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SLC2A2
solute carrier family 2 member 2
SLC2A2 is located on the long (q) arm of chromosome 3, at band 3q26.2. Arm ratio per GRCh38 - banding schematic.
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Overview
SLC2A2 encodes the glucose transporter type 2 protein (GLUT2), a member of the facilitative glucose transporter family. This protein plays an essential role in maintaining glucose homeostasis by enabling bidirectional glucose transport across cell membranes in key metabolic tissues. GLUT2 is expressed predominantly in hepatocytes, pancreatic beta cells, renal tubular cells, and the basolateral membrane of intestinal epithelial cells, where it functions as a glucose sensor and transporter. Pathogenic variants in SLC2A2 result in impaired glucose and galactose transport, leading to Fanconi-Bickel syndrome, a rare autosomal recessive disorder characterised by hepatorenal glycogen accumulation, renal tubular dysfunction, and impaired glucose homeostasis.
What the gene does
The GLUT2 protein facilitates the bidirectional transport of glucose and galactose across cell membranes, enabling cells to equilibrate their internal glucose concentration with extracellular levels. In pancreatic beta cells, GLUT2 serves as a glucose sensor that couples blood glucose levels to insulin secretion, allowing the pancreas to respond appropriately to changes in glycaemia. In hepatocytes, GLUT2 permits glucose uptake when blood glucose is elevated and glucose release during fasting, supporting the liver's role in glucose buffering. Within the kidney, GLUT2 is located on the basolateral membrane of proximal tubular cells, where it mediates glucose reabsorption from the filtrate back into the bloodstream. In the small intestine, GLUT2 facilitates glucose absorption across the basolateral membrane following digestion. The protein's relatively low affinity for glucose compared to other glucose transporters enables it to function effectively as a sensor across a physiological range of glucose concentrations, making it particularly suited to tissues involved in glucose homeostasis.
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Chromosome location
SLC2A2 is located on the long arm of chromosome 3 at position 26.2 (3q26.2). The gene spans approximately 31 kilobases of genomic DNA and comprises 11 exons that encode the GLUT2 protein. This chromosomal region contains several genes involved in metabolic regulation, and the precise genomic context may influence gene expression patterns in different tissues.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The GLUT2 protein is 524 amino acids in length and belongs to the major facilitator superfamily of membrane transporters. Structural predictions indicate that GLUT2 contains 12 transmembrane helical segments that form a central pore through which glucose molecules pass. The protein adopts conformational changes during the transport cycle, alternating between inward-facing and outward-facing states to enable substrate translocation across the membrane.
Key variants
Pathogenic variants in SLC2A2 are typically loss-of-function changes that reduce or eliminate GLUT2 transporter activity. Most reported variants are inherited in an autosomal recessive pattern, meaning that affected individuals carry two copies of a pathogenic variant. The variant spectrum includes missense changes that disrupt protein folding or substrate binding, nonsense mutations that introduce premature stop codons, and frameshift variants that alter the reading frame. Reduced GLUT2 function impairs glucose transport in multiple tissues, resulting in the metabolic and renal features characteristic of Fanconi-Bickel syndrome.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Biallelic pathogenic variants in SLC2A2 cause Fanconi-Bickel syndrome, a rare autosomal recessive disorder affecting glucose and galactose metabolism. Individuals with this condition typically present in infancy with failure to thrive, hepatomegaly due to glycogen accumulation, and renal tubular dysfunction manifesting as glucosuria, phosphaturia, and aminoaciduria. Fasting hypoglycaemia and postprandial hyperglycaemia reflect impaired glucose homeostasis, whilst rickets may develop secondary to renal phosphate wasting. The condition follows a chronic course, with supportive management focused on nutritional support, correction of electrolyte imbalances, and monitoring for complications.
UK clinical status
SLC2A2 is included on multiple NHS Genomic Medicine Service gene panels as a green-rated gene, reflecting strong evidence for its role in monogenic disease. The gene appears on panels for glycogen storage disease (R274), neonatal diabetes (R143), renal tubulopathies (R198), and likely inborn errors of metabolism (R98), among others. This broad panel membership reflects the multisystem impact of GLUT2 deficiency, which affects hepatic glucose metabolism, pancreatic insulin secretion, and renal tubular function. Green classification indicates that pathogenic variants in SLC2A2 are reportable in NHS diagnostic genomic testing for relevant clinical presentations.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the difference between GLUT2 and other glucose transporters?
GLUT2 has a relatively low affinity for glucose compared to transporters like GLUT1 and GLUT4, which allows it to function as a glucose sensor that responds proportionally across a wide range of blood glucose concentrations. This property makes GLUT2 particularly suited to its role in pancreatic beta cells and hepatocytes, where glucose sensing is critical.
How is Fanconi-Bickel syndrome inherited?
Fanconi-Bickel syndrome follows an autosomal recessive inheritance pattern, meaning an affected individual inherits one pathogenic SLC2A2 variant from each parent. Parents who each carry one variant typically do not show symptoms but have a 25% chance with each pregnancy of having an affected child.
Can genetic testing for SLC2A2 variants help diagnose unexplained metabolic symptoms?
Genetic testing may be informative for individuals presenting with a combination of hepatomegaly, fasting hypoglycaemia, renal tubular dysfunction, and growth delay, particularly when biochemical findings suggest a disorder of glucose homeostasis. A clinical genetics consultation can help determine whether testing is appropriate based on the specific clinical picture.