Affinage

PNPLA6

Patatin-like phospholipase domain-containing protein 6 · UniProt Q8IY17

Length
1375 aa
Mass
151.0 kDa
Annotated
2026-06-10
88 papers in source corpus 26 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PNPLA6 (neuropathy target esterase, NTE; Drosophila ortholog SWS) is an ER-anchored integral membrane serine phospholipase that maintains cellular phospholipid homeostasis and is essential for nervous system integrity and development (PMID:16464473, PMID:25574898). Through its conserved C-terminal catalytic domain, in which a single active-site serine sits within a hydrophobic helical segment (PMID:10421490), it hydrolyzes lysophosphatidylcholine and phosphatidylcholine, and loss of activity drives accumulation of LPC/LPA in photoreceptors and elevated PC, linking the enzyme directly to membrane lipid balance (PMID:25574898, PMID:31780887). This phospholipase activity is governed by three cyclic-nucleotide (cNMP) binding sites: progressive disruption of these sites impairs PC turnover, establishing cyclic-nucleotide binding as a regulator of catalysis (PMID:31780887, PMID:41415407). In the retina, PNPLA6 acting as a phospholipase B mobilizes choline from phosphatidylcholine in RPE cells and supplies it to adjacent photoreceptors, with retina-specific deletion producing retinitis pigmentosa-like degeneration fully rescued by choline supplementation (PMID:40082403). In the nervous system PNPLA6 preserves neuronal survival and glial ensheathment of axons, and in blood-brain-barrier glia its loss disrupts membrane domain and tight-junction organization, causes lipid/lysosomal accumulation, and triggers age-dependent inflammation (PMID:26634819, PMID:28206686, PMID:38660940). The active-site serine is the target of organophosphate esters; covalent modification followed by aging—not simple inhibition—initiates delayed axonopathy, and aged SWS acts as a regulatory subunit that binds and irreversibly inhibits the PKA catalytic subunit PKA-C3 (PMID:12879443, PMID:2180130, PMID:8343996, PMID:24558370). Notably, the enzyme's neurodevelopmental role is separable from its esterase activity, since genetic silencing produces phenotypes not reproduced by pharmacological esterase inhibition (PMID:27475862). Loss-of-function PNPLA6 mutations cluster in the catalytic domain and cause Gordon Holmes and Boucher-Neuhäuser syndromes, with residual NTE activity inversely correlating with retinopathy and endocrinopathy (PMID:24355708, PMID:25033069, PMID:38735647).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 Medium

    Establishing PNPLA6/NTE as a serine hydrolase with a novel, evolutionarily conserved catalytic domain defined its biochemical identity and the location of its functional active site.

    Evidence Molecular cloning, sequence and domain analysis

    PMID:10421490

    Open questions at the time
    • No physiological substrate identified at this stage
    • No structural model of the catalytic domain
  2. 2003 High

    Distinguishing organophosphate inhibition from 'aging' of the modified active-site serine resolved why only some OPs trigger neuropathy, defining the molecular initiating event of OPIDN.

    Evidence In vitro/in vivo OP inhibition and prophylaxis assays, structure-activity analysis, plus subcellular NTE fractionation in nerve

    PMID:12879443 PMID:2180130 PMID:8140588 PMID:8343996

    Open questions at the time
    • Downstream molecular consequence of aging not yet defined
    • Endogenous catalytic substrate still unknown
  3. 2003 High

    Genetic loss-of-function in fly and mouse revealed an essential developmental role beyond esterase chemistry, separating NTE's enzymatic and developmental functions.

    Evidence Mouse conventional knockout (embryonic lethal) and Drosophila sws mutant analysis

    PMID:12879443

    Open questions at the time
    • Molecular basis of the essential developmental function undefined
    • Tissue-of-action for lethality not pinpointed
  4. 2006 Medium

    Purification confirmed NTE as a ~155 kDa integral membrane serine hydrolase requiring lipid context for solubilization, anchoring it biochemically to membranes.

    Evidence Biochemical purification from rat brain microsomes, SDS-PAGE, activity assay

    PMID:16464473

    Open questions at the time
    • Membrane topology not resolved
    • Specific lipid substrate not assigned in vitro here
  5. 2014 High

    Identification of NTE as the lysophospholipase converting LPC to glycerophosphocholine, with disease-mutant rescue failure, connected catalytic loss to human Gordon Holmes syndrome and to GnRH-stimulated LH exocytosis in gonadotropes.

    Evidence Whole exome sequencing, Drosophila mutant-vs-WT rescue, NTE inhibition in LβT2 gonadotrope cells with LH exocytosis readout

    PMID:24355708 PMID:25033069

    Open questions at the time
    • Mechanistic link between lipid product and exocytosis machinery unresolved
    • Whether choline/GPC supply mediates the endocrine effect not tested
  6. 2014 High

    Discovery that OP-modified SWS sequesters and inhibits the PKA catalytic subunit PKA-C3 provided a non-esterase signaling mechanism for OP-induced axonopathy.

    Evidence Drosophila genetics, PKA activity assays in flies and rat neurons, TOCP treatment, PKA-C3 epistasis

    PMID:24558370

    Open questions at the time
    • Whether normal (un-aged) NTE regulates PKA physiologically unclear
    • Human PKA subunit interaction not directly demonstrated
  7. 2015 High

    Linking PNPLA6 loss to LPC/LPA accumulation in photoreceptors and to glial ensheathment defects established phospholipid homeostasis as the cellular function across neurons and glia.

    Evidence Drosophila mutant lipidomics; cell-type-specific glial RNAi with morphology, electrophysiology, behavior, and human NTE rescue; mouse Schwann-cell conditional knockout

    PMID:25574898 PMID:26634819 PMID:28206686

    Open questions at the time
    • How lipid imbalance causes cell death vs. ensheathment failure differs by tissue and is unresolved
    • Quantitative substrate flux in vivo not measured
  8. 2016 Medium

    Comparing genetic silencing against pharmacological esterase inhibition showed PNPLA6's neurodevelopmental role is at least partly independent of its catalytic esterase activity.

    Evidence siRNA knockdown vs mipafox inhibition in human NT2 cells with electrophysiology and marker readouts; transcriptomic profiling

    PMID:24142151 PMID:25255935 PMID:27475862

    Open questions at the time
    • The non-esterase molecular function remains unidentified
    • Off-target effects of knockdown vs inhibitor not fully excluded
  9. 2016 Medium

    Identification of Destruction-box motifs controlling proteasomal turnover of NTE revealed post-translational regulation of NTE abundance independent of its ER localization.

    Evidence Deletion/site-directed mutagenesis, proteasome inhibitor experiments, fluorescence localization in cells

    PMID:27558092

    Open questions at the time
    • E3 ligase / degron-recognition machinery unidentified
    • Physiological trigger for degradation unknown
  10. 2019 High

    Showing that disease alleles and cNMP-site mutations fail to restore normal lipid levels established cyclic-nucleotide binding as a regulator of PNPLA6 phospholipase activity in vivo.

    Evidence Drosophila sws-null transgenic rescue with disease and cNMP-site alleles, lipidomics, behavior, histology

    PMID:31780887

    Open questions at the time
    • Identity of the endogenous cyclic nucleotide ligand not established
    • Structural mechanism of cNMP-coupled activation unknown
  11. 2024 High

    Quantifying esterase activity across 66 variants alongside an allelic mouse series defined a genotype:activity:phenotype axis, explaining why residual activity dictates retinopathy and endocrinopathy.

    Evidence In vitro NTE activity assay of disease/common variants, allelic mouse series, clinical cohort analysis

    PMID:38735647

    Open questions at the time
    • Tissue-specific activity thresholds not directly measured
    • Why specific tissues are most sensitive remains unexplained
  12. 2025 High

    Demonstrating RPE-to-photoreceptor choline transfer driven by PNPLA6 phospholipase B activity, with full rescue by choline supplementation, defined the mechanism of PNPLA6 retinal degeneration and a candidate therapeutic.

    Evidence Retina-specific conditional knockout mouse, phospholipid metabolite assays, choline supplementation rescue, RPE/photoreceptor assays; cNMP-site mutagenesis lipidomics (preprint)

    PMID:40082403 PMID:41415407

    Open questions at the time
    • Choline transporter/route between RPE and photoreceptors not defined
    • Whether the same choline-supply mechanism operates in brain/endocrine tissues untested
  13. 2026 Low

    Correlative hepatic and germ-cell studies extend PNPLA6 substrate scope (LPE catabolism) and proliferative roles, but without direct enzymatic validation.

    Evidence LC-MS/MS lipidomics in mouse MASH liver; NTE inhibition/knockdown in GC-1 spg spermatogonial cells with proliferation and ER-stress readouts

    PMID:41752007 PMID:42043102

    Open questions at the time
    • LPE hydrolysis by PNPLA6 not directly demonstrated (correlative only)
    • Mechanism linking NTE activity to germ-cell proliferation undefined
    • Independent confirmation in vivo lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of PNPLA6's esterase-independent developmental function and the endogenous cyclic-nucleotide ligand that tunes its phospholipase activity remain unresolved.
  • Non-catalytic developmental partner/mechanism unidentified
  • Physiological cNMP ligand and regulatory structure unknown
  • Mammalian PKA regulatory interaction not directly demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140098 catalytic activity, acting on RNA 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-1430728 Metabolism 3
Partners
PKA-C3

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 NTE (PNPLA6) was molecularly cloned and shown to contain a novel C-terminal domain conserved from bacteria to humans, with the catalytic serine located within this domain at the center of a helical hydrophobic segment; the protein is unrelated to any known serine hydrolases. Molecular cloning, sequence analysis, domain characterization Chemico-biological interactions Medium 10421490
2000 The murine Msws/NTE ortholog is expressed during embryonic development in the respiratory system, epithelial structures, and spinal ganglia; postnatally it is expressed in all brain areas with increasingly restrictive pattern, most prominently in Purkinje cells, granule cells, pyramidal neurons of the hippocampus, and large neurons in the medulla oblongata. In situ hybridization, Northern blot (expression pattern in mouse development) Mechanisms of development Medium 10640712
2003 NTE (PNPLA6) activity in hen sciatic nerve exists as two forms: a particulate form (P-NTE, ~40–50% of total in sciatic nerve, >90% in brain) and a soluble form (S-NTE); in vivo, S-NTE is more sensitive to mipafox inhibition than P-NTE despite opposite sensitivity in vitro. In vivo inhibition assay with mipafox, subcellular fractionation of sciatic nerve and brain Toxicology letters Medium 8140588
2003 NTE (PNPLA6) is a serine esterase; covalent modification of its active-site serine by organophosphate esters initiates axon degeneration, and simple inhibition without aging of the bound OP does not initiate neuropathy — only OPs that undergo aging produce OPIDN. In vitro and in vivo enzyme inhibition assays, structure-activity analysis, prophylaxis experiments BioEssays High 12879443 2180130 8343996
2003 Loss of NTE function in Drosophila sws mutants causes massive apoptosis in the brain, and conventional knockout of the NTE gene in mice is embryonic lethal, establishing that NTE has an essential non-esterase developmental function. Conventional gene knockout (mouse), Drosophila sws mutant genetic analysis BioEssays High 12879443
2006 NTE (PNPLA6) purified from rat brain microsomes is an integral membrane protein of ~155 kDa with serine hydrolase activity; solubilization required phospholipase A2 treatment of microsomes. Biochemical purification (gel filtration, affinity chromatography), SDS-PAGE, enzyme activity assay Life sciences Medium 16464473
2012 Morpholino knockdown of pnpla6 in zebrafish causes developmental abnormalities and motor neuron defects including axon truncation and branching; these phenotypes were rescued by wild-type but not mutant human PNPLA6 mRNA, and BMP signaling was found to be overactivated in knockdown morphants. Morpholino knockdown in zebrafish, mRNA rescue experiments, BMP signaling analysis Disease models & mechanisms Medium 22996643
2013 PNPLA6 mutations causing Boucher-Neuhäuser and Gordon Holmes syndromes cluster predominantly in the C-terminal phospholipid esterase domain, suggesting these mutations inhibit the catalytic activity of PNPLA6; PNPLA6 provides the precursor (lysophosphatidylcholine→glycerophosphocholine) for acetylcholine biosynthesis. Whole exome sequencing, structural analysis of mutation clustering in catalytic domain Brain Medium 24355708
2013 Silencing Pnpla6 in mouse embryonic stem cells (D3) during differentiation alters 545 genes in pathways including cell migration, vesicle regulation, and cell adhesion, impairing formation of neural, vascular, and respiratory tube structures, consistent with the embryonic lethality of NTE null mice. siRNA knockdown, microarray gene expression analysis in embryoid bodies In vitro cellular & developmental biology Medium 24142151
2014 Loss-of-function mutations in PNPLA6 (encoding the lysophospholipase NTE that converts lysophosphatidylcholine to glycerophosphocholine) cause Gordon Holmes syndrome; wild-type PNPLA6 but not disease mutants rescued the Drosophila sws neurodegenerative phenotype. Inhibition of NTE activity in gonadotrope LβT2 cells diminished LH response to GnRH by reducing GnRH-stimulated LH exocytosis without affecting GnRH receptor signaling or LHβ synthesis. Drosophila rescue assay, NTE pharmacological inhibition in LβT2 gonadotrope cell line, LH exocytosis assay The Journal of clinical endocrinology and metabolism High 25033069
2014 Organophosphate TOCP treatment of Drosophila causes behavioral deficits and neurodegeneration two weeks post-exposure; TOCP decreases PKA activity in flies and rat hippocampal neurons. SWS (Drosophila PNPLA6 ortholog) acts as a regulatory PKA subunit by binding and inhibiting the C3 catalytic subunit; OP-modified SWS cannot release PKA-C3, causing loss of PKA-C3 activity. Expressing additional PKA-C3 protected against behavioral/degenerative phenotypes, while PKA-C3 knockdown phenocopied TOCP effects. Drosophila genetics (SWS overexpression/knockdown), PKA activity assay in flies and rat neurons, TOCP treatment, epistasis with PKA-C3 PloS one High 24558370
2014 Silencing PNPLA6 in human NT2 embryonal carcinoma stem cells reduces NTE enzymatic activity by ~50%, causes ~80% decrease in neuronal cells at 13 DIV, absence of neuronal markers at 66 DIV, reduced electrical activity, and altered neuronal phenotype; microarray analysis showed alterations in neurogenesis and epithelium tube morphogenesis pathways. siRNA knockdown, NTE enzyme activity assay, immunocytochemistry, electrophysiology, microarray Neuroscience Medium 25255935
2015 PNPLA6 mutations in Drosophila cause photoreceptor cell death, and lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila, establishing a role for PNPLA6 in phospholipid homeostasis in photoreceptors. Drosophila sws/PNPLA6 mutant analysis, lipidomics (LPC and LPA measurement) Nature communications High 25574898
2015 SWS (Drosophila PNPLA6 ortholog) loss in pseudocartridge glia causes formation of multi-layered glial whorls in the lamina cortex; loss in ensheathing glia impairs glial wrapping of neurons and causes axonal damage and locomotion deficits. This glial phenotype was rescued by SWS or human NTE expression, demonstrating conserved glial function. Tissue-specific RNAi knockdown in Drosophila glia, behavioral assay, electrophysiology (giant fibre system), confocal microscopy, rescue with human NTE Disease models & mechanisms High 26634819
2015 Neuron-specific expression of wild-type human NTE in Drosophila sws5 null mutants reduces vacuole formation and rescues mobility defects, even when induced after 10 days of adult life when significant neurodegeneration has already occurred. Inducible transgene expression in Drosophila sws mutant, negative geotaxis assay, brain histology PloS one Medium 26671664
2016 NTE/PNPLA6 is expressed in mature Schwann cells, enriched at Schmidt-Lanterman incisures and around the nucleus; expression is absent in promyelinating Schwann cells but increases with maturation. Conditional GFAP-based knockout of NTE/PNPLA6 causes incomplete ensheathment of Remak fibers by nonmyelinating Schwann cells without affecting myelination, and NTE levels are upregulated after nerve crush. Immunofluorescence, immunohistochemistry of mouse sciatic nerve, GFAP-Cre conditional knockout, electron microscopy Glia High 28206686
2016 Silencing Pnpla6 in differentiated human NT2 cells causes effects (reduced electrical activity, loss of neural markers) that are not reproduced by pharmacological NTE esterase inhibition with mipafox, indicating that PNPLA6's role in neurodevelopment is not dependent on its esterase enzymatic activity. siRNA knockdown vs. pharmacological inhibition (mipafox) comparison in NT2 cells Chemico-biological interactions Medium 27475862
2019 Disease-causing PNPLA6 point mutations expressed in Drosophila sws null mutants fail to restore lipid (LPC/PC) levels to normal, though they partially suppress behavioral and degenerative phenotypes in early stages. Mutations in the cNMP binding sites of PNPLA6 specifically prevent restoration of normal lipid levels, supporting that cyclic nucleotide binding regulates the phospholipase activity of PNPLA6. Transgene rescue assay in Drosophila sws null mutant, lipidomics, locomotion assay, histology Frontiers in neuroscience High 31780887
2024 PNPLA6 (NTE) esterase activity was directly measured for 46 disease-associated and 20 common variants; an inverse relationship exists between residual NTE enzymatic activity and presence of retinopathy and endocrinopathy. A similar NTE activity threshold for retinopathy was demonstrated in an allelic mouse series, establishing a genotype:NTE activity:phenotype relationship across PNPLA6 disorders. In vitro NTE esterase activity assay of 66 variants, allelic mouse series, clinical cohort analysis Brain High 38735647
2024 NTE/SWS is present in surface glia forming the blood-brain barrier in Drosophila; loss of SWS in BBB glia causes abnormal plasma membrane domain organization, tight junction raft disruption, accumulation of lipid droplets, lysosomes, and multilamellar bodies (resembling lysosomal storage disease), elevated fatty acid levels, and age-dependent upregulation of innate immunity factors. BBB glia-specific expression of NTE/SWS normalizes inflammatory response, and anti-inflammatory treatment prevents abnormal BBB architecture. Glia-specific Drosophila knockdown/rescue genetics, confocal microscopy, lipidomics (fatty acids), immunostaining for immune factors, pharmacological anti-inflammatory treatment eLife High 38660940
2025 PNPLA6, acting as a phospholipase B, regulates choline mobilization from phosphatidylcholine in retinal pigment epithelial (RPE) cells and subsequent choline turnover for phosphatidylcholine regeneration. PNPLA6-derived choline is supplied from RPE cells to adjacent photoreceptors to support their survival. Mice with retina-specific PNPLA6 deletion develop retinitis pigmentosa-like degeneration; abnormalities in RPE morphology, proliferation, metabolism, and function are entirely rescued by choline supplementation. Retina-specific conditional knockout mouse, phospholipid metabolite assay, choline supplementation rescue, RPE and photoreceptor cell biology assays Nature communications High 40082403
2025 The three cyclic nucleotide binding (cNMP) sites in SWS (Drosophila PNPLA6 ortholog) are required for full catalytic phospholipase function: mutating a single site (SWSG558E) yields a partially functional protein that can decrease PC when overexpressed, while mutating all three sites (SWSΔCNB) renders SWS non-functional and causes PC accumulation when overexpressed, demonstrating that cyclic nucleotide binding regulates the phospholipase activity. Site-directed mutagenesis of cNMP binding sites in Drosophila SWS, transgenic rescue assay in sws null, lipid (PC) measurements bioRxivpreprint Medium 41415407
2026 Enhanced degradation of lysophosphatidylethanolamine (LPE) to glycerophosphorylethanolamine in a murine MASH model is associated with upregulation of Pnpla6 in the liver, implicating PNPLA6 as a lysophospholipase for LPE catabolism in hepatic phospholipid metabolism. LC-MS/MS lipidomics, protein expression analysis in mouse MASH model International journal of molecular sciences Low 41752007
2026 TOCP inhibits NTE enzymatic activity in mouse GC-1 spg spermatogonial cells (~by 30%), and NTE knockdown in these cells suppresses cell proliferation and mitotic progression, phenocopying TOCP effects; however, ER stress was not activated upon NTE knockdown alone (unlike TOCP treatment), indicating NTE activity supports germ cell proliferation through a mechanism distinct from ER stress. NTE enzymatic inhibition, siRNA knockdown in GC-1 spg cells, proliferation/mitosis assays, ER stress markers Toxics Medium 42043102
2016 Destruction (D) box motifs in the regulatory domain of NTE are required for proteasomal degradation; deletion or mutation of the D box prevents proteasomal degradation without affecting subcellular ER localization. Deletion of the regulatory region (containing D box) leads to protein accumulation, and both regulatory region deletion and D box deletion similarly inhibit cell growth. Western blot, deletion/site-directed mutagenesis, proteasome inhibitor experiments, subcellular localization by fluorescence Molecular biology reports Medium 27558092

Source papers

Stage 0 corpus · 88 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. Brain : a journal of neurology 170 24355708
1990 Organophosphates and delayed neuropathy--is NTE alive and well? Toxicology and applied pharmacology 148 2180130
2012 Neuropathy target esterase (NTE): overview and future. Chemico-biological interactions 79 23220002
2012 Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 78 22237311
2014 Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome. The Journal of clinical endocrinology and metabolism 76 25033069
2015 Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness. Nature communications 75 25574898
2003 Relation between insulin resistance and hematological parameters in elderly Koreans-Southwest Seoul (SWS) Study. Diabetes research and clinical practice 51 12757983
2000 Cloning and expression of the murine sws/NTE gene. Mechanisms of development 47 10640712
2012 Knockdown of Pnpla6 protein results in motor neuron defects in zebrafish. Disease models & mechanisms 43 22996643
2015 Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function. Disease models & mechanisms 38 26634819
2020 Neuropathy target esterase (NTE/PNPLA6) and organophosphorus compound-induced delayed neurotoxicity (OPIDN). Advances in neurotoxicology 36 32518884
1993 The role of neurotoxic esterase (NTE) in the prevention and potentiation of organophosphorus-induced delayed neurotoxicity (OPIDN). Chemico-biological interactions 36 8343996
2003 NTE: one target protein for different toxic syndromes with distinct mechanisms? BioEssays : news and reviews in molecular, cellular and developmental biology 32 12879443
2014 Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia. Journal of neurology 31 25267340
2007 SwS: a solvation web service for nucleic acids. Bioinformatics (Oxford, England) 30 17324939
2017 Pure Cerebellar Ataxia with Homozygous Mutations in the PNPLA6 Gene. Cerebellum (London, England) 29 26995604
2019 An IncR Plasmid Harbored by a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Strain Possesses Five Tandem Repeats of the blaKPC-2::NTEKPC-Id Fragment. Antimicrobial agents and chemotherapy 26 30530604
2017 NTE/PNPLA6 is expressed in mature Schwann cells and is required for glial ensheathment of Remak fibers. Glia 26 28206686
2016 Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans. Genetics 26 26936927
2016 Roles of NTE protein and encoding gene in development and neurodevelopmental toxicity. Chemico-biological interactions 24 27475862
2018 Different Cerebellar Ataxia Phenotypes Associated with Mutations of the PNPLA6 Gene in Brazilian Patients with Recessive Ataxias. Cerebellum (London, England) 23 29248984
2021 Prevalence of the NTEKPC-I on IncF Plasmids Among Hypervirulent Klebsiella pneumoniae Isolates in Jiangxi Province, South China. Frontiers in microbiology 20 34234750
2019 Disease-Associated PNPLA6 Mutations Maintain Partial Functions When Analyzed in Drosophila. Frontiers in neuroscience 20 31780887
2020 Novel variants in PNPLA6 causing syndromic retinal dystrophy. Experimental eye research 18 33141049
2010 An alternative in vitro method for detecting neuropathic compounds based on acetylcholinesterase inhibition and on inhibition and aging of neuropathy target esterase (NTE). Toxicology in vitro : an international journal published in association with BIBRA 18 20097283
2016 Boucher Neuhäuser Syndrome - A rare cause of inherited hypogonadotropic hypogonadism. A case of two adult siblings with two novel mutations in PNPLA6. European journal of medical genetics 17 27866050
2014 Organophosphate-induced changes in the PKA regulatory function of Swiss Cheese/NTE lead to behavioral deficits and neurodegeneration. PloS one 17 24558370
2014 Silencing of PNPLA6, the neuropathy target esterase (NTE) codifying gene, alters neurodifferentiation of human embryonal carcinoma stem cells (NT2). Neuroscience 17 25255935
2022 PNPLA6/NTE, an Evolutionary Conserved Phospholipase Linked to a Group of Complex Human Diseases. Metabolites 16 35448471
2020 A novel PNPLA6 mutation in a Turkish family with intractable Holmes tremor and spastic ataxia. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 16 33210227
2019 Detailed retinal phenotype of Boucher-Neuhäuser syndrome associated with mutations in PNPLA6 mimicking choroideremia. Ophthalmic genetics 16 31135245
2018 A novel PNPLA6 compound heterozygous mutation identified in a Chinese patient with Boucher‑Neuhäuser syndrome. Molecular medicine reports 16 29749493
2015 Delayed Induction of Human NTE (PNPLA6) Rescues Neurodegeneration and Mobility Defects of Drosophila swiss cheese (sws) Mutants. PloS one 16 26671664
2003 Rat NTE-related esterase is a membrane-associated protein, hydrolyzes phenyl valerate, and interacts with diisopropylfluorophosphate through a serine catalytic machinery. Archives of biochemistry and biophysics 16 12893290
2021 Within patient genetic diversity of blaKPC harboring Klebsiella pneumoniae in a Colombian hospital and identification of a new NTEKPC platform. Scientific reports 15 34725422
2013 Functional pathways altered after silencing Pnpla6 (the codifying gene of neuropathy target esterase) in mouse embryonic stem cells under differentiation. In vitro cellular & developmental biology. Animal 15 24142151
2015 Novel mutations in the PNPLA6 gene in Boucher-Neuhäuser syndrome. Journal of human genetics 14 25631098
2023 PNPLA6 disorders: what's in a name? Ophthalmic genetics 13 37732399
2020 Bi-allelic variants in PNPLA6 possibly associated with Parkinsonian features in addition to spastic paraplegia phenotype. Journal of neurology 13 32623594
2018 Gordon Holmes syndrome due to compound heterozygosity of two new PNPLA6 variants - A diagnostic challenge. eNeurologicalSci 13 30555943
2003 Peripheral resolution for achromatic and SWS gratings in early to moderate glaucoma and the implications for selective ganglion cell density loss. Investigative ophthalmology & visual science 13 14578399
1999 Molecular cloning of neuropathy target esterase (NTE). Chemico-biological interactions 13 10421490
2020 Identification of Oliver-McFarlane syndrome caused by novel compound heterozygous variants of PNPLA6. Gene 12 32758583
2022 Multifaceted and Age-Dependent Phenotypes Associated With Biallelic PNPLA6 Gene Variants: Eight Novel Cases and Review of the Literature. Frontiers in neurology 11 35069422
2021 Gordon Holmes syndrome caused by two novel mutations in the PNPLA6 gene. Clinical neurology and neurosurgery 11 34157508
2020 REVIEW OF QUANTITATIVE MECHANISTIC MODELS OF RADIATION-INDUCED NON-TARGETED EFFECTS (NTE). Radiation protection dosimetry 11 33395702
2007 Molecular cloning and expression of the C-terminal domain of mouse NTE-related esterase. Molecular and cellular biochemistry 10 17673953
1999 Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and high-density lipoprotein-induced cholesterol efflux in macrophages. Japanese journal of pharmacology 10 10202851
2023 Predominant transmission of KPC-2 carbapenemase in Germany by a unique IncN plasmid variant harboring a novel non-transposable element (NTE -Y). Microbiology spectrum 9 38084979
2021 Chorioretinal dystrophy, hypogonadotropic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome due to a homozygous (c.3524C>G (p.Ser1175Cys)) variant in PNPLA6 gene. Ophthalmic genetics 9 33650466
1999 Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and secretions of apolipoprotein B-containing lipoprotein and bile acids in HepG2. Japanese journal of pharmacology 9 10202850
1994 In vivo inhibition by mipafox of soluble and particulate forms of organophosphorus neuropathy target esterase (NTE) in hen sciatic nerve. Toxicology letters 8 8140588
1994 Avian embryonic brain reaggregate culture system. II. NTE activity discriminates between effects of a single neuropathic or nonneuropathic organophosphorus compound exposure. Toxicology and applied pharmacology 8 8291056
2025 PNPLA6 regulates retinal homeostasis by choline through phospholipid turnover. Nature communications 7 40082403
2024 The NTE domain of PTENα/β promotes cancer progression by interacting with WDR5 via its SSSRRSS motif. Cell death & disease 7 38744853
2011 Fabrication of GaAs subwavelength structure (SWS) for solar cell applications. Optics express 7 21643374
2024 Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders. Brain : a journal of neurology 6 38735647
2008 Identification and characterization of a splice variant of the catalytic domain of mouse NTE-related esterase. Gene 6 18486363
1993 The search for the physiological functions of NTE; is NTE a receptor? Chemico-biological interactions 6 8393746
2024 Unraveling the link between neuropathy target esterase NTE/SWS, lysosomal storage diseases, inflammation, abnormal fatty acid metabolism, and leaky brain barrier. eLife 5 38660940
2022 Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher-Neuhäuser Syndrome. Frontiers in genetics 5 35198007
2012 Identification of two novel splicing variants of murine NTE-related esterase. Gene 5 22326266
2009 Fibronectin: characterization of a somatic mutation in Sturge-Weber syndrome (SWS). Medical hypotheses 4 19359105
2001 QSAR for the organophosphate-induced inhibition and 'aging' of the enzyme neuropathy target esterase (NTE). SAR and QSAR in environmental research 4 11696925
1999 Effects of NTE-122, an acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and lipid secretion from CaCo-2 cells, and cholesterol absorption in rats. Japanese journal of pharmacology 4 10446760
2025 Dissemination of IncQ1 Plasmids Harboring NTEKPC-IId in a Brazilian Hospital. Microorganisms 3 39858948
2016 CRISPR Technology Reveals RAD(51)-ical Mechanisms of Repair in Roundworms: An Educational Primer for Use with "Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans". Genetics 3 28114101
2012 Degradation of mouse NTE-related esterase by macroautophagy and the proteasome. Molecular biology reports 3 22307796
2010 Protein domains, catalytic activity, and subcellular distribution of mouse NTE-related esterase. Molecular and cellular biochemistry 3 20058052
2023 [A case of Oliver-McFarlane syndrome caused by PNPLA6 gene mutation]. [Zhonghua yan ke za zhi] Chinese journal of ophthalmology 2 37264580
2016 The destruction box is involved in the degradation of the NTE family proteins by the proteasome. Molecular biology reports 2 27558092
2015 Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia. Molecular and cellular probes 2 26714052
1990 In vitro modifications of rat NTE and other esterases by chemicals which induce delayed neurotoxicity in vivo. Veterinary and human toxicology 2 2238440
2013 Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese. Environmental toxicology 1 23418070
2006 Purification and characterization of neuropathy target esterase (NTE) from rat brain. Life sciences 1 16464473
2026 Lysophosphatidylethanolamine Degradation Associated with Upregulation of Pnpla6/7 in a Murine Model of Metabolic Dysfunction-Associated Steatohepatitis. International journal of molecular sciences 0 41752007
2026 Establishment of MURAi007-A, a human induced pluripotent stem cell line from a patient with inherited retinal dystrophy carrying compound heterozygous mutations in the PNPLA6 gene. Stem cell research 0 41880975
2026 Tri-Ortho-Cresyl Phosphate Inhibits Proliferation of Mouse Germ Cells by Activating Endoplasmic Reticulum Stress and Suppressing NTE Activity. Toxics 0 42043102
2026 Homozygous PNPLA6 Mutation (p.Arg1183Trp) Associated With Isolated Cerebellar Ataxia: A Familial Case Report. Cureus 0 42147656
2025 New Insights in blaKPC Gene Mobilization in Pseudomonas aeruginosa: Acquisition of blaKPC-3 and Identification of a New Tn2-like NTE Mobilizing blaKPC-2. Antibiotics (Basel, Switzerland) 0 41009925
2025 Case Report: Novel compound heterozygous mutations in PNPLA6 gene associated with Oliver-McFarlane syndrome. Frontiers in genetics 0 41282473
2025 Analysis of physiological and molecular mechanisms of cotton trichome aphid resistance based on SWS-1 mutant. BMC plant biology 0 41316000
2025 Novel variant in PNPLA6 gene causes Oliver-McFarlane syndrome in a Chinese family: 13 years follow-up. Frontiers in genetics 0 41321566
2025 The cyclic nucleotide binding sites of Swiss-Cheese, the Drosophila orthologue of human PNPLA6, are required for its catalytic function. bioRxiv : the preprint server for biology 0 41415407
2024 Two case reports of a novel missense mutation in the PNPLA6 gene in two siblings with chorioretinal dystrophy, hypogonadotropic hypogonadism, and cerebellar ataxia. Molecular biology reports 0 38683245
2023 Neuropathy target esterase activity predicts retinopathy among PNPLA6 disorders. bioRxiv : the preprint server for biology 0 37333224
2006 [Construction of RNA interference expression vectors of human neuropathy target esterase and its inhibition for expression of NTE in mammalian cells]. Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 0 16600090
2000 [Regulation of SWS by hormones and cytokines]. Sheng li ke xue jin zhan [Progress in physiology] 0 12532764

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