Affinage

GDAP1

Ganglioside-induced differentiation-associated protein 1 · UniProt Q8TB36

Length
358 aa
Mass
41.3 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GDAP1 is a tail-anchored outer mitochondrial membrane protein that functions as a fission factor for both mitochondria and peroxisomes, coordinating organelle dynamics with cytoskeletal organization, inter-organelle membrane contact sites, and calcium homeostasis in neurons and Schwann cells. It promotes Drp1/Fis1/Mff-dependent fission and maintains mitochondria–ER, mitochondria–lysosome (via LAMP-1 tethering), and mitochondria–peroxisome contact sites; its loss impairs store-operated Ca²⁺ entry, Ca²⁺-stimulated mitochondrial respiration, axonal mitochondrial transport, and autophagic lysosome reformation (PMID:19782751, PMID:23542510, PMID:33372681, PMID:33582224). GDAP1 contains a GST-like fold with a novel dimerization mode and possesses theta-class-like GST activity autoinhibited by its C-terminal hydrophobic domain 1 (HD1), though it has lost classical glutathione-binding capacity; it interacts with Cofilin-1 and β-tubulin in a redox-dependent manner to maintain perimiochondrial F-actin required for Drp1 recruitment (PMID:27841286, PMID:33585569, PMID:32274853, PMID:35662277). Biallelic loss-of-function mutations cause autosomal recessive Charcot–Marie–Tooth disease (CMT4A) through reduced fission and impaired calcium signaling, whereas dominant mutations interfere with fusion and increase ROS, and CMT-linked variants destabilize the protein without major structural disruption (PMID:19782751, PMID:35509130, PMID:25860513).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 Medium

    Sequence analysis established that GDAP1 belongs to a novel GST-related protein family, providing the structural framework for understanding its enzymatic and non-enzymatic functions.

    Evidence Comparative genomics and domain prediction identifying GST-like domains and unique C-terminal transmembrane regions

    PMID:14595091

    Open questions at the time
    • No experimental verification of enzymatic activity at this stage
    • 3D structure not determined
    • Functional significance of GST-like domain unknown
  2. 2005 High

    Direct localization experiments resolved that GDAP1 resides on the mitochondrial outer membrane and that overexpression fragments mitochondria, establishing it as a candidate fission factor.

    Evidence Transient overexpression in COS-7 cells with organelle marker co-localization, subcellular fractionation, and C-terminal deletion analysis

    PMID:15772096

    Open questions at the time
    • Mechanism of fission induction unknown
    • Dependence on canonical fission machinery not tested
    • Endogenous protein behavior not characterized
  3. 2009 High

    Genetic epistasis demonstrated that GDAP1-mediated fission requires Drp1 and Fis1, and revealed a genotype-mechanism correlation where recessive CMT mutations reduce fission while dominant mutations impair fusion and elevate ROS.

    Evidence Overexpression/knockdown with epistasis to Drp1/Fis1, ROS measurement, and apoptosis assays; plus tail-anchor topology mapping by mutagenesis

    PMID:19340293 PMID:19782751

    Open questions at the time
    • Direct physical interaction with Drp1/Fis1 not demonstrated
    • How dominant mutations impair fusion mechanistically unclear
    • In vivo validation lacking
  4. 2011 High

    Two parallel advances linked GDAP1 to glutathione metabolism and the cytoskeleton: GDAP1 increases cellular GSH and protects against oxidative stress, while it physically interacts with β-tubulin and complements yeast fis1Δ cell-cycle defects.

    Evidence GSH quantification with overexpression/knockdown in neuronal lines and patient fibroblasts; yeast complementation with co-immunoprecipitation of GDAP1–β-tubulin

    PMID:21890626 PMID:21965300

    Open questions at the time
    • Whether GSH increase reflects direct enzymatic activity or indirect effect unknown
    • Physiological relevance of tubulin interaction in neurons not tested
  5. 2013 High

    GDAP1 was shown to regulate inter-organelle communication: its loss disrupts mitochondria–ER contacts and store-operated Ca²⁺ entry, and it additionally promotes Drp1/Mff-dependent peroxisomal fission via Pex19-mediated dual targeting.

    Evidence siRNA knockdown with Ca²⁺ imaging and ER–mitochondria contact quantification in SH-SY5Y cells; immunofluorescence co-localization with peroxisomal markers and epistasis with Mff

    PMID:23542510 PMID:23628762

    Open questions at the time
    • Molecular mechanism of ER–mitochondria tethering not identified
    • Whether peroxisomal and mitochondrial fission roles are independent or coordinated unknown
  6. 2014 High

    In vivo studies in Gdap1 knockout mice and Drosophila confirmed that GDAP1 loss causes enlarged mitochondria, impaired axonal transport, and cell-autonomous Schwann cell pathology, while JPH1 was identified as a genetic modifier acting through SOCE.

    Evidence Gdap1 constitutive and conditional knockout mice with live-cell transport imaging and morphological analysis; Drosophila tissue-specific RNAi; JPH1 rescue of SOCE in GDAP1-silenced cells with patient genetic epistasis

    PMID:24480485 PMID:25122658 PMID:25168384

    Open questions at the time
    • Molecular basis of GDAP1 role in Schwann cell myelination unclear
    • Whether JPH1–STIM1 interaction requires direct GDAP1 binding unresolved
  7. 2015 High

    Gdap1 knockout motor neurons revealed a comprehensive phenotype—reduced SOCE, ER cisternae changes, decreased α-tubulin acetylation, and increased autophagy—establishing GDAP1 as a nexus for mitochondria–ER interaction and cytoskeletal integrity.

    Evidence Gdap1 knockout mouse embryonic motor neuron cultures with Ca²⁺ imaging, electron microscopy, and immunofluorescence

    PMID:25860513

    Open questions at the time
    • Causal hierarchy among cytoskeletal, ER, and mitochondrial phenotypes not resolved
    • Direct tubulin acetylation mechanism unknown
  8. 2016 High

    Biochemical reconstitution demonstrated that GDAP1 possesses theta-class-like GST enzymatic activity autoinhibited by HD1, linking HD1 integrity to both enzymatic and fission functions through a conformational switch.

    Evidence In vitro GST assay with recombinant GDAP1 and HD1 domain mutagenesis

    PMID:27841286

    Open questions at the time
    • Physiological substrate of GST activity not identified
    • Whether enzymatic activity is required for fission in vivo unresolved
  9. 2017 High

    Mechanistic dissection showed that recessive α-loop mutations specifically impair Ca²⁺-dependent upregulation of mitochondrial respiration through reduced SOCE, linking GDAP1 to mitochondrial Ca²⁺ uptake via MCU.

    Evidence siRNA knockdown, MCU silencing, mitochondrial depolarization, and Seahorse respirometry with recessive vs. dominant mutation comparison

    PMID:28220846

    Open questions at the time
    • Whether GDAP1 directly interacts with MCU pathway components unknown
    • Neuron-type specificity of this metabolic defect not explored
  10. 2020 High

    Refined biochemical analysis showed that GDAP1 has lost the canonical glutathione-binding G-site while retaining substrate binding at the H-site (α-loop), and that its fission-promoting activity is mechanistically distinct from oxidative-stress-induced fragmentation.

    Evidence Recombinant GDAP1 binding assays, G-site and α-loop mutagenesis, mitochondrial morphology in HeLa cells

    PMID:32274853

    Open questions at the time
    • Identity of endogenous H-site substrates/ligands in cells unknown
    • Relationship between H-site occupancy and fission activity not tested in vivo
  11. 2021 High

    Structural and functional studies converged: the crystal structure revealed a novel GST-family dimer with a long insertion helix and fatty acid ligand binding near CMT residues, while cell biology showed GDAP1 tethers mitochondria to lysosomes via LAMP-1 interaction and regulates autophagy and axonal bioenergetics.

    Evidence X-ray crystallography with metabolite screening; Co-IP of GDAP1–LAMP-1/PIKfyve with autophagy flux assays; Gdap1 KO motor neuron ATP/Ca²⁺/transport measurements

    PMID:33372681 PMID:33582224 PMID:33585569

    Open questions at the time
    • Physiological relevance of fatty acid ligand binding not confirmed in cells
    • Whether LAMP-1 tethering is direct or mediated by intermediary proteins in vivo unclear
  12. 2022 High

    The mechanistic chain from GDAP1 to fission was completed: GDAP1 interacts with Cofilin-1 in a redox-dependent manner to maintain perimiochondrial F-actin required for Drp1 recruitment, and its loss shifts metabolism to glutamine dependence via reduced mitochondrial Ca²⁺ and PDC inhibition. Crystal structures of five CMT variants showed destabilization without gross structural changes.

    Evidence Co-IP of GDAP1–Cofilin-1, F-actin and Drp1 localization imaging, Seahorse metabolomics in patient-derived motoneurons; X-ray crystallography and thermal stability of disease variants

    PMID:35509130 PMID:35662277

    Open questions at the time
    • Whether GDAP1 enzymatically modifies Cofilin-1 or acts as a scaffold unknown
    • How reduced protein stability translates to dominant vs. recessive disease phenotypes not fully explained
  13. 2023 Medium

    Biophysical characterization provided the first experimental model of how GDAP1 is anchored in the outer mitochondrial membrane, with peripheral helices interacting with both leaflets flanking a single transmembrane helix, and live-cell imaging showed that dominant and recessive variants have opposite effects on mitochondria–lysosome contacts.

    Evidence Synchrotron radiation circular dichroism and SAXS of membrane-associated GDAP1 peptides; quantitative live-cell imaging of mitochondria–lysosome MCSs with dominant (T157P) vs. recessive (R161H) variants

    PMID:36912213 PMID:37778197

    Open questions at the time
    • Full-length membrane-embedded structure not yet resolved at atomic level
    • Direction of Ca²⁺ transfer at mitochondria–lysosome contacts not directly measured

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the identity of endogenous GDAP1 substrates/ligands, how its GST-like enzymatic activity is coupled to fission or tethering functions, the structural basis of full-length membrane-embedded GDAP1 in organelle contact sites, and how dominant versus recessive mutations produce opposite effects on organelle dynamics despite similarly destabilizing the protein.
  • Endogenous substrate/ligand of H-site not identified
  • Full-length cryo-EM or crystal structure in membrane context absent
  • Mechanism distinguishing dominant from recessive pathogenesis at the molecular level remains incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0016740 transferase activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005739 mitochondrion 6 GO:0005777 peroxisome 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-9612973 Autophagy 2
Partners
CFL1DRP1FIS1JPH1LAMP1MFFPIKFYVETUBB

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 GDAP1 localizes to the mitochondrial outer membrane, with C-terminal transmembrane domains necessary for correct mitochondrial targeting. Overexpression of GDAP1 induces mitochondrial fragmentation, suggesting a role in the fission pathway of mitochondrial network dynamics. Transient overexpression, co-localization with organelle markers in COS-7 cells, western blot of subcellular fractions, C-terminal domain deletion analysis Human molecular genetics High 15772096
2009 GDAP1 is a mitochondrial fission factor whose activity is dependent on the fission factors Drp1 and Fis1. Recessively inherited CMT mutations reduce fission activity, while dominantly inherited mutations interfere with mitochondrial fusion and increase ROS production and apoptosis susceptibility. GDAP1 overexpression and knockdown in cells, mitochondrial morphology assays, ROS measurement, apoptosis assays, epistasis with Drp1 and Fis1 Neurobiology of disease High 19782751
2009 GDAP1 is a tail-anchored mitochondrial outer membrane protein. A single transmembrane domain (TMD) together with adjacent basic amino acids is critical for MOM targeting. Basic amino acids bordering the TMD in the cytoplasm are required for both targeting and GDAP1-mediated fission function. Domain mutagenesis, subcellular fractionation, mitochondrial morphology assays, deletion and chimeric constructs PloS one High 19340293
2003 GDAP1 protein shows sequence similarity to glutathione S-transferases (GSTs) and contains an extended region in GST domain II absent in most GSTs, plus C-terminal transmembrane domains. GDAP1 and its paralogue GDAP1L1 define a novel class of GST-related genes. Comparative genomics, sequence analysis, structural domain prediction Molecular biology and evolution Medium 14595091
2013 GDAP1 silencing causes abnormal mitochondrial distribution, reduces mitochondrial-ER contacts, and decreases store-operated Ca2+ entry (SOCE) following ER-Ca2+ mobilization. GDAP1 interacts with vesicle-organelle trafficking proteins RAB6B and caytaxin, suggesting a role in mitochondrial movement. siRNA knockdown in SH-SY5Y cells, co-immunoprecipitation, Ca2+ imaging, mitochondrial distribution analysis, ER-mitochondria contact site quantification Neurobiology of disease High 23542510
2013 GDAP1 localizes to peroxisomes in addition to mitochondria, mediated by the import receptor Pex19. GDAP1 knockdown causes peroxisomal elongation rescued by re-expression. GDAP1-induced peroxisomal fission depends on integrity of hydrophobic domain 1 (HD1) and on Drp1 and Mff, similar to mitochondrial fission. Immunofluorescence co-localization, siRNA knockdown, rescue experiments with wild-type and CMT mutant GDAP1, epistasis with Drp1 and Mff EMBO reports High 23628762
2011 GDAP1 overexpression increases total cellular glutathione (GSH) content and mitochondrial membrane potential. GDAP1 knockdown increases susceptibility to GSH depletion. CMT-causing recessive mutations with reduced fission activity fail to increase GSH, linking GDAP1's potential GST activity to oxidative stress protection. Overexpression and siRNA knockdown in neuronal cell lines (HT22, NSC34), glutathione measurement, mitochondrial membrane potential assay, analysis of CMT patient fibroblasts Human molecular genetics High 21965300
2014 GDAP1L1, the paralogue of GDAP1 expressed in the CNS, responds to elevated oxidized glutathione by translocating from the cytosol to mitochondria and inserting into the mitochondrial outer membrane, compensating for GDAP1 loss in the CNS of Gdap1 knockout mice. Gdap1 knockout mouse model, subcellular fractionation, western blot, comparison of CNS vs PNS Brain : a journal of neurology High 24480485
2014 In Gdap1 knockout mice, intra-axonal mitochondria of peripheral neurons are larger and mitochondrial transport is impaired in cultured sensory neurons. Loss of Gdap1 in Schwann cells recapitulates hypomyelinating peripheral neuropathy, demonstrating cell-autonomous function in Schwann cells. Gdap1 conditional and constitutive knockout mice, live-cell mitochondrial transport imaging, morphological analysis Brain : a journal of neurology High 24480485
2015 Loss of GDAP1 in knockout mice results in large and defective mitochondria in motor neurons, changes in ER cisternae, reduced cytoskeletal α-tubulin acetylation, increased autophagy, reduced cytosolic calcium, and reduced SOCE response, consistent with impaired mitochondria-ER interaction. Gdap1 knockout mouse, embryonic motor neuron cultures, Ca2+ imaging, electron microscopy, electrophysiology, immunofluorescence PLoS genetics High 25860513
2011 GDAP1 complements G2/M cell cycle delay in yeast fis1Δ cells. GDAP1 interacts with β-tubulin (TUBB in human, Tub2p in yeast), and CMT-causing missense mutations rescue fis1Δ mitochondrial phenotypes but not the cell cycle delay, suggesting GDAP1 links mitochondria to the microtubule cytoskeleton. Yeast complementation assay, cell cycle analysis, co-immunoprecipitation of GDAP1 with β-tubulin in yeast and human cells, CMT mutant analysis The Journal of biological chemistry High 21890626
2016 GDAP1 exhibits theta-class-like glutathione S-transferase (GST) activity in vitro using recombinant protein. This activity is regulated in an autoinhibitory manner by the C-terminal hydrophobic domain 1 (HD1). The amphipathic pattern of HD1 is also required for GDAP1 to induce membrane dynamics/fission, suggesting a molecular switch between pro-fission active and auto-inhibited inactive conformations. In vitro GST enzymatic assay with recombinant GDAP1, HD1 domain mutagenesis, membrane dynamics assay Scientific reports High 27841286
2017 Loss-of-function recessive GDAP1 mutations (in the α-loop) reduce SOCE and blunt Ca2+-dependent upregulation of mitochondrial respiration, while dominant mutations do not. MCU silencing or mitochondrial depolarization mimics the SOCE defect, indicating that mitochondrial Ca2+ uptake is required for normal SOCE-stimulated respiration. siRNA knockdown, MCU silencing, mitochondrial depolarization, Ca2+ imaging, oxygen consumption rate measurement (Seahorse) Scientific reports High 28220846
2014 Junctophilin-1 (JPH1) can rescue SOCE activity in GDAP1-silenced cells. JPH1 colocalizes with STIM1 (SOCE activator) at ER-plasma membrane puncta in a GDAP1-dependent manner. The combination of GDAP1(p.R120W) and JPH1(p.R213P) dramatically reduces SOCE activity, establishing JPH1 as a genetic modifier of GDAP1-related CMT acting in the same Ca2+ homeostasis pathway. siRNA rescue experiments, co-localization imaging, Ca2+ imaging, genetic epistasis in patient cohort Human molecular genetics High 25168384
2021 GDAP1 participates in basal autophagy and interacts with PIKfyve kinase (a lysosomal regulator) and with LAMP-1, establishing GDAP1-LAMP-1 as a new tethering pair for mitochondria-lysosome membrane contact sites (MCSs). GDAP1 deficiency causes giant lysosomes, delays autophagic lysosome reformation, and reduces mitochondria-lysosome MCSs. Co-immunoprecipitation (GDAP1-LAMP-1, GDAP1-PIKfyve), live-cell imaging of MCSs, autophagy flux assays, GSH rescue experiments Human molecular genetics High 33372681
2022 GDAP1 interacts with the actin-depolymerizing protein Cofilin-1 and beta-tubulin in a redox-dependent manner. GDAP1 loss reduces F-actin near mitochondria, restricts mitochondrial localization of the fission factor Drp1, causing tubular mitochondria. GDAP1 loss also disrupts mitochondria-ER contact sites and lowers mitochondrial Ca2+ levels, inhibiting the pyruvate dehydrogenase complex (PDC) and causing metabolic shift to glutamine dependence. Co-immunoprecipitation (GDAP1-Cofilin-1, GDAP1-tubulin), F-actin staining, Drp1 localization, Seahorse metabolic assay, Ca2+ imaging, patient-derived motoneurons and SH-SY5Y knockdown Communications biology High 35662277
2020 GDAP1 has lost the ability to bind glutathione (G-site critical residues are altered) while retaining substrate-binding activity at the H-site (α-loop is primary determinant). GDAP1 overexpression produces a mitochondrial fragmentation phenotype distinct from oxidative-stress-induced fragmentation, dependent on the transmembrane domain and a unique hydrophobic domain absent in canonical GSTs. Biochemical binding assays with recombinant GDAP1, structural analysis, mutagenesis of G-site and α-loop, overexpression in HeLa cells with mitochondrial morphology readout FASEB journal High 32274853
2021 Crystal structure of the complete human GDAP1 core domain reveals a novel dimerization mode within the GST family. The long GDAP1-specific insertion forms an extended helix and flexible loop. GDAP1 is catalytically inactive toward classical GST substrates. A ligand (fatty acid hexadecanedioic acid) was identified binding near CMT-linked residues, increasing protein stability and inducing conformational and oligomerization changes, suggesting allosteric regulation. X-ray crystallography, metabolite screening, thermal stability assay, oligomerization analysis Frontiers in molecular biosciences High 33585569
2009 YY1 transcription factor directly regulates human GDAP1 gene expression. A consensus YY1 binding site in the GDAP1 core promoter is functional in vitro and in living cells; YY1 overexpression activates the GDAP1 promoter and increases endogenous mRNA, while YY1 knockdown decreases GDAP1 expression. Promoter-reporter assay, in vitro binding assay, RNAi knockdown of YY1 in HEK293 cells, YY1 overexpression Genomics Medium 19720140
2023 Using synchrotron radiation oriented circular dichroism and SAXS, GDAP1 is shown to be anchored in the mitochondrial outer membrane via a single transmembrane helix flanked by two peripheral helices that interact with opposite leaflets of the outer mitochondrial membrane. This provides the first experimental structural model for full-length GDAP1 membrane assembly. Oriented circular dichroism spectroscopy with synchrotron radiation, small-angle X-ray scattering, peptide studies in lipidic environment Biophysical chemistry Medium 37778197
2021 Loss of GDAP1 in Gdap1-/- embryonic motor neurons causes defective mitochondrial axonal transport, reduced ATP production, deteriorated bioenergetic status, and increased axonal calcium levels both basally and after glutamate stimulation. Glutamate-stimulated respiration is blunted, linking GDAP1-dependent mitochondrial function directly to calcium homeostasis in axons. Gdap1 knockout mouse embryonic motor neuron cultures, live-cell mitochondrial transport imaging, ATP bioluminescence assay, Ca2+ imaging, Seahorse respirometry Neurobiology of disease High 33582224
2014 Drosophila Gdap1 ortholog alters mitochondrial size, morphology and distribution when up- or downregulated in a tissue-specific manner, causing neuronal and muscular degeneration. Muscular degeneration is tissue-autonomous and not dependent on innervation. Metabolic analyses indicate alterations in oxidative stress are a long-term consequence, not a primary cause, of the mitochondrial dysfunction. Tissue-specific Drosophila Gdap1 overexpression and RNAi knockdown, mitochondrial morphology analysis, neuromuscular degeneration scoring, metabolic profiling Human molecular genetics Medium 25122658
2022 Crystal structures of CMT-linked GDAP1 variants (H123R, R120W, R120Q, A247V, R282H) reveal that disease mutations decrease protein thermal stability without major structural disruption. A side-chain interaction network between helices α3, α6, and α7 and a hinge in helix α6 are identified as structurally critical regions affected by CMT mutations. X-ray crystallography of disease variants, thermal stability assays, solution behavior analysis FEBS open bio High 35509130
2021 GDAP1 mutations influence structure and function of the trans-Golgi network (TGN). Some CMT-causing mutations reduce GDAP1 protein expression and cause selective disruption of Golgi apparatus structure and function in yeast and human cell models. Yeast and human cell expression models, Golgi morphology analysis, functional Golgi assays International journal of molecular sciences Medium 33477664
2023 Dominant GDAP1 variant p.Thr157Pro increases mitochondria-lysosome MCSs correlating with hyper-fissioned mitochondrial network, while recessive variant p.Arg161His decreases these contacts and causes elongated mitochondria. These opposite effects on MCSs support GDAP1's role in regulating Ca2+ transfer from lysosomes to mitochondria. High-resolution live-cell imaging of mitochondria-lysosome contacts, mitochondrial network morphology analysis, comparison of dominant vs. recessive variants Biology open Medium 36912213
2024 GDAP1 acts as a tether of mitochondria-peroxisome membrane contact sites (MCSs), maintaining peroxisomal number and integrity. GDAP1 deficiency disrupts these MCSs causing peroxisomal abnormalities reversible by PPARγ activation or glutathione supplementation. GDAP1 also regulates the redox state at mitochondria-lysosome contacts. In Gdap1-/- sciatic nerve, nodes of Ranvier are disrupted with abnormal distribution of mitochondria, lysosomes, and peroxisomes. High-resolution microscopy, live-cell imaging with pH-sensitive probes, transcriptomics, lipidomics, Gdap1-/- mouse model, patient-derived fibroblasts, pharmacological rescue Research square (preprint)preprint Medium 39801517

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 GDAP1, the protein causing Charcot-Marie-Tooth disease type 4A, is expressed in neurons and is associated with mitochondria. Human molecular genetics 147 15772096
2002 Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy. Neurology 123 12499475
2009 GDAP1 mutations differ in their effects on mitochondrial dynamics and apoptosis depending on the mode of inheritance. Neurobiology of disease 117 19782751
1993 Linkage of a locus (CMT4A) for autosomal recessive Charcot-Marie-Tooth disease to chromosome 8q. Human molecular genetics 116 8268915
2003 Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy. Brain : a journal of neurology 98 12566285
2003 Evolutionary and structural analyses of GDAP1, involved in Charcot-Marie-Tooth disease, characterize a novel class of glutathione transferase-related genes. Molecular biology and evolution 87 14595091
2003 Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene. Brain : a journal of neurology 82 12821518
2010 Mitochondrial dysfunction and pathophysiology of Charcot-Marie-Tooth disease involving GDAP1 mutations. Experimental neurology 77 20849849
2008 Vocal cord paresis and diaphragmatic dysfunction are severe and frequent symptoms of GDAP1-associated neuropathy. Brain : a journal of neurology 75 18812441
2013 Silencing of the Charcot-Marie-Tooth disease-associated gene GDAP1 induces abnormal mitochondrial distribution and affects Ca2+ homeostasis by reducing store-operated Ca2+ entry. Neurobiology of disease 73 23542510
2013 Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission. EMBO reports 72 23628762
2011 Dominant GDAP1 mutations cause predominantly mild CMT phenotypes. Neurology 71 21753178
2011 Charcot-Marie-Tooth disease CMT4A: GDAP1 increases cellular glutathione and the mitochondrial membrane potential. Human molecular genetics 70 21965300
2008 Mitochondrial complex I deficiency in GDAP1-related autosomal dominant Charcot-Marie-Tooth disease (CMT2K). Neurogenetics 68 19089472
2015 Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout mouse model of charcot-marie-tooth neuropathy. PLoS genetics 67 25860513
2007 Cell expression of GDAP1 in the nervous system and pathogenesis of Charcot-Marie-Tooth type 4A disease. Journal of cellular and molecular medicine 63 18021315
2014 The Gdap1 knockout mouse mechanistically links redox control to Charcot-Marie-Tooth disease. Brain : a journal of neurology 60 24480485
2021 Mitochondria-lysosome membrane contacts are defective in GDAP1-related Charcot-Marie-Tooth disease. Human molecular genetics 58 33372681
2010 Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot-Marie-Tooth disease. Journal of the peripheral nervous system : JPNS 54 21199105
2003 CMT4A: identification of a Hispanic GDAP1 founder mutation. Annals of neurology 53 12601710
2003 Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene. Archives of neurology 48 12707075
2003 Variability of disease progression in a family with autosomal recessive CMT associated with a S194X and new R310Q mutation in the GDAP1 gene. Neuromuscular disorders : NMD 47 12868504
2008 A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease. Journal of human genetics 46 18231710
2003 Identification of novel GDAP1 mutations causing autosomal recessive Charcot-Marie-Tooth disease. Neuromuscular disorders : NMD 44 14561495
2010 The GST domain of GDAP1 is a frequent target of mutations in the dominant form of axonal Charcot Marie Tooth type 2K. Journal of medical genetics 42 20685671
2014 Junctophilin-1 is a modifier gene of GDAP1-related Charcot-Marie-Tooth disease. Human molecular genetics 41 25168384
2009 Targeting and function of the mitochondrial fission factor GDAP1 are dependent on its tail-anchor. PloS one 40 19340293
2016 Screening for SH3TC2 gene mutations in a series of demyelinating recessive Charcot-Marie-Tooth disease (CMT4). Journal of the peripheral nervous system : JPNS 39 27231023
2017 CMT-linked loss-of-function mutations in GDAP1 impair store-operated Ca2+ entry-stimulated respiration. Scientific reports 36 28220846
2004 Vocal cord and diaphragm paralysis, as clinical features of a French family with autosomal recessive Charcot-Marie-Tooth disease, associated with a new mutation in the GDAP1 gene. Neuromuscular disorders : NMD 36 15019704
2014 Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy. Human molecular genetics 35 25122658
2012 A French family with Charcot-Marie-Tooth disease related to simultaneous heterozygous MFN2 and GDAP1 mutations. Neuromuscular disorders : NMD 35 22546700
2011 A locus-specific database for mutations in GDAP1 allows analysis of genotype-phenotype correlations in Charcot-Marie-Tooth diseases type 4A and 2K. Orphanet journal of rare diseases 32 22200116
2011 Charcot-Marie-Tooth-related gene GDAP1 complements cell cycle delay at G2/M phase in Saccharomyces cerevisiae fis1 gene-defective cells. The Journal of biological chemistry 30 21890626
2019 Neuroinflammation in the pathogenesis of axonal Charcot-Marie-Tooth disease caused by lack of GDAP1. Experimental neurology 29 31271761
2016 Glutathione-conjugating and membrane-remodeling activity of GDAP1 relies on amphipathic C-terminal domain. Scientific reports 29 27841286
2013 Dominant GDAP1 founder mutation is a common cause of axonal Charcot-Marie-Tooth disease in Finland. Neurogenetics 29 23456260
2017 Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain. Scientific reports 27 28751717
2023 Mutational screening of GDAP1 in dysphonia associated with Charcot-Marie-Tooth disease: clinical insights and phenotypic effects. Journal, genetic engineering & biotechnology 26 37966693
2016 Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome. Epigenetics 26 27128683
2004 A novel mutation of GDAP1 associated with Charcot-Marie-Tooth disease in three Italian families: evidence for a founder effect. Journal of neurology, neurosurgery, and psychiatry 24 15377708
2022 GDAP1 loss of function inhibits the mitochondrial pyruvate dehydrogenase complex by altering the actin cytoskeleton. Communications biology 23 35662277
2019 Calcium Deregulation and Mitochondrial Bioenergetics in GDAP1-Related CMT Disease. International journal of molecular sciences 23 30669311
2009 Novel mutations in the GDAP1 gene in patients affected with early-onset axonal Charcot-Marie-Tooth type 4A. Neuromuscular disorders : NMD 23 19500985
2018 A role for the GDAP1 gene in the molecular pathogenesis of Charcot‑Marie‑Tooth disease. Acta neurobiologiae experimentalis 22 29694336
2008 Two novel mutations in the GDAP1 and PRX genes in early onset Charcot-Marie-Tooth syndrome. Neuropediatrics 22 18504680
2021 Mitochondria and calcium defects correlate with axonal dysfunction in GDAP1-related Charcot-Marie-Tooth mouse model. Neurobiology of disease 21 33582224
1995 Physical and genetic mapping of the CMT4A locus and exclusion of PMP-2 as the defect in CMT4A. Genomics 21 8530038
2015 GDAP1 mutations in Italian axonal Charcot-Marie-Tooth patients: Phenotypic features and clinical course. Neuromuscular disorders : NMD 20 26525999
2021 GDAP1 Involvement in Mitochondrial Function and Oxidative Stress, Investigated in a Charcot-Marie-Tooth Model of hiPSCs-Derived Motor Neurons. Biomedicines 19 34440148
2020 Structural and functional divergence of GDAP1 from the glutathione S-transferase superfamily. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 32274853
2018 Genotype-phenotype correlation and frequency of distribution in a cohort of Chinese Charcot-Marie-Tooth patients associated with GDAP1 mutations. Journal of neurology 17 29372391
2017 A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration. Biochimica et biophysica acta. Molecular basis of disease 16 28065847
2011 A new missense GDAP1 mutation disturbing targeting to the mitochondrial membrane causes a severe form of AR-CMT2C disease. Neurogenetics 16 21365284
2010 L239F founder mutation in GDAP1 is associated with a mild Charcot-Marie-Tooth type 4C4 (CMT4C4) phenotype. Neurogenetics 16 20232219
2007 GDAP1 mutations in Czech families with early-onset CMT. Neuromuscular disorders : NMD 16 17433678
2021 Clinical and Neuroimaging Features in Charcot-Marie-Tooth Patients with GDAP1 Mutations. Journal of clinical neurology (Seoul, Korea) 14 33480199
2019 Novel GDAP1 Mutation in a Vietnamese Family with Charcot-Marie-Tooth Disease. BioMed research international 14 31179332
2017 Clinical and mutational spectrum of Japanese patients with Charcot-Marie-Tooth disease caused by GDAP1 variants. Clinical genetics 14 28244113
2014 Exome sequencing reveals mutations in MFN2 and GDAP1 in severe Charcot-Marie-Tooth disease. Journal of the peripheral nervous system : JPNS 14 25403865
2009 YY1-dependent transcriptional regulation of the human GDAP1 gene. Genomics 14 19720140
2021 Mutations in GDAP1 Influence Structure and Function of the Trans-Golgi Network. International journal of molecular sciences 13 33477664
2021 Structure of the Complete Dimeric Human GDAP1 Core Domain Provides Insights into Ligand Binding and Clustering of Disease Mutations. Frontiers in molecular biosciences 12 33585569
2020 Pathogenic Effect of GDAP1 Gene Mutations in a Yeast Model. Genes 12 32183277
2011 Two recessive intermediate Charcot-Marie-Tooth patients with GDAP1 mutations. Journal of the peripheral nervous system : JPNS 12 21692914
2023 Differential effects of Mendelian GDAP1 clinical variants on mitochondria-lysosome membrane contacts sites. Biology open 11 36912213
2012 A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family. Journal of the peripheral nervous system : JPNS 11 22971097
2005 Autosomal recessive axonal form of Charcot-Marie-Tooth Disease caused by compound heterozygous 3'-splice site and Ser130Cys mutation in the GDAP1 gene. Neuropediatrics 11 15944907
2005 A novel Met116Thr mutation in the GDAP1 gene in a Polish family with the axonal recessive Charcot-Marie-Tooth type 4 disease. Journal of the neurological sciences 11 16343542
2023 Rapid degeneration of iPSC-derived motor neurons lacking Gdap1 engages a mitochondrial-sustained innate immune response. Cell death discovery 10 37393339
2014 A severe recessive and a mild dominant form of Charcot-Marie-Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation. Acta biochimica Polonica 10 25337607
2007 Charcot-Marie-Tooth disease type 4C4 caused by a novel Pro153Leu substitution in the GDAP1 gene. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 10 18421898
1998 Fine localization of the CMT4A locus using a PAC contig and haplotype analysis. Neurogenetics 10 9933296
2015 Mitochondrial Dysfunction in a Patient with 8q21.11 Deletion and Charcot-Marie-Tooth Disease Type 2K due to GDAP1 Haploinsufficiency. Molecular syndromology 9 26648837
2007 A novel GDAP1 mutation P78L responsible for CMT4A disease in three Moroccan families. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 9 18062449
2023 Amlexanox: Readthrough Induction and Nonsense-Mediated mRNA Decay Inhibition in a Charcot-Marie-Tooth Model of hiPSCs-Derived Neuronal Cells Harboring a Nonsense Mutation in GDAP1 Gene. Pharmaceuticals (Basel, Switzerland) 8 37513945
2022 One PMP22/MPZ and Three MFN2/GDAP1 Concomitant Variants Occurred in a Cohort of 189 Chinese Charcot-Marie-Tooth Families. Frontiers in neurology 8 35153971
2006 A novel GDAP1 mutation 439delA is associated with autosomal recessive CMT disease. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 8 17001820
2006 Early onset Charcot-Marie-Tooth disease caused by a homozygous Leu239Phe mutation in the GDAP1 gene. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 8 17039978
2020 Cigarette smoke exposure has region-specific effects on GDAP1 expression in mouse hippocampus. Psychiatry research 7 32438208
2020 Deep geno- and phenotyping in two consanguineous families with CMT2 reveals HADHA as an unusual disease-causing gene and an intronic variant in GDAP1 as an unusual mutation. Journal of neurology 7 32897397
2009 Novel GDAP1 mutation in a Turkish family with CMT2K (CMT2K with novel GDAP1 mutation). Neuromolecular medicine 7 19381883
2008 A novel mutation in the GDAP1 gene is associated with autosomal recessive Charcot-Marie-Tooth disease in an Amish family. Clinical genetics 7 18492089
2008 Clinical, electrophysiological and genetic studies of two families with mutations in the GDAP1 gene. Neuropediatrics 7 18991200
2021 GDAP1 mutations are frequent among Brazilian patients with autosomal recessive axonal Charcot-Marie-Tooth disease. Neuromuscular disorders : NMD 6 33903021
2020 Identification and functional characterization of novel GDAP1 variants in Chinese patients with Charcot-Marie-Tooth disease. Annals of clinical and translational neurology 6 33136338
2018 WES homozygosity mapping in a recessive form of Charcot-Marie-Tooth neuropathy reveals intronic GDAP1 variant leading to a premature stop codon. Neurogenetics 6 29396836
2017 Phenotypical features of a new dominant GDAP1 pathogenic variant (p.R226del) in axonal Charcot-Marie-Tooth disease. Neuromuscular disorders : NMD 6 28236508
2023 Conserved intramolecular networks in GDAP1 are closely connected to CMT-linked mutations and protein stability. PloS one 5 37058526
2022 Structural insights into Charcot-Marie-Tooth disease-linked mutations in human GDAP1. FEBS open bio 5 35509130
2016 Generation of a disease-specific iPS cell line derived from a patient with Charcot-Marie-Tooth type 2K lacking functional GDAP1 gene. Stem cell research 5 28395795
2022 The GDAP1 p.Glu222Lys Variant-Weak Pathogenic Effect, Cumulative Effect of Weak Sequence Variants, or Synergy of Both Factors? Genes 4 36140714
2017 Pseudodominant inheritance pattern in a family with CMT2 caused by GDAP1 mutations. Journal of the peripheral nervous system : JPNS 4 28837237
2021 Phenotype of Patients With Charcot-Marie-Tooth With the p.His123Arg Mutation in GDAP1 in Northern Finland. Neurology. Genetics 3 34632054
2015 Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a Colombian family. Colombia medica (Cali, Colombia) 3 26848201
2025 GDAP1 Is Dysregulated at DNA Methylation and H3K4me3 Levels in Alcohol Use Disorder. International journal of molecular sciences 2 40004086
2025 Digenesis in Charcot-Marie-Tooth Disease: Impact of Combined Mutations in the MFN2 and GDAP1 Genes. Journal of the peripheral nervous system : JPNS 2 40588830
2024 Abnormal redox balance at membrane contact sites causes axonopathy in GDAP1-related Charcot-Marie-Tooth disease. Research square 2 39801517
2023 Conformational analysis of membrane-proximal segments of GDAP1 in a lipidic environment using synchrotron radiation suggests a mode of assembly at the mitochondrial outer membrane. Biophysical chemistry 2 37778197
2022 Autosomal dominant GDAP1 mutation with severe phenotype and respiratory involvement: A case report. Frontiers in neurology 2 36353131