SLC25A19

Chr 17

solute carrier family 25 member 19

Also known as: DNC, MCPHA, MTPPT, MUP1, THMD3, THMD4, TPC

NCBI Gene: 60386 ENSG00000125454 UniProt: Q9HC21

This gene encodes a mitochondrial transporter that mediates uptake of thiamine diphosphate (thiamine pyrophosphate) into mitochondria. Mutations cause autosomal recessive disorders including microcephaly, Amish type (characterized by severe congenital microcephaly, 2-ketoglutaric aciduria, and death within the first year) and thiamine metabolism dysfunction syndrome 4 with progressive polyneuropathy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.524), reflecting its essential role in mitochondrial thiamine metabolism.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a mitochondrial protein that is a member of the solute carrier family. Although this protein was initially thought to be the mitochondrial deoxynucleotide carrier involved in the uptake of deoxynucleotides into the matrix of the mitochondria, further studies have demonstrated that this protein instead functions as the mitochondrial thiamine pyrophosphate carrier, which transports thiamine pyrophosphates into mitochondria. Mutations in this gene cause microcephaly, Amish type, a metabolic disease that results in severe congenital microcephaly, severe 2-ketoglutaric aciduria, and death within the first year. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMicrocephaly, Amish type

UniProtThiamine metabolism dysfunction syndrome 4, bilateral striatal degeneration and progressive polyneuropathy type

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARLimitednot for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.52

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — SLC25A19