DPM3-congenital disorder of glycosylation

Summary

DPM3-congenital disorder of glycosylation (MONDO:0013049) is a disease caused by DPM3 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DPM3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 54
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0012363	Decreased sialylation of O-linked protein glycosylation	Very frequent (80-99%)
HP:0001315	Reduced tendon reflexes	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001644	Dilated cardiomyopathy	Frequent (30-79%)
HP:0001763	Pes planus	Frequent (30-79%)
HP:0002187	Intellectual disability, profound	Frequent (30-79%)
HP:0002401	Stroke-like episode	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0003560	Muscular dystrophy	Frequent (30-79%)
HP:0003749	Pelvic girdle muscle weakness	Frequent (30-79%)
HP:0003805	Rimmed vacuoles	Frequent (30-79%)
HP:0008331	Elevated creatine kinase after exercise	Frequent (30-79%)
HP:0008981	Calf muscle hypertrophy	Frequent (30-79%)
HP:0100749	Chest pain	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	DPM3-congenital disorder of glycosylation
Mondo ID	MONDO:0013049
MeSH	C567857
OMIM	612937
Orphanet	263494
SNOMED CT	725044000
UMLS	C2752007
MedGen	414534
GARD	0012395
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type Io · CDG syndrome type Io · CDG-Io · CDG1O · CDGIo · congenital disorder of glycosylation type 1o · congenital disorder of glycosylation type Io · congenital disorder of glycosylation, type Io · DG1O · DPM3-CDG · DPM3-CDG (CDG-Io) · DPM3-congenital disorder of glycosylation · muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15

Data availability: 54 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › congenital disorder of glycosylation type I › DPM3-congenital disorder of glycosylation

Related subtypes (27): PMM2-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 36, SSR4-congenital disorder of glycosylation, ALG3-congenital disorder of glycosylation, MPI-congenital disorder of glycosylation, ALG6-congenital disorder of glycosylation 1C, ALG12-congenital disorder of glycosylation, ALG2-congenital disorder of glycosylation, DPAGT1-congenital disorder of glycosylation, ALG8-congenital disorder of glycosylation, ALG1-congenital disorder of glycosylation, ALG9-congenital disorder of glycosylation, congenital disorder of glycosylation type 1E, MPDU1-congenital disorder of glycosylation, DK1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, SRD5A3-congenital disorder of glycosylation, ALG11-congenital disorder of glycosylation, DDOST-congenital disorder of glycosylation, PGM1-congenital disorder of glycosylation, congenital muscular dystrophy with intellectual disability and severe epilepsy, STT3A-congenital disorder of glycosylation, STT3B-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 50, congenital disorder of glycosylation, type IAA, congenital disorder of glycosylation, type ICC, SSR3-CDG

Subtypes (1): muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

54 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 12 pathogenic, 11 likely benign, 2 conflicting classifications of pathogenicity, 1 benign, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1060967	NM_153741.2(DPM3):c.129_130del (p.Tyr44fs)	DPM3	Pathogenic	criteria provided, single submitter
1074098	NM_153741.2(DPM3):c.229C>T (p.Gln77Ter)	DPM3	Pathogenic	criteria provided, single submitter
1446016	NM_153741.2(DPM3):c.244C>T (p.Arg82Ter)	DPM3	Pathogenic	criteria provided, single submitter
1989778	NM_153741.2(DPM3):c.27G>A (p.Trp9Ter)	DPM3	Pathogenic	criteria provided, single submitter
2043355	NM_153741.2(DPM3):c.5del (p.Thr2fs)	DPM3	Pathogenic	criteria provided, single submitter
2762867	NM_153741.2(DPM3):c.205del (p.Asp69fs)	DPM3	Pathogenic	criteria provided, single submitter
3247791	NC_000001.10:g.(?155112418)(155112826_?)del	DPM3	Pathogenic	criteria provided, single submitter
4702	NM_153741.2(DPM3):c.254T>C (p.Leu85Ser)	DPM3	Pathogenic	no assertion criteria provided
4736163	NM_153741.2(DPM3):c.54G>A (p.Trp18Ter)	DPM3	Pathogenic	criteria provided, single submitter
585021	NM_153741.2(DPM3):c.41T>C (p.Leu14Pro)	DPM3	Pathogenic	criteria provided, single submitter
658481	NM_153741.2(DPM3):c.21G>A (p.Trp7Ter)	DPM3	Pathogenic	criteria provided, single submitter
694278	NM_153741.2(DPM3):c.254T>A (p.Leu85Ter)	DPM3	Pathogenic	no assertion criteria provided
694292	NM_153741.2(DPM3):c.124C>G (p.Pro42Ala)	DPM3	Pathogenic/Likely pathogenic	no assertion criteria provided
1981094	NM_153741.2(DPM3):c.179del (p.Arg60fs)	DPM3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292789	NM_153741.2(DPM3):c.249C>A (p.Ala83=)	DPM3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1004176	NM_153741.2(DPM3):c.257C>A (p.Ala86Asp)	DPM3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1016244	NM_153741.2(DPM3):c.196G>T (p.Asp66Tyr)	DPM3	Uncertain significance	criteria provided, single submitter
1383874	NM_153741.2(DPM3):c.248C>T (p.Ala83Val)	DPM3	Uncertain significance	criteria provided, single submitter
1407462	NM_153741.2(DPM3):c.184G>C (p.Ala62Pro)	DPM3	Uncertain significance	criteria provided, single submitter
1410172	NM_153741.2(DPM3):c.19T>C (p.Trp7Arg)	DPM3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1412853	NC_000001.10:g.(?155112438)(155112716_?)dup	DPM3	Uncertain significance	criteria provided, single submitter
1491262	NM_153741.2(DPM3):c.44G>T (p.Gly15Val)	DPM3	Uncertain significance	criteria provided, single submitter
1493482	NM_153741.2(DPM3):c.29G>A (p.Gly10Glu)	DPM3	Uncertain significance	criteria provided, single submitter
2048065	NM_153741.2(DPM3):c.11T>C (p.Leu4Ser)	DPM3	Uncertain significance	criteria provided, single submitter
2061375	NM_153741.2(DPM3):c.193C>T (p.His65Tyr)	DPM3	Uncertain significance	criteria provided, single submitter
2104655	NM_153741.2(DPM3):c.215G>A (p.Arg72His)	DPM3	Uncertain significance	criteria provided, single submitter
2143389	NM_153741.2(DPM3):c.104A>G (p.Gln35Arg)	DPM3	Uncertain significance	criteria provided, single submitter
2413473	NM_153741.2(DPM3):c.59C>T (p.Ala20Val)	DPM3	Uncertain significance	criteria provided, single submitter
2788399	NM_153741.2(DPM3):c.21G>C (p.Trp7Cys)	DPM3	Uncertain significance	criteria provided, single submitter
471063	NM_153741.2(DPM3):c.179G>T (p.Arg60Leu)	DPM3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DPM3	Strong	Autosomal recessive	DPM3-congenital disorder of glycosylation	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DPM3	Orphanet:263494	DPM3-CDG

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DPM3	HGNC:3007	ENSG00000179085	Q9P2X0	Dolichol-phosphate mannosyltransferase subunit 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DPM3	Dolichol-phosphate mannosyltransferase subunit 3	Stabilizer subunit of the dolichol-phosphate mannose (DPM) synthase complex; tethers catalytic subunit DPM1 to the endoplasmic reticulum.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DPM3	Enzyme (other)	yes	2.4.1.83	DPM3

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
mucosa of transverse colon	1
pituitary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DPM3	286	ubiquitous	marker	mucosa of transverse colon, adenohypophysis, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DPM3	1,046

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DPM3	Q9P2X0	88.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of dolichyl-phosphate mannose	1	3806.7×	3e-04	DPM3
Defective DPM1 causes DPM1-CDG	1	3806.7×	3e-04	DPM3
Defective DPM3 causes DPM3-CDG	1	3806.7×	3e-04	DPM3
Defective DPM2 causes DPM2-CDG	1	3806.7×	3e-04	DPM3
Maturation of DENV proteins	1	211.5×	0.005	DPM3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
dolichol phosphate mannose biosynthetic process	1	5617.3×	5e-04	DPM3
dolichyl monophosphate biosynthetic process	1	1872.4×	8e-04	DPM3
protein O-linked glycosylation via mannose	1	936.2×	0.001	DPM3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DPM3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DPM3	2.4.1.83	dolichyl-phosphate beta-D-mannosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	DPM3
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DPM3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.