MPDU1-congenital disorder of glycosylation

Summary

MPDU1-congenital disorder of glycosylation (MONDO:0012211) is a disease caused by MPDU1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MPDU1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 80
• Phenotypes (HPO): 26

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0003642	Type I transferrin isoform profile	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0012379	Abnormal enzyme/coenzyme activity	Very frequent (80-99%)
HP:0008947	Floppy infant	Frequent (30-79%)
HP:0000233	Thin vermilion border	Occasional (5-29%)
HP:0000242	Parietal bossing	Occasional (5-29%)
HP:0000260	Wide anterior fontanel	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000803	Renal cortical cysts	Occasional (5-29%)
HP:0000824	Decreased response to growth hormone stimulation test	Occasional (5-29%)
HP:0000964	Eczematoid dermatitis	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002521	Hypsarrhythmia	Occasional (5-29%)
HP:0003236	Elevated circulating creatine kinase concentration	Occasional (5-29%)
HP:0005478	Prominent frontal sinuses	Occasional (5-29%)
HP:0007965	Undetectable visual evoked potentials	Occasional (5-29%)
HP:0008064	Ichthyosis	Occasional (5-29%)
HP:0008529	Absence of acoustic reflex	Occasional (5-29%)
HP:0011968	Feeding difficulties	Occasional (5-29%)
HP:0012704	Widened subarachnoid space	Occasional (5-29%)
HP:0025474	Erythematous plaque	Occasional (5-29%)
HP:0030353	Decreased serum insulin-like growth factor 1	Occasional (5-29%)
HP:0040189	Scaling skin	Occasional (5-29%)
HP:0040288	Nasogastric tube feeding	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	MPDU1-congenital disorder of glycosylation
Mondo ID	MONDO:0012211
MeSH	C535744
OMIM	609180
Orphanet	79323
DOID	DOID:0080558
NCIT	C126872
SNOMED CT	724096007
UMLS	C1836669
MedGen	322968
GARD	0009832
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type If · carbohydrate-deficient glycoprotein syndrome type 1F · CDG 1F · CDG syndrome type If · CDG-If · CDG1F · CDGIf · congenital disorder of glycosylation type 1f · congenital disorder of glycosylation type If · congenital disorder of glycosylation, type If · MPDU1-CDG · MPDU1-CDG (CDG-If)

Data availability: 80 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

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 › MPDU1-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, DK1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, SRD5A3-congenital disorder of glycosylation, DPM3-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

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

80 retrieved; paginated sample, class counts are floors:

39 uncertain significance, 19 likely benign, 8 conflicting classifications of pathogenicity, 6 likely pathogenic, 4 benign, 3 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
5868	NM_004870.4(MPDU1):c.356T>C (p.Leu119Pro)	MPDU1	Pathogenic	no assertion criteria provided
5871	NM_004870.4(MPDU1):c.221T>C (p.Leu74Ser)	MPDU1	Pathogenic	no assertion criteria provided
5869	NM_004870.4(MPDU1):c.2T>C (p.Met1Thr)	MPDU1-AS1	Pathogenic	no assertion criteria provided
3381955	NM_004870.4(MPDU1):c.193del (p.Ile65fs)	MPDU1	Likely pathogenic	criteria provided, single submitter
4081517	NM_004870.4(MPDU1):c.389-2A>T	MPDU1	Likely pathogenic	criteria provided, single submitter
495318	NM_004870.4(MPDU1):c.310G>A (p.Gly104Ser)	MPDU1	Likely pathogenic	criteria provided, single submitter
495319	NM_004870.4(MPDU1):c.377A>C (p.Gln126Pro)	MPDU1	Likely pathogenic	criteria provided, single submitter
930801	NM_004870.4(MPDU1):c.514C>T (p.Gln172Ter)	MPDU1	Likely pathogenic	criteria provided, single submitter
1333683	NM_004870.4(MPDU1):c.69del (p.Cys22_Tyr23insTer)	MPDU1-AS1	Likely pathogenic	criteria provided, single submitter
325513	NM_004870.4(MPDU1):c.43C>T (p.Pro15Ser)	MPDU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325514	NM_004870.4(MPDU1):c.121C>G (p.Leu41Val)	MPDU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325515	NM_004870.4(MPDU1):c.393C>T (p.Val131=)	MPDU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325516	NM_004870.4(MPDU1):c.411C>T (p.Tyr137=)	MPDU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
387361	NM_004870.4(MPDU1):c.618+14C>T	MPDU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523948	NM_004870.4(MPDU1):c.511del (p.Leu171fs)	MPDU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5867	NM_004870.4(MPDU1):c.218G>A (p.Gly73Glu)	MPDU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
684508	NM_004870.4(MPDU1):c.19G>T (p.Gly7Ter)	MPDU1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017785	NM_004870.4(MPDU1):c.184G>A (p.Val62Met)	MPDU1	Uncertain significance	criteria provided, single submitter
1034126	NM_004870.4(MPDU1):c.613A>G (p.Ile205Val)	MPDU1	Uncertain significance	criteria provided, single submitter
1036624	NM_004870.4(MPDU1):c.573C>A (p.Phe191Leu)	MPDU1	Uncertain significance	criteria provided, single submitter
1302252	NM_004870.4(MPDU1):c.149T>C (p.Ile50Thr)	MPDU1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1347327	NM_004870.4(MPDU1):c.303-16A>G	MPDU1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1444219	NM_004870.4(MPDU1):c.713A>G (p.Lys238Arg)	MPDU1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1511958	NM_004870.4(MPDU1):c.631C>G (p.Pro211Ala)	MPDU1	Uncertain significance	criteria provided, single submitter
1903250	NM_004870.4(MPDU1):c.337A>T (p.Thr113Ser)	MPDU1	Uncertain significance	criteria provided, single submitter
1937258	NM_004870.4(MPDU1):c.410A>G (p.Tyr137Cys)	MPDU1	Uncertain significance	criteria provided, single submitter
1970053	NM_004870.4(MPDU1):c.170-1G>A	MPDU1	Uncertain significance	criteria provided, single submitter
2052017	NM_004870.4(MPDU1):c.589T>C (p.Ser197Pro)	MPDU1	Uncertain significance	criteria provided, single submitter
2689438	NM_004870.4(MPDU1):c.740A>T (p.Gln247Leu)	MPDU1	Uncertain significance	criteria provided, single submitter
3064734	NM_004870.4(MPDU1):c.388+17del	MPDU1	Uncertain significance	criteria provided, single submitter

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
MPDU1	Definitive	Autosomal recessive	MPDU1-congenital disorder of glycosylation	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MPDU1	Orphanet:79323	MPDU1-CDG

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MPDU1	HGNC:7207	ENSG00000129255	O75352	Mannose-P-dolichol utilization defect 1 protein	gencc,clinvar
MPDU1-AS1	HGNC:40379	ENSG00000233223		MPDU1 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MPDU1	Mannose-P-dolichol utilization defect 1 protein	Required for normal utilization of mannose-dolichol phosphate (Dol-P-Man) in the synthesis of N-linked and O-linked oligosaccharides and GPI anchors.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MPDU1	Other/Unknown	no		PQ-loop_rpt, MannP-dilichol_defect-1
MPDU1-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
islet of Langerhans	1
mucosa of transverse colon	1
rectum	1
colonic epithelium	1
primordial germ cell in gonad	1
skeletal muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MPDU1	234	ubiquitous	marker	rectum, mucosa of transverse colon, islet of Langerhans
MPDU1-AS1	134		yes	colonic epithelium, skeletal muscle tissue, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MPDU1	743
MPDU1-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MPDU1	O75352	88.57

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 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
Defective MPDU1 causes CDG-1f	1	11420.0×	8e-04	MPDU1
Diseases associated with N-glycosylation of proteins	1	634.4×	0.007	MPDU1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.014	MPDU1
Diseases of glycosylation	1	131.3×	0.017	MPDU1
Diseases of metabolism	1	80.4×	0.022	MPDU1
Asparagine N-linked glycosylation	1	60.1×	0.025	MPDU1
Post-translational protein modification	1	19.2×	0.067	MPDU1
Disease	1	13.1×	0.081	MPDU1
Metabolism of proteins	1	12.4×	0.081	MPDU1

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-linked oligosaccharide biosynthetic process	1	842.6×	0.002	MPDU1
oligosaccharide biosynthetic process	1	648.1×	0.002	MPDU1
protein folding	1	103.4×	0.010	MPDU1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MPDU1	0	0
MPDU1-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MPDU1	1	Binding:1

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	0
E	Difficult family or no structure, no drug	2	MPDU1, MPDU1-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MPDU1	1	—
MPDU1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.