SLC19A3

Chr 2AR

solute carrier family 19 member 3

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

This gene encodes a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity. Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild cognitive disability, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy.[provided by RefSeq, Jan 2010]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.591 OMIM phenotype
VCEP Guidelines: Mitochondrial DiseaseReleased
View SpecificationsClinGen Panel
Clinical SummarySLC19A3
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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
85 unique Pathogenic / Likely Pathogenic· 285 VUS of 723 total submissions
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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

Moderate LoF intolerance
LoF Constraint?
0.59LOEUF
pLI 0.104
Z-score 2.82
OE 0.28 (0.140.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
-0.37Z-score
OE missense 1.06 (0.961.17)
283 obs / 266.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.28 (0.140.59)
00.351.4
Missense OE?1.06 (0.961.17)
00.61.4
Synonymous OE?0.82
01.21.6
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

This gene — mechanism propensity

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

723 submitted variants in ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic35
VUS285
Likely Benign242
Benign62
Conflicting43
50
Pathogenic
35
Likely Pathogenic
285
VUS
242
Likely Benign
62
Benign
43
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
33
9
8
0
50
Likely Pathogenic
20
12
3
0
35
VUS
5
233
46
1
285
Likely Benign
0
5
62
175
242
Benign
0
3
54
5
62
Conflicting
43
Total58262173181717

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap SLC19A3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

SLC19A3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →