G6PC1

Summary

G6PC1 (glucose-6-phosphatase catalytic subunit 1, HGNC:4056) is a protein-coding gene on chromosome 17q21.31, encoding Glucose-6-phosphatase catalytic subunit 1 (P35575). Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum.

Glucose-6-phosphatase (G6Pase) is a multi-subunit integral membrane protein of the endoplasmic reticulum that is composed of a catalytic subunit and transporters for G6P, inorganic phosphate, and glucose. This gene (G6PC) is one of the three glucose-6-phosphatase catalytic-subunit-encoding genes in human: G6PC, G6PC2 and G6PC3. Glucose-6-phosphatase catalyzes the hydrolysis of D-glucose 6-phosphate to D-glucose and orthophosphate and is a key enzyme in glucose homeostasis, functioning in gluconeogenesis and glycogenolysis. Mutations in this gene cause glycogen storage disease type I (GSD1). This disease, also known as von Gierke disease, is a metabolic disorder characterized by severe hypoglycemia associated with the accumulation of glycogen and fat in the liver and kidneys.

Source: NCBI Gene 2538 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycogen storage disease I (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 630 total — 87 pathogenic, 63 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes
• MANE Select transcript: NM_000151

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4056
Approved symbol	G6PC1
Name	glucose-6-phosphatase catalytic subunit 1
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	GSD1a
Ensembl gene	ENSG00000131482
Ensembl biotype	protein_coding
OMIM	613742
Entrez	2538

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000253801, ENST00000585489, ENST00000588481, ENST00000592383, ENST00000887112, ENST00000887113

RefSeq mRNA: 2 — MANE Select: NM_000151 NM_000151, NM_001270397

CCDS: CCDS11446, CCDS59291

Canonical transcript exons

ENST00000253801 — 5 exons

Exon	Start	End
ENSE00001118511	42903931	42904040
ENSE00001178369	42900799	42901106
ENSE00001327557	42907523	42907628
ENSE00001604939	42910915	42914438
ENSE00003628186	42909303	42909418

Expression profiles

Bgee: expression breadth broad, 66 present calls, max score 98.01.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.7567 / max 1847.3368, expressed in 27 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161027	2.7567	27

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.01	gold quality
liver	UBERON:0002107	96.72	gold quality
nephron tubule	UBERON:0001231	91.94	gold quality
buccal mucosa cell	CL:0002336	90.41	silver quality
jejunal mucosa	UBERON:0000399	90.28	gold quality
kidney epithelium	UBERON:0004819	89.83	gold quality
renal glomerulus	UBERON:0000074	87.15	silver quality
metanephric glomerulus	UBERON:0004736	86.51	silver quality
adult mammalian kidney	UBERON:0000082	82.90	gold quality
kidney	UBERON:0002113	80.66	gold quality
duodenum	UBERON:0002114	76.05	gold quality
cortex of kidney	UBERON:0001225	73.91	gold quality
ileal mucosa	UBERON:0000331	72.61	gold quality
renal medulla	UBERON:0000362	72.14	gold quality
gall bladder	UBERON:0002110	72.08	gold quality
adult organism	UBERON:0007023	70.19	gold quality
jejunum	UBERON:0002115	69.72	gold quality
small intestine	UBERON:0002108	69.36	gold quality
islet of Langerhans	UBERON:0000006	69.26	gold quality
metanephros	UBERON:0000081	68.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.19	gold quality
colonic epithelium	UBERON:0000397	59.58	silver quality
oocyte	CL:0000023	59.15	gold quality
amniotic fluid	UBERON:0000173	58.92	gold quality
upper leg skin	UBERON:0004262	58.08	silver quality
gingival epithelium	UBERON:0001949	55.09	gold quality
myocardium	UBERON:0002349	54.56	gold quality
endometrium epithelium	UBERON:0004811	53.98	gold quality
squamous epithelium	UBERON:0006914	53.77	gold quality
epithelium of esophagus	UBERON:0001976	53.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF6, CEBPA, CEBPB, CREB1, CREB3L3, CRTC2, DNMT1, ELF1, ESR1, FOXA1, FOXA2, FOXC1, FOXM1, FOXO1, FOXO3, FOXO4, HIF1A, HNF1A, HNF4A, MYC, NCOA2, NFKB, NFKBIA, NR0B1, NR0B2, NR1D1, NR1H2, NR1H3, NR1I2, NR3C1, NR4A1, ONECUT1, PPARA, PPARG, PRKAA1, RORA, SPI1, STAT3, TCF3, TCF7L2

miRNA regulators (miRDB)

87 targeting G6PC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-1273H-5P	99.77	66.32	2471

Literature-anchored findings (GeneRIF, showing 40)

• we report the results of structure and function studies of the 48 missense mutations and the DeltaF327 codon deletion mutation, grouped as active site, helical, and nonhelical mutations (PMID:11739393)
• active site of G6Pase: role of HIS176 as the nucleophile forming the phosphohistidine-enzyme intermediate during catalysis (PMID:12093795)
• homozygosity for one G6PC mutation, G188R, seems to be associated with a glycogen storage disease type I non-a phenotype and homozygosity for the 727G>T mutation may be associated with a milder phenotype but an increased risk for hepatocellular carcinoma (PMID:12373566)
• The amino-terminal domain of G6PT is required for optimal glucose-6-phosphate uptake activity. (PMID:12444104)
• maximum repression of basal glucose-6-phosphatase catalytic subunit (G6Pase) gene transcription by insulin requires two distinct promoter regions, designated that together form an insulin response unit. (PMID:12556524)
• Five mutants lack microsomal G6P uptake activity and one retains residual activity, suggesting that in G6PT the signature motif is a functional element required for microsomal glucose-6-phosphate transport. (PMID:12560945)
• a novel, widely expressed G6Pase-related protein, PAP2.8/UGRP, renamed here G6Pase-beta couples with the G6P transporter to form an active G6Pase complex that can hydrolyze G6P to glucose (PMID:13129915)
• Glc-6-Pase-alpha and Glc-6-Pase-beta share a similar active site structure, topology, and mechanism of action (PMID:14718531)
• G6pc expression was functionally silenced by adenovirus-mediated delivery of short hairpin RNA. (PMID:14759518)
• Findings suggest that the screening for 727G–>T and R83H mutations of glucose-6-phosphatase gene in conjunction with the 1176 polymorphism linkage analysis is a good method for gene and prenatal diagnosis of glycogen storage disease Ia. (PMID:15696478)
• HNF4alpha, CREM, HNF1alpha, and C/EBPalpha have roles in transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine (PMID:16893891)
• G6PC1 hepatic activity was abnormally low in 98 SIDS (preterm, n=13; term, n=85), and non-SIDS preterm infants (n=35) compared to term non-SIDS infants (n=29) and adults (n=9) (PMID:17354259)
• analysis of mutation spectrum of glycogen storage disease type Ia in Tunisia (PMID:18008183)
• summary of the reported G6PC mutations and review what mutagenesis studies have revealed about the structure and function of the G6PC catalytic unit [review] (PMID:18449899)
• HNF-4 and Foxo1 are required for reciprocal transcriptional regulation of glucokinase and glucose-6-phosphatase genes in response to fasting and feeding (PMID:18805788)
• EGF also inhibits hepatic G6Pase gene expression in vivo (PMID:18847435)
• Identification of a risk conferring single nucleotide polymorphism in G6PC for type 2 diabetes in a Chinese population. (PMID:19082990)
• Increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with type 2 diabetes mellitus. (PMID:19587243)
• description of G6PC mutations in Thailand patients with glycogen storage disease type Ia (PMID:19832742)
• data mitigate against G6PD deficiency contributing to stroke risk in individuals with sickle cell anemia. (PMID:21328436)
• results reveal a novel link between glucose metabolism and the DNA damage signaling pathway and suggest a possible role for PEPCK and G6P in the DNA damage response (PMID:21733854)
• Both GSD-1a and G6PT strongly colocalised in perinuclear membranes. showed that GSD1 mutations did neither alter the G6PC or G6PT chimera localisation, nor the interaction between G6PT termini. (PMID:21983240)
• Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. (PMID:23465595)
• LSD1 regulates transcription activation of two gluconeogenic genes, FBP1 and G6Pase. (PMID:23755305)
• The spectrum of mutations in the G6PC gene. (PMID:24355556)
• By direct DNA sequencing, three novel G6PC variations were identified which expanded the G6PC mutation spectrum, and provided conclusive genetic evidences for the definitive diagnosis of the Chinese patients. (PMID:24980439)
• This study is the first to demonstrate a functional relationship between the critical gluconeogenic and glycogenolytic enzyme G6PC with the metabolic adaptations during glioblastoma invasion. (PMID:25001192)
• ApoA-IV colocalizes with NR4A1, which suppresses G6Pase and PEPCK gene expression at the transcriptional level, reducing hepatic glucose output and lowering blood glucose. (PMID:26556724)
• Post-translational regulation of the glucose-6-phosphatase complex by cyclic AMP is a crucial determinant of endogenous glucose production and is controlled by the glucose-6-phosphate transporter. (PMID:26958868)
• Notch1 expression is reduced and glucose-6-phosphatase and perilipin-5 (G6PC/PLIN5) are upregulated in liver biopsies from nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) patients. (PMID:27428080)
• crystal structures of the FoxO1 DNA binding domain in complex with the G6PC1 promoter (PMID:28223045)
• Mutation analysis of the G6PC gene revealed that GSD Ia accounted for 11% in GSD patients with involvement of liver. Three patients were homozygous for R83C mutation. In addition, a novel stop mutation, Y85X, was identified in a patient with the typical features of GSD Ia. (PMID:28360385)
• 3’-UTR SNP rs2229611 in G6PC1 affects mRNA stability, expression and Glycogen Storage Disease type-Ia risk (PMID:28502559)
• Microarrays revealed that G6PC mRNA was upregulated following GDNF-mediated dopaminergic differentiation of SH-SY5Y cells. Array association analysis showed three downregulated microRNAs that could possibly influence G6PC translation. Although qRT-PCR results were not significant, they did support the microarray findings with regard to trend. Western blotting also confirmed increased G6PC protein expression following GDNF (PMID:28829278)
• The results distinguished two ovarian cancer phenotypes, one with elevated HK activity and low G6Pase activity, and another with the opposite characteristics. (PMID:29987620)
• The neutropenia in patients with G6PC3 or G6PT mutations is a metabolite-repair deficiency. (PMID:30626647)
• Five novel mutations, p.V99Cfs*3, p.G125R, IVS1-2A>T, IVS3+39G>A and IVS3+42G>A are reported for the first time to cause Glycogen storage disease type-1a among Indian ethnicity, suggesting separate ethnic founder effects for some mutations among Indian ethnicity. Functional characterization revealed that glucose-6-phosphatase activity was completely abrogated with the mutant proteins. (PMID:30890478)
• Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia. (PMID:32046761)
• Correction of metabolic abnormalities in a mouse model of glycogen storage disease type Ia by CRISPR/Cas9-based gene editing. (PMID:33359667)
• G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo. (PMID:35277194)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	g6pc1a.2	ENSDARG00000013721
danio_rerio	g6pc1b	ENSDARG00000014967
mus_musculus	G6pc1	ENSMUSG00000078650
rattus_norvegicus	Psme3	ENSRNOG00000053448
drosophila_melanogaster	G6P	FBGN0031463

Paralogs (2): G6PC3 (ENSG00000141349), G6PC2 (ENSG00000152254)

Protein

Protein identifiers

Glucose-6-phosphatase catalytic subunit 1 — P35575 (reviewed: P35575)

Alternative names: Glucose-6-phosphatase, Glucose-6-phosphatase alpha

All UniProt accessions (2): P35575, K7ELS6

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. Forms with the glucose-6-phosphate transporter (SLC37A4/G6PT) the complex responsible for glucose production in the terminal step of glycogenolysis and gluconeogenesis. Hence, it is the key enzyme in homeostatic regulation of blood glucose levels.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Glycogen storage disease 1A (GSD1A) [MIM:232200] A metabolic disorder characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Patients manifest a wide range of clinical symptoms and biochemical abnormalities, including hypoglycemia, severe hepatomegaly due to excessive accumulation of glycogen, kidney enlargement, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Carbohydrate biosynthesis; gluconeogenesis.

Similarity. Belongs to the glucose-6-phosphatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35575-1	1	yes
P35575-2	2

RefSeq proteins (2): NP_000142, NP_001257326 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000326	PAP2/HPO	Domain
IPR016275	Glucose-6-phosphatase	Family
IPR036938	PAP2/HPO_sf	Homologous_superfamily

Pfam: PF01569

Enzyme classification (BRENDA):

• EC 3.1.3.9 — glucose-6-phosphatase (BRENDA: 75 organisms, 95 substrates, 121 inhibitors, 58 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-GLUCOSE 6-PHOSPHATE	0.1–5.3	30
CARBAMOYL PHOSPHATE	0.6–2.5	6
GLUCOSE 6-PHOSPHATE	0.51–2.7	6
DIPHOSPHATE	1.3–1.8	2
ADP	11.1	1
ATP	4.7	1
CDP	3.8	1
CTP	3.1	1
DCTP	2.6	1
GDP	2.7	1
GTP	3.6	1
ITP	6.1	1
PHOSPHOENOLPYRUVATE	6.9	1
PHOSPHORAMIDE	2.8	1

Catalyzed reactions (Rhea), 1 shown:

• D-glucose 6-phosphate + H2O = D-glucose + phosphate (RHEA:16689)

UniProt features (122 total): sequence variant 56, helix 22, topological domain 10, transmembrane region 9, mutagenesis site 9, turn 4, strand 2, active site 2, binding site 2, splice variant 2, sequence conflict 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9JTM	ELECTRON MICROSCOPY	2.9
9JTN	ELECTRON MICROSCOPY	3.1
9J7U	ELECTRON MICROSCOPY	3.14
9J7V	ELECTRON MICROSCOPY	3.3
9JTO	ELECTRON MICROSCOPY	3.3
9JTL	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35575-F1	92.21	0.81

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 119 (proton donor); 176 (nucleophile)

Ligand- & substrate-binding residues (2): 83; 170

Glycosylation sites (1): 96

Mutagenesis-validated functional residues (9):

Position	Phenotype
9	partial loss of glucose-6-phosphatase activity.
52	partial loss of glucose-6-phosphatase activity.
119	loss of glucose-6-phosphatase activity.
176	loss of glucose-6-phosphatase activity.
179	loss of glucose-6-phosphatase activity.
197	partial loss of glucose-6-phosphatase activity.
252	partial loss of glucose-6-phosphatase activity.
307	partial loss of glucose-6-phosphatase activity.
353	partial loss of glucose-6-phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3274531	Glycogen storage disease type Ia (G6PC)
R-HSA-70263	Gluconeogenesis
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9940951	Interaction of NuRD complexes with transcription factors

MSigDB gene sets: 284 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MOOTHA_GLYCOGEN_METABOLISM, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, PID_HNF3B_PATHWAY, GOBP_STEROL_HOMEOSTASIS, GNF2_GSTM1, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_FOOD, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, HNF1_Q6, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, LEE_LIVER_CANCER_CIPROFIBRATE_DN, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS

GO Biological Process (21): glycogen metabolic process (GO:0005977), glycogen catabolic process (GO:0005980), gluconeogenesis (GO:0006094), triglyceride metabolic process (GO:0006641), steroid metabolic process (GO:0008202), response to carbohydrate (GO:0009743), regulation of gene expression (GO:0010468), glucose-6-phosphate transport (GO:0015760), response to food (GO:0032094), cellular response to insulin stimulus (GO:0032869), multicellular organism growth (GO:0035264), glucose homeostasis (GO:0042593), cholesterol homeostasis (GO:0042632), urate metabolic process (GO:0046415), glucose 6-phosphate metabolic process (GO:0051156), response to caloric restriction (GO:0061771), response to resveratrol (GO:1904638), response to nutrient levels (GO:0031667), response to insulin (GO:0032868), chemical homeostasis (GO:0048878), lipid homeostasis (GO:0055088)

GO Molecular Function (5): glucose-6-phosphatase activity (GO:0004346), phosphotransferase activity, alcohol group as acceptor (GO:0016773), phosphate ion binding (GO:0042301), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Glycogen storage diseases	1
Glucose metabolism	1
FOXO-mediated transcription	1
NuRD complex assembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to oxygen-containing compound	2
response to nutrient levels	2
energy reserve metabolic process	1
glucan metabolic process	1
glycogen metabolic process	1
glucan catabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
acylglycerol metabolic process	1
lipid metabolic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
hexose phosphate transport	1
response to chemical	1
response to insulin	1
cellular response to peptide hormone stimulus	1
multicellular organismal process	1
developmental growth	1
carbohydrate homeostasis	1
sterol homeostasis	1
small molecule metabolic process	1
purine-containing compound metabolic process	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
response to stress	1
response to stilbenoid	1
response to stimulus	1
response to peptide hormone	1
homeostatic process	1
sugar-terminal-phosphatase activity	1
transferase activity, transferring phosphorus-containing groups	1
anion binding	1
binding	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

2178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
G6PC1	SLC37A4	O43826	972
G6PC1	PCK1	P35558	926
G6PC1	PCK2	Q16822	924
G6PC1	INS	P01308	909
G6PC1	GCK	P35557	862
G6PC1	GCG	P01275	859
G6PC1	FBP1	P09467	824
G6PC1	AGL	P35573	819
G6PC1	PYGL	P06737	791
G6PC1	PYGM	P11217	789
G6PC1	PYGB	P11216	786
G6PC1	FOXO1	Q12778	785
G6PC1	PFKM	P08237	782
G6PC1	PPARGC1A	Q9UBK2	773
G6PC1	PC	P11498	751

IntAct

10 interactions, top by confidence:

A	B	Type	Score
G6PC1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
G6PC1	RNF11	psi-mi:“MI:0915”(physical association)	0.560
CDH16	G6PC1	psi-mi:“MI:0915”(physical association)	0.370
G6PC1	SNX13	psi-mi:“MI:0915”(physical association)	0.370
NSL1	G6PC1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (5): G6PC (Negative Genetic), G6PC (Negative Genetic), G6PC (Two-hybrid), NSL1 (Two-hybrid), SNX13 (Two-hybrid)

ESM2 similar proteins: A0A8C2M425, A1A5Z0, A5D6W6, A7YWN2, B0BNG2, B2MVP8, D2HSA6, O19133, O42153, O42154, O75908, O77759, O88908, P35575, P35576, P43428, Q148G2, Q19KA1, Q29RU6, Q4FZU9, Q5E9R1, Q5KR61, Q5RKL5, Q5XK03, Q658P3, Q6AX73, Q6AZ83, Q6GQ62, Q6NSQ9, Q7TPN3, Q7TQM4, Q810K3, Q8BJ52, Q8CI59, Q8IWX5, Q8R1J1, Q8R2R1, Q8WTR4, Q91V79, Q99PR0

Diamond homologs: A1A5Z0, O19133, O42153, O42154, P35575, P35576, P43428, Q148G2, Q19KA1, Q29RU6, Q6AZ83, Q6NSQ9, Q9BUM1, Q9NQR9, Q9Z186

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
FOXO1	“up-regulates quantity by expression”	G6PC1	“transcriptional regulation”
HNF4A	“up-regulates quantity by expression”	G6PC1	“transcriptional regulation”
metformin	“up-regulates quantity by expression”	G6PC1
NR0B2	“up-regulates quantity by expression”	G6PC1	“transcriptional regulation”
PRKAA1	“down-regulates quantity by repression”	G6PC1	“transcriptional regulation”
FOXO	“up-regulates quantity by expression”	G6PC1	“transcriptional regulation”
CRTC2	“up-regulates quantity”	G6PC1	“transcriptional regulation”
NR3C1	“up-regulates quantity”	G6PC1	“transcriptional regulation”
CREB1	“up-regulates quantity”	G6PC1	“transcriptional regulation”
G6PC1	“up-regulates quantity”	α-D-glucose	“chemical modification”
G6PC1	“down-regulates quantity”	“alpha-D-glucose 6-phosphate(2-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

630 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	87
Likely pathogenic	63
Uncertain significance	169
Likely benign	215
Benign	23

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071784	NM_000151.4(G6PC1):c.160_224dup (p.Phe75_Lys76insArgLysLeuTrpAlaLeuAsnSerPheGlyTer)	Pathogenic
1072073	NC_000017.10:g.(?41055938)(41063453_?)del	Pathogenic
1073829	NC_000017.10:g.(?41059530)(41059655_?)del	Pathogenic
1074029	NM_000151.4(G6PC1):c.708G>A (p.Trp236Ter)	Pathogenic
1076177	NM_000151.4(G6PC1):c.324del (p.Cys109fs)	Pathogenic
11997	NM_000151.4(G6PC1):c.379_380dup (p.Tyr128fs)	Pathogenic
11998	NM_000151.4(G6PC1):c.247C>T (p.Arg83Cys)	Pathogenic
12000	NM_000151.4(G6PC1):c.1039C>T (p.Gln347Ter)	Pathogenic
12001	NM_000151.4(G6PC1):c.229T>C (p.Trp77Arg)	Pathogenic
12002	NM_000151.4(G6PC1):c.230+4A>G	Pathogenic
12004	NM_000151.4(G6PC1):c.113A>T (p.Asp38Val)	Pathogenic
12008	NM_000151.4(G6PC1):c.562G>C (p.Gly188Arg)	Pathogenic
12009	NM_000151.4(G6PC1):c.1022T>A (p.Ile341Asn)	Pathogenic
12010	NM_000151.4(G6PC1):c.497T>G (p.Val166Gly)	Pathogenic
1328936	NM_000151.4(G6PC1):c.592_593del (p.Ile198fs)	Pathogenic
1682491	NM_000151.4(G6PC1):c.302del (p.Leu101fs)	Pathogenic
1682496	NM_000151.4(G6PC1):c.352G>A (p.Gly118Ser)	Pathogenic
1682502	NM_000151.4(G6PC1):c.403_404del (p.Leu135fs)	Pathogenic
1682506	NM_000151.4(G6PC1):c.450del (p.Cys150_Leu151insTer)	Pathogenic
1682510	NM_000151.4(G6PC1):c.503_506dup (p.Arg170fs)	Pathogenic
1682516	NM_000151.4(G6PC1):c.549dup (p.Gly184fs)	Pathogenic
1682520	NM_000151.4(G6PC1):c.750G>A (p.Trp250Ter)	Pathogenic
1682538	NM_000151.4(G6PC1):c.1018_1026del (p.Val340_Pro342del)	Pathogenic
1685830	NM_000151.4(G6PC1):c.70C>T (p.Gln24Ter)	Pathogenic
188777	NM_000151.4(G6PC1):c.969C>A (p.Tyr323Ter)	Pathogenic
188966	NM_000151.4(G6PC1):c.189G>A (p.Trp63Ter)	Pathogenic
1999210	NM_000151.4(G6PC1):c.480G>A (p.Trp160Ter)	Pathogenic
2054942	NM_000151.4(G6PC1):c.267_268delinsC (p.Leu89fs)	Pathogenic
2103671	NM_000151.4(G6PC1):c.826_830del (p.Asn276fs)	Pathogenic
21062	NM_000151.4(G6PC1):c.79del (p.Gln27fs)	Pathogenic

SpliceAI

685 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42901039:G:GT	donor_gain	1.0000
17:42901104:GTG:G	donor_gain	1.0000
17:42903927:ATAG:A	acceptor_gain	1.0000
17:42903929:A:AG	acceptor_gain	1.0000
17:42903929:A:T	acceptor_loss	1.0000
17:42903929:AG:A	acceptor_gain	1.0000
17:42903930:G:GG	acceptor_gain	1.0000
17:42903930:GG:G	acceptor_gain	1.0000
17:42903930:GGA:G	acceptor_gain	1.0000
17:42903930:GGATT:G	acceptor_gain	1.0000
17:42904038:CAGGT:C	donor_loss	1.0000
17:42904041:GTA:G	donor_loss	1.0000
17:42904042:T:A	donor_loss	1.0000
17:42907629:G:GG	donor_gain	1.0000
17:42900996:G:GT	donor_gain	0.9900
17:42903927:A:AG	acceptor_gain	0.9900
17:42903928:T:G	acceptor_gain	0.9900
17:42903928:TAGGA:T	acceptor_gain	0.9900
17:42903930:GGAT:G	acceptor_gain	0.9900
17:42904041:G:GG	donor_gain	0.9900
17:42907517:CTTTA:C	acceptor_loss	0.9900
17:42907518:TTTA:T	acceptor_loss	0.9900
17:42907521:A:C	acceptor_loss	0.9900
17:42907521:AG:A	acceptor_gain	0.9900
17:42907522:G:GA	acceptor_loss	0.9900
17:42907522:GG:G	acceptor_gain	0.9900
17:42907522:GGGA:G	acceptor_gain	0.9900
17:42907627:CGGT:C	donor_loss	0.9900
17:42907630:T:G	donor_loss	0.9900
17:42909297:TTGCA:T	acceptor_loss	0.9900

AlphaMissense

2335 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42901104:G:C	K76N	0.997
17:42901104:G:T	K76N	0.997
17:42909385:T:C	F177L	0.997
17:42909387:T:A	F177L	0.997
17:42909387:T:G	F177L	0.997
17:42903947:C:A	R83S	0.996
17:42909386:T:G	F177C	0.996
17:42904026:G:A	C109Y	0.995
17:42904040:G:T	G114W	0.995
17:42907525:A:C	S115R	0.995
17:42907527:C:A	S115R	0.995
17:42907527:C:G	S115R	0.995
17:42901105:T:A	W77R	0.994
17:42901105:T:C	W77R	0.994
17:42903958:G:C	W86C	0.994
17:42903958:G:T	W86C	0.994
17:42907523:G:A	G114E	0.994
17:42909386:T:C	F177S	0.994
17:42903951:C:A	P84Q	0.993
17:42903956:T:A	W86R	0.993
17:42903956:T:C	W86R	0.993
17:42904025:T:A	C109S	0.993
17:42904026:G:C	C109S	0.993
17:42907529:C:A	P116H	0.993
17:42909365:G:C	R170P	0.993
17:42901063:T:A	W63R	0.992
17:42901063:T:C	W63R	0.992
17:42901084:T:A	W70R	0.992
17:42901084:T:C	W70R	0.992
17:42901102:A:G	K76E	0.992

dbSNP variants (sampled 300 via entrez): RS1000536754 (17:42903087 T>C), RS1000779483 (17:42903172 C>G,T), RS1000888072 (17:42908438 G>A), RS1000949226 (17:42910094 G>A), RS1001085140 (17:42910338 G>A,T), RS1001200147 (17:42906254 T>C), RS1001254496 (17:42899320 C>T), RS1001624548 (17:42913034 C>G,T), RS1001760517 (17:42913349 T>C), RS1001961594 (17:42911521 G>A,C), RS1002097557 (17:42911884 G>A,T), RS1002572357 (17:42904543 T>C), RS1002612746 (17:42901232 C>A), RS1002627552 (17:42914611 G>A), RS1002721875 (17:42908093 C>T)

Disease associations

OMIM: gene MIM:613742 | disease phenotypes: MIM:232200

GenCC curated gene-disease

Disease	Classification	Inheritance
glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
glycogen storage disease I	Definitive	AR

Mondo (4): glycogen storage disease due to glucose-6-phosphatase deficiency type IA (MONDO:0009287), glycogen storage disease I (MONDO:0002413), disorder of glycogen metabolism (MONDO:0002412), hypoglycemia (MONDO:0004946)

Orphanet (3): Glycogen storage disease due to glucose-6-phosphatase deficiency (Orphanet:364), Glycogen storage disease due to glucose-6-phosphatase deficiency type Ia (Orphanet:79258), Glycogen storage disease (Orphanet:79201)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000105	Enlarged kidney
HP:0000295	Doll-like facies
HP:0000660	Lipemia retinalis
HP:0000787	Nephrolithiasis
HP:0000822	Hypertension
HP:0000823	Delayed puberty
HP:0000939	Osteoporosis
HP:0000991	Xanthomatosis
HP:0001114	Xanthelasma
HP:0001402	Hepatocellular carcinoma
HP:0001510	Growth delay
HP:0001538	Protuberant abdomen
HP:0001733	Pancreatitis
HP:0001892	Abnormal bleeding
HP:0001943	Hypoglycemia
HP:0001997	Gout
HP:0002149	Hyperuricemia
HP:0002240	Hepatomegaly
HP:0002254	Intermittent diarrhea
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003077	Hyperlipidemia
HP:0003128	Lactic acidosis
HP:0003162	Fasting hypoglycemia
HP:0003199	Decreased muscle mass
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0011463	Childhood onset

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012490_305	Femur bone mineral density x serum urate levels interaction	9.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D006008	Glycogen Storage Disease	C16.320.565.202.449; C18.452.648.202.449
D005953	Glycogen Storage Disease Type I	C16.320.565.202.449.448; C18.452.648.202.449.448
D007003	Hypoglycemia	C18.452.394.984
C538655	Hepatorenal form of glycogen storage disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2282 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

13 potent at pChembl≥5 of 19 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.77	IC50	170	nM	CHEMBL66059
6.66	IC50	220	nM	CHEMBL69115
6.62	IC50	240	nM	CHEMBL69665
6.48	IC50	330	nM	CHEMBL302504
6.16	IC50	700	nM	CHEMBL65842
5.96	IC50	1100	nM	CHEMBL68984
5.82	IC50	1500	nM	CHEMBL69334
5.82	IC50	1500	nM	CHEMBL69480
5.70	IC50	2000	nM	CHEMBL305258
5.62	IC50	2400	nM	CHEMBL69541
5.62	IC50	2400	nM	CHEMBL70032
5.43	IC50	3700	nM	CHEMBL68011
5.00	IC50	1e+04	nM	CHEMBL69497

PubChem BioAssay actives

13 with measured affinity, of 126 total; 13 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-benzyl-N-[(E)-(5-chlorothiophen-2-yl)methylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	0.1700	uM
N-benzyl-N-[(E)-(4-methoxyphenyl)methylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	0.2200	uM
N-benzyl-N-[(E)-(4-chlorophenyl)methylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	0.2400	uM
N-benzyl-N-[(E)-(5-ethylfuran-2-yl)methylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	0.3300	uM
N-benzyl-N-[(E)-(3-methoxyphenyl)methylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	0.7000	uM
N-benzyl-N-[(E)-furan-2-ylmethylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	1.1000	uM
N-benzyl-N-[(E)-benzylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	1.5000	uM
N-benzyl-1-phenyl-N-[(E)-thiophen-2-ylmethylideneamino]methanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	1.5000	uM
N-benzyl-N-[(E)-(3,4-dichlorophenyl)methylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	2.0000	uM
4-[(E)-(dibenzylhydrazinylidene)methyl]phenol	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	2.4000	uM
N-benzyl-N-[(E)-cyclohexylmethylideneamino]-1-phenylmethanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	2.4000	uM
N-benzyl-1-phenyl-N-[(E)-pyridin-3-ylmethylideneamino]methanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	3.7000	uM
N-benzyl-1-phenyl-N-[(E)-pyridin-2-ylmethylideneamino]methanamine	74514: Compound was evaluated for inhibition of Glucose-6-Phosphatase from Triton X-100 disrupted pig liver microsomes.	ic50	10.0000	uM

CTD chemical–gene interactions

98 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases reaction, affects cotreatment, affects expression, decreases reaction, increases expression (+1 more)	4
sodium arsenite	decreases expression	3
perfluorooctane sulfonic acid	decreases expression	3
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, increases reaction, affects binding, decreases reaction, decreases expression (+1 more)	3
Benzo(a)pyrene	affects expression, decreases expression, increases expression	3
Dexamethasone	decreases expression, increases expression, affects cotreatment, decreases reaction	3
Estradiol	affects binding, decreases reaction, decreases expression, affects cotreatment, increases reaction	3
Palmitic Acid	decreases reaction, increases abundance, increases expression, decreases expression	3
enilconazole	decreases expression	2
propiconazole	decreases expression	2
tebuconazole	decreases expression	2
Cadmium	decreases reaction, increases abundance, increases expression, affects binding, increases reaction	2
Endosulfan	increases expression, increases reaction, affects cotreatment, decreases expression	2
Glucose	affects binding, increases expression, increases reaction, increases stability	2
Phenobarbital	decreases expression, decreases reaction, affects expression, affects cotreatment	2
Rifampin	decreases reaction, increases expression, affects expression, decreases expression, affects reaction (+1 more)	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
fluxapyroxad	decreases expression	1
bisphenol F	increases expression	1
dihydroouabain	affects binding, increases reaction, increases expression	1
ethoprop	decreases expression	1
betulin	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	decreases expression	1
carbendazim	decreases expression	1
bisphenol A	affects expression	1
withaferin A	decreases expression	1
diethyl maleate	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002090	Binding	Inhibition of glucose-6-phosphatase at 100 uM	5,6-Diarylanthranilo-1,3-dinitriles as a new class of antihyperglycemic agents. — Bioorg Med Chem Lett

Cellosaurus cell lines

14 cell lines: 6 induced pluripotent stem cell, 5 transformed cell line, 2 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1K62	GM11470	Transformed cell line	Female
CVCL_1K63	GM11471	Transformed cell line	Male
CVCL_B5YD	A431-AC3	Cancer cell line	Female
CVCL_D7QE	Ubigene A-549 G6PC1 KO	Cancer cell line	Male
CVCL_E4EN	RCMGi015-A	Induced pluripotent stem cell	Female
CVCL_E4EP	RCMGi016-A	Induced pluripotent stem cell	Female
CVCL_V389	GM00574	Finite cell line	Male
CVCL_V390	GM11215	Transformed cell line	Male
CVCL_V391	GM11416	Transformed cell line	Female
CVCL_V392	GM11468	Transformed cell line	Female

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00490893	PHASE4	TERMINATED	Hypoglycemia Counterregulation and Symptom Perception With Insulin Detemir
NCT00641407	PHASE4	COMPLETED	Bedtime Insulins and Oral Antihyperglycemic Drugs in Type 2 Diabetes
NCT00766441	PHASE4	TERMINATED	Sitagliptin Versus Sulphonylurea in Type 2 Diabetes During Ramadan
NCT01013402	PHASE4	COMPLETED	Investigating the Accuracy of the Home Glucose Monitors in Hypoglycemia
NCT01147276	PHASE4	COMPLETED	Vildagliptin and the Glucagon Response to Hypoglycemia in Type 1 Diabetes
NCT01387477	PHASE4	WITHDRAWN	Lactate to Treat Hypoglycemia
NCT01841359	PHASE4	COMPLETED	Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery
NCT02007278	PHASE4	COMPLETED	Glycemic Excursions in Type 2 Diabetic Patients With Vildagliptin and Metformin Versus Vildagliptin and Glimepiride
NCT02336438	PHASE4	COMPLETED	The Effect of Glucomannan Soluble Fiber on Glucose Homeostasis in Patients With Roux En Y (RNY) Gastric Bypass Surgery
NCT02527993	PHASE4	COMPLETED	Treatment of Hypoglycemia Following Gastric Bypass Surgery
NCT02578498	PHASE4	COMPLETED	Glucagon Efficiency After High and Low Carbohydrate Diet
NCT02881060	PHASE4	COMPLETED	The Late Effects of Ethanol Intake on the Glucose Response to Subcutaneous Glucagon in Type 1 Diabetes
NCT03429946	PHASE4	COMPLETED	Hypoglycemia and Autonomic Nervous System Function-B
NCT03608163	PHASE4	TERMINATED	Novel Approach for the Prevention of Hypoglycemia Associated Autonomic Failure (HAAF)
NCT04053712	PHASE4	COMPLETED	Dual-hormone Closed-loop Glucose Control in Type 1 Diabetes
NCT06986603	PHASE4	ACTIVE_NOT_RECRUITING	Glucagon Dose-Response in Patients With Post-Bariatric Hypoglycemia
NCT05139316	PHASE3	COMPLETED	A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa)
NCT02782741	PHASE3	COMPLETED	Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease
NCT04808505	PHASE3	RECRUITING	A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18
NCT00554281	PHASE3	COMPLETED	Using Glucose Sensors to Prevent Hypoglycemia
NCT00804297	PHASE3	COMPLETED	Octreotide for the Treatment of Sulfonylurea-Associated Hypoglycemia
NCT02171130	PHASE3	COMPLETED	Clinical Usability of Intranasal Glucagon in Treatment of Hypoglycemia
NCT02402933	PHASE3	COMPLETED	Clinical Usability of Nasal Glucagon in Treatment of Hypoglycemia in Children and Adolescents
NCT02656069	PHASE3	COMPLETED	Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics
NCT03216226	PHASE3	COMPLETED	A Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen in Patients With Type 1 Diabetes Mellitus
NCT03378635	PHASE3	COMPLETED	A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects
NCT03439072	PHASE3	COMPLETED	G-Pen™ Compared to Lilly Glucagon for Hypoglycemia Rescue in Adults With Type 1 Diabetes
NCT03667053	PHASE3	COMPLETED	Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in T1DM Children
NCT03688711	PHASE3	COMPLETED	Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Subjects With T1DM
NCT03738865	PHASE3	COMPLETED	G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes
NCT03802942	PHASE3	UNKNOWN	Prevention of Hypoglycemia Among Diabetes Patients Admitted to Internal Medicine Departments With Nutritional Care
NCT03895697	PHASE3	COMPLETED	A Trial to Compare the Efficacy and Safety of 2 Different Batches of Subcutaneous Dasiglucagon in Patients With T1DM
NCT04786262	PHASE3	RECRUITING	A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes
NCT05378672	PHASE3	COMPLETED	A Study to Inv. Safety, Efficacy & PD of Dasiglucagon as Hypoglycemia Rescue Therapy in Children <6 Years With T1D
NCT04138251	PHASE2	UNKNOWN	Safety, Efficacy Evaluation of Empagliflozin Administration for Neutropenia in Glycogenosis Type 1b and G6PC3 Deficiency
NCT00765414	PHASE2	COMPLETED	Extension Study of Long-term Safety and Efficacy of Myozyme for a Single Patient With Pompe Disease Who Were Previously Enrolled in Genzyme Sponsored ERT Studies.
NCT02032524	PHASE2	COMPLETED	Avalglucosidase Alfa Extension Study
NCT03019406	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa
NCT06130228	PHASE2	UNKNOWN	Nutritional Therapy in Late-onset Pompe Disease
NCT00434772	PHASE2	COMPLETED	Glucagon in the Treatment of Hypoglycemia in Newborn Infants of Diabetic Mothers