DPM1

Chr 20AR

dolichyl-phosphate mannosyltransferase subunit 1, catalytic

Also known as: CDGIE, MPDS

NCBI Gene: 8813 ENSG00000000419 UniProt: O60762 OMIM: 603503

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.

GeneReviews 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. Human DPM1 lacks a carboxy-terminal transmembrane domain and signal sequence and is regulated by DPM2. Mutations in this gene are associated with congenital disorder of glycosylation type Ie. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.871 OMIM phenotype

Clinical Summary— DPM1

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Gene-Disease Validity (ClinGen)

congenital disorder of glycosylation type 1E · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

27 unique Pathogenic / Likely Pathogenic· 135 VUS of 318 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — DPM1

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?

0.87LOEUF

pLI 0.000

Z-score 1.96

OE 0.50 (0.30–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.38Z-score

OE missense 0.91 (0.79–1.05)

129 obs / 141.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.30–0.87)

0≤0.351.4

Missense OE?0.91 (0.79–1.05)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

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

This gene — mechanism propensity

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

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

318 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic10

VUS135

Likely Benign120

Benign9

Conflicting15

Pathogenic

Likely Pathogenic

135

VUS

120

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	1	5	0	17
Likely Pathogenic	5	4	1	0	10
VUS	1	119	12	3	135
Likely Benign	1	2	65	52	120
Benign	0	0	9	0	9
Conflicting	—				15
Total	18	126	92	55	306

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap DPM1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →