id: Q96HY7
gene_symbol: DHTKD1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  DHTKD1 is the E1 component (E1a; 2-oxoadipate dehydrogenase, OADH-E1) of the
  mitochondrial 2-oxoadipate dehydrogenase complex (OADHC). It is a thiamine
  diphosphate (ThDP)-dependent decarboxylase and a paralog of OGDH, the
  2-oxoglutarate dehydrogenase E1. DHTKD1 catalyzes the first, rate-limiting and
  irreversible step of the complex: the oxidative decarboxylation of 2-oxoadipate
  (alpha-ketoadipate), transferring the decarboxylated glutaryl intermediate onto
  the lipoyl group of the shared E2 subunit (DLST), with the overall complex
  producing glutaryl-CoA and CO2. OADHC uses the same E2 (DLST) and E3 (DLD)
  components as the TCA-cycle 2-oxoglutarate dehydrogenase complex, but the E1
  subunit is complex-specific; DHTKD1 strongly prefers 2-oxoadipate over
  2-oxoglutarate as substrate. This reaction is the final common step of L-lysine,
  L-hydroxylysine and L-tryptophan degradation, whose convergent intermediate is
  2-oxoadipate. The enzyme functions as a homodimer in the mitochondrial matrix.
  Loss-of-function variants cause alpha-aminoadipic and alpha-ketoadipic aciduria
  (AAKAD, frequently benign), and DHTKD1 has also been linked to axonal
  Charcot-Marie-Tooth disease type 2Q.
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Subcellular-location IEA placing DHTKD1 in the mitochondrion, consistent
      with all experimental evidence and the mitochondrial transit peptide.
      Correct but less precise than the mitochondrial matrix localization
      supported by Reactome/Ensembl orthology.
    action: ACCEPT
    reason: >-
      DHTKD1 is a validated mitochondrial matrix enzyme (UniProt SUBCELLULAR
      LOCATION, PMID:23141294). The generic mitochondrion term is correct.
    supported_by:
    - reference_id: PMID:23141294
      supporting_text: >-
        implicating an important role for DHTKD1 in mitochondrial energy
        production and neurological development.
- term:
    id: GO:0016624
    label: oxidoreductase activity, acting on the aldehyde or oxo group of donors,
      disulfide as acceptor
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Broad InterPro/orthology-based oxidoreductase term describing the
      overall E1+E2+E3 (disulfide-acceptor) chemistry of the 2-oxo-acid
      dehydrogenase family. The precise activity of the E1a subunit is the
      ThDP-dependent decarboxylation captured by GO:0160166.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This family-level term describes the full dehydrogenase complex reaction
      in which the ultimate electron acceptor is a disulfide (lipoyl/E3). The
      DHTKD1 E1a subunit itself performs ThDP-dependent decarboxylation of
      2-oxoadipate and transfers the acyl group to the E2 lipoyl moiety; the
      more specific and accurate MF for DHTKD1 is GO:0160166 (2-oxoadipate
      dehydrogenase activity), which is separately annotated with IDA support.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        It is involved in the oxidative decarboxylation of 2-oxoadipate (OA) to
        glutaryl-CoA on the final degradative pathway of L-lysine
- term:
    id: GO:0030976
    label: thiamine pyrophosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based annotation of thiamine diphosphate (ThDP) binding. ThDP is
      the essential catalytic cofactor of DHTKD1, confirmed biochemically and by
      crystal structures of the DHTKD1-ThDP complex.
    action: ACCEPT
    reason: >-
      DHTKD1 is a ThDP-dependent decarboxylase; ThDP is documented as its
      cofactor (UniProt COFACTOR, PMID:32695416; DHTKD1-ThDP crystal structure
      PMID:32633484). The InterPro TPP-binding domain (IPR011603/IPR029061) is
      present. This is a core molecular function.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        Herein are reported unique properties of the novel human thiamin
        diphosphate (ThDP)-dependent enzyme 2-oxoadipate dehydrogenase (hE1a)
- term:
    id: GO:0160166
    label: 2-oxoadipate dehydrogenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: >-
      RHEA-mapped IEA for the core catalytic activity of DHTKD1: the
      ThDP-dependent oxidative decarboxylation of 2-oxoadipate (RHEA:69576).
      This is the primary, experimentally validated molecular function.
    action: ACCEPT
    reason: >-
      Matches the reaction assigned in UniProt (RHEA:69576) and is directly
      supported by biochemistry (PMID:29191460, PMID:32633484) and structure.
      Duplicate of the IDA-supported GO:0160166 below; both are correct.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        hE1a displays an approximately 49-fold preference in catalytic
        efficiency for OA over OG, indicating that hE1a is specific to the
        2-oxoadipate dehydrogenase complex
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: >-
      High-throughput affinity-purification/mass-spectrometry interactome
      (BioPlex 2.0) IPI to PGLYRP3 (Q96LB9). Bare "protein binding" is
      uninformative about DHTKD1's molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is a proteome-scale AP-MS screen, not a directed study of DHTKD1's
      biology; the recorded partner (PGLYRP3) has no established functional
      relationship to 2-oxoadipate catabolism. Per curation guidance, bare
      GO:0005515 protein binding IPIs are uninformative and are marked as
      over-annotation rather than removed. The biologically meaningful
      interaction of DHTKD1 is with the E2 subunit DLST, captured by the
      oxoadipate dehydrogenase complex annotation.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: >-
        BioPlex 2.0 exceeds previous experimentally derived interaction networks
        in depth and breadth
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Binary yeast-two-hybrid interactome (HuRI) IPI to an isoform of BMAL1
      (O00327-8). Bare "protein binding" is uninformative about DHTKD1's
      molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is a genome-scale binary interaction map, not a directed functional
      study of DHTKD1. The reported partner has no established role in
      2-oxoadipate/lysine catabolism. Per curation guidance, bare protein
      binding IPIs are marked as over-annotation rather than removed.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: A reference map of the human binary protein interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      High-throughput AP-MS interactome (BioPlex-derived, cell-specific
      networks) IPI to PGLYRP3 (Q96LB9). Bare "protein binding" is
      uninformative about DHTKD1's molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Proteome-scale interactome dataset rather than a directed DHTKD1 study;
      the reported partner has no established connection to 2-oxoadipate
      catabolism. Per curation guidance, bare protein binding IPIs are marked
      as over-annotation rather than removed.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling
        of the human interactome.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: >-
      Orthology-based (Ensembl Compara) is_active_in annotation to the
      mitochondrial matrix, transferred from mouse ortholog. Consistent with
      the matrix localization of a soluble ThDP-dependent dehydrogenase.
    action: ACCEPT
    reason: >-
      DHTKD1 has an N-terminal mitochondrial transit peptide and functions as a
      soluble matrix enzyme of the OADHC; matrix localization is supported by
      Reactome and by the shared architecture with the OGDH complex.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        the dihydrolipoyl succinyltransferase (hE2o) and the dihydrolipoyl
        dehydrogenase (hE3) components of the tricarboxylic acid cycle
        2-oxoglutarate dehydrogenase complex (OGDHc) for its activity
- term:
    id: GO:0009063
    label: amino acid catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-based involvement in amino acid catabolism. Correct but a
      generic parent of the specific L-lysine/L-tryptophan catabolic processes
      DHTKD1 participates in.
    action: KEEP_AS_NON_CORE
    reason: >-
      Accurate at a high level (DHTKD1 acts on the convergent 2-oxoadipate step
      of lysine/hydroxylysine/tryptophan degradation) but subsumed by the more
      specific L-lysine catabolic process (GO:0019477). Retained as non-core
      background rather than as a distinct core function.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        on the final degradative pathway of L-lysine and is critical for
        mitochondrial metabolism
- term:
    id: GO:0019477
    label: L-lysine catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-based annotation to L-lysine catabolism. This is the principal
      biological process in which DHTKD1 acts, catalyzing the final common
      2-oxoadipate step of the lysine (and hydroxylysine/tryptophan)
      degradation pathway.
    action: ACCEPT
    reason: >-
      Well supported: DHTKD1 performs the rate-limiting decarboxylation of
      2-oxoadipate, the convergent intermediate of L-lysine catabolism; disease
      variants cause elevated 2-oxoadipate/2-aminoadipate. Core process.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        It is involved in the oxidative decarboxylation of 2-oxoadipate (OA) to
        glutaryl-CoA on the final degradative pathway of L-lysine
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Immunofluorescence-based (HPA) IDA localizing DHTKD1 to the
      mitochondrion. Consistent with all other evidence.
    action: ACCEPT
    reason: >-
      Directly observed mitochondrial localization by immunofluorescence,
      concordant with the mitochondrial matrix function of the OADHC E1a
      subunit.
    supported_by:
    - reference_id: PMID:23141294
      supporting_text: >-
        implicating an important role for DHTKD1 in mitochondrial energy
        production and neurological development.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: >-
      High-throughput mitochondrial proteomics (MitoCoP) detecting DHTKD1 in
      the high-confidence human mitochondrial proteome.
    action: ACCEPT
    reason: >-
      Independent proteomic confirmation of mitochondrial localization,
      consistent with the transit peptide and matrix function.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: >-
        defined a mitochondrial high-confidence proteome of >1,100 proteins
        (MitoCoP)
- term:
    id: GO:0160166
    label: 2-oxoadipate dehydrogenase activity
  evidence_type: IDA
  original_reference_id: PMID:29191460
  qualifier: enables
  review:
    summary: >-
      Direct biochemical demonstration that recombinant human E1a (DHTKD1)
      oxidatively decarboxylates 2-oxoadipate, with ~49-fold catalytic
      preference for 2-oxoadipate over 2-oxoglutarate. This is the defining,
      experimentally validated molecular function of the gene.
    action: ACCEPT
    reason: >-
      Gold-standard IDA evidence for the core catalytic activity; corroborated
      by kinetics (KM 0.012-0.015 mM for 2-oxoadipate) and crystal structures
      (PMID:32633484, PMID:32695416).
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        hE1a displays an approximately 49-fold preference in catalytic
        efficiency for OA over OG, indicating that hE1a is specific to the
        2-oxoadipate dehydrogenase complex
- term:
    id: GO:0160167
    label: oxoadipate dehydrogenase complex
  evidence_type: IDA
  original_reference_id: PMID:29191460
  qualifier: part_of
  review:
    summary: >-
      DHTKD1 is the E1a subunit of the 2-oxoadipate dehydrogenase complex,
      which it forms together with the shared E2 (DLST) and E3 (DLD) components
      of the 2-oxoglutarate dehydrogenase machinery. Directly demonstrated by
      reconstitution of an active complex.
    action: ACCEPT
    reason: >-
      Core cellular-component annotation. DHTKD1 recruits E2 (DLST) and E3 (DLD)
      to assemble a functional OADHC; the E1 subunit is complex-specific. This
      is the biologically meaningful protein-protein assembly for DHTKD1.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        The hE1a has recruited the dihydrolipoyl succinyltransferase (hE2o) and
        the dihydrolipoyl dehydrogenase (hE3) components of the tricarboxylic
        acid cycle 2-oxoglutarate dehydrogenase complex (OGDHc) for its activity
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9858321
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localizing the DHTKD1-catalyzed 2-oxoadipate decarboxylation
      to the mitochondrial matrix, the compartment of the OADHC.
    action: ACCEPT
    reason: >-
      Consistent with the soluble matrix location of the E1a subunit of the
      OADHC and with orthology/proteomic evidence.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex
        (OGDHc) for its activity
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9858589
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localizing the OADHC E3 (DLD) dihydrolipoyl dehydrogenation
      step to the mitochondrial matrix, the compartment where DHTKD1 acts.
    action: ACCEPT
    reason: >-
      Matrix localization is well established for the OADHC in which DHTKD1 is
      the E1 subunit.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        the dihydrolipoyl dehydrogenase (hE3) components of the tricarboxylic
        acid cycle 2-oxoglutarate dehydrogenase complex (OGDHc) for its activity
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9858590
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localizing the OADHC E2 (DLST) glutaryl transfer to CoA in
      the mitochondrial matrix, the compartment where DHTKD1 acts.
    action: ACCEPT
    reason: >-
      Consistent with matrix localization of the OADHC and of DHTKD1.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        the dihydrolipoyl succinyltransferase (hE2o) and the dihydrolipoyl
        dehydrogenase (hE3) components of the tricarboxylic acid cycle
        2-oxoglutarate dehydrogenase complex (OGDHc) for its activity
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:23141294
  qualifier: located_in
  review:
    summary: >-
      IDA localizing DHTKD1 to the mitochondrion, from the study that
      established the DHTKD1-CMT2 link and reported subcellular localization.
    action: ACCEPT
    reason: >-
      Direct experimental evidence for mitochondrial localization (UniProt
      SUBCELLULAR LOCATION cites this paper); concordant with all other data.
    supported_by:
    - reference_id: PMID:23141294
      supporting_text: >-
        implicating an important role for DHTKD1 in mitochondrial energy
        production and neurological development.
- term:
    id: GO:0006091
    label: generation of precursor metabolites and energy
  evidence_type: IMP
  original_reference_id: PMID:23141294
  qualifier: involved_in
  review:
    summary: >-
      IMP from a DHTKD1-silencing study reporting decreased ATP and total
      NAD(+)/NADH. This is a downstream physiological consequence of losing a
      lysine-catabolic enzyme rather than a direct biological process of DHTKD1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      DHTKD1 knockdown reduces cellular ATP/NAD(H) (an indirect metabolic
      readout), but DHTKD1 is not part of primary energy-generating machinery
      such as the TCA cycle or oxidative phosphorylation; its direct role is the
      2-oxoadipate step of amino-acid (lysine/tryptophan) catabolism. This term
      over-generalizes a secondary phenotype. Note this contrasts with the OGDH
      paralog, which is a bona fide TCA-cycle energy enzyme. Retained (not
      removed) as it derives from an experimental IMP.
    supported_by:
    - reference_id: PMID:23141294
      supporting_text: >-
        DHTKD1 silencing was found to lead to impaired energy production,
        evidenced by decreased ATP, total NAD(+) and NADH, and NADH levels
- term:
    id: GO:0006569
    label: L-tryptophan catabolic process
  evidence_type: IEA
  original_reference_id: PMID:29191460
  qualifier: involved_in
  review:
    summary: >-
      Proposed additional biological-process annotation. 2-oxoadipate is the
      convergent intermediate of L-lysine, L-hydroxylysine AND L-tryptophan
      catabolism; by decarboxylating 2-oxoadipate, DHTKD1 catalyzes the final
      common step of the tryptophan degradation pathway as well as the lysine
      pathway.
    action: NEW
    reason: >-
      UniProt explicitly states DHTKD1 is responsible for the last step of
      L-lysine, L-hydroxylysine and L-tryptophan catabolism (common product
      2-oxoadipate). The tryptophan-catabolic role is not otherwise captured in
      GOA and complements the existing L-lysine catabolic process annotation.
    supported_by:
    - reference_id: PMID:29191460
      supporting_text: >-
        It is involved in the oxidative decarboxylation of 2-oxoadipate (OA) to
        glutaryl-CoA on the final degradative pathway of L-lysine
core_functions:
- description: >-
    Thiamine diphosphate-dependent 2-oxoadipate dehydrogenase (E1a) activity: the
    first, rate-limiting oxidative decarboxylation step of the mitochondrial
    2-oxoadipate dehydrogenase complex, acting on the L-lysine/L-hydroxylysine/
    L-tryptophan catabolic pathway.
  molecular_function:
    id: GO:0160166
    label: 2-oxoadipate dehydrogenase activity
  directly_involved_in:
  - id: GO:0019477
    label: L-lysine catabolic process
  - id: GO:0006569
    label: L-tryptophan catabolic process
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  in_complex:
    id: GO:0160167
    label: oxoadipate dehydrogenase complex
  supported_by:
  - reference_id: PMID:29191460
    supporting_text: >-
      It is involved in the oxidative decarboxylation of 2-oxoadipate (OA) to
      glutaryl-CoA on the final degradative pathway of L-lysine
  - reference_id: PMID:29191460
    supporting_text: >-
      hE1a displays an approximately 49-fold preference in catalytic efficiency
      for OA over OG, indicating that hE1a is specific to the 2-oxoadipate
      dehydrogenase complex
- description: >-
    Thiamine diphosphate cofactor binding required for the decarboxylase activity
    of the E1a subunit.
  molecular_function:
    id: GO:0030976
    label: thiamine pyrophosphate binding
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:29191460
    supporting_text: >-
      Herein are reported unique properties of the novel human thiamin
      diphosphate (ThDP)-dependent enzyme 2-oxoadipate dehydrogenase (hE1a)
proposed_new_terms: []
suggested_questions:
- question: >-
    Given that DHTKD1 shares E2 (DLST) and E3 (DLD) with the 2-oxoglutarate
    dehydrogenase complex, how is flux partitioned between the OGDHC and OADHC in
    tissues where both are expressed (e.g. liver)?
- question: >-
    Why is alpha-aminoadipic/alpha-ketoadipic aciduria caused by DHTKD1 loss so
    frequently asymptomatic, and what genetic or metabolic factors modify the
    CMT2Q neuropathy phenotype?
suggested_experiments:
- description: >-
    Tissue-resolved metabolic flux analysis (e.g. 13C-lysine tracing) in
    DHTKD1-knockout versus wild-type cells to quantify the contribution of DHTKD1
    to 2-oxoadipate turnover and downstream glutaryl-CoA and energy metabolism.
  hypothesis: >-
    DHTKD1 loss diverts 2-oxoadipate away from glutaryl-CoA, causing measurable
    accumulation of 2-oxoadipate/2-aminoadipate without major bioenergetic deficit.
- description: >-
    Structural and kinetic characterization of the assembled DHTKD1-DLST-DLD
    megacomplex to define substrate channeling and the effect of AAKAD variants
    (e.g. G729R, R715C) on complex assembly and activity.
  hypothesis: >-
    AAKAD-causing variants impair DHTKD1-DLST assembly, disrupting intermediate
    channeling rather than abolishing intrinsic decarboxylase chemistry.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  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:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:23141294
  title: A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in
    a large Chinese pedigree.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Establishes DHTKD1 loss-of-function in CMT2Q and reports
      mitochondrial localization and impaired ATP/NAD(H) on silencing. Cited
      correctly for the mitochondrion (IDA) and energy (IMP) annotations.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex 2.0 AP-MS interactome. Correctly cited as the source of a
      high-throughput protein-binding IPI, but not a directed study of DHTKD1
      function; the recorded partner is not functionally informative.
- id: PMID:29191460
  title: The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes
    share their E2 and E3 components for their function and both generate reactive
    oxygen species.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Primary biochemical characterization of human E1a (DHTKD1): ThDP-dependent
      2-oxoadipate decarboxylation, ~49x preference for 2-oxoadipate over
      2-oxoglutarate, and recruitment of shared E2/E3. Anchors the core MF and
      complex annotations.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      HuRI binary Y2H interactome. Source of a high-throughput protein-binding
      IPI; not a directed DHTKD1 study and functionally uninformative for this
      gene.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex-derived proteome-scale interactome. Source of a high-throughput
      protein-binding IPI; not functionally informative for DHTKD1.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      MitoCoP high-confidence mitochondrial proteome; independently confirms
      DHTKD1 mitochondrial localization.
- id: Reactome:R-HSA-9858321
  title: DHTKD1 dimer decarboxylates 2-OA
  findings: []
- id: Reactome:R-HSA-9858589
  title: DLD dimer dehydrogenates dihydrolipoyl
  findings: []
- id: Reactome:R-HSA-9858590
  title: DLST transfers glutaryl to CoA
  findings: []