PGM1-congenital disorder of glycosylation

Summary

PGM1-congenital disorder of glycosylation (MONDO:0013968) is a disease caused by PGM1 (GenCC Definitive), with 2 cohort genes and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PGM1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 356
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		46	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	PGM1-congenital disorder of glycosylation
Mondo ID	MONDO:0013968
MeSH	C567859
OMIM	614921
Orphanet	319646
DOID	DOID:0080570
ICD-11	1592319293
UMLS	C2752015
MedGen	414536
GARD	0004329
Is cancer (heuristic)	no

Also known as: CDG syndrome type It · CDG-It · CDG1T · congenital disorder of glycosylation type 1t · congenital disorder of glycosylation type It · congenital disorder of glycosylation, type It · glycogen storage disease due to phosphoglucomutase deficiency · GSD type 14 · GSDXIV · PGM1-CDG · PGM1-congenital disorder of glycosylation · phosphoglucomutase deficiency type 1 · phosphoglucomutase-1 deficiency · type 14 glycogenosis

Data availability: 356 ClinVar variants · 6 GenCC gene-disease records.

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 › PGM1-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, DPM3-congenital disorder of glycosylation, ALG11-congenital disorder of glycosylation, DDOST-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

356 retrieved; paginated sample, class counts are floors:

153 likely benign, 120 uncertain significance, 31 pathogenic, 20 conflicting classifications of pathogenicity, 11 benign/likely benign, 10 benign, 6 pathogenic/likely pathogenic, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
133287	NM_002633.3(PGM1):c.112A>T (p.Asn38Tyr)	LOC129930668	Pathogenic	criteria provided, multiple submitters, no conflicts
1694516	NM_002633.3(PGM1):c.28_37del (p.Gln10fs)	LOC129930668	Pathogenic	criteria provided, multiple submitters, no conflicts
2151877	NM_002633.3(PGM1):c.119del (p.Ile40fs)	LOC129930668	Pathogenic	criteria provided, single submitter
3658561	NM_002633.3(PGM1):c.88C>T (p.Gln30Ter)	LOC129930668	Pathogenic	criteria provided, single submitter
3719549	NM_002633.3(PGM1):c.28C>T (p.Gln10Ter)	LOC129930668	Pathogenic	criteria provided, single submitter
965085	NM_002633.3(PGM1):c.157_158delinsG (p.Gln53fs)	LOC129930668	Pathogenic	criteria provided, multiple submitters, no conflicts
1064684	PGM1, ARG521TER	PGM1	Pathogenic	no assertion criteria provided
1067257	NM_002633.3(PGM1):c.988G>C (p.Gly330Arg)	PGM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1302006	NM_002633.3(PGM1):c.423del (p.Ala142fs)	PGM1	Pathogenic	criteria provided, single submitter
133286	NM_002633.3(PGM1):c.1547T>C (p.Leu516Pro)	PGM1	Pathogenic	criteria provided, single submitter
133289	NM_002633.3(PGM1):c.787G>T (p.Asp263Tyr)	PGM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
133290	NM_002633.3(PGM1):c.661del (p.Arg221fs)	PGM1	Pathogenic	criteria provided, single submitter
1359807	NM_002633.3(PGM1):c.1544G>A (p.Arg515Gln)	PGM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13650	NM_002633.3(PGM1):c.343A>G (p.Thr115Ala)	PGM1	Pathogenic	no assertion criteria provided
13651	NM_002633.3(PGM1):c.1145-1G>C	PGM1	Pathogenic	no assertion criteria provided
1383900	NM_002633.3(PGM1):c.929_930del (p.Val310fs)	PGM1	Pathogenic	criteria provided, single submitter
1442891	NM_002633.3(PGM1):c.1474del (p.Leu492fs)	PGM1	Pathogenic	criteria provided, single submitter
1803009	NM_002633.3(PGM1):c.689dup (p.Pro231fs)	PGM1	Pathogenic	criteria provided, single submitter
1803010	NM_002633.3(PGM1):c.696_699del (p.Pro231_Tyr232insTer)	PGM1	Pathogenic	criteria provided, single submitter
2013476	NM_002633.3(PGM1):c.511G>T (p.Gly171Ter)	PGM1	Pathogenic	criteria provided, single submitter
2149215	NM_002633.3(PGM1):c.877C>T (p.Arg293Ter)	PGM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2202765	NM_002633.3(PGM1):c.871G>A (p.Gly291Arg)	PGM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2581183	NM_002633.3(PGM1):c.87_94del (p.Phe29fs)	PGM1	Pathogenic	criteria provided, multiple submitters, no conflicts
2696539	NM_002633.3(PGM1):c.1500del (p.Ile500fs)	PGM1	Pathogenic	criteria provided, single submitter
2792756	NM_002633.3(PGM1):c.946_997dup (p.Arg333fs)	PGM1	Pathogenic	criteria provided, single submitter
3247792	NC_000001.10:g.(?64119983)(64125346_?)del	PGM1	Pathogenic	criteria provided, single submitter
3727616	NM_002633.3(PGM1):c.1422dup (p.Glu475Ter)	PGM1	Pathogenic	criteria provided, single submitter
39771	NM_002633.3(PGM1):c.361G>C (p.Gly121Arg)	PGM1	Pathogenic	no assertion criteria provided
39772	NM_002633.3(PGM1):c.1507C>T (p.Arg503Ter)	PGM1	Pathogenic	criteria provided, multiple submitters, no conflicts
4291923	NM_002633.3(PGM1):c.1519_1545delinsC (p.Thr507fs)	PGM1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
PGM1	Definitive	Autosomal recessive	PGM1-congenital disorder of glycosylation	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PGM1	Orphanet:319646	PGM1-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
PGM1	HGNC:8905	ENSG00000079739	P36871	Phosphoglucomutase-1	gencc,clinvar
MIR101-1	HGNC:31488	ENSG00000199135		microRNA 101-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PGM1	Phosphoglucomutase-1	Catalyzes the reversible isomerization of alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PGM1	Enzyme (other)	yes	5.4.2.2	Alpha-D-phosphohexomutase_SF, A-D-PHexomutase_a/b/a-I, A-D-PHexomutase_a/b/a-II
MIR101-1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
vastus lateralis	1
blood	1
calcaneal tendon	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PGM1	292	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, vastus lateralis
MIR101-1	73		marker	calcaneal tendon, sural nerve, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PGM1	2,366
MIR101-1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PGM1	P36871	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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 PGM1 causes PGM1-CDG	1	11420.0×	4e-04	PGM1
Galactose catabolism	1	1631.4×	0.002	PGM1
Glycogen synthesis	1	815.7×	0.002	PGM1
Glycogen breakdown (glycogenolysis)	1	761.3×	0.002	PGM1
Neutrophil degranulation	1	23.1×	0.043	PGM1

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
beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	1	3370.4×	0.002	PGM1
glycogen catabolic process	1	1203.7×	0.002	PGM1
glycolytic process	1	383.0×	0.005	PGM1
gluconeogenesis	1	324.1×	0.005	PGM1
glucose metabolic process	1	255.3×	0.005	PGM1
carbohydrate metabolic process	1	135.9×	0.007	PGM1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
PGM1	0	0
MIR101-1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PGM1	5.4.2.2	phosphoglucomutase (alpha-D-glucose-1,6-bisphosphate-dependent)

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	PGM1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MIR101-1

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)
PGM1	0	—
MIR101-1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening