DPM2

Chr 9AR

dolichyl-phosphate mannosyltransferase subunit 2, regulatory

Also known as: CDG1U

DPM2 encodes a regulatory subunit of the dolichol-phosphate mannose synthase complex that is essential for ER localization and stable expression of DPM1, and also participates in GPI biosynthesis by regulating the GPI-N-acetylglucosaminyltransferase complex. Mutations cause congenital disorder of glycosylation type Iu, inherited in an autosomal recessive pattern. This condition affects protein glycosylation pathways critical for proper cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.121 OMIM phenotype
Clinical SummaryDPM2
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Gene-Disease Validity (ClinGen)
congenital muscular dystrophy with intellectual disability and severe epilepsy · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.12LOEUF
pLI 0.318
Z-score 1.44
OE 0.24 (0.081.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.60Z-score
OE missense 0.74 (0.550.99)
31 obs / 42.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.081.12)
00.351.4
Missense OE0.74 (0.550.99)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 1 / 4.2Missense obs/exp: 31 / 42.0Syn Z: 0.61
DN
0.75top 25%
GOF
0.78top 25%
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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