DPM2

Chr 9AR

dolichyl-phosphate mannosyltransferase subunit 2, regulatory

Also known as: CDG1U

NCBI Gene: 8818 ENSG00000136908 UniProt: O94777 OMIM: 603564

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. The protein encoded by this gene is a hydrophobic protein that contains 2 predicted transmembrane domains and a putative ER localization signal near the C terminus. This protein associates with DPM1 in vivo and is required for the ER localization and stable expression of DPM1 and also enhances the binding of dolichol-phosphate to DPM1. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IuMIM #615042

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · congenital muscular dystrophy with intellectual disability and severe epilepsy · AR · ClinGen 2024

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.318

Z-score 1.44

OE 0.24 (0.08–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.60Z-score

OE missense 0.74 (0.55–0.99)

31 obs / 42.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.08–1.12)

0≤0.351.4

Missense OE?0.74 (0.55–0.99)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 1 / 4.2Missense obs/exp: 31 / 42.0Syn Z: 0.61

Background carrier burden — how many people carry a rare variant somewhere in DPM2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 420

183 rare PASS variants

Rare truncating (LoF)

1 in 1,300

36 rare PASS variants

Rare synonymous (reference)

1 in 220

78 rare PASS variants

Rare missense and truncating variants are carried at similar rates in DPM2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 540	1 in 6,400
South Asian	~43k	1 in 430	1 in 850
Remaining (unassigned)	~30k	1 in 320	1 in 780
European (Finnish)	~27k	1 in 1,400	none seen
Admixed American	~22k	1 in 440	1 in 990
African / African American	~21k	1 in 450	1 in 2,700
East Asian	~20k	1 in 390	1 in 1,800
Ashkenazi Jewish	~13k	none seen	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 280	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 4.? see exons ↓