GLUT1 deficiency syndrome

Summary

GLUT1 deficiency syndrome (MONDO:0000188) is a disease caused by SLC2A1 (GenCC Strong), with 1 cohort gene and 8 clinical trials. Top therapeutic interventions include triheptanoin.

At a glance

• Causal gene: SLC2A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8
• Clinical trials: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	GLUT1 deficiency syndrome
Mondo ID	MONDO:0000188
OMIM	606777
DOID	DOID:0070560
UMLS	C1847501
MedGen	337833
GARD	0022724
Is cancer (heuristic)	no

Also known as: GLUT1 deficiency syndrome · GLUT1DS

Data availability: 8 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

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 › GLUT1 deficiency syndrome

Related subtypes (17): disorder of glycogen metabolism, primary hyperoxaluria, G6PD deficiency, hyperinsulinemic hypoglycemia, multiple carboxylase deficiency, disorder of glycolysis, disorder of fructose metabolism, disorder of galactose metabolism, disorder of carbohydrate transmembrane transport and absorption, disorders of pentose/polyol metabolism, pyruvate dehydrogenase deficiency, disorder of gluconeogenesis, mucopolysaccharidosis, oligosaccharidosis, lactose intolerance, congenital disorder of deglycosylation 1, disorder of galactose and fructose metabolism

Subtypes (2): encephalopathy due to GLUT1 deficiency, childhood onset GLUT1 deficiency syndrome 2

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

8 retrieved; paginated sample, class counts are floors:

5 pathogenic, 2 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16117	NM_006516.4(SLC2A1):c.277C>T (p.Arg93Trp)	SLC2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
198842	NM_006516.4(SLC2A1):c.997C>T (p.Arg333Trp)	SLC2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
207229	NM_006516.4(SLC2A1):c.884C>T (p.Thr295Met)	SLC2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
3906858	NM_006516.4(SLC2A1):c.968_972del (p.Val323fs)	SLC2A1	Pathogenic	no assertion criteria provided
436754	NM_006516.4(SLC2A1):c.49G>T (p.Gly17Ter)	SLC2A1	Pathogenic	criteria provided, single submitter
488790	NM_006516.4(SLC2A1):c.2T>C (p.Met1Thr)	SLC2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627587	NM_006516.4(SLC2A1):c.388G>A (p.Gly130Ser)	SLC2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1699355	NM_006516.4(SLC2A1):c.728A>T (p.Glu243Val)	SLC2A1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 7 · 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
SLC2A1	Definitive	Autosomal dominant	encephalopathy due to GLUT1 deficiency	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC2A1	Orphanet:168577	Hereditary cryohydrocytosis with reduced stomatin
SLC2A1	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SLC2A1	Orphanet:2131	Alternating hemiplegia of childhood
SLC2A1	Orphanet:53583	Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity
SLC2A1	Orphanet:71277	Classic glucose transporter type 1 deficiency syndrome
SLC2A1	Orphanet:86911	Epilepsy with myoclonic absences
SLC2A1	Orphanet:98811	Paroxysmal exertion-induced dyskinesia

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
SLC2A1	HGNC:11005	ENSG00000117394	P11166	Solute carrier family 2, facilitated glucose transporter member 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC2A1	Solute carrier family 2, facilitated glucose transporter member 1	Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC2A1	Transporter	yes		Glu_transpt_1, Sugar/inositol_transpt, MFS_sugar_transport-like

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
skin of abdomen	1
sural nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC2A1	250	ubiquitous	marker	tibial nerve, sural nerve, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC2A1	5,711

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC2A1	P11166	5

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
Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1)	1	11420.0×	4e-04	SLC2A1
Lactose synthesis	1	3806.7×	7e-04	SLC2A1
Vitamin C (ascorbate) metabolism	1	1427.5×	0.001	SLC2A1
Cellular hexose transport	1	543.8×	0.002	SLC2A1
Regulation of insulin secretion	1	219.6×	0.005	SLC2A1

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
response to Thyroglobulin triiodothyronine	1	5617.3×	0.002	SLC2A1
long-chain fatty acid import across plasma membrane	1	4213.0×	0.002	SLC2A1
GDP-L-fucose salvage	1	4213.0×	0.002	SLC2A1
D-glucose import across plasma membrane	1	2808.7×	0.002	SLC2A1
L-ascorbic acid metabolic process	1	1532.0×	0.002	SLC2A1
dehydroascorbic acid transport	1	1203.7×	0.002	SLC2A1
cellular hyperosmotic response	1	1203.7×	0.002	SLC2A1
D-glucose transmembrane transport	1	936.2×	0.003	SLC2A1
obsolete D-glucose import	1	842.6×	0.003	SLC2A1
photoreceptor cell maintenance	1	358.6×	0.005	SLC2A1
cellular response to glucose starvation	1	337.0×	0.005	SLC2A1
response to insulin	1	230.8×	0.006	SLC2A1
cellular response to mechanical stimulus	1	216.1×	0.006	SLC2A1
female pregnancy	1	210.7×	0.006	SLC2A1
cerebral cortex development	1	205.5×	0.006	SLC2A1
transport across blood-brain barrier	1	179.3×	0.007	SLC2A1
central nervous system development	1	115.4×	0.009	SLC2A1
protein-containing complex assembly	1	113.9×	0.009	SLC2A1
response to hypoxia	1	95.8×	0.010	SLC2A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC2A1	EMETINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC2A1	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EMETINE	4	SLC2A1
GOSSYPOL	3	SLC2A1
CYCLOHEXIMIDE	2	SLC2A1
GENISTEIN	2	SLC2A1
COLFORSIN	2	SLC2A1
KAEMPFEROL	1	SLC2A1
PD-0166285	1	SLC2A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC2A1	158	Binding:130, ADMET:24, Functional:4

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SLC2A1	158

Pharmacogenomics

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

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

Chemical tractability of cohort targets

7 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)
EMETINE	4	SLC2A1
GOSSYPOL	3	SLC2A1
CYCLOHEXIMIDE	2	SLC2A1
GENISTEIN	2	SLC2A1
COLFORSIN	2	SLC2A1
KAEMPFEROL	1	SLC2A1
PD-0166285	1	SLC2A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC2A1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE2	1
PHASE1/PHASE2	1
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02014883	PHASE2	COMPLETED	Phase II Open Label Study Using Triheptanoin in Patients With Glucose Type 1 Transporter Deficiency GLUT1-DS
NCT02021526	PHASE1/PHASE2	WITHDRAWN	Triheptanoin (C7 Oil), a Food Supplement, for Glucose Transporter Type I Deficiency (G1D)
NCT02018315	PHASE1	COMPLETED	Treatment Development for Glucose Transporter Type I Deficiency Syndrome (G1D)
NCT04112862	EARLY_PHASE1	COMPLETED	Sodium Lactate Infusion in GLUT1DS Patients
NCT02013583	Not specified	COMPLETED	The Glucose Transporter Type I Deficiency (G1D) Registry
NCT02018302	Not specified	NO_LONGER_AVAILABLE	Post Study Continuation of C7 for G1D
NCT03722212	Not specified	COMPLETED	Early Diagnosis of the GLUT1 Deficiency Syndrome With a Blood Based Test
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TRIHEPTANOIN	4	3