SLC25A19: Mitochondrial Thiamine Pyrophosphate Transporter
Solute Carrier Family 25 Member 19 – Key Role in Thiamine Metabolism and Mitochondrial Disorders
Gene Information Card
| Symbol | SLC25A19 |
|---|---|
| Full Name | Solute Carrier Family 25 Member 19 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.1 |
| NCBI Gene ID | 6036 ncbi.nlm.nih.gov/gene/6036 |
| Ensembl ID | ENSG00000125454 |
| UniProt ID | Q9Y6M9 |
| OMIM ID | 606521 |
| HGNC ID | 10983 |
| Aliases | DNC, MCPHA, TPC, MUP1 |
Description
SLC25A19 (Solute Carrier Family 25 Member 19) encodes a mitochondrial inner membrane carrier that transports thiamine pyrophosphate (TPP) into the mitochondrial matrix. TPP is a critical cofactor for several mitochondrial enzymes, including pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched-chain alpha-keto acid dehydrogenase. Loss-of-function mutations impair TPP import, leading to mitochondrial dysfunction and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amish microcephaly (MCPHA) | Biallelic loss-of-function mutations in SLC25A19 impair mitochondrial TPP transport, disrupting energy metabolism and causing microcephaly, developmental delay, and early lethality. | OMIM #607196; ClinVar |
| Thiamine metabolism dysfunction syndrome 4 (THMD4) | Mutations in SLC25A19 cause a progressive encephalopathy with basal ganglia involvement, responsive to thiamine supplementation. | OMIM #613710; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 10.2 | Medium |
| Liver | 8.9 | Medium |
| Kidney | 7.1 | Low |
| Skeletal Muscle | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression |
| HeLa | 11.8 | Medium expression |
| HepG2 | 9.4 | Medium expression |
| SH-SY5Y | 14.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.373G>A (p.Gly125Arg) | Missense | Founder mutation in Amish population | Loss of TPP transport activity |
| c.530G>A (p.Arg177Gln) | Missense | Rare | Reduced TPP binding affinity |
| c.740C>T (p.Pro247Leu) | Missense | Reported in THMD4 | Impaired mitochondrial localization |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (e.g., p.Gly125Arg, p.Arg177Gln) reduce or abolish TPP transport, leading to mitochondrial dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Thiamine metabolism (Reactome: R-HSA-196849)
• Mitochondrial transport (Reactome: R-HSA-1268020)
• Pyruvate metabolism and citric acid cycle (KEGG: hsa00620)
Protein Summary
SLC25A19 is a 320-amino acid mitochondrial inner membrane carrier protein with six transmembrane domains. It functions as a homodimer to import thiamine pyrophosphate (TPP) from the cytosol into the mitochondrial matrix. TPP is essential for the activity of key mitochondrial dehydrogenases. Defects in SLC25A19 cause thiamine-responsive metabolic disorders, including Amish microcephaly and THMD4.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC25A19 Knockout HEK293 Cell Line | EDJ-KQ15308 | Human | 60386 | Details Get a Quote |
| SLC25A19 Knockout A-549 Cell Line | EDJ-KQ46006 | Human | 60386 | Details Get a Quote |
| SLC25A19 Knockout HCT 116 Cell Line | EDJ-KQ46007 | Human | 60386 | Details Get a Quote |
| SLC25A19 Knockout HeLa Cell Line | EDJ-KQ46008 | Human | 60386 | Details Get a Quote |
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