SLC19A3

Chr 2AR

solute carrier family 19 member 3

Also known as: BBGD, THMD2, THTR2, hTHTR2, thTr-2

NCBI Gene: 80704ENSG00000135917UniProt: Q9BZV2OMIM: 606152

This protein functions as a ubiquitously expressed transmembrane thiamine transporter. Autosomal recessive mutations cause biotin-responsive basal ganglia disease (BBGD), which presents in childhood with progressive encephalopathy, dystonia, quadriparesis, and bilateral caudate and putaminal necrosis that can be fatal if untreated. Early treatment with high-dose biotin eliminates pathological symptoms, while delayed treatment may result in residual neurological deficits.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.591 OMIM phenotype
VCEP Guidelines: Mitochondrial DiseaseReleased
View SpecificationsClinGen Panel
Clinical Summary— SLC19A3
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 37 VUS of 157 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — SLC19A3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.104
Z-score 2.82
OE 0.28 (0.14–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.37Z-score
OE missense 1.06 (0.96–1.17)
283 obs / 266.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.28 (0.14–0.59)
0≤0.351.4
Missense OE1.06 (0.96–1.17)
0≤0.61.4
Synonymous OE0.82
0≤1.21.6
LoF obs/exp: 5 / 17.8Missense obs/exp: 283 / 266.2Syn Z: 1.52
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC19A3-related thiamine metabolism dysfunction syndromeLOFAR

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

DN
0.80top 25%
GOF
0.7028th %ile
LOF
0.2091th %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

157 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic12
VUS37
Likely Benign42
Benign21
Conflicting14
25
Pathogenic
12
Likely Pathogenic
37
VUS
42
Likely Benign
21
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
4
14
0
25
Likely Pathogenic
4
7
1
0
12
VUS
1
28
8
0
37
Likely Benign
0
2
10
30
42
Benign
0
2
15
4
21
Conflicting
—14
Total12434834151

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC19A3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients