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SLC19A2
solute carrier family 19 member 2
The SLC19A2 gene provides instructions for making thiamine transporter 1, a protein essential for transporting vitamin B1 (thiamine) into cells, which is crucial for energy metabolism and nervous system function. SLC19A2 encodes a protein responsible for cellular uptake of thiamine, also known as vitamin B1.
SLC19A2 is located on the long (q) arm of chromosome 1, at band 1q24.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The SLC19A2 gene, also known as solute carrier family 19 member 2, plays a crucial role in human physiology by encoding a protein called thiamine transporter 1. This protein is responsible for facilitating the entry of vitamin B1, or thiamine, into cells. Thiamine is an essential nutrient that the body cannot produce on its own and must be obtained through diet.
Dysfunction of the SLC19A2 gene can lead to impaired thiamine transport, affecting various bodily systems that rely heavily on this vitamin. This gene is primarily associated with an inherited condition known as Thiamine-responsive megaloblastic anaemia.
What the gene does
The primary function of the SLC19A2 gene is to produce thiamine transporter 1 (THT1), a protein located on the cell surface. THT1 acts as a gatekeeper, actively moving vitamin B1 (thiamine) from outside the cell to the inside. Thiamine is indispensable for numerous metabolic processes, particularly the conversion of carbohydrates into usable energy for the body.
Beyond energy production, thiamine is also vital for the proper functioning of the heart, muscles, and the nervous system. As the human body cannot synthesise thiamine, its cellular uptake via transporters like THT1 is critical for overall health. The efficient transport of thiamine into cells ensures that these essential functions can proceed without disruption.
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Chromosome location
The SLC19A2 gene is located on chromosome 1, specifically at position 1q24.2. This indicates its precise address within the human genome, residing on the long arm (q) of chromosome 1. Genes at this location contribute to a range of biological functions relevant to health.
Protein structure
The SLC19A2 gene produces a protein that is 497 amino acids long. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the SLC19A2 gene can alter the function of the thiamine transporter 1 protein. These genetic changes can range from small alterations in DNA sequence to larger deletions or insertions. Such variants may lead to a reduced ability of cells to take up thiamine, impacting the body's metabolic processes.
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.1001G>A | p.Gly334Asp | Pathogenic/Likely pathogenic | ★★☆☆ | SLC19A2-related disorder |
c.1189A>T | p.Arg397Ter | Pathogenic/Likely pathogenic | ★★☆☆ | SLC19A2-related disorder |
c.1223+1G>A | - | Pathogenic | ★★☆☆ | SLC19A2-related disorder |
c.196G>T | p.Glu66Ter | Pathogenic | ★★☆☆ | Sensorineural hearing loss disorder |
c.314G>A | p.Gly105Glu | Pathogenic/Likely pathogenic | ★★☆☆ | Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness |
c.428C>T | p.Ser143Phe | Pathogenic | ★★☆☆ | Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness |
c.429_432del | p.Tyr144fs | Pathogenic/Likely pathogenic | ★★☆☆ | Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness |
c.697C>T | p.Gln233Ter | Pathogenic | ★★☆☆ | Ear malformation |
c.749G>A | p.Trp250Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness |
c.759dup | p.Glu254Ter | Pathogenic | ★★☆☆ | Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness |
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 SLC19A2 gene are primarily associated with an inherited disorder known as Thiamine-responsive megaloblastic anaemia. This condition is characterised by a specific set of symptoms resulting from impaired thiamine utilisation. It is named "thiamine-responsive" because some of its features, particularly the anaemia, can improve with thiamine supplementation.
- Thiamine-responsive megaloblastic anaemia Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic SLC19A2 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 SLC19A2 gene is included in several NHS Genomic Medicine Service national test directories, indicating its clinical relevance within the UK healthcare system. It is listed as 'green' in PanelApp UK for various conditions, meaning there is sufficient evidence for its inclusion in diagnostic testing panels. These include 'Cytopenias and congenital anaemias', 'Diabetes with additional phenotypes suggestive of a monogenic aetiology', 'Familial diabetes', 'Likely inborn error of metabolism', 'Mitochondrial disorders', 'Neonatal diabetes', 'Possible mitochondrial disorder, nuclear genes', 'Pyruvate dehydrogenase (PDH) deficiency', 'Rare anaemia', and 'Undiagnosed metabolic disorders'.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is thiamine (vitamin B1)?
Thiamine, also known as vitamin B1, is an essential nutrient that the human body cannot produce on its own. It is crucial for converting carbohydrates into energy, and it supports the healthy function of the heart, muscles, and nervous system.
What is Thiamine-responsive megaloblastic anaemia?
Thiamine-responsive megaloblastic anaemia is a rare inherited condition caused by variants in the SLC19A2 gene. It is characterised by hearing loss, diabetes, and a type of blood disorder called megaloblastic anaemia, which can often be treated with daily doses of thiamine.
How does the SLC19A2 gene relate to diet?
The SLC19A2 gene encodes a protein that transports thiamine (vitamin B1) into cells. Since the body cannot produce thiamine, it must be obtained from food sources such as whole grains, lean meats, fish, and beans. The SLC19A2 gene ensures this dietary thiamine reaches the cells that need it.
References
- Ricketts CJ, Minton JA, Samuel J. Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families. Acta paediatrica (Oslo, Norway : 1992). 2006. PMID: 16373304
- Liberman MC, Tartaglini E, Fleming JC. Deletion of SLC19A2, the high affinity thiamine transporter, causes selective inner hair cell loss and an auditory neuropathy phenotype. Journal of the Association for Research in Otolaryngology : JARO. 2006. PMID: 16642288
- Subramanian VS, Marchant JS, Parker I. Cell biology of the human thiamine transporter-1 (hTHTR1). Intracellular trafficking and membrane targeting mechanisms. The Journal of biological chemistry. 2003. PMID: 12454006
- Baron D, Assaraf YG, Cohen N. Lack of plasma membrane targeting of a G172D mutant thiamine transporter derived from Rogers syndrome family. Molecular medicine (Cambridge, Mass.). 2002. PMID: 12435857
- Diaz GA, Banikazemi M, Oishi K. Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome. Nature genetics. 1999. PMID: 10391223
- Adam MP, Bick S, Mirzaa GM. Thiamine-Responsive Megaloblastic Anemia Syndrome. 1993. PMID: 20301459