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SLC2A10
solute carrier family 2 member 10
The SLC2A10 gene provides instructions for making the GLUT10 protein, which plays a role in regulating cellular processes critical for blood vessel and connective tissue development. The SLC2A10 gene is responsible for producing the GLUT10 protein, a member of the glucose transporter family.
SLC2A10 is located on the long (q) arm of chromosome 20, at band 20q13.12. Arm ratio per GRCh38 - banding schematic.
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Overview
The SLC2A10 gene, also known as solute carrier family 2 member 10, contains the genetic blueprint for a protein called GLUT10. This protein is broadly categorised as a glucose transporter, meaning it is involved in moving glucose across cell membranes to maintain appropriate cellular sugar levels. However, GLUT10 possesses unique structural features that differentiate it from other glucose transporters, and its specific role in substance transport is still being investigated.
Beyond its potential role in glucose transport, GLUT10 is understood to be involved in the transforming growth factor-beta (TGF-β) signalling pathway. This pathway is fundamental for various cellular functions, including cell proliferation, differentiation, and the development of bone and blood vessels. It also contributes to the formation of the extracellular matrix, which provides structural support and flexibility to tissues like blood vessels, skin, and joints.
What the gene does
The GLUT10 protein, encoded by the SLC2A10 gene, is classified within the glucose transporter family. These proteins typically facilitate the movement of glucose across cell membranes, maintaining intracellular glucose homeostasis. However, GLUT10 exhibits structural differences compared to other transporters, and its precise function in glucose or other substance transport is not fully elucidated.
Evidence suggests GLUT10 plays a role in modulating the transforming growth factor-beta (TGF-β) signalling pathway. This pathway is a critical regulator of cell growth, division, and the specialisation of cells into specific types (differentiation). It is also important for the normal development of bone and blood vessels, as well as the creation of the extracellular matrix - the network of molecules that provides structural integrity to connective tissues throughout the body. Furthermore, GLUT10 may contribute to the function of mitochondria, the organelles responsible for energy production within cells.
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Chromosome location
The SLC2A10 gene is located on chromosome 20. Specifically, its chromosomal address is 20q13.12, meaning it resides on the long (q) arm of chromosome 20, within region 13, band 12.
Protein structure
The SLC2A10 gene codes for the GLUT10 protein, which comprises 541 amino acids. The protein includes a notable Disordered region spanning amino acids 340-388. This region suggests flexibility and potential for interaction with various molecular partners, which can be important for protein function and regulation.
Key variants
Genetic variations within the SLC2A10 gene can influence the structure and function of the GLUT10 protein. These changes, known as variants or mutations, can range from single nucleotide substitutions to larger deletions or insertions. Pathogenic variants in SLC2A10 are typically inherited in an autosomal recessive manner, meaning a person must inherit two copies of a pathogenic variant (one from each parent) to develop an associated condition.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1411+2T>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Arterial tortuosity syndrome |
c.1A>T | p.Met1Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Familial thoracic aortic aneurysm and aortic dissection |
c.313C>T | p.Arg105Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Familial aortopathy |
c.473_476del | p.Ala158fs | Pathogenic | ★★☆☆ | Arterial tortuosity syndrome |
c.483del | p.Trp162fs | Pathogenic/Likely pathogenic | ★★☆☆ | Familial thoracic aortic aneurysm and aortic dissection |
c.648C>G | p.Tyr216Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Arterial tortuosity syndrome |
c.691C>T | p.Arg231Trp | Pathogenic/Likely pathogenic | ★★☆☆ | Familial thoracic aortic aneurysm and aortic dissection |
c.731_734del | p.Leu244fs | Pathogenic | ★★☆☆ | Familial thoracic aortic aneurysm and aortic dissection |
c.761_762del | p.Ala254fs | Pathogenic/Likely pathogenic | ★★☆☆ | Arterial tortuosity syndrome |
c.899T>G | p.Leu300Trp | Pathogenic/Likely pathogenic | ★★☆☆ | Familial aortopathy |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the SLC2A10 gene are primarily associated with Arterial tortuosity syndrome (ATS). This is a connective tissue disorder characterised by the abnormal curving and twisting of arteries, as well as other systemic health issues. The identified mutations often lead to a reduction or complete loss of GLUT10 protein function, disrupting the normal processes it influences.
Inheritance pattern
Conditions caused by pathogenic SLC2A10 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The SLC2A10 gene is included in several NHS Genomic Medicine Service (GMS) national genomics panels in the UK, indicating its clinical relevance for specific conditions. It is part of the 'Cerebral vascular malformations' panel, the 'Foetal anomalies' panel (R21), and the 'Thoracic aortic aneurysm or dissection' panel (R125). Its presence on these panels signifies that testing for SLC2A10 variants is considered clinically appropriate for individuals presenting with symptoms related to these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the GLUT10 protein?
The GLUT10 protein, encoded by the SLC2A10 gene, is thought to be involved in glucose transport across cell membranes. It also plays a role in regulating the TGF-β signalling pathway, which is crucial for cell growth, differentiation, and the development of connective tissues and blood vessels.
What is Arterial Tortuosity Syndrome (ATS)?
Arterial Tortuosity Syndrome (ATS) is an inherited connective tissue disorder primarily caused by pathogenic variants in the SLC2A10 gene. It is characterised by abnormally twisted and elongated arteries throughout the body, which can lead to significant health complications affecting various organ systems.
How is Arterial Tortuosity Syndrome inherited?
Arterial Tortuosity Syndrome (ATS) is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of a pathogenic SLC2A10 variant - one from each parent - to develop the condition. Individuals with only one pathogenic variant are typically carriers and do not show symptoms.
References
- Ritelli M, Chiarelli N, Dordoni C. Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent SLC2A10 missense mutations in three families with severe cardiopulmonary complications in infancy and a literature review. BMC medical genetics. 2014. PMID: 25373504
- Willaert A, Khatri S, Callewaert BL. GLUT10 is required for the development of the cardiovascular system and the notochord and connects mitochondrial function to TGFβ signaling. Human molecular genetics. 2012. PMID: 22116938
- Castori M, Ritelli M, Zoppi N. Adult presentation of arterial tortuosity syndrome in a 51-year-old woman with a novel homozygous c.1411+1G>A mutation in the SLC2A10 gene. American journal of medical genetics. Part A. 2012. PMID: 22488877
- Segade F. Glucose transporter 10 and arterial tortuosity syndrome: the vitamin C connection. FEBS letters. 2010. PMID: 20547159
- Jiang YD, Chang YC, Chiu YF. SLC2A10 genetic polymorphism predicts development of peripheral arterial disease in patients with type 2 diabetes. SLC2A10 and PAD in type 2 diabetes. BMC medical genetics. 2010. PMID: 20735855
- Ritelli M, Drera B, Vicchio M. Arterial tortuosity syndrome in two Italian paediatric patients. Orphanet journal of rare diseases. 2009. PMID: 19781076
- Callewaert BL, Willaert A, Kerstjens-Frederikse WS. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. Human mutation. 2008. PMID: 17935213
- Coucke PJ, Willaert A, Wessels MW. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nature genetics. 2006. PMID: 16550171
- Akhurst RJ. A sweet link between TGFbeta and vascular disease? Nature genetics. 2006. PMID: 16570059