Affinage

HSD17B4

Peroxisomal multifunctional enzyme type 2 · UniProt P51659

Length
736 aa
Mass
79.7 kDa
Annotated
2026-06-10
49 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSD17B4 encodes a multifunctional 80 kDa peroxisomal enzyme (D-bifunctional protein) organized into three catalytic/functional modules: an N-terminal D-specific 3-hydroxyacyl-CoA dehydrogenase/17β-hydroxysteroid dehydrogenase domain, a central 2-enoyl-acyl-CoA hydratase domain, and a C-terminal sterol carrier protein-2-like (SCP-2L) domain that mediates lipid transfer between membranes (PMID:10343282). Through these activities it executes peroxisomal β-oxidation of medium- and long-chain fatty acids—and of acylcarnitines when mitochondrial fatty acid oxidation is impaired—generating acetyl-CoA and polyunsaturated fatty acids such as DHA (PMID:30540494, PMID:40102401). The SCP-2L domain doubles as a regulated targeting module: it carries the C-terminal PTS1 import signal, and binding of lipids such as ceramide or phosphatidylserine to this domain controls the protein's interaction with the import receptor Pex5 and thereby partitions HSD17B4 between mitochondria-associated membranes and peroxisomes (PMID:31176039, PMID:33935042). Enzyme abundance is further set post-translationally by competing modifications—CREBBP-mediated K669 acetylation drives chaperone-mediated autophagy and is opposed by SIRT3 deacetylation, while DTX2-mediated K48-linked ubiquitination at K645 targets the SCP domain for proteasomal degradation (PMID:28296597, PMID:32678070, PMID:40058099). Downstream of its metabolic output, HSD17B4-derived acetyl-CoA supports HDAC6-dependent primary ciliogenesis, and loss of the enzyme produces lipid accumulation, oxidative stress, and neuroinflammation in microglia (PMID:40102401, PMID:41162676). Compound heterozygous and homozygous loss-of-function mutations that destabilize the protein cause Perrault syndrome (PMID:20673864, PMID:32042923). A splice isoform-specific androgen-inactivating activity (isoform 2) links HSD17B4 to castration-resistant prostate cancer (PMID:29346776).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Established the fundamental architecture and chemistry of HSD17B4, defining it as a single polypeptide carrying three distinct activities relevant to both fatty acid and steroid metabolism.

    Evidence In vitro enzymatic assays on truncated recombinant domains plus membrane lipid transfer assays, with mutational mapping of the NAD+-binding dehydrogenase site

    PMID:10343282 PMID:10419023

    Open questions at the time
    • Physiological substrate hierarchy not established in vitro
    • Did not address how the three domains coordinate flux in the holoenzyme
  2. 2002 Low

    Proposed a ligand-assisted peroxisomal targeting mechanism in which SCP-2L ligand occupancy gates exposure of the C-terminal PTS1 signal.

    Evidence Molecular dynamics simulation of the SCP-2L crystal structure

    PMID:12368102

    Open questions at the time
    • Computational only with no experimental validation at the time
    • Identity of physiological gating ligand unknown
  3. 2010 Medium

    Connected HSD17B4 loss of function to human disease, showing that destabilizing mutations cause Perrault syndrome.

    Evidence Whole-exome sequencing with Sanger confirmation, Western blot of patient cells, structural prediction

    PMID:20673864

    Open questions at the time
    • Tissue-specific basis of the ovarian and auditory phenotype not resolved
    • Single family / single lab
  4. 2013 Medium

    Confirmed that the SCP-2L domain is an integral structural element of the full-length holoenzyme rather than an isolated module, supporting its biological role in the intact protein.

    Evidence Synchrotron SAXS with ab initio and rigid-body modeling of human full-length protein in solution

    PMID:23313254

    Open questions at the time
    • Low-resolution solution model only
    • Did not capture ligand-dependent conformational changes
  5. 2017 High

    Revealed that HSD17B4 abundance is dynamically controlled by reversible K669 acetylation coupling its degradation to estrogen signaling.

    Evidence Site-directed mutagenesis, reciprocal Co-IP identifying CREBBP/SIRT3, CMA degradation and migration/invasion assays in MCF7 cells

    PMID:28296597

    Open questions at the time
    • How acetylation routes the protein specifically into CMA not detailed
    • Link between enzyme abundance and metastatic phenotype mechanistically indirect
  6. 2018 High

    Demonstrated that HSD17B4 is required for peroxisomal oxidation of medium- and long-chain fatty acids and acylcarnitines, a pathway that becomes important when mitochondrial FAO is blocked.

    Evidence CRISPR-Cas9 KO cell lines, isotope tracing, Hsd17b4 KO mice with plasma acylcarnitine profiling after CPT2 inhibition

    PMID:30540494

    Open questions at the time
    • Quantitative contribution of peroxisomal FAO under normal physiology unclear
    • Mechanism of acylcarnitine entry into peroxisomes not defined
  7. 2018 High

    Identified an isoform-specific androgen-inactivating function, linking suppression of HSD17B4 isoform 2 to castration-resistant prostate cancer.

    Evidence Isoform-specific enzymatic assays, genetic silencing with androgen and AR signaling readouts, patient tissue expression analysis

    PMID:29346776

    Open questions at the time
    • Mechanism suppressing isoform 2 expression in CRPC not defined
    • Subcellular site of androgen inactivation not localized
  8. 2019 High

    Established ceramide as a molecular switch for HSD17B4 peroxisomal import by binding SCP-2L and blocking Pex5 interaction, experimentally validating the ligand-assisted targeting concept.

    Evidence Affinity chromatography, Co-IP, proximity ligation, immunocytochemistry, docking and mutagenesis

    PMID:31176039

    Open questions at the time
    • In vivo relevance of CEMAM retention not tested
    • How ceramide levels are sensed to time import not resolved
  9. 2020 Medium

    Extended the acetylation-controlled stability model to prostate cancer, showing androgen stimulus drives K669 acetylation and degradation with functional consequences for proliferation.

    Evidence Co-IP, acetylation and CMA degradation assays, siRNA knockdown with proliferation/migration/invasion readouts

    PMID:32678070

    Open questions at the time
    • Single lab corroboration of the CREBBP/SIRT3 axis
    • Direct enzymatic-output basis of the proliferative phenotype not isolated
  10. 2020 Medium

    Showed that disease-associated mutations act by impairing protein dimerization and stability rather than by altering transcription.

    Evidence Immunoblot for protein level and dimerization, qRT-PCR for mRNA in patient fibroblasts

    PMID:32042923

    Open questions at the time
    • Structural basis of dimerization defect not resolved
    • Genotype-phenotype correlation based on small patient set
  11. 2021 Medium

    Identified phosphatidylserine as a second SCP-2L-binding lipid that regulates HSD17B4 peroxisomal localization, broadening the lipid-sensing control of targeting.

    Evidence Biotin-PS bead pulldown with truncation mapping and immunofluorescence localization upon PS translocation

    PMID:33935042

    Open questions at the time
    • Physiological trigger linking PS exposure to import not defined
    • Relationship to the ceramide switch not reconciled
  12. 2025 High

    Defined a second degradation route via DTX2-mediated K48 ubiquitination of the SCP domain at K645, linking HSD17B4 turnover to peroxisomal DHA output and ferroptosis suppression in hepatocellular carcinoma.

    Evidence CRISPR screen, Co-IP, ubiquitination assays, K645 mutagenesis, lipidomics, xenografts and DHA rescue

    PMID:40058099

    Open questions at the time
    • Interplay between K645 ubiquitination and K669 acetylation not tested
    • Generality beyond STAT3-driven HCC unknown
  13. 2025 High

    Connected HSD17B4 metabolic output to organelle biogenesis, showing that acetyl-CoA generated by peroxisomal β-oxidation drives HDAC6-dependent primary ciliogenesis.

    Evidence KO cell lines and KO mice, primary cilia imaging, acetate supplementation rescue, HDAC6 pathway analysis, motor and Purkinje cell readouts

    PMID:40102401

    Open questions at the time
    • Direct molecular link between acetyl-CoA pool and HDAC6 activity not fully traced
    • Neuronal cell-type specificity of the rescue not delineated
  14. 2025 High

    Demonstrated a cell-type-specific role in microglia where HSD17B4 loss causes lipid accumulation, ROS, and neuroinflammation driving Alzheimer's-like pathology.

    Evidence Microglia-specific conditional KO mice, lipidomics, ROS and cytokine assays, AD model readouts with CKBA pharmacological rescue

    PMID:41162676

    Open questions at the time
    • Mechanism linking arachidonic acid accumulation to cytokine production not fully defined
    • Whether findings extend to human microglia untested
  15. 2023 Medium

    Showed that HSD17B4 loss rewires fatty acid pools toward VLCFA accumulation and DHA depletion, activating Akt and mitochondrial respiration and sensitizing HER2+ breast cancer to lapatinib.

    Evidence CRISPR KO cells, Seahorse metabolic flux, lipidomics, Western blot for signaling

    PMID:37378696

    Open questions at the time
    • Causal chain from DHA loss to Akt activation only correlative
    • Single cell-line context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the lipid-sensing (ceramide/PS), acetylation (K669), and ubiquitination (K645) control layers are integrated to set HSD17B4 localization and abundance in a given tissue remains unresolved.
  • No study tests acetylation, ubiquitination, and lipid-gated import together
  • Tissue-specific dominance of each regulatory layer unknown
  • Structural model of the regulated SCP-2L/PTS1 switch in the holoenzyme not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0008289 lipid binding 3 GO:0016829 lyase activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005777 peroxisome 4 GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 2
Partners
CREBBPDTX2PEX5SIRT3

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 HSD17B4 encodes a multifunctional 80 kDa peroxisomal enzyme with three distinct functional domains: (1) N-terminal domain (amino acids 1-323) with 3-hydroxyacyl-CoA dehydrogenase and 17β-hydroxysteroid dehydrogenase activity (oxidizing D- but not L-stereoisomers), (2) central domain (amino acids 324-596) with 2-enoyl-acyl-CoA hydratase activity, and (3) C-terminal domain (amino acids 597-737) with sterol carrier protein activity facilitating lipid transfer between membranes in vitro. The 80 kDa protein is N-terminally cleaved to a 32 kDa enzymatically active fragment. In vitro enzymatic assays with truncated recombinant protein domains, membrane lipid transfer assays Journal of molecular endocrinology High 10343282
1999 The G16S mutation in HSD17B4 inactivates the enzyme by abolishing interaction with NAD+, establishing that the dehydrogenase active site requires Gly16 for cofactor binding. Mutation analysis with functional enzymatic assay The Journal of steroid biochemistry and molecular biology Medium 10419023
2002 Molecular dynamics simulations of the SCP-2L domain of HSD17B4 revealed that upon ligand removal, the binding pocket closes (occupied by Phe93 making hydrophobic contact with Trp36) and the C-terminal peroxisomal targeting signal (PTS1) becomes buried. An anti-correlation exists between burial of PTS1 and binding pocket size, supporting a ligand-assisted peroxisomal targeting mechanism. Molecular dynamics simulation of crystal structure of SCP-2L domain Journal of molecular biology Low 12368102
2010 Compound heterozygous mutations in HSD17B4 (p.Y217C in the dehydrogenase domain and p.Y568X nonsense mutation) cause severely reduced HSD17B4 protein expression, establishing that loss of HSD17B4 function underlies Perrault syndrome. Structural analysis predicted that the Y217C missense mutation destabilizes the dehydrogenase domain. Whole-exome sequencing, Sanger confirmation, Western blot of patient-derived cells American journal of human genetics Medium 20673864
2013 Small-angle X-ray scattering (SAXS) of human MFE-2 (HSD17B4) in solution determined that the SCP-2L domain is positioned as part of the full-length protein quaternary structure, providing direct structural support for the biological role of the SCP-2L domain in the holoenzyme. Synchrotron SAXS with ab initio and rigid body modeling FEBS letters Medium 23313254
2017 Estrone (E1) upregulates HSD17B4 acetylation at lysine 669 (K669), promoting its degradation via chaperone-mediated autophagy (CMA). CREBBP acts as the acetyltransferase (writer) and SIRT3 as the deacetylase (eraser) dynamically controlling K669 acetylation. A K669 mutation that prevents acetylation stabilizes HSD17B4 and confers migratory/invasive properties to MCF7 cells upon E1 treatment. Site-directed mutagenesis, co-immunoprecipitation, acetylation assays, CMA degradation assays, cell migration/invasion assays Autophagy High 28296597
2017 Cytisine-linked isoflavonoids (CLIFs) specifically bind the C-terminus (SCP-2L domain) of HSD17B4, identified by pull-down assay with biotin-modified CLIF. CLIFs selectively inhibit the enoyl-CoA hydratase activity of HSD17B4 but not the D-3-hydroxyacyl-CoA dehydrogenase activity, establishing domain-specific inhibition. Biotin-affinity pull-down assay, truncated domain constructs, enzymatic activity assays Organic & biomolecular chemistry Medium 28868548
2018 Using CRISPR knockout cell lines and pharmacological inhibition, HSD17B4 was established as essential for peroxisomal oxidation of medium- and long-chain fatty acids (lauric and palmitic acid) when mitochondrial fatty acid oxidation is impaired. HSD17B4 KO mice showed altered plasma acylcarnitine profiles after acute CPT2 inhibition, confirming in vivo relevance. Peroxisomes can oxidize both acyl-CoAs and acylcarnitines via this pathway. CRISPR-Cas9 knockout cell lines, pharmacological inhibition, isotope tracing, Hsd17b4 KO mouse model, plasma acylcarnitine profiling FASEB journal High 30540494
2018 Of five alternative splice forms of HSD17B4, only isoform 2 encodes an enzyme capable of inactivating testosterone and dihydrotestosterone (converting them to their respective 17-keto steroids). Functional expression of isoform 2 is specifically suppressed in castration-resistant prostate cancer. Genetic silencing of isoform 2 shifts metabolic balance toward active 17β-OH androgens, stimulating androgen receptor signaling and CRPC development. Splice isoform expression analysis in patient samples, isoform-specific enzymatic assays, genetic silencing with androgen measurement and androgen receptor signaling readouts Cell reports High 29346776
2019 Ceramide interacts with HSD17B4 via its sterol carrier protein 2-like (SCP-2L) domain, adjacent to the C-terminal peroxisomal targeting signal PTS1. Ceramide binding prevents interaction of HSD17B4 with the peroxin Pex5 (the import receptor) and retains HSD17B4 at ceramide-enriched mitochondria-associated membranes (CEMAMs). Inhibition of ceramide biosynthesis induces HSD17B4 translocation to peroxisomes, its interaction with Pex5, and upregulation of DHA production, establishing ceramide as a molecular switch for HSD17B4 peroxisomal import. Affinity chromatography, co-immunoprecipitation, proximity ligation assay, immunocytochemistry, molecular docking, in vitro mutagenesis Biochimica et biophysica acta. Molecular and cell biology of lipids High 31176039
2020 HSD17B4 protein stability is regulated by K669 acetylation in prostate cancer cells: SIRT3 directly interacts with HSD17B4 to inhibit acetylation (enhancing stability), while CREBBP promotes K669 acetylation leading to CMA-mediated degradation. Dihydrotestosterone (DHT) increases HSD17B4 acetylation and promotes its degradation. HSD17B4 knockdown suppresses PCa cell proliferation, migration, and invasion. Co-immunoprecipitation, acetylation assays, CMA degradation assays, siRNA knockdown, cell proliferation/migration/invasion assays Aging Medium 32678070
2020 HSD17B4 deficiency in fibroblasts reduces dimerization of DBP protein. Protein levels of HSD17B4 mutants (p.Ala175Thr) are diminished by Western blot without change in mRNA levels, indicating a post-translational stability effect of this mutation. Residual functional DBP correlates with milder clinical phenotype. Immunoblot for protein levels and dimerization, quantitative RT-PCR for mRNA Neurology. Genetics Medium 32042923
2021 Phosphatidylserine (PS) interacts with HSD17B4 via its SCP-2L domain. PS association was specific (not phosphatidylcholine or sphingomyelin), disrupted by PS in liposomes but not free PS. Translocation of PS to the outer leaflet of the plasma membrane enriched HSD17B4 in peroxisomes, establishing PS as a regulator of HSD17B4 subcellular localization. Pulldown assay with biotin-PS-coated magnetic beads, domain-mapping with truncation constructs, immunofluorescence localization assay upon PS translocation Molecules and cells Medium 33935042
2025 DTX2 (an E3 ubiquitin ligase) ubiquitinates HSD17B4 at lysine K645 via its RING domain targeting the SCP structural domain of HSD17B4, leading to K48-linked ubiquitination-mediated proteasomal degradation of HSD17B4. This reduces HSD17B4-dependent peroxisomal β-oxidation, lowers DHA-phospholipid levels, and suppresses ferroptosis in hepatocellular carcinoma cells. STAT3 activation drives DTX2 transcription upstream of this pathway. CRISPR screening, Co-IP, ubiquitination assays, site-specific mutagenesis (K645), lipidomics, in vivo xenograft models, DHA supplementation rescue experiments Drug resistance updates High 40058099
2025 HSD17B4 deficiency impairs primary ciliogenesis and alters cilia-mediated signaling. HSD17B4 is required for peroxisomal β-oxidation and acetyl-CoA synthesis; its loss reduces acetyl-CoA levels. Elevation of acetyl-CoA (via acetate administration) rescues ciliary defects through HDAC6-mediated ciliogenesis in HSD17B4-deficient cells, and restores motor function and Purkinje cell layer preservation in Hsd17b4-KO mice. HSD17B4-KO cell lines and mouse model, primary cilia imaging, acetate supplementation rescue, HDAC6 pathway analysis, metabolite measurement Nature communications High 40102401
2025 Loss of MFE-2 (HSD17B4) in microglia leads to lipid accumulation with excessive arachidonic acid, increased mitochondrial reactive oxygen species, and proinflammatory cytokine production. Microglia-specific ablation of MFE-2 drove neuroinflammation and Aβ deposition in Alzheimer's disease models. The compound CKBA binds to MFE-2 and restores its levels, ameliorating AD pathology. Microglia-specific conditional KO mouse model, lipidomics, ROS measurement, cytokine assays, CKBA binding assay, AD model behavioral and pathological readouts Nature aging High 41162676
2023 HSD17B4 knockout in BT-474 HER2-positive breast cancer cells caused accumulation of very long-chain fatty acids (VLCFA), decreased polyunsaturated fatty acids (DHA and arachidonic acid), increased Akt phosphorylation (attributed to decreased DHA), upregulation of oxidative phosphorylation and electron transport chain genes, increased mitochondrial ATP production, and enhanced glucose dependence, resulting in approximately tenfold increased sensitivity to the HER2/Akt inhibitor lapatinib. CRISPR KO cell lines, Seahorse metabolic flux analysis, lipidomics, Western blot for signaling pathway activation Breast cancer research and treatment Medium 37378696
2025 Gamma-tocotrienol (γ-T3) directly interacts with HSD17B4 protein (identified by anti-FLAG immunoprecipitation with quantification of γ-T3 in precipitate), and inhibits HSD17B4 catalytic activity in converting estradiol (E2) to estrone, reducing cyclin D1 expression and suppressing ERK, MEK, AKT, and STAT3 signaling, inhibiting proliferation of HSD17B4-overexpressing HepG2 cells. Co-immunoprecipitation/pulldown with FLAG-tagged HSD17B4 and γ-T3 quantification, enzymatic activity assay, Western blot for signaling pathways, xenograft mouse model Current cancer drug targets Medium 38934283
2017 A homozygous HSD17B4 missense variant (p.A100S) leads to markedly reduced HSD17B4 protein expression compared to wild-type when expressed in SH-SY5Y cells, establishing pathogenicity through protein instability. Transfection of wild-type vs. mutant HSD17B4 plasmids in SH-SY5Y cells with Western blot comparison BMC medical genetics Low 28830375

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. American journal of human genetics 199 20673864
2018 Peroxisomes can oxidize medium- and long-chain fatty acids through a pathway involving ABCD3 and HSD17B4. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 103 30540494
1999 Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome. Journal of molecular endocrinology 70 10343282
2012 Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency. Orphanet journal of rare diseases 56 23181892
2008 HSD17B4 overexpression, an independent biomarker of poor patient outcome in prostate cancer. Molecular and cellular endocrinology 45 19100308
2017 Acetylation targets HSD17B4 for degradation via the CMA pathway in response to estrone. Autophagy 38 28296597
2018 Loss of an Androgen-Inactivating and Isoform-Specific HSD17B4 Splice Form Enables Emergence of Castration-Resistant Prostate Cancer. Cell reports 36 29346776
2014 Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency. BMC medical genetics 34 24602372
2009 Knocking out the MFE-2 gene of Candida bombicola leads to improved medium-chain sophorolipid production. FEMS yeast research 32 19416371
2019 Enzyme mimetic activities of spinel substituted nanoferrites (MFe2O4): A review of synthesis, mechanism and potential applications. Materials science & engineering. C, Materials for biological applications 30 30889678
1999 Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17beta-hydroxysteroid dehydrogenase IV. The Journal of steroid biochemistry and molecular biology 26 10419023
2017 Pathological complete response of HER2-positive breast cancer to trastuzumab and chemotherapy can be predicted by HSD17B4 methylation. Oncotarget 21 28186977
2020 HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer. Frontiers in genetics 19 32265992
2020 Acetylation-mediated degradation of HSD17B4 regulates the progression of prostate cancer. Aging 19 32678070
2017 Developing antineoplastic agents that target peroxisomal enzymes: cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4). Organic & biomolecular chemistry 18 28868548
2022 A novel comparative study for electrochemical urea biosensor design: Effect of different ferrite nanoparticles (MFe2O4, M: Cu, Co, Ni, Zn) in urease immobilized composite system. Bioelectrochemistry (Amsterdam, Netherlands) 16 36401962
2020 Multi-omics analyses identify HSD17B4 methylation-silencing as a predictive and response marker of HER2-positive breast cancer to HER2-directed therapy. Scientific reports 16 32968149
2017 PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian syndrome and breast cancer. Oncotarget 16 29050221
2016 Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency. Neurology. Genetics 15 27790638
2017 A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome. BMC medical genetics 14 28830375
2025 DTX2 attenuates Lenvatinib-induced ferroptosis by suppressing docosahexaenoic acid biosynthesis through HSD17B4-dependent peroxisomal β-oxidation in hepatocellular carcinoma. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 13 40058099
2020 First Case of Peroxisomal D-bifunctional Protein Deficiency with Novel HSD17B4 Mutations and Progressive Neuropathy in Korea. Journal of Korean medical science 13 33045774
2021 Two Novel HSD17B4 Heterozygous Mutations in Association With D-Bifunctional Protein Deficiency: A Case Report and Literature Review. Frontiers in pediatrics 12 34368026
2019 Ceramide regulates interaction of Hsd17b4 with Pex5 and function of peroxisomes. Biochimica et biophysica acta. Molecular and cell biology of lipids 12 31176039
2012 Epistasis between the HSD17B4 and TG polymorphisms is associated with premature ovarian failure. Fertility and sterility 12 22265031
2002 Response of SCP-2L domain of human MFE-2 to ligand removal: binding site closure and burial of peroxisomal targeting signal. Journal of molecular biology 12 12368102
2018 Correlation between HSD17B4 expression in rat liver cancer tissues and inflammation or proliferation. European review for medical and pharmacological sciences 11 29917219
2025 Coupling Nitrate-to-Ammonia Conversion and Sulfion Oxidation Reaction Over Hierarchical Porous Spinel MFe2O4 (M═Ni, Co, Fe, Mn) in Wastewater. Small (Weinheim an der Bergstrasse, Germany) 10 39763410
2025 Loss of MFE-2 impairs microglial lipid homeostasis and drives neuroinflammation in Alzheimer's pathogenesis. Nature aging 10 41162676
2020 Biallelic mutation of HSD17B4 induces middle age-onset spinocerebellar ataxia. Neurology. Genetics 9 32042923
2018 Selective adsorption of uranyl and potentially toxic metal ions at the core-shell MFe2O4-TiO2 (M=Mn, Fe, Zn, Co, or Ni) nanoparticles. Journal of hazardous materials 9 30481734
2016 Association between a non-synonymous HSD17B4 single nucleotide polymorphism and meat-quality traits in Berkshire pigs. Genetics and molecular research : GMR 9 27819726
2021 The Peroxisomal Localization of Hsd17b4 Is Regulated by Its Interaction with Phosphatidylserine. Molecules and cells 7 33935042
2020 Rapid whole-genome sequencing identifies a homozygous novel variant, His540Arg, in HSD17B4 resulting in D-bifunctional protein deficiency disorder diagnosis. Cold Spring Harbor molecular case studies 7 33115767
2017 Overexpression of HSD17B4 exerts tumor suppressive function in adrenocortical carcinoma and is not associated with hormone excess. Oncotarget 7 29383116
2021 Novel HSD17B4 Variants Cause Progressive Leukodystrophy in Childhood: Case Report and Literature Review. Child neurology open 6 34660840
2013 Quaternary structure of human, Drosophila melanogaster and Caenorhabditis elegans MFE-2 in solution from synchrotron small-angle X-ray scattering. FEBS letters 5 23313254
2025 HSD17B4 deficiency causes dysregulation of primary cilia and is alleviated by acetyl-CoA. Nature communications 3 40102401
2023 HSD17B4 methylation enhances glucose dependence of BT-474 breast cancer cells and increases lapatinib sensitivity. Breast cancer research and treatment 3 37378696
2021 D-bifunctional protein deficiency caused by HSD17B4 gene mutation in a neonate. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 3 34719423
2025 D-Bifunctional Protein Deficiency Type III: Two Turkish Cases and a Novel HSD17B4 Gene Variant. Molecular syndromology 2 40416444
2023 Susceptibility to Colorectal Cancer Based on HSD17B4 rs721673 and rs721675 Polymorphisms and Alcohol Intake among Taiwan Biobank Participants: A Retrospective Case Control Study Using the Nationwide Claims Data. Journal of personalized medicine 1 37108962
2023 A Homozygous Missense Variant in HSD17B4 Identified in Two Different Families. Molecular syndromology 1 38585549
2026 One novel HSD17B4 mutation in association with D-bifunctional protein deficiency: a case report and literature review. Frontiers in pediatrics 0 41567431
2026 HSD17B4-Related Disorder: Defining the Phenotype in Adult-Onset Patients. Neurology. Genetics 0 42231982
2025 Gamma-tocotrienol Inhibits Proliferation and Growth of HSD17B4 Overexpressing HepG2 Liver Cancer Cells. Current cancer drug targets 0 38934283
2025 Case Report: D-bifunctional protein deficiency caused by novel compound heterozygote HSD17B4 variants in a neonate in China. Frontiers in genetics 0 41282484
2024 Exome sequencing reveals pathogenic mutations in the LARS2 and HSD17B4 genes associated with Perrault syndrome and D-bifunctional protein deficiency in Moroccan families. Molecular biology reports 0 39052101
2005 [Altered expression of the HSD17B4 gene in esophageal squamous cell carcinoma and loss of heterozygosity analysis]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 0 16038258

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