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SLC6A19
solute carrier family 6 member 19
SLC6A19 is located on the short (p) arm of chromosome 5, at band 5p15.33. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
SLC6A19 encodes the B0AT1 protein, a sodium-dependent transporter responsible for moving neutral amino acids across cell membranes in the intestine and kidney. This gene is located on chromosome 5 and plays a critical role in maintaining adequate levels of essential amino acids in the circulation. Neutral amino acids - such as tryptophan, leucine, and phenylalanine - are building blocks for proteins and precursors for neurotransmitters and other vital molecules.
Pathogenic variants in SLC6A19 disrupt the protein's transport function, leading to Hartnup disease, a rare metabolic condition inherited in an autosomal recessive pattern. Affected individuals may experience episodes of skin rashes, unsteady movements, or cognitive difficulties, typically triggered by illness, stress, or nutritional deficiency. The gene is included on UK clinical genomics panels for intellectual disability and metabolic disorders, reflecting its importance in diagnosing unexplained aminoaciduria and related presentations.
What the gene does
The B0AT1 protein operates as a sodium-coupled symporter, harnessing the electrochemical gradient of sodium ions to drive the uptake of neutral amino acids into epithelial cells. In the intestinal brush border, B0AT1 captures neutral amino acids released during protein digestion, transferring them from the intestinal lumen into enterocytes. Once inside these cells, the amino acids are released into the bloodstream to be distributed throughout the body for protein synthesis, energy metabolism, and biosynthesis of neurotransmitters such as serotonin.
Within the proximal tubules of the kidney, B0AT1 performs a parallel reabsorptive function, reclaiming filtered neutral amino acids from the urinary filtrate and returning them to the circulation. This prevents the wasteful excretion of essential nutrients. The transporter exhibits specificity for amino acids with uncharged side chains, distinguishing it from other members of the solute carrier family 6, which handle different classes of substrates including neurotransmitters and charged amino acids. Proper B0AT1 function is therefore essential for maintaining nitrogen balance and supporting the metabolic demands of tissues that rely on a steady supply of amino acids.
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Chromosome location
SLC6A19 is located on the short arm of chromosome 5 at cytogenetic band 5p15.33, a region near the telomere of the chromosome. The gene spans approximately 28 kilobases of genomic DNA and comprises 11 exons that encode a mature transcript. This chromosomal location is not associated with common structural variation or frequent copy number alterations in the general population.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The B0AT1 transporter is predicted to contain 12 transmembrane-spanning helices that form a pore through which neutral amino acids and sodium ions pass across the cell membrane. The protein consists of 634 amino acids and belongs to the neurotransmitter:sodium symporter family, sharing structural features with related transporters that couple substrate movement to ion gradients. The precise arrangement of substrate-binding sites and gating mechanisms remains an area of ongoing structural research.
Key variants
At least 23 pathogenic variants in SLC6A19 have been reported in association with Hartnup disease. The majority are missense changes that substitute individual amino acids within the transporter protein, impairing its ability to bind or move neutral amino acids efficiently. Loss-of-function variants, including nonsense and frameshift changes, have also been identified and result in absent or severely truncated protein products. Most affected individuals carry two pathogenic variants, consistent with autosomal recessive inheritance, though compound heterozygosity is common.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Hartnup disease is the primary condition associated with biallelic pathogenic variants in SLC6A19. This metabolic disorder results from defective intestinal and renal transport of neutral amino acids, leading to increased urinary excretion of these nutrients. Many individuals with Hartnup disease remain asymptomatic throughout life, but some experience episodic symptoms including pellagra-like skin rashes, ataxia, tremor, and psychiatric disturbances. These episodes often correlate with periods of nutritional stress, infection, or inadequate dietary protein intake. The variable expressivity of the condition suggests that other genetic or environmental factors may modulate clinical severity.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SLC6A19 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
SLC6A19 is listed as a green gene on several NHS Genomic Medicine Service panels, including the Intellectual Disability panel (version R29), the Likely Inborn Error of Metabolism panel (version R98), and the Undiagnosed Metabolic Disorders panel. Green classification indicates strong evidence linking the gene to the relevant clinical presentations. These panel memberships reflect the gene's role in explaining cases of unexplained aminoaciduria, developmental concerns, or metabolic symptoms where traditional biochemical screening has identified neutral amino acid abnormalities.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
How is Hartnup disease inherited?
Hartnup disease follows an autosomal recessive inheritance pattern, meaning an individual must inherit two pathogenic variants in SLC6A19 - one from each parent - to develop the condition. Carriers with a single variant are typically unaffected.
Do all people with SLC6A19 variants develop symptoms?
No, many individuals with confirmed Hartnup disease based on genetic and biochemical testing remain asymptomatic throughout their lives. Symptoms, when they occur, are often episodic and may be triggered by illness, poor nutrition, or metabolic stress.
Why is SLC6A19 included on UK metabolic disorder panels?
The gene is included because variants cause a recognised inborn error of amino acid metabolism that can present with intellectual disability, unexplained rashes, or neurological symptoms. Identifying SLC6A19 variants helps clinicians diagnose and manage aminoaciduria and guides dietary or supportive interventions.