SLC6A19

Chr 5

solute carrier family 6 member 19

Also known as: B0AT1, HND

NCBI Gene: 340024 ENSG00000174358 UniProt: Q695T7

The protein functions as a sodium-dependent transporter that mediates resorption of neutral amino acids across the apical membrane of renal and intestinal epithelial cells, requiring accessory proteins (CLTRN in kidney, ACE2 in intestine) for proper cell surface expression and activity. Mutations cause Hartnup disorder, an autosomal recessive condition characterized by pellagra-like symptoms, cerebellar ataxia, and psychosis. The gene shows very low constraint against loss-of-function variants (LOEUF 1.42), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.42

Clinical Summary— SLC6A19

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Gene-Disease Validity (ClinGen)

Hartnup disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

42 unique Pathogenic / Likely Pathogenic· 261 VUS of 585 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.04Z-score

OE missense 1.01 (0.93–1.09)

388 obs / 385.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.07 (0.82–1.42)

0≤0.351.4

Missense OE?1.01 (0.93–1.09)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 35 / 32.6Missense obs/exp: 388 / 385.8Syn Z: -1.67

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC6A19-related Hartnup diseaseLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.74top 25%

GOF

0.84top 5%

LOF

0.2190th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

585 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic31

VUS261

Likely Benign212

Benign42

Conflicting26

Pathogenic

Likely Pathogenic

261

VUS

212

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	0	0	11
Likely Pathogenic	23	8	0	0	31
VUS	3	238	14	6	261
Likely Benign	0	8	72	132	212
Benign	0	2	33	7	42
Conflicting	—				26
Total	37	256	119	145	583

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

View in ClinVar →

137 pathogenic / likely-pathogenic (of 169) ClinVar copy-number / structural variants overlap SLC6A19 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →