glycogen storage disease due to GLUT2 deficiency

Summary

glycogen storage disease due to GLUT2 deficiency (MONDO:0009216) is a disease caused by SLC2A2 (GenCC Definitive), with 2 cohort genes and 2 clinical trials. Top therapeutic interventions include lactic acid and d-lactic acid.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC2A2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 296
• Phenotypes (HPO): 31
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		200	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Prevalence at birth	1-9 / 1 000 000	0.3	Israel	Validated
Prevalence at birth	1-9 / 1 000 000	0.5	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001947	Renal tubular acidosis	Very frequent (80-99%)
HP:0002148	Hypophosphatemia	Very frequent (80-99%)
HP:0003109	Hyperphosphaturia	Very frequent (80-99%)
HP:0004919	Galactose intolerance	Very frequent (80-99%)
HP:0006568	Increased hepatic glycogen content	Very frequent (80-99%)
HP:0040270	Impaired glucose tolerance	Very frequent (80-99%)
HP:0500030	Abnormal hepatic glycogen storage	Very frequent (80-99%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001942	Metabolic acidosis	Frequent (30-79%)
HP:0002150	Hypercalciuria	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002748	Rickets	Frequent (30-79%)
HP:0003076	Glycosuria	Frequent (30-79%)
HP:0003162	Fasting hypoglycemia	Frequent (30-79%)
HP:0003270	Abdominal distention	Frequent (30-79%)
HP:0011998	Postprandial hyperglycemia	Frequent (30-79%)
HP:0000112	Nephropathy	Occasional (5-29%)
HP:0000121	Nephrocalcinosis	Occasional (5-29%)
HP:0000819	Diabetes mellitus	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)
HP:0001399	Hepatic failure	Occasional (5-29%)
HP:0002155	Hypertriglyceridemia	Occasional (5-29%)
HP:0002909	Generalized aminoaciduria	Occasional (5-29%)
HP:0003155	Elevated circulating alkaline phosphatase concentration	Occasional (5-29%)
HP:0006487	Bowing of the long bones	Occasional (5-29%)
HP:0020110	Bone fracture	Occasional (5-29%)
HP:0031956	Elevated circulating aspartate aminotransferase concentration	Occasional (5-29%)
HP:0031964	Elevated circulating alanine aminotransferase concentration	Occasional (5-29%)
HP:0000295	Doll-like facies	Very rare (<1-4%)
HP:0001402	Hepatocellular carcinoma	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease due to GLUT2 deficiency
Mondo ID	MONDO:0009216
OMIM	227810
Orphanet	2088
DOID	DOID:0070562
ICD-11	426701963
SNOMED CT	61598006
UMLS	C3495427
MedGen	501176
GARD	0002268
Is cancer (heuristic)	no

Also known as: Bickel-Fanconi glycogenosis · Fanconi Bickel syndrome · Fanconi syndrome with intestinal malabsorption and galactose intolerance · Fanconi-Bickel disease · Fanconi-Bickel syndrome · FBS · GLUT2 deficiency · glycogen storage disease 11 · glycogen storage disease due to GLUT2 deficiency · glycogen storage disease type 11 · glycogen storage disease type XI · glycogen storage disease XI · glycogenosis due to GLUT2 deficiency · glycogenosis Fanconi EXACT · GSD due to GLUT2 deficiency · GSD type 11 · GSD type XI · hepatic glycogenosis with amino aciduria and glucosuria · hepatorenal glycogenosis with renal Fanconi syndrome · hepatorenal glycogenosis with renal fanconi syndrome (+1 more)

Data availability: 296 ClinVar variants · 5 GenCC gene-disease records · 4 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of glycogen metabolism › glycogen storage disease due to GLUT2 deficiency

Related subtypes (23): glycogen storage disease I, glycogen storage disease II, glycogen storage disease III, glycogen storage disease due to glycogen branching enzyme deficiency, glycogen storage disease V, glycogen storage disease VI, glycogen storage disease VII, glycogen storage disorder due to hepatic glycogen synthase deficiency, Lafora disease, glycogen storage disease due to phosphoglycerate mutase deficiency, lethal congenital glycogen storage disease of heart, Danon disease, glycogen storage disease IXd, glycogen storage disease due to phosphoglycerate kinase 1 deficiency, glycogen storage disease due to muscle and heart glycogen synthase deficiency, glycogen storage disease due to muscle beta-enolase deficiency, glycogen storage disease due to lactate dehydrogenase M-subunit deficiency, polyglucosan body myopathy 1 with or without immunodeficiency, glycogen storage disease due to lactate dehydrogenase deficiency, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, glycogen storage disease due to liver phosphorylase kinase deficiency, GYG1-related disorder of glycogen metabolism, glycogen storage disease IX

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

296 retrieved; paginated sample, class counts are floors:

117 uncertain significance, 82 likely benign, 38 pathogenic, 22 benign, 13 conflicting classifications of pathogenicity, 12 likely pathogenic, 6 pathogenic/likely pathogenic, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1045992	NM_000340.2(SLC2A2):c.1359T>A (p.Cys453Ter)	SLC2A2	Pathogenic	criteria provided, single submitter
1339447	NM_000340.2(SLC2A2):c.2T>G (p.Met1Arg)	SLC2A2	Pathogenic	criteria provided, single submitter
1339448	NM_000340.2(SLC2A2):c.144del (p.Pro49fs)	SLC2A2	Pathogenic	criteria provided, single submitter
1355333	NM_000340.2(SLC2A2):c.1280del (p.Phe427fs)	SLC2A2	Pathogenic	criteria provided, single submitter
1400896	NM_000340.2(SLC2A2):c.457_462del (p.Leu153_Ile154del)	SLC2A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1434311	NC_000003.11:g.(?170727727)(170727891_?)del	SLC2A2	Pathogenic	criteria provided, single submitter
1451164	NM_000340.2(SLC2A2):c.1170+1G>T	SLC2A2	Pathogenic	criteria provided, single submitter
16091	NM_000340.2(SLC2A2):c.137del (p.Leu46fs)	SLC2A2	Pathogenic	no assertion criteria provided
16092	NM_000340.2(SLC2A2):c.1093C>T (p.Arg365Ter)	SLC2A2	Pathogenic	criteria provided, multiple submitters, no conflicts
16093	NM_000340.2(SLC2A2):c.901C>T (p.Arg301Ter)	SLC2A2	Pathogenic	criteria provided, multiple submitters, no conflicts
16095	NM_000340.2(SLC2A2):c.1250C>T (p.Pro417Leu)	SLC2A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16096	NM_000340.2(SLC2A2):c.1259G>A (p.Trp420Ter)	SLC2A2	Pathogenic	no assertion criteria provided
16097	NM_000340.2(SLC2A2):c.1051del (p.Val351fs)	SLC2A2	Pathogenic	no assertion criteria provided
16098	SLC2A2, 1-BP INS, 793C	SLC2A2	Pathogenic	no assertion criteria provided
16099	NM_000340.2(SLC2A2):c.952G>A (p.Gly318Arg)	SLC2A2	Pathogenic	criteria provided, single submitter
16100	NM_000340.2(SLC2A2):c.157C>T (p.Arg53Ter)	SLC2A2	Pathogenic	criteria provided, single submitter
16101	NM_000340.2(SLC2A2):c.1268T>A (p.Val423Glu)	SLC2A2	Pathogenic	no assertion criteria provided
16102	NM_000340.2(SLC2A2):c.109-2A>G	SLC2A2	Pathogenic	no assertion criteria provided
16103	NM_000340.2(SLC2A2):c.859C>T (p.Gln287Ter)	SLC2A2	Pathogenic	no assertion criteria provided
16104	NM_000340.2(SLC2A2):c.1166T>C (p.Leu389Pro)	SLC2A2	Pathogenic	no assertion criteria provided
1686207	NM_000340.2(SLC2A2):c.682C>T (p.Arg228Ter)	SLC2A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1687276	NM_000340.2(SLC2A2):c.351G>A (p.Trp117Ter)	SLC2A2	Pathogenic	criteria provided, single submitter
2422929	NC_000003.11:g.(?170732238)(170732540_?)del	SLC2A2	Pathogenic	criteria provided, single submitter
2572454	NM_000340.2(SLC2A2):c.482dup (p.Gly162fs)	SLC2A2	Pathogenic	criteria provided, single submitter
2815922	NM_000340.2(SLC2A2):c.1183del (p.Trp395fs)	SLC2A2	Pathogenic	criteria provided, single submitter
2832588	NM_000340.2(SLC2A2):c.1392T>A (p.Tyr464Ter)	SLC2A2	Pathogenic	criteria provided, single submitter
3367193	NM_000340.2(SLC2A2):c.1020T>G (p.Tyr340Ter)	SLC2A2	Pathogenic	criteria provided, single submitter
3588928	NM_000340.2(SLC2A2):c.775+1del	SLC2A2	Pathogenic	criteria provided, single submitter
3588939	NM_000340.2(SLC2A2):c.250G>T (p.Glu84Ter)	SLC2A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3588943	NM_000340.2(SLC2A2):c.2T>C (p.Met1Thr)	SLC2A2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
SLC2A2	Definitive	Autosomal recessive	glycogen storage disease due to GLUT2 deficiency	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC2A2	Orphanet:2088	Fanconi-Bickel syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC2A2	HGNC:11006	ENSG00000163581	P11168	Solute carrier family 2, facilitated glucose transporter member 2	gencc,clinvar
TNFSF10	HGNC:11925	ENSG00000121858	P50591	Tumor necrosis factor ligand superfamily member 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC2A2	Solute carrier family 2, facilitated glucose transporter member 2	Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose.
TNFSF10	Tumor necrosis factor ligand superfamily member 10	Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG.

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC2A2	Transporter	yes		Glc_transpt_2, Sugar/inositol_transpt, MFS_sugar_transport-like
TNFSF10	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_ligand_10/11

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
jejunal mucosa	1
liver	1
right lobe of liver	1
monocyte	1
nasal cavity epithelium	1
urethra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC2A2	80	tissue_specific	marker	right lobe of liver, liver, jejunal mucosa
TNFSF10	285	ubiquitous	marker	nasal cavity epithelium, urethra, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC2A2	2,839
TNFSF10	2,700

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNFSF10	P50591	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC2A2	P11168	86.56

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC2A2 causes Fanconi-Bickel syndrome (FBS)	1	5710.0×	0.002	SLC2A2
Intestinal hexose absorption	1	1903.3×	0.003	SLC2A2
TRAIL signaling	1	713.8×	0.004	TNFSF10
Regulation by c-FLIP	1	519.1×	0.004	TNFSF10
CASP8 activity is inhibited	1	519.1×	0.004	TNFSF10
Dimerization of procaspase-8	1	519.1×	0.004	TNFSF10
Caspase activation via Death Receptors in the presence of ligand	1	380.7×	0.004	TNFSF10
Cellular hexose transport	1	271.9×	0.005	SLC2A2
Regulation of gene expression in beta cells	1	259.6×	0.005	SLC2A2
RIPK1-mediated regulated necrosis	1	228.4×	0.005	TNFSF10
Regulation of insulin secretion	1	109.8×	0.009	SLC2A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
galactose transmembrane transport	1	1685.2×	0.006	SLC2A2
fructose transmembrane transport	1	1053.2×	0.006	SLC2A2
TRAIL-activated apoptotic signaling pathway	1	936.2×	0.006	TNFSF10
dehydroascorbic acid transport	1	601.9×	0.006	SLC2A2
D-glucose transmembrane transport	1	468.1×	0.006	SLC2A2
obsolete D-glucose import	1	421.3×	0.006	SLC2A2
positive regulation of release of cytochrome c from mitochondria	1	383.0×	0.006	TNFSF10
positive regulation of extrinsic apoptotic signaling pathway	1	227.7×	0.009	TNFSF10
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	187.2×	0.010	SLC2A2
carbohydrate metabolic process	1	68.0×	0.025	SLC2A2
positive regulation of canonical NF-kappaB signal transduction	1	36.3×	0.040	TNFSF10
cell-cell signaling	1	34.8×	0.040	TNFSF10
cell surface receptor signaling pathway	1	32.0×	0.040	TNFSF10
positive regulation of apoptotic process	1	28.4×	0.042	TNFSF10
immune response	1	23.5×	0.048	TNFSF10
apoptotic process	1	14.3×	0.073	TNFSF10
signal transduction	1	8.0×	0.121	TNFSF10

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC2A2	1	3
TNFSF10	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
QUERCETIN	3	SLC2A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC2A2	12	Binding:11, Functional:1
TNFSF10	3	Functional:2, Binding:1

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
QUERCETIN	3	SLC2A2

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	1	SLC2A2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TNFSF10

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)
TNFSF10	3	—

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
NCT07459582	Not specified	RECRUITING	Accuracy of Home Lactate Meter and Accu-chek Glucometer in Patients With Glycogen Storage Disease
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LACTIC ACID	4	1
D-LACTIC ACID	3	1