SLC19A2

Chr 1

solute carrier family 19 member 2

Also known as: TC1, THMD1, THT1, THTR1, TRMA

NCBI Gene: 10560 ENSG00000117479 UniProt: O60779

This gene encodes a high-affinity thiamine transporter that mediates cellular uptake of thiamine (vitamin B1) and also transports pyridoxine in a proton-dependent manner. Mutations cause thiamine-responsive megaloblastic anemia syndrome, an autosomal recessive disorder characterized by the triad of diabetes mellitus, megaloblastic anemia, and sensorineural deafness. The gene shows low constraint against loss-of-function variants (pLI 0.0004), consistent with its recessive inheritance pattern.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the thiamin transporter protein. Mutations in this gene cause thiamin-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

GeneReviews ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.76

Clinical Summary— SLC19A2

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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

64 unique Pathogenic / Likely Pathogenic· 192 VUS of 521 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC19A2

Authoritative clinical overview · Recommended first read

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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?

0.76LOEUF

pLI 0.000

Z-score 2.36

OE 0.44 (0.26–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.19Z-score

OE missense 0.97 (0.87–1.07)

263 obs / 271.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.26–0.76)

0≤0.351.4

Missense OE?0.97 (0.87–1.07)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 9 / 20.6Missense obs/exp: 263 / 271.9Syn Z: 0.30

This gene — mechanism propensity

0.74top 25%

GOF

0.74top 25%

LOF

0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

521 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47

Likely Pathogenic17

VUS192

Likely Benign223

Benign13

Conflicting23

Pathogenic

Likely Pathogenic

192

VUS

223

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	40	2	5	0	47
Likely Pathogenic	8	9	0	0	17
VUS	4	159	25	4	192
Likely Benign	0	1	81	141	223
Benign	0	2	11	0	13
Conflicting	—				23
Total	52	173	122	145	515

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap SLC19A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →