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G6PC

glucose-6-phosphatase catalytic subunit 1

Chromosome 17q21.31 Autosomal recessive HGNC:4056 Tier C
G6PC 17q21.31 p arm q arm 17

G6PC is located on the long (q) arm of chromosome 17, at band 17q21.31. Arm ratio per GRCh38 - banding schematic.

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Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
G6PC is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
G6PC is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The G6PC gene encodes glucose-6-phosphatase, an enzyme anchored in the endoplasmic reticulum membrane that performs the final step in glucose synthesis. This enzyme is predominantly active in the liver, kidneys, and intestinal mucosa, where it converts glucose-6-phosphate into free glucose that can be released into the bloodstream. The gene is located on chromosome 17 and follows an autosomal recessive inheritance pattern.

Disruption of G6PC function prevents the body from maintaining adequate blood glucose levels during fasting, leading to glycogen storage disease type Ia. This condition is included on several NHS clinical panels for metabolic disorders and represents a well-characterised example of how enzyme deficiencies can cause severe metabolic dysregulation.

What the gene does

Glucose-6-phosphatase catalyses the hydrolysis of glucose-6-phosphate to produce free glucose and inorganic phosphate. This reaction represents the terminal step in both gluconeogenesis (synthesis of glucose from non-carbohydrate precursors) and glycogenolysis (breakdown of stored glycogen). The enzyme functions as part of a multi-component system within the endoplasmic reticulum membrane, working in concert with the glucose-6-phosphate translocase protein encoded by SLC37A4.

The enzyme's activity is particularly crucial in hepatocytes, where it serves as the principal regulator of glucose output from the liver. During periods between meals or overnight fasting, the liver relies on glucose-6-phosphatase to release glucose into circulation, thereby maintaining blood glucose homeostasis. Without functional enzyme activity, glucose-6-phosphate accumulates within cells and cannot be converted to the form of glucose that can cross cellular membranes and enter the bloodstream.

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Chromosome location

G6PC is located on the long arm of chromosome 17 at position 21.31 (17q21.31). This chromosomal region contains numerous genes involved in metabolic and developmental processes. The gene spans multiple exons and produces a transcript encoding a 357 amino acid protein that localises to the endoplasmic reticulum membrane.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein. The glucose-6-phosphatase enzyme consists of 357 amino acids and contains multiple transmembrane helices that anchor it within the endoplasmic reticulum membrane. The catalytic site faces the lumen of the endoplasmic reticulum, positioning the enzyme to hydrolyse glucose-6-phosphate molecules transported into this compartment.

Key variants

More than 85 pathogenic variants in G6PC have been identified in individuals with glycogen storage disease type Ia. The majority of these variants are missense changes that alter single amino acids within the enzyme, impairing its catalytic activity or stability. Certain pathogenic variants show increased frequency in specific populations due to founder effects, though the variant spectrum is globally diverse.

No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.

Associated conditions

Pathogenic variants in G6PC cause glycogen storage disease type Ia, an autosomal recessive disorder characterised by the inability to maintain adequate blood glucose levels during fasting. Affected individuals typically present in infancy with severe hypoglycaemia, hepatomegaly due to glycogen accumulation, lactic acidosis, and hyperuricaemia. The condition requires lifelong dietary management to prevent metabolic crises and long-term complications including liver adenomas, kidney disease, and growth impairment.

Inheritance pattern

Conditions caused by pathogenic G6PC variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous G6PC carrier status across ancestry groups?

UK clinical status

G6PC is included on multiple NHS Genomic Medicine Service panels with green (high evidence) classification. The gene appears on the Glycogen storage disease panel (R274), the Ketotic hypoglycaemia panel, the Likely inborn error of metabolism panel (R98), and the Undiagnosed metabolic disorders panel. This classification reflects strong evidence supporting the gene-disease relationship and its clinical utility for diagnosis in the NHS.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Glycogen storage disease · R274 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What does the G6PC gene do?

G6PC encodes an enzyme called glucose-6-phosphatase that performs the final step in glucose production within the liver, kidneys, and intestines. This enzyme is essential for releasing glucose into the bloodstream during fasting periods to maintain normal blood glucose levels.

How is glycogen storage disease type Ia inherited?

Glycogen storage disease type Ia follows an autosomal recessive inheritance pattern, meaning an individual must inherit two pathogenic variants in G6PC (one from each parent) to develop the condition. Carriers with one pathogenic variant typically remain unaffected.

Is G6PC testing available through the NHS?

Yes, G6PC is included on several NHS Genomic Medicine Service panels for metabolic disorders, including glycogen storage disease and ketotic hypoglycaemia panels. Testing is typically arranged through specialist metabolic services when clinical features suggest a diagnosis.

References

  1. Hutton JC, O'Brien RM. Glucose-6-phosphatase catalytic subunit gene family. The Journal of biological chemistry. 2009. PMID: 19700406
  2. Chou JY, Mansfield BC. Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. Human mutation. 2008. PMID: 18449899
  3. van Schaftingen E, Gerin I. The glucose-6-phosphatase system. The Biochemical journal. 2002. PMID: 11879177
  4. Matern D, Seydewitz HH, Bali D. Glycogen storage disease type I: diagnosis and phenotype/genotype correlation. European journal of pediatrics. 2002. PMID: 12373566
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 17 April 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .