G6PC1: Glucose-6-Phosphatase Catalytic Subunit 1
Key regulator of glucose homeostasis; mutations cause glycogen storage disease type Ia
Gene Information Card
| Symbol | G6PC1 |
|---|---|
| Full Name | Glucose-6-Phosphatase Catalytic Subunit 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.31 |
| NCBI Gene ID | 2538 ncbi.nlm.nih.gov/gene/2538 |
| Ensembl ID | ENSG00000131482 |
| UniProt ID | P35575 |
| OMIM ID | 613742 |
| HGNC ID | 4056 |
| Aliases | G6PC, G6Pase, G6PT1 |
Description
G6PC1 encodes the catalytic subunit of glucose-6-phosphatase (G6Pase), an integral membrane protein of the endoplasmic reticulum. This enzyme catalyzes the final common step of gluconeogenesis and glycogenolysis, converting glucose-6-phosphate to glucose for release into the bloodstream. G6PC1 is primarily expressed in the liver, kidney, and intestine. Mutations in G6PC1 cause glycogen storage disease type Ia (von Gierke disease), characterized by severe fasting hypoglycemia, hepatomegaly, and metabolic disturbances.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen storage disease type Ia (von Gierke disease) | Loss-of-function mutations impair glucose-6-phosphate hydrolysis, leading to glycogen accumulation and hypoglycemia | OMIM #232200; ClinVar |
| Glycogen storage disease type Ib (G6PC1-related) | Defective glucose-6-phosphate transport (via G6PT1) causes similar phenotype; G6PC1 mutations are causative in type Ia | OMIM #232220; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High |
| Kidney | Medium | Medium |
| Small intestine | Low | Low |
| Pancreas | Not detected | Not detected |
| Brain | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Liver cancer cell line |
| HEK293 | Low | Embryonic kidney cells |
| Caco-2 | Low | Colorectal adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.247G>A (p.Gly83Arg) | Missense | Common in GSD Ia | Loss of catalytic activity |
| c.1039C>T (p.Gln347Ter) | Nonsense | Rare | Premature truncation, loss of function |
| c.648G>T (p.Leu216Phe) | Missense | Found in several populations | Impaired enzyme activity |
| c.79delC (p.Leu27CysfsTer28) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most G6PC1 mutations are loss-of-function, reducing or abolishing glucose-6-phosphatase activity, leading to glycogen storage disease type Ia.
Gain of Function (GOF)
No gain-of-function mutations reported in G6PC1.
Dominant Negative (DN)
No dominant-negative mutations described; GSD Ia is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • Glucose-6-phosphatase activity (GO:0004346) | • Endoplasmic reticulum membrane (GO:0005789) |
| • Glucose homeostasis (GO:0042593) | • Gluconeogenesis (GO:0006094) |
| • Glycogen catabolic process (GO:0005980) |
Pathways
• Gluconeogenesis (Reactome R-HSA-70263)
• Glycogen breakdown (glycogenolysis) (Reactome R-HSA-70221)
• Glucose metabolism (KEGG hsa00010)
Protein Summary
Glucose-6-phosphatase catalytic subunit 1 (G6PC1) is a 357-amino acid integral membrane protein with nine transmembrane domains, localized to the endoplasmic reticulum. It catalyzes the dephosphorylation of glucose-6-phosphate to glucose and inorganic phosphate, the final step in glucose release from the liver and kidney. The active site faces the ER lumen. G6PC1 requires association with the glucose-6-phosphate transporter (G6PT1/SLC37A4) for full activity. Deficiency leads to glycogen storage disease type Ia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| G6PC1 Knockout HEK293 Cell Line | EDJ-KQ796 | Human | 2538 | Details Get a Quote |
| G6PC1 Knockout A-549 Cell Line | EDJ-KQ19517 | Human | 2538 | Details Get a Quote |
| G6PC1 Knockout HCT 116 Cell Line | EDJ-KQ19518 | Human | 2538 | Details Get a Quote |
| G6PC1 Knockout HeLa Cell Line | EDJ-KQ19519 | Human | 2538 | Details Get a Quote |
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