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SLC19A3
solute carrier family 19 member 3
The SLC19A3 gene provides instructions for a thiamine transporter protein, vital for moving vitamin B1 into cells, especially those of the nervous system. SLC19A3 encodes a thiamine transporter protein, which is essential for cellular uptake of thiamine (vitamin B1).
SLC19A3 is located on the long (q) arm of chromosome 2, at band 2q36.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The SLC19A3 gene, also known as solute carrier family 19 member 3, is responsible for producing a protein that acts as a thiamine transporter. Thiamine, or vitamin B1, is an essential nutrient obtained from the diet, playing a crucial role in cellular metabolism and nervous system function.
Pathogenic variants in SLC19A3 can impair the transport of thiamine into cells, leading to a range of neurological disorders. These conditions are typically inherited in an autosomal recessive manner.
What the gene does
The SLC19A3 gene encodes a thiamine transporter protein, specifically facilitating the movement of thiamine (vitamin B1) into cells. Thiamine is a vital coenzyme involved in numerous cellular processes, including the breakdown of sugars and amino acids, which are fundamental for energy production.
In the nervous system, thiamine is particularly important for the synthesis of certain neurotransmitters, which are chemical messengers that relay signals between nerve cells. Proper thiamine transport by the SLC19A3 protein is therefore critical for maintaining nervous system health and overall metabolic balance. Impaired thiamine uptake due to SLC19A3 variants can disrupt these essential functions.
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Chromosome location
The SLC19A3 gene is located on chromosome 2, specifically at position 2q36.3. This chromosomal location indicates its precise position on the long arm of chromosome 2. The gene directs the production of a protein composed of 496 amino acids.
Protein structure
The SLC19A3 protein is 496 amino acids long. It contains a region described as Disordered, spanning amino acids 468-496. This region may indicate flexibility or a lack of stable secondary structure in this part of the protein.
Key variants
Variants within the SLC19A3 gene can impact the function of the thiamine transporter protein. These genetic changes can reduce the protein's ability to effectively move thiamine into cells, leading to a deficiency of this crucial vitamin within specific tissues, particularly the brain. Such variants are typically associated with autosomal recessive inheritance patterns.
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.1172+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.1172+2T>G | - | Pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.1173-1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.171del | p.Val58fs | Pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.307dup | p.Val103fs | Pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.35G>A | p.Trp12Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.36G>A | p.Trp12Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.513C>A | p.Tyr171Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.597del | p.His200fs | Pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
c.623_626del | p.Lys208fs | Pathogenic/Likely pathogenic | ★★☆☆ | Biotin-responsive basal ganglia disease |
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
Variants in the SLC19A3 gene are primarily associated with biotin-thiamine-responsive basal ganglia disease. This disorder is characterised by recurrent episodes of brain dysfunction and progressive neurological problems. SLC19A3 variants have also been identified in individuals with other severe neurological conditions, including early infantile lethal encephalopathy and disorders causing seizures and brain atrophy, which show overlapping symptoms with biotin-thiamine-responsive basal ganglia disease.
Inheritance pattern
Conditions caused by pathogenic SLC19A3 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 SLC19A3 gene is recognised in the UK National Health Service (NHS) Genomic Medicine Service. It is listed on several NHS Genomic Test Directory panels via PanelApp, including those for Dystonia, chorea or related movement disorder (childhood and adult onset), Intellectual disability, Mitochondrial disorders, and Thiamine metabolism dysfunction syndrome 2 (R395). This indicates its clinical relevance for diagnosing a range of neurological and metabolic conditions within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the SLC19A3 gene?
The SLC19A3 gene provides instructions for making a thiamine transporter protein, which is crucial for moving vitamin B1 (thiamine) into cells, where it is used for various metabolic processes and nervous system function.
What health conditions are associated with SLC19A3 gene variants?
Variants in the SLC19A3 gene are primarily associated with biotin-thiamine-responsive basal ganglia disease, a neurological disorder. They have also been linked to other severe neurological conditions that involve brain dysfunction and developmental issues.
How is biotin-thiamine-responsive basal ganglia disease inherited?
Biotin-thiamine-responsive basal ganglia disease, linked to SLC19A3 variants, is typically inherited in an autosomal recessive manner. This means an individual must inherit two copies of a pathogenic variant, one from each parent, to develop the condition.
References
- Tabarki B, Al-Shafi S, Al-Shahwan S. Biotin-responsive basal ganglia disease revisited: clinical, radiologic, and genetic findings. Neurology. 2013. PMID: 23269594
- Gerards M, Kamps R, van Oevelen J. Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome. Brain : a journal of neurology. 2013. PMID: 23423671
- Kevelam SH, Bugiani M, Salomons GS. Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy. Brain : a journal of neurology. 2013. PMID: 23482991
- Alfadhel M, Almuntashri M, Jadah RH. Biotin-responsive basal ganglia disease should be renamed biotin-thiamine-responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of 18 new cases. Orphanet journal of rare diseases. 2013. PMID: 23742248
- Debs R, Depienne C, Rastetter A. Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations. Archives of neurology. 2010. PMID: 20065143
- El-Hajj TI, Karam PE, Mikati MA. Biotin-responsive basal ganglia disease: case report and review of the literature. Neuropediatrics. 2008. PMID: 19294600