SLC19A3

Chr 2AR

solute carrier family 19 member 3

NCBI Gene: 80704 ENSG00000135917 UniProt: Q9BZV2 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism (PubMed:11731220, PubMed:33008889, PubMed:35512554, PubMed:35724964). Has no folate transport activity (PubMed:11731220). Mediates H(+)-dependent pyridoxine transport (PubMed:33008889, PubMed:35512554, PubMed:35724964, PubMed:36456177)

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.591 OMIM phenotype

VCEP Guidelines: Mitochondrial DiseaseReleased

View Specifications ClinGen 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

51 unique Pathogenic / Likely Pathogenic· 96 VUS of 342 total submissions

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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 OE?0.28 (0.14–0.59)

0≤0.351.4

Missense OE?1.06 (0.96–1.17)

0≤0.61.4

Synonymous OE?0.82

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

This gene — mechanism propensity

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

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

342 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32

Likely Pathogenic19

VUS96

Likely Benign144

Benign27

Conflicting18

Pathogenic

Likely Pathogenic

VUS

144

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	24	4	4	0	32
Likely Pathogenic	10	8	1	0	19
VUS	2	74	20	0	96
Likely Benign	0	2	30	112	144
Benign	0	3	20	4	27
Conflicting	—				18
Total	36	91	75	116	336

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 18) 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 →