· 41 VUS of 100 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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 1.96
OE 0.50 (0.300.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.38Z-score
OE missense 0.91 (0.791.05)
129 obs / 141.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.300.87)
00.351.4
Missense OE0.91 (0.791.05)
00.61.4
Synonymous OE1.32
01.21.6
LoF obs/exp: 9 / 18.0Missense obs/exp: 129 / 141.7Syn Z: -1.76
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDPM1-related congenital disorder of glycosylationLOFAR

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

DN
0.7327th %ile
GOF
0.6541th %ile
LOF
0.3165th %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

100 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS41
Likely Benign44
Benign5
Conflicting3
5
Pathogenic
2
Likely Pathogenic
41
VUS
44
Likely Benign
5
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
1
0
5
Likely Pathogenic
2
0
0
0
2
VUS
0
36
4
1
41
Likely Benign
1
0
28
15
44
Benign
0
0
5
0
5
Conflicting
3
Total7363816100

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →