Affinage

PEX1

Peroxisomal ATPase PEX1 · UniProt O43933

Length
1283 aa
Mass
142.9 kDa
Annotated
2026-04-29
79 papers in source corpus 25 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PEX1 is a type II AAA+ ATPase essential for peroxisomal matrix protein import, functioning as the motor component of a heterohexameric PEX1–PEX6 complex that extracts monoubiquitinated PEX5 from the peroxisomal membrane to recycle this import receptor (PMID:9398847, PMID:29884772, PMID:26066397). The PEX1–PEX6 complex adopts a double-ring architecture in which the D1 ring is catalytically inactive and the active D2 ring engages substrate through pore-loop staircases, processively threading and unfolding PEX5 through the central channel in an ATP-hydrolysis-dependent manner (PMID:26170309, PMID:37741838, PMID:29321502). The complex is anchored to the peroxisomal membrane via the PEX6 N1 domain–Pex15/PEX26 interaction, and loss of PEX1 triggers pexophagy through a TBK1–MARCHF7–PXMP4–NBR1 signaling axis (PMID:38036174, PMID:41267209). Biallelic PEX1 mutations cause Zellweger spectrum disorders; the common G843D allele produces a motor-competent but misfolded, proteasome-susceptible protein with reduced PEX6 affinity whose function can be partially rescued by lowering temperature or by proteasome inhibition (PMID:9817926, PMID:11439091, PMID:40158855).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 High

    Establishing that PEX1 encodes an AAA-ATPase required for peroxisomal matrix protein import resolved the molecular basis of complementation group 1 peroxisome biogenesis disorders and showed that peroxisomal membrane assembly proceeds independently of PEX1.

    Evidence Functional complementation of CG1 patient fibroblasts with PEX1 cDNA; PEX5 stability analysis in patient cells

    PMID:9398847 PMID:9398848

    Open questions at the time
    • Mechanism by which PEX1 supports import was unknown
    • Identity of PEX1 substrates was unclear
    • Subcellular localization of PEX1 was not determined
  2. 1998 High

    Demonstrating a direct PEX1–PEX6 physical interaction and that the G843D disease mutation weakens this interaction established the functional unit as a PEX1–PEX6 complex and provided the first molecular explanation for the most common PBD allele.

    Evidence Yeast two-hybrid, in vitro pull-down, and genetic suppression between PEX1 and PEX6; temperature-shift experiments in G843D patient fibroblasts

    PMID:9671729 PMID:9817926

    Open questions at the time
    • Stoichiometry and architecture of the PEX1–PEX6 complex were unknown
    • Whether G843D affects ATPase activity or protein stability was unresolved
  3. 2001 High

    Correlating PEX1 protein levels and PEX6-binding capacity with disease severity across multiple alleles showed that G843D is a misfolded but partially functional protein whose temperature-sensitive degradation underlies the milder IRD phenotype, while null or interaction-dead alleles cause severe Zellweger syndrome.

    Evidence Immunoblotting and co-immunoprecipitation of PEX1 mutants; peroxisomal function assays at permissive vs. non-permissive temperature in patient fibroblasts

    PMID:11389485 PMID:11439091

    Open questions at the time
    • Whether G843D retains intrinsic ATPase activity was not tested
    • Mechanism of PEX1 degradation (proteasomal vs. other) was not defined
  4. 2004 High

    Solving the crystal structure of the PEX1 N-terminal domain revealed a double-psi-barrel fold shared with p97/NSF, classifying PEX1 as a membrane-associated type II AAA-ATPase and implicating the NTD as an adaptor-binding platform.

    Evidence X-ray crystallography of mouse PEX1 NTD at 2.05 Å resolution

    PMID:15328346

    Open questions at the time
    • No adaptor or substrate bound to the NTD was identified
    • Full-length PEX1 structure remained unavailable
  5. 2006 Medium

    Identifying phosphoinositide binding by the PEX1 NTD and showing that a Walker A1 mutation in the D1 cassette disrupts PEX6 interaction and peroxisomal targeting suggested that both lipid binding and D1-domain integrity contribute to PEX1 recruitment to peroxisomes.

    Evidence In vitro lipid-binding assays with mutagenesis; CHO pex1 temperature-sensitive mutant analysis with co-IP and immunofluorescence

    PMID:16723118 PMID:17018057

    Open questions at the time
    • Physiological relevance of PI binding in vivo was not demonstrated
    • Whether D1 ATP binding is structural or regulatory was unclear
  6. 2015 High

    Cryo-EM structures of the PEX1–PEX6 heterohexamer revealed an alternating double-ring architecture with an active, asymmetric D2 ring and an inactive, symmetric D1 ring, establishing the structural basis for a processive translocation mechanism analogous to p97.

    Evidence Cryo-EM in multiple nucleotide states; ATPase assays; Walker B mutagenesis

    PMID:26066397 PMID:26170309

    Open questions at the time
    • No substrate was captured in the pore
    • How the complex is tethered to the peroxisomal membrane was structurally unresolved
  7. 2015 High

    Conditional depletion of Pex1 confirmed it is directly required for matrix protein import and not for membrane protein insertion, and showed that re-introduction of Pex1 restores import into pre-existing peroxisomal membrane ghosts.

    Evidence Conditional Pex1 depletion in yeast; electron microscopy/tomography; complementation rescue

    PMID:26644511 PMID:26644516

    Open questions at the time
    • Identity of the specific PEX1–PEX6 substrate during import remained unproven
  8. 2018 High

    Biochemical reconstitution demonstrated that PEX1–PEX6 is a bona fide protein translocase that unfolds substrates through its central pore: Pex15 is threaded via pore-loop engagement, and monoubiquitinated PEX5 is globally unfolded during ATP-dependent extraction, definitively identifying the import receptor as the physiological substrate.

    Evidence In vitro unfolding assays; cryo-EM of Pex15-bound complex; photoaffinity cross-linking and PEGylation of Ub-PEX5

    PMID:29321502 PMID:29884772

    Open questions at the time
    • Whether PEX5 unfolding is coupled to cargo release was not shown
    • Structural view of PEX5 engaged in the pore was lacking
  9. 2023 High

    Substrate-engaged cryo-EM structures revealed the D2 pore-loop staircase mechanism and a twin-seam heterodimer disengagement cycle that drives processive translocation, while crystallography of the Pex6 N1 domain showed it bridges both the Pex15 membrane anchor and a Pex1 D2 loop to stabilize the functional hexamer at the peroxisome.

    Evidence CryoEM of substrate-trapped Pex1/Pex6; X-ray crystallography of Pex6 N1; in vivo complementation

    PMID:37741838 PMID:38036174

    Open questions at the time
    • How the twin-seam mechanism coordinates with ubiquitin recognition is unknown
    • Structural basis for PEX26 engagement in the human complex not resolved
  10. 2025 High

    Demonstrating that PEX1-G843D retains full ATPase motor activity but is rapidly degraded by the proteasome due to impaired PEX6 binding resolved the long-standing question of whether the disease allele is catalytically dead or unstable, and showed that stabilization alone is sufficient to restore peroxisome import.

    Evidence In vitro ATPase assays with ScPex1-G700D; proteasome inhibition; deubiquitinase fusion; co-IP affinity measurements in human cells

    PMID:40158855

    Open questions at the time
    • Whether proteasome inhibition is therapeutically viable in patients is untested
    • Structural basis of G843D misfolding remains unresolved
  11. 2014 Medium

    Genetic studies in yeast established that PEX1 deficiency triggers pexophagy via ubiquitinated receptor accumulation at the peroxisomal membrane, and that blocking autophagy does not restore import, separating the import and pexophagy phenotypes.

    Evidence Genetic epistasis in S. cerevisiae pex1Δ with autophagy mutants; autophagy and import assays

    PMID:24657987 PMID:32013259

    Open questions at the time
    • Mammalian pexophagy signaling downstream of PEX1 loss was not defined
    • Whether pexophagy contributes to pathology independently of import failure was unclear
  12. 2025 Medium

    A mammalian pexophagy signaling cascade was delineated: PEX1 depletion causes ROS-dependent TBK1 activation, which phosphorylates MARCHF7, leading to ubiquitination of PXMP4 at K20 and NBR1-mediated pexophagy, revealing the specific molecular chain linking PEX1 loss to selective peroxisome degradation.

    Evidence Functional screening, co-IP, MARCHF7 depletion, PXMP4-K20 mutagenesis, NBR1 recruitment assays in PEX1-KD HeLa cells

    PMID:41267209

    Open questions at the time
    • Whether this pathway operates in vivo in patient tissues is untested
    • Contribution of pexophagy to Zellweger spectrum pathology versus primary import failure is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis for ubiquitin recognition by PEX1–PEX6 during PEX5 extraction; how cargo release from PEX5 is coupled to receptor unfolding; the therapeutic potential of PEX1-G843D stabilization strategies in animal models; and whether the PEX1 N-terminal alternatively spliced isoform has a physiologically distinct function in pre-peroxisomal vesicle regulation.
  • No structure of ubiquitin-engaged PEX1–PEX6 complex exists
  • Cargo–receptor uncoupling mechanism is undefined
  • In vivo therapeutic validation of G843D stabilization is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0140096 catalytic activity, acting on a protein 3 GO:0008289 lipid binding 1
Localization
GO:0005777 peroxisome 3 GO:0005829 cytosol 2
Pathway
R-HSA-9612973 Autophagy 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1430728 Metabolism 2
Partners
HNRNPA1MARCHF7NBR1PEX15PEX26PEX5PEX6
Complex memberships
PEX1–PEX6 heterohexamer

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Human PEX1 encodes a 147-kDa AAA-ATPase required for peroxisomal matrix protein import; PEX1-deficient cells show severe defects in matrix protein import and destabilization of PEX5 (the PTS1 receptor), even though peroxisomes are present and capable of importing peroxisomal membrane proteins. Functional complementation of CG1 patient fibroblasts by PEX1 expression; biochemical analysis of PEX5 stability in PEX1-deficient cells Nature genetics High 9398847 9398848
1998 PEX1 and PEX6 physically interact with each other; overexpression of PEX6 can suppress PEX1-deficient phenotypes and vice versa in an allele-specific manner. The common disease mutation G843D attenuates the PEX1–PEX6 interaction both in the yeast two-hybrid system and in vitro pull-down. Yeast two-hybrid assay, in vitro pull-down, genetic suppression by overexpression Proceedings of the National Academy of Sciences of the United States of America High 9671729
1998 The PEX1-G843D missense mutation causes a temperature-sensitive peroxisome assembly defect: peroxisomes form at 30°C but not at 37°C in IRD patient fibroblasts, indicating the mutation results in a temperature-sensitive protein. Temperature-shift experiments in patient fibroblasts and transfected CHO mutant cells; morphological and biochemical analysis of peroxisome formation Human molecular genetics High 9817926
2001 PEX1-G843D protein is largely degraded in vivo at 37°C but is stabilized at 30°C; Pex1p-G843D interacts with Pex6p at ~50% of normal efficiency, while ZS-associated PEX1 mutants (L664P; deletion 634–690) are stable but fail to bind Pex6p, linking PEX1–PEX6 interaction failure to severe disease. Immunoblotting for PEX1 protein levels at permissive/nonpermissive temperature; co-immunoprecipitation of Pex1p mutants with Pex6p The Biochemical journal High 11439091
2001 Complete absence of PEX1 protein correlates with severe Zellweger syndrome, whereas residual PEX1 protein (especially from the G843D allele) is found in milder NALD/IRD phenotypes. Growing patient fibroblasts at 30°C increases PEX1-G843D protein 2–3-fold and restores peroxisomal function, indicating the G843D mutation produces a misfolded but partially functional protein. Immunoblotting of patient fibroblasts; peroxisomal function assays at 30°C vs. 37°C American journal of human genetics High 11389485
2004 Crystal structure of the mouse PEX1 N-terminal domain (NTD) at 2.05 Å resolution reveals a double-psi-barrel fold homologous to the N-terminal domains of VCP/p97 and NSF, classifying PEX1 as a membrane-related type II AAA-ATPase and suggesting its NTD may serve as an adaptor-binding domain. X-ray crystallography; computational structure comparison The Journal of biological chemistry High 15328346
2006 The N-terminal domain of PEX1 binds phosphoinositides (preferentially PI3P and PI4P); a conserved arginine residue surrounded by hydrophobic residues is essential for this lipid binding as demonstrated by mutagenesis. Lipid-binding assay with isolated N-terminal domain; site-directed mutagenesis of conserved arginine The FEBS journal Medium 17018057
2006 Mutation of the Walker A1 motif of Pex1p (G606E in CHO cells, equivalent to a residue in the first AAA cassette) abolishes Pex1p–Pex6p interaction at 37°C but not at 30°C, and prevents Pex1p targeting to peroxisomes at 37°C while allowing peroxisomal localization at 30°C. Temperature-sensitive CHO pex1 mutant isolation; RT-PCR mutation identification; co-immunoprecipitation; immunofluorescence Biochemical and biophysical research communications Medium 16723118
2015 Pex1 and Pex6 form a heterohexameric type II AAA+ ATPase complex (trimer of Pex1/Pex6 dimers) with triangular geometry. The D2 domains of Pex6 constitute the main ATPase activity; both D2 domains harbor essential substrate-binding motifs. ATP hydrolysis produces a pumping motion suggesting substrate translocation through the central channel. Walker B mutation in one D2 domain leads to ATP hydrolysis in the neighboring domain. Cryo-EM structural analysis; ATPase activity assays; Walker B mutagenesis Nature communications High 26066397
2015 Cryo-EM structures of Pex1/Pex6 in different nucleotide states reveal that Pex1 and Pex6 alternate in an unprecedented heterohexameric double ring; N1 of Pex1 is mobile; the D1 ring is catalytically inactive and symmetric while the D2 ring is active and asymmetric. These features are analogous to p97, supporting a role for Pex1/Pex6 in receptor extraction from the peroxisomal membrane analogous to p97 in ERAD. Cryo-EM with computational domain fitting; nucleotide-state-dependent structural comparison Proceedings of the National Academy of Sciences of the United States of America High 26170309
2015 Induced depletion of Pex1 in yeast blocks import of peroxisomal matrix proteins but does not affect delivery of peroxisomal membrane proteins; pex1 cells contain peroxisomal membrane remnants (ghosts) that lack matrix proteins. Re-introduction of Pex1 into pex1-deficient cells restores matrix protein import into these ghosts, confirming Pex1's direct and essential role in matrix protein import. Conditional depletion of Pex1; electron microscopy including tomography; immunocytochemistry; complementation by Pex1 re-introduction The Journal of cell biology High 26644511 26644516
2018 The Pex1/Pex6 complex is a protein translocase that unfolds its substrate Pex15 in a pore-loop-dependent and ATP-hydrolysis-dependent manner by processive threading through the central pore. Pex15 binds the N-terminal domains of Pex6 before its disordered C-terminal region engages pore loops. Pex15 also directly binds the cargo receptor Pex5, linking Pex1/Pex6 to peroxisomal import machinery. In vitro unfolding assays; cryo-EM of Pex15–Pex1/Pex6 complex; pore-loop mutagenesis; binding assays Nature communications High 29321502
2018 DTM-embedded monoubiquitinated PEX5 (Ub-PEX5) interacts directly with both PEX1 and PEX6 through its ubiquitin moiety, and the PEX5 polypeptide chain is globally unfolded during the ATP-dependent extraction event, demonstrating that Ub-PEX5 is a bona fide substrate of the PEX1–PEX6 complex. Cell-free in vitro system with photoaffinity cross-linking and protein PEGylation assays The Journal of biological chemistry High 29884772
2010 PEX1-G843D is a misfolded protein amenable to chaperone therapy; small-molecule compounds can partially recover peroxisomal matrix protein import in PEX1-G843D patient fibroblasts, as shown by redistribution of a GFP-PTS1 reporter from cytosol to peroxisomes. High-content screening assay with GFP-PTS1 reporter in patient fibroblasts; confirmatory biochemical assays Proceedings of the National Academy of Sciences of the United States of America Medium 20212125
2014 Deficiency in Pex1 (and Pex6/Pex15) leads to accumulation of ubiquitinated receptors at the peroxisomal membrane and enhanced pexophagy mediated by the Atg36 receptor and Atg11; genetic analysis showed that preventing receptor ubiquitin accumulation does not abolish pexophagy in S. cerevisiae. Genetic epistasis in S. cerevisiae pex1Δ mutants; autophagy assays; immunofluorescence Autophagy Medium 24657987
2020 Blocking pexophagy (by deleting ATG genes) in yeast pex1Δ cells does not restore peroxisomal matrix protein import or beta-oxidation function, demonstrating that Pex1 is directly and essentially required for matrix protein import, and that pexophagy is a consequence, not the cause, of import defects. Genetic epistasis (pex1Δ combined with autophagy gene deletions); peroxisomal import and beta-oxidation functional assays in S. cerevisiae International journal of molecular sciences Medium 32013259
2022 An alternatively spliced human PEX1 isoform lacking 321 amino acids of the N-terminal region fails to rescue peroxisomal import defects in PEX1-KO HEK293 cells but does reduce the number of pre-peroxisomal vesicles, suggesting a dual moonlighting function of human PEX1 in both matrix protein import and regulation of pre-peroxisomal vesicles. CRISPR/Cas9 PEX1 knockout in HEK293 cells; complementation with full-length vs. N-terminal truncated PEX1 isoform; peroxisome import and morphology assays Biological chemistry Medium 36534601
2022 Conditional knockout of Pex1 specifically in inner hair cells (IHCs) of the mouse inner ear causes progressive hearing loss with decreased ABR wave I amplitude, reduction in ribbon synapse volume, functional impairment of exocytosis, and decreased peroxisome number—demonstrating a direct role of PEX1 in IHC synapse development and auditory function. Conditional Pex1 knockout (Gfi1-Cre or VGlut3-Cre crossed to floxed Pex1); ABR recordings; IHC synapse morphology and functional analysis; immunofluorescence Cells Medium 36552747
2023 CryoEM structures of S. cerevisiae Pex1/Pex6 with endogenous substrate trapped in the D2 pore reveal that pairs of Pex1/Pex6 D2 subdomains engage substrate via a staircase of pore-1 loops; the D1 ring is catalytically inactive but undergoes conformational changes driven by D2 ATP hydrolysis; a 'twin-seam' Pex1/Pex6 D2 heterodimer disengages from the staircase to drive translocation; mechanical forces propagate along unique Pex1/Pex6 interfaces. CryoEM of substrate-engaged Pex1/Pex6 complex Nature communications High 37741838
2023 The N1 domain of Pex6 binds to both the peroxisomal membrane tether Pex15 and to an extended loop from the D2 ATPase domain of Pex1, influencing Pex1/Pex6 heterohexamer stability; deletion of the Pex6 N1 domain yields an active ATPase in vitro but abolishes Pex1/Pex6 function at the peroxisome in vivo. X-ray crystallography of Pex6 N1 domain; cryo-EM of Pex1/Pex6; AlphaFold2 predictions; biochemical pull-down assays; in vivo functional complementation The Journal of biological chemistry High 38036174
2025 The HsPEX1-G843D protein is functional as an AAA-ATPase motor but is rapidly degraded by the proteasome due to reduced affinity for PEX6; impaired PEX1–PEX6 assembly is sufficient to trigger PEX1 degradation; fusing a deubiquitinase to PEX1-G843D stabilizes the protein; overexpression of PEX1-G843D restores peroxisome import. In vitro ATPase assays with ScPex1-G700D; HsPEX1-G843D cell line generation; proteasome inhibition; co-immunoprecipitation affinity measurements; deubiquitinase fusion experiments The Journal of biological chemistry High 40158855
2021 HNRNPA1 controls PEX1 expression post-transcriptionally; depletion of HNRNPA1 downregulates PEX1, leading to increased peroxisomal ROS and pexophagy that is blocked by ATG5 knockout and by NAC (ROS scavenger) treatment. HNRNPA1 knockdown; PEX1 expression measurement; ATG5-KO epistasis; ROS assays; pexophagy flux assays Biochemical and biophysical research communications Medium 33545634
2025 In PEX1-depleted HeLa cells, TBK1 becomes phosphorylated and activated (driven by ROS accumulation), which phosphorylates MARCHF7; MARCHF7 ubiquitinates PXMP4 at lysine 20, and ubiquitinated PXMP4 serves as a recognition signal for the pexophagy receptor NBR1. Functional screening; MARCHF7 depletion; co-immunoprecipitation; site-directed mutagenesis of PXMP4-K20; NBR1 recruitment assays in PEX1-KD cells Autophagy Medium 41267209

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. Nature genetics 193 9398847
1997 Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders. Nature genetics 128 9398848
1998 Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. Proceedings of the National Academy of Sciences of the United States of America 105 9671729
1998 Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I. Proceedings of the National Academy of Sciences of the United States of America 98 9539740
2001 Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels. American journal of human genetics 76 11389485
1995 Pex1, a pollen-specific gene with an extensin-like domain. Proceedings of the National Academy of Sciences of the United States of America 76 7724520
2011 Arabidopsis ABERRANT PEROXISOME MORPHOLOGY9 is a peroxin that recruits the PEX1-PEX6 complex to peroxisomes. The Plant cell 73 21487094
2015 Molecular snapshots of the Pex1/6 AAA+ complex in action. Nature communications 68 26066397
2015 Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy. Proceedings of the National Academy of Sciences of the United States of America 68 26170309
2004 Structure of the N-terminal domain of PEX1 AAA-ATPase. Characterization of a putative adaptor-binding domain. The Journal of biological chemistry 66 15328346
1998 Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders. Human molecular genetics 63 9817926
2014 Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae. Autophagy 57 24657987
2018 The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading. Nature communications 52 29321502
2010 Recovery of PEX1-Gly843Asp peroxisome dysfunction by small-molecule compounds. Proceedings of the National Academy of Sciences of the United States of America 52 20212125
2002 PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease. Pediatric research 50 12032265
1999 Identification of a common PEX1 mutation in Zellweger syndrome. Human mutation 50 10447258
2014 The Pex1-G844D mouse: a model for mild human Zellweger spectrum disorder. Molecular genetics and metabolism 48 24503136
2005 Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations. Journal of medical genetics 42 16141001
2018 Peroxisomal monoubiquitinated PEX5 interacts with the AAA ATPases PEX1 and PEX6 and is unfolded during its dislocation into the cytosol. The Journal of biological chemistry 39 29884772
2015 Reevaluation of the role of Pex1 and dynamin-related proteins in peroxisome membrane biogenesis. The Journal of cell biology 37 26644516
2001 Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction. The Biochemical journal 36 11439091
2002 Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients. Human mutation 32 12402331
1999 A common PEX1 frameshift mutation in patients with disorders of peroxisome biogenesis correlates with the severe Zellweger syndrome phenotype. Human genetics 32 10480353
2019 A longitudinal study of retinopathy in the PEX1-Gly844Asp mouse model for mild Zellweger Spectrum Disorder. Experimental eye research 29 31254513
2006 The common phospholipid-binding activity of the N-terminal domains of PEX1 and VCP/p97. The FEBS journal 27 17018057
2005 PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders. Human mutation 27 16086329
2017 Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes. Frontiers in molecular biosciences 24 28611990
2016 Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene. European journal of medical genetics 24 27633571
2015 Yeast pex1 cells contain peroxisomal ghosts that import matrix proteins upon reintroduction of Pex1. The Journal of cell biology 24 26644511
2019 Structural Mapping of Missense Mutations in the Pex1/Pex6 Complex. International journal of molecular sciences 20 31374812
2018 Zellweger spectrum disorder patient-derived fibroblasts with the PEX1-Gly843Asp allele recover peroxisome functions in response to flavonoids. Journal of cellular biochemistry 19 30362618
2000 Temperature-sensitive mutation of PEX6 in peroxisome biogenesis disorders in complementation group C (CG-C): comparative study of PEX6 and PEX1. Pediatric research 19 11004248
2021 AAV-mediated PEX1 gene augmentation improves visual function in the PEX1-Gly844Asp mouse model for mild Zellweger spectrum disorder. Molecular therapy. Methods & clinical development 17 34703844
2018 A pex1 missense mutation improves peroxisome function in a subset of Arabidopsis pex6 mutants without restoring PEX5 recycling. Proceedings of the National Academy of Sciences of the United States of America 17 29555730
2017 The PEX1 ATPase Stabilizes PEX6 and Plays Essential Roles in Peroxisome Biology. Plant physiology 17 28600347
2023 Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate. Nature communications 15 37741838
2020 Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female. Molecular genetics and metabolism reports 15 32596134
2005 Novel PEX1 coding mutations and 5' UTR regulatory polymorphisms. Human mutation 14 16088892
2020 Longitudinal study of Pex1-G844D NMRI mouse model: A robust pre-clinical model for mild Zellweger spectrum disorder. Biochimica et biophysica acta. Molecular basis of disease 13 32693164
2004 PEX1 deficiency presenting as Leber congenital amaurosis. Pediatric neurology 13 15301838
2019 Mild Zellweger syndrome due to functionally confirmed novel PEX1 variants. Journal of applied genetics 12 31628608
2019 A Mechanistic Perspective on PEX1 and PEX6, Two AAA+ Proteins of the Peroxisomal Protein Import Machinery. International journal of molecular sciences 12 31652724
2016 Transcription factor PEX1 modulates extracellular matrix turnover through regulation of MMP-9 expression. Cell and tissue research 12 27826738
2012 Analysis of a Chinese pedigree with Zellweger syndrome reveals a novel PEX1 mutation by next-generation sequencing. Clinica chimica acta; international journal of clinical chemistry 12 23247051
2022 Comparison of human PEX knockout cell lines suggests a dual role of PEX1 in peroxisome biogenesis. Biological chemistry 9 36534601
2021 Depletion of HNRNPA1 induces peroxisomal autophagy by regulating PEX1 expression. Biochemical and biophysical research communications 9 33545634
2023 The lignin-degrading abilities of Gelatoporia subvermispora gat1 and pex1 mutants generated via CRISPR/Cas9. Environmental microbiology 7 36959722
2022 Loss of Pex1 in Inner Ear Hair Cells Contributes to Cochlear Synaptopathy and Hearing Loss. Cells 7 36552747
2017 A novel PEX1 mutation in a Moroccan family with Zellweger spectrum disorders. Human genome variation 7 28446956
2021 Two siblings with Heimler syndrome caused by PEX1 variants: follow-up of ophthalmologic findings. Ophthalmic genetics 6 33955814
2020 The Peroxisomal PTS1-Import Defect of PEX1- Deficient Cells Is Independent of Pexophagy in Saccharomyces cerevisiae. International journal of molecular sciences 6 32013259
2016 Dysmorphic Facial Features and Other Clinical Characteristics in Two Patients with PEX1 Gene Mutations. Case reports in pediatrics 6 27882258
2023 The N1 domain of the peroxisomal AAA-ATPase Pex6 is required for Pex15 binding and proper assembly with Pex1. The Journal of biological chemistry 5 38036174
2022 Diagnostic Odyssey in an Adult Patient with Ophthalmologic Abnormalities and Hearing Loss: Contribution of RNA-Seq to the Diagnosis of a PEX1 Deficiency. International journal of molecular sciences 5 36293220
2012 Zellweger syndrome and associated brain malformations: report of a novel Peroxin1 (PEX1) mutation in a Native American infant. Journal of child neurology 5 22378672
2025 Spatial characterization of RPE structure and lipids in the PEX1-p.Gly844Asp mouse model for Zellweger spectrum disorder. Journal of lipid research 4 40058592
2024 PEX1 is essential for glycosome biogenesis and trypanosomatid parasite survival. Frontiers in cellular and infection microbiology 4 38510966
2021 A Chinese newborn with Zellweger syndrome and compound heterozygous mutations novel in the PEX1 gene: a case report and literature review. Translational pediatrics 4 33708531
2021 Compound heterozygous p. Arg949Trp and p. Gly970Ala mutations deteriorated the function of PEX1p: A study on PEX1 in a patient with Zellweger syndrome. Journal of cellular biochemistry 4 33955040
2011 Two novel PEX1 mutations in a patient with Zellweger syndrome: the first Korean case confirmed by biochemical, and molecular evidence. Annals of clinical and laboratory science 4 21844578
2024 Zebrafish PEX1 Is Required for the Generation of GABAergic Neuron in p3 Domain. Development & reproduction 3 39845513
2011 Characterization of two common 5' polymorphisms in PEX1 and correlation to survival in PEX1 peroxisome biogenesis disorder patients. BMC medical genetics 3 21846392
2006 A temperature-sensitive CHO pex1 mutant with a novel mutation in the AAA Walker A1 motif. Biochemical and biophysical research communications 3 16723118
2025 Heimler Syndrome With Tooth Agenesis, Abnormal Enamel and Dentin Mineralization, Root Maldevelopment, and PEX1 Mutation. International dental journal 2 40466212
2025 Regulation of pexophagy by a novel TBK1-MARCHF7-PXMP4-NBR1 axis in PEX1-depleted HeLa cells. Autophagy 2 41267209
2023 Ophthalmic Manifestations of Heimler Syndrome in Two Siblings With PEX1 Variants. Journal of pediatric ophthalmology and strabismus 2 37092661
2023 Analysis of Altered Flowering Related Genes in a Multi-Silique Rapeseed (Brassica napus L.) Line zws-ms Based on Combination of Genome, Transcriptome and Proteome Data. Plants (Basel, Switzerland) 2 37446989
2021 Allogeneic Hematopoietic Stem Cell Transplantation for PEX1-Related Zellweger Spectrum Disorder: A Case Report and Literature Review. Frontiers in pediatrics 2 34513757
2017 Novel compound heterozygous mutations in the PEX1 gene in two Chinese newborns with Zellweger syndrome based on whole exome sequencing. Clinica chimica acta; international journal of clinical chemistry 2 28432012
2025 PEX1G843D remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome. The Journal of biological chemistry 1 40158855
2025 Estimation of PEX1-mediated Zellweger spectrum disorder births and population prevalence by population genetics modeling. Genetics in medicine open 1 40519747
2023 A novel compound heterozygous PEX1 variant in Heimler syndrome. Experimental eye research 1 37871882
2022 PEX1 is a mediator of α1-adrenergic signaling attenuating doxorubicin-induced cardiotoxicity. Journal of biochemical and molecular toxicology 1 35979984
2004 Crystallographic characterization of the N-terminal domain of PEX1. Acta crystallographica. Section D, Biological crystallography 1 15502339
2025 Pex1 loss-of-function in zebrafish is viable and recapitulates hallmarks of Zellweger spectrum disorders. Frontiers in molecular neuroscience 0 41268363
2024 PEX1G843D remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome. bioRxiv : the preprint server for biology 0 39713301
2023 Purification of a Recombinant Human PEX1/PEX6 AAA+ ATPase Complex from HEK293TT Cells. Methods in molecular biology (Clifton, N.J.) 0 36952198
2023 Novel PEX1 mutations in fibroblasts from children with Zellweger spectrum disorders exhibit temperature sensitive characteristics. Epilepsy & behavior : E&B 0 37385119
2023 The Pex6 N1 domain is required for Pex15 binding and proper assembly with Pex1. bioRxiv : the preprint server for biology 0 37745580