id: Q9HC21
gene_symbol: SLC25A19
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  SLC25A19 is the mitochondrial thiamine pyrophosphate carrier (MTPPT), a
  multi-pass protein of the SLC25 mitochondrial carrier family embedded in the
  mitochondrial inner membrane. It imports thiamine pyrophosphate (TPP/ThPP, the
  activated cofactor form of vitamin B1) from the cytosol into the mitochondrial
  matrix, operating as an exchanger that couples TPP uptake to thiamine
  monophosphate efflux. Because mitochondria cannot synthesize TPP, this carrier
  supplies the essential cofactor for matrix TPP-dependent enzyme complexes,
  including the pyruvate dehydrogenase, 2-oxoglutarate (alpha-ketoglutarate)
  dehydrogenase, and branched-chain 2-oxo-acid dehydrogenase complexes, and is
  thereby required for oxidative energy metabolism and TCA-cycle flux. The gene
  was originally described as a mitochondrial deoxynucleotide carrier (DNC), but
  knockout and transport studies established that its physiological substrate is
  thiamine pyrophosphate rather than deoxynucleotides. Loss-of-function
  mutations cause Amish lethal microcephaly (with 2-oxoglutaric aciduria) and
  thiamine metabolism dysfunction syndrome 4 (bilateral striatal necrosis with
  progressive polyneuropathy).
alternative_products:
- name: '1'
  id: Q9HC21-1
- name: '2'
  id: Q9HC21-2
  sequence_note: VSP_053908
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) localization to mitochondrion. Correct but a broad
      parent of the specific inner-membrane location; kept as supporting the
      mitochondrial residence, with the mitochondrial inner membrane annotation
      carried as the more precise core location.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Mitochondrion membrane
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) localization to the mitochondrial inner membrane. This
      is the correct, specific location for a functional SLC25 carrier and is
      consistent with the experimental mitochondrial-membrane and multipass
      evidence. Core cellular component.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        Multi-pass membrane protein
- term:
    id: GO:0090422
    label: thiamine pyrophosphate transmembrane transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) assignment of the specific molecular function, thiamine
      pyrophosphate transmembrane transporter activity. This matches the
      experimentally established physiological function and is the core MF.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        Mitochondrial transporter mediating uptake of thiamine
- term:
    id: GO:0030974
    label: thiamine pyrophosphate transmembrane transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) assignment of the biological process, thiamine
      pyrophosphate transmembrane transport. Consistent with experimental data;
      core biological process.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:17035501
      supporting_text: >-
        We conclude that SLC25A19 transports ThPP
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      Electronic (ARBA) localization to mitochondrion, matching the UniProt
      subcellular location. Redundant with the more specific mitochondrial inner
      membrane location and with experimental mitochondrial annotations, but
      correct and supporting the core localization.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Mitochondrion membrane
- term:
    id: GO:0015932
    label: nucleobase-containing compound transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: >-
      Electronic (ARBA) molecular-function prediction of nucleobase-containing
      compound transmembrane transporter activity. This is a wrong-substrate
      over-prediction rooted in the obsolete "deoxynucleotide carrier" view of
      SLC25A19. The physiological substrate is thiamine pyrophosphate, not
      nucleotides, and GOA carries explicit NOT annotations against
      deoxynucleotide transporter activity. Remove this electronic annotation.
    action: REMOVE
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        Previously identified as the mitochondrial deoxyribonucleotide
    - reference_id: PMID:15539640
      supporting_text: >-
        DNC does not play an important role in the delayed
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic subcellular-location mapping to mitochondrial membrane,
      matching the UniProt SUBCELLULAR LOCATION and the experimental
      mitochondrial-membrane annotations. Correct; less precise than
      mitochondrial inner membrane.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Mitochondrion membrane
- term:
    id: GO:0042723
    label: thiamine-containing compound metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) assignment of the broad process thiamine-containing
      compound metabolic process. True at a high level (TPP transport is part of
      thiamine metabolism) but much less informative than the specific TPP
      transport process; non-core.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:17035501
      supporting_text: >-
        We conclude that SLC25A19 transports ThPP
- term:
    id: GO:0055085
    label: transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Electronic (InterPro2GO) assignment of the generic process transmembrane
      transport from the mitochondrial carrier domain signature. Correct broad
      parent of the specific TPP transport process; non-core.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:27188525
      supporting_text: >-
        uptake of TPP by mitochondria
- term:
    id: GO:0090422
    label: thiamine pyrophosphate transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: >-
      Electronic (ARBA) assignment of the specific molecular function, matching
      the experimentally established TPP transporter activity. Correct; the
      experimental (IDA) instance of this same term is the core annotation.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        Mitochondrial transporter mediating uptake of thiamine
- term:
    id: GO:0042723
    label: thiamine-containing compound metabolic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-196819
  qualifier: involved_in
  review:
    summary: >-
      Reactome (TAS) placement of SLC25A19 within vitamin B1 (thiamin)
      metabolism. Correct pathway context but a broad process relative to the
      specific TPP transport function; non-core.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: Reactome:R-HSA-196819
      supporting_text: >-
        thiamin is converted into the coenzyme thiamin pyrophosphate
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      HPA immunofluorescence (IDA) localization to mitochondrion. Consistent
      with the established mitochondrial residence. Correct but less precise
      than the inner-membrane location; supports the core localization.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Mitochondrion membrane
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: EXP
  original_reference_id: PMID:15539640
  qualifier: located_in
  review:
    summary: >-
      Experimental localization to the mitochondrial membrane. Consistent with
      SLC25A19 being an inner-membrane carrier. Correct; less precise than
      mitochondrial inner membrane.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Mitochondrion membrane
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: EXP
  original_reference_id: PMID:27188525
  qualifier: located_in
  review:
    summary: >-
      Experimental localization to the mitochondrial membrane (GFP-tagged
      hMTPPT delivered to mitochondria in HepG2 cells; TPP uptake by isolated
      mitochondria). Correct; less precise than mitochondrial inner membrane.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:27188525
      supporting_text: >-
        delivery of the protein to mitochondria
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: EXP
  original_reference_id: PMID:31506564
  qualifier: located_in
  review:
    summary: >-
      Experimental localization to the mitochondrial membrane (WT and Q192H
      hMTPPT expression and mitochondrial isolation in HepG2 cells). Correct;
      less precise than mitochondrial inner membrane.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:31506564
      supporting_text: >-
        Mitochondria were isolated from HepG2 cells stably expressing WT hMTPPT
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: >-
      High-throughput mitochondrial proteomics places SLC25A19 in the
      high-confidence human mitochondrial proteome (MitoCoP). Corroborates the
      mitochondrial localization.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: >-
        mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:15539640
  qualifier: located_in
  review:
    summary: >-
      Direct experimental (IDA) mitochondrial localization. Supports the core
      mitochondrial residence; less precise than the inner-membrane location.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Mitochondrion membrane
- term:
    id: GO:0030233
    label: deoxynucleotide transmembrane transporter activity
  evidence_type: IDA
  original_reference_id: PMID:15539640
  qualifier: enables
  negated: true
  review:
    summary: >-
      NOT annotation: experimental evidence shows SLC25A19 (DNC) does not
      function physiologically as a deoxynucleotide transporter. Reconstituted
      DNC transported dNTPs only at millimolar Km (~1000x above physiological),
      and DNC over-expression/knockdown did not affect mitochondrial dNTP
      uptake or mtDNA depletion. Correctly recorded as a negated annotation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:15539640
      supporting_text: >-
        DNC does not play an important role in the delayed
    - reference_id: PMID:15539640
      supporting_text: >-
        which is a thousandfold higher than that of the
- term:
    id: GO:0030233
    label: deoxynucleotide transmembrane transporter activity
  evidence_type: IDA
  original_reference_id: PMID:17035501
  qualifier: enables
  negated: true
  review:
    summary: >-
      NOT annotation supported by the Slc25a19 knockout mouse: mitochondrial
      ribo- and deoxyribonucleoside triphosphate levels were normal and no mtDNA
      depletion occurred, showing deoxynucleotide transport is not the primary
      function. Correctly recorded as negated.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:17035501
      supporting_text: >-
        normal mitochondrial ribo- and deoxyribonucleoside triphosphate levels
- term:
    id: GO:0030302
    label: deoxynucleotide transport
  evidence_type: IDA
  original_reference_id: PMID:15539640
  qualifier: involved_in
  negated: true
  review:
    summary: >-
      NOT annotation: SLC25A19 is not physiologically involved in
      deoxynucleotide transport (no effect on mitochondrial dNTP uptake or
      mtDNA maintenance). Correctly recorded as negated.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:15539640
      supporting_text: >-
        DNC does not play an important role in the delayed
- term:
    id: GO:0030974
    label: thiamine pyrophosphate transmembrane transport
  evidence_type: IDA
  original_reference_id: PMID:17035501
  qualifier: involved_in
  review:
    summary: >-
      Direct experimental evidence that SLC25A19 mediates thiamine pyrophosphate
      transport: reconstituted protein exchanged TPP, and knockout cells had
      undetectable mitochondrial ThPP. Core biological process.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:17035501
      supporting_text: >-
        We conclude that SLC25A19 transports ThPP
- term:
    id: GO:0090422
    label: thiamine pyrophosphate transmembrane transporter activity
  evidence_type: IDA
  original_reference_id: PMID:17035501
  qualifier: enables
  review:
    summary: >-
      Direct experimental evidence for TPP transmembrane transporter activity
      (reconstituted recombinant protein exchange assay; ThPP transport
      confirmed). This is the core molecular function of SLC25A19.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:17035501
      supporting_text: >-
        confirmed it by using transport assays of the recombinant reconstituted protein
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:31506564
  qualifier: located_in
  review:
    summary: >-
      Direct experimental (IDA) mitochondrial localization from the THMD4
      functional study (WT and mutant hMTPPT expression and mitochondrial
      isolation). Supports the core mitochondrial localization.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:31506564
      supporting_text: >-
        expression of the mutant hMTPPT protein in mitochondria
- term:
    id: GO:0090422
    label: thiamine pyrophosphate transmembrane transporter activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8875838
  qualifier: enables
  review:
    summary: >-
      Reactome (TAS) assertion of the core TPP transporter activity, describing
      transport of ThDP from cytosol to the mitochondrial matrix. Consistent
      with the experimental evidence; supports the core MF.
    action: ACCEPT
    supported_by:
    - reference_id: Reactome:R-HSA-8875838
      supporting_text: >-
        transporter of thiamine pyrophosphate (ThDP) into mitochondria
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8875838
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) localization to the mitochondrial inner membrane, the
      specific and correct location for this SLC25 carrier. Core cellular
      component.
    action: ACCEPT
    supported_by:
    - reference_id: Reactome:R-HSA-8875838
      supporting_text: >-
        transporter of thiamine pyrophosphate (ThDP) into mitochondria
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  qualifier: located_in
  review:
    summary: >-
      High-throughput (HDA) nucleus assignment from a human sperm-nucleus
      proteome. For a mitochondrial inner-membrane carrier this is almost
      certainly a proteomic contaminant rather than a functional nuclear
      localization, and it is not supported by any targeted evidence. Retained
      as non-core (high-throughput, not removed) but flagged as unlikely to be
      biologically meaningful.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:21630459
      supporting_text: >-
        several chromatin-related proteins, such as zinc fingers and
- term:
    id: GO:0030302
    label: deoxynucleotide transport
  evidence_type: NAS
  original_reference_id: PMID:11226231
  qualifier: involved_in
  review:
    summary: >-
      Author-statement (NAS) that SLC25A19/DNC mediates deoxynucleotide
      transport, from the original characterization paper. This reflects the
      obsolete "deoxynucleotide carrier" interpretation that was subsequently
      overturned; GOA now records explicit NOT annotations against
      deoxynucleotide transport. Over-annotated relative to the corrected
      physiological function (TPP transport).
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        Previously identified as the mitochondrial deoxyribonucleotide
    - reference_id: PMID:17035501
      supporting_text: >-
        normal mitochondrial ribo- and deoxyribonucleoside triphosphate levels
- term:
    id: GO:0030233
    label: deoxynucleotide transmembrane transporter activity
  evidence_type: TAS
  original_reference_id: PMID:11226231
  qualifier: enables
  review:
    summary: >-
      Author/TAS assignment of deoxynucleotide transmembrane transporter
      activity from the original DNC characterization. Reconstituted transport
      was observed in vitro but only at non-physiological (millimolar) Km, and
      the physiological function was later established as TPP transport; GOA
      carries explicit NOT annotations against this activity. Over-annotated;
      not the physiological molecular function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
      supporting_text: >-
        SLC25A19 is a thiamine diphosphate transporter and not a
    - reference_id: PMID:15539640
      supporting_text: >-
        which is a thousandfold higher than that of the
core_functions:
- description: >-
    Mitochondrial thiamine pyrophosphate carrier: transports thiamine
    pyrophosphate (TPP/ThDP) across the mitochondrial inner membrane from the
    cytosol into the matrix, functioning as an exchanger (TPP in, thiamine
    monophosphate out). This supplies the TPP cofactor required by matrix
    TPP-dependent dehydrogenase complexes (pyruvate dehydrogenase,
    2-oxoglutarate dehydrogenase, branched-chain 2-oxo-acid dehydrogenase).
  molecular_function:
    id: GO:0090422
    label: thiamine pyrophosphate transmembrane transporter activity
  directly_involved_in:
  - id: GO:0030974
    label: thiamine pyrophosphate transmembrane transport
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  supported_by:
  - reference_id: PMID:17035501
    supporting_text: >-
      We conclude that SLC25A19 transports ThPP
  - reference_id: PMID:17035501
    supporting_text: >-
      confirmed it by using transport assays of the recombinant reconstituted protein
  - reference_id: file:human/SLC25A19/SLC25A19-uniprot.txt
    supporting_text: >-
      Mitochondrial transporter mediating uptake of thiamine
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:11226231
  title: The human mitochondrial deoxynucleotide carrier and its role in the toxicity
    of nucleoside antivirals.
  findings:
  - statement: >-
      Original characterization of SLC25A19/DNC: recombinant reconstituted
      protein transported dNDPs (and less efficiently dNTPs) in exchange for
      dNDPs, ADP or ATP. This deoxynucleotide-carrier interpretation was later
      superseded by identification of TPP as the physiological substrate.
    reference_section_type: ABSTRACT
    supporting_text: >-
      catalyzed the transport of all four deoxy (d) NDPs, and, less efficiently,
      the corresponding dNTPs, in exchange for dNDPs, ADP, or ATP
  reference_review:
    relevance: MEDIUM
    correctness: DISPUTED
    review_notes: >-
      PubMed-verified. Foundational paper but its central claim (SLC25A19 is the
      mitochondrial deoxynucleotide carrier) was overturned by later knockout
      and transport studies; the physiological substrate is thiamine
      pyrophosphate, not deoxynucleotides.
- id: PMID:15539640
  title: Expression of deoxynucleotide carrier is not associated with the mitochondrial
    DNA depletion caused by anti-HIV dideoxynucleoside analogs and mitochondrial dNTP
    uptake.
  findings:
  - statement: >-
      DNC/SLC25A19 does not play a physiological role in deoxynucleotide
      transport: reconstituted dNTP uptake had millimolar Km (~1000x above
      physiological), and DNC over-expression/knockdown did not affect mtDNA
      depletion or mitochondrial dNTP uptake.
    reference_section_type: ABSTRACT
    supporting_text: >-
      DNC does not play an important role in the delayed cytotoxicity (mtDNA
      depletion) of anti-HIV dideoxynucleoside analogs and dNTPs uptake into
      mitochondria
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Provides the cellular evidence against the deoxynucleotide
      transporter role and underpins the NOT annotations for GO:0030233 and
      GO:0030302.
- id: PMID:17035501
  title: Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion,
    embryonic lethality, CNS malformations, and anemia.
  findings:
  - statement: >-
      Slc25a19 knockout mice have normal mitochondrial dNTP/rNTP pools and no
      mtDNA depletion, but undetectable mitochondrial ThPP; reconstituted
      recombinant SLC25A19 transports ThPP. Establishes TPP transport as the
      physiological function, with loss causing OGDH dysfunction and
      2-oxoglutaric aciduria.
    reference_section_type: ABSTRACT
    supporting_text: >-
      We identified thiamine pyrophosphate (ThPP) transport as a candidate
      function of SLC25A19 through homology searching and confirmed it by using
      transport assays of the recombinant reconstituted protein
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; full text available. Definitive genetic and biochemical
      evidence that the physiological substrate is thiamine pyrophosphate, not
      deoxynucleotides. Primary support for the core molecular function.
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings:
  - statement: >-
      Large-scale proteomic catalogue of the human sperm nucleus in which
      SLC25A19 was detected. As a mitochondrial inner-membrane carrier, its
      presence in this nuclear preparation most likely reflects a proteomic
      contaminant rather than functional nuclear localization.
    reference_section_type: ABSTRACT
    supporting_text: >-
      403 different proteins have been identified from the isolated sperm nuclei
  reference_review:
    relevance: LOW
    correctness: LOW_QUALITY
    review_notes: >-
      PubMed-verified. High-throughput sperm-nucleus proteome; source of the
      HDA nucleus annotation, which is not biologically informative for a
      mitochondrial carrier and is likely a contaminant.
- id: PMID:27188525
  title: 'Structure-function characterization of the human mitochondrial thiamin pyrophosphate
    transporter (hMTPPT; SLC25A19): Important roles for Ile(33), Ser(34), Asp(37),
    His(137) and Lys(291).'
  findings:
  - statement: >-
      Site-directed mutagenesis with TPP uptake assays on isolated mitochondria
      identified Ile33, Ser34, Asp37, His137 and Lys291 as important for hMTPPT
      function, confirming SLC25A19 as the mitochondrial TPP uptake carrier.
    reference_section_type: ABSTRACT
    supporting_text: >-
      an important role for Ile33, Ser34, Asp37, His137 and Lys291 residues in
      function of the hMTPPT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; full text available. Structure-function study confirming
      TPP transport activity and mitochondrial delivery of hMTPPT.
- id: PMID:31506564
  title: Functional analysis of the third identified SLC25A19 mutation causative for
    the thiamine metabolism dysfunction syndrome 4.
  findings:
  - statement: >-
      Functional analysis of the THMD4-causing Q192H variant: it reduces
      3H-TPP uptake by isolated mitochondria and lowers hMTPPT protein
      expression/mitochondrial delivery without affecting mRNA, supporting TPP
      transport as the disease-relevant function.
    reference_section_type: ABSTRACT
    supporting_text: >-
      mitochondrial TPP transporter (hMTPPT)
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; full text available. Clinical/functional confirmation of
      TPP transport and mitochondrial localization; source of THMD4 variant
      Q192H.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings:
  - statement: >-
      SLC25A19 is included in the high-confidence human mitochondrial proteome
      (MitoCoP), corroborating its mitochondrial localization.
    reference_section_type: ABSTRACT
    supporting_text: >-
      mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. High-throughput mitochondrial proteomics supporting the
      mitochondrial localization annotation.
- id: Reactome:R-HSA-196819
  title: Vitamin B1 (thiamin) metabolism
  findings:
  - statement: >-
      Reactome pathway placing SLC25A19 within vitamin B1 (thiamin) metabolism;
      thiamin is pyrophosphorylated to the coenzyme thiamin pyrophosphate.
    reference_section_type: OTHER
    supporting_text: >-
      thiamin is converted into the coenzyme thiamin pyrophosphate
- id: Reactome:R-HSA-8875838
  title: SLC25A19 transports ThDP from cytosol to mitochondrial matrix
  findings:
  - statement: >-
      Reactome reaction describing SLC25A19-mediated transport of thiamine
      pyrophosphate (ThDP) from cytosol into the mitochondrial matrix, where it
      serves as a cofactor for PDH, alpha-ketoglutarate dehydrogenase and
      branched-chain amino acid dehydrogenase.
    reference_section_type: OTHER
    supporting_text: >-
      transporter of thiamine pyrophosphate (ThDP) into mitochondria
- id: file:human/SLC25A19/SLC25A19-uniprot.txt
  title: UniProtKB Q9HC21 (TPC_HUMAN) record
  findings:
  - statement: >-
      UniProt describes SLC25A19 as the mitochondrial thiamine pyrophosphate
      carrier mediating uptake of thiamine diphosphate into mitochondria, a
      multi-pass inner-membrane protein of the mitochondrial carrier family,
      and documents its historical mis-identification as a deoxyribonucleotide
      carrier.
    reference_section_type: OTHER
    supporting_text: >-
      Mitochondrial transporter mediating uptake of thiamine
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []