SLC6A19

Chr 5AR

solute carrier family 6 member 19

Also known as: B0AT1, HND

NCBI Gene: 340024ENSG00000174358UniProt: Q695T7

This gene encodes a system B(0) transmembrane protein that actively transports most neutral amino acids across the apical membrane of epithelial cells. Mutations in this gene may result in Hartnup disorder, an inherited disease with symptoms such as pellagra, cerebellar ataxia, and psychosis. The expression and function of B0AT1 (SLC6A19) in intestinal cells depends on the presence of the accessory protein angiotensin-converting enzyme 2 (ACE2) which, among other functions, acts as a chaperone for membrane trafficking of B0AT1. The ACE2 is also the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and for SARS-CoV-2 that is causing the coronavirus 2019 (COVID-19) pandemic [provided by RefSeq, Jul 2020]

Primary Disease Associations & Inheritance

Hartnup disorderMIM #234500
AR
UniProtHyperglycinuria
UniProtIminoglycinuria
746
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC6A19
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 162 VUS of 746 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.42LOEUF
pLI 0.000
Z-score -0.38
OE 1.07 (0.82–1.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.04Z-score
OE missense 1.01 (0.93–1.09)
388 obs / 385.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.07 (0.82–1.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.93–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 35 / 32.6Missense obs/exp: 388 / 385.8Syn Z: -1.67

ClinVar Variant Classifications

746 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic21
VUS162
Likely Benign94
Benign7
Conflicting9
52
Pathogenic
21
Likely Pathogenic
162
VUS
94
Likely Benign
7
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
50
0
52
Likely Pathogenic
7
5
9
0
21
VUS
0
136
21
5
162
Likely Benign
0
3
37
54
94
Benign
0
2
3
2
7
Conflicting
—9
Total914612061345

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC6A19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC6A19-related Hartnup disease

definitive
ARLoss Of FunctionAbsent Gene Product
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hartnup disorder

MIM #234500

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SLC6A19 inhibition facilitates urinary neutral amino acid excretion and lowers plasma phenylalanine.
Wobst HJ et al.·JCI Insight
2024Clinical trial
The SLC6A19 gene mutation in a young man with hyperglycinuria and nephrolithiasis: a case report and literature review.
Pan Y et al.·BMC Urol
2022Review
CRRT 2023 Meeting: Targeting Amino Acid Transport to Improve Acute Kidney Injury Outcome.
Oe Y et al.·Nephron
2023Review
Identification of a novel prognostic and therapeutic prediction model in clear cell renal carcinoma based on Renin-angiotensin system related genes.
Chang Q et al.·Front Endocrinol (Lausanne)
2025Functional
Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19.
Seow HF et al.·Nat Genet
2004
The transport of glutamine into mammalian cells.
McGivan JD et al.·Front Biosci
2007Review
Differential DNA Methylation in Monozygotic Twins Discordant for Female Sexual Functioning.
Burri A et al.·J Sex Med
2017
Hartnup disease presenting as hereditary spastic paraplegia and severe peripheral neuropathy.
Wang X et al.·Am J Med Genet A
2022Case report
Gut-brain communication in COVID-19: molecular mechanisms, mediators, biomarkers, and therapeutics.
Wais T et al.·Expert Rev Clin Immunol
2022Functional
A Circular Network of Coregulated L-Threonine and L-Tryptophan Metabolism Dictates Acute Lower Limb Ischemic Injury.
Li L et al.·Int J Med Sci
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SLC6A19-mediated tryptophan uptake suppresses renal cell carcinoma metastasis via activating NAD+-dependent deacetylase SIRT1.
Chen Z et al.·Oncogenesis
2025🔓 Open Access
Engineering and immobilization of imine reductase enable chemoenzymatic synthesis of SLC6A19 inhibitor JNT-517.
Ren M et al.·Bioresour Technol
2026
Hartnup disease-causing SLC6A19 mutations lead to B0AT1 aberrant trafficking and ACE2 mis-localisation implicating the endoplasmic reticulum protein quality control.
Alkhofash NF et al.·Front Cell Dev Biol
2025🔓 Open Access
Novel Substituted Cyclic Compounds as SLC6A19 Inhibitors for Treating Phenylketonuria and Other Amino Acidurias.
Sabnis RW.·ACS Med Chem Lett
2025
MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy.
Xing Y et al.·Sci Rep
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools