DPM3

Chr 1AR

dolichyl-phosphate mannosyltransferase subunit 3, regulatory

Also known as: CDG1O, MDDGB15, MDDGC15

NCBI Gene: 54344 ENSG00000179085 UniProt: Q9P2X0 OMIM: 605951

The protein is a stabilizer subunit of the dolichol-phosphate mannose synthase complex that tethers the catalytic subunit to the endoplasmic reticulum, essential for synthesizing mannose donors required for proper glycosylation of proteins including dystroglycan. Mutations cause autosomal recessive muscular dystrophy-dystroglycanopathy, presenting as either congenital muscular dystrophy with intellectual disability or limb-girdle muscular dystrophy. This affects both muscle and brain development due to defective glycosylation of dystroglycan and other glycoproteins.

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 subunit of dolichyl-phosphate mannosyltransferase and acts as a stabilizer subunit of the dolichyl-phosphate mannosyltransferase complex. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.402 OMIM phenotypes

Clinical Summary— DPM3

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Gene-Disease Validity (ClinGen)

DPM3-congenital disorder of glycosylation · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 38 VUS of 80 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.40LOEUF

pLI 0.233

Z-score 1.14

OE 0.31 (0.11–1.40)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.42Z-score

OE missense 0.86 (0.70–1.07)

59 obs / 68.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.11–1.40)

0≤0.351.4

Missense OE?0.86 (0.70–1.07)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 1 / 3.2Missense obs/exp: 59 / 68.7Syn Z: 0.05

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongDPM3-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

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

0.7132th %ile

GOF

0.7029th %ile

LOF

0.2777th %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

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12

Likely Pathogenic2

VUS38

Likely Benign22

Benign3

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	2	1	0	12
Likely Pathogenic	0	2	0	0	2
VUS	0	36	2	0	38
Likely Benign	0	0	8	14	22
Benign	0	0	2	1	3
Conflicting	—				2
Total	9	40	13	15	79

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap DPM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →