Affinage

CLEC16A

Protein CLEC16A · UniProt Q2KHT3

Length
1053 aa
Mass
117.7 kDa
Annotated
2026-06-09
55 papers in source corpus 20 papers cited in narrative 20 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

CLEC16A is a membrane-associated endosomal E3 ubiquitin ligase that governs mitochondrial quality control through autophagy across pancreatic β-cells, immune cells, astrocytes, and hematopoietic progenitors (PMID:24949970, PMID:29180353, PMID:40033124). It functions as the organizing component of a ubiquitin-dependent tripartite complex with the E3 ligase RNF41/Nrdp1 and the deubiquitinase USP8, in which CLEC16A-driven non-degradative ubiquitin conjugates direct mitophagy effectors and are required for complex assembly and stability (PMID:29180353); loss of CLEC16A elevates the Nrdp1 target Parkin and produces dysfunctional mitochondria with reduced respiration and impaired glucose-stimulated insulin secretion (PMID:24949970). CLEC16A sits downstream of the transcription factor Pdx1 in a Pdx1–Clec16a–Nrdp1 mitophagy axis, where it is needed for autophagosome–lysosome fusion and mitochondrial trafficking (PMID:26085571), and more broadly is required for autolysosome clearance, such that its loss causes accumulation of undigested autolysosomes and neurodegeneration with Purkinje cell loss (PMID:26987296). Beyond mitophagy, CLEC16A controls late-endosomal membrane trafficking by binding RILP and the HOPS/Vps16A complex to drive dynein-dependent positioning and biogenesis of HLA class II–positive late endosomes in antigen-presenting cells (PMID:25823473, PMID:30774629), and it interacts with retromer subunits and the endosomal E3 ligase TRIM27 to regulate endosomal sorting (PMID:36538041). Its activity depends on intrinsically disordered regions: a C-terminal IDPR controls CLEC16A stability and mitophagy-complex assembly via a proline-biased sequence (PMID:35604110), while an internal IDPR is the site of RNF41-mediated destabilization (PMID:36822331). By sustaining mitophagy, CLEC16A limits accumulation of damaged mitochondria and thereby suppresses NF-κB/NLRP3/gasdermin D inflammatory signaling, with astrocyte-specific loss worsening experimental autoimmune encephalomyelitis (PMID:40033124). A disease-associated C-terminal truncation abolishes endosomal localization and TRIM27 binding and fails to rescue mitophagy defects in zebrafish (PMID:36538041).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2014 High

    Established CLEC16A as an endosomal protein physically and functionally linked to mitophagy, answering what cellular process this disease-associated gene controls.

    Evidence Reciprocal Co-IP with Nrdp1, pancreas-specific conditional KO mouse with mitochondrial respiration, ATP, and insulin-secretion readouts

    PMID:24949970

    Open questions at the time
    • Whether CLEC16A itself has catalytic E3 activity not yet shown
    • Direct ubiquitination substrate not defined
  2. 2015 High

    Defined CLEC16A as required for autophagy/late-endosome biology in two immunologically relevant settings, linking it to both T cell selection and antigen presentation.

    Evidence shRNA KD NOD mouse showing TEC autophagy and altered thymocyte selection; siRNA KD in dendritic cells with Co-IP of RILP/HOPS and EM of HLA class II late endosomes

    PMID:25823473 PMID:25979422

    Open questions at the time
    • Molecular link between autophagy machinery and HLA class II trafficking not resolved
    • Whether the same biochemical complex operates in TECs and DCs unknown
  3. 2015 High

    Placed CLEC16A within a defined transcriptional-to-mitophagy pathway, showing it acts downstream of Pdx1 and upstream of autophagosome-lysosome fusion.

    Evidence ChIP showing Pdx1 occupancy at Clec16a, expression analysis, and Clec16a re-expression rescue of mitochondrial trafficking and insulin secretion

    PMID:26085571

    Open questions at the time
    • Direct molecular mechanism of CLEC16A in fusion step not defined
    • Generality beyond β-cells untested here
  4. 2016 High

    Pinpointed the autophagy defect to autolysosome clearance rather than autophagosome formation, and linked CLEC16A loss to neurodegeneration.

    Evidence Two independent Clec16a-mutant mouse strains with LC3/LAMP-1 accumulation, p62 buildup, and motor/Purkinje phenotypes; normal endocytosis, lysosome, Golgi function

    PMID:26987296

    Open questions at the time
    • Molecular basis for selective autolysosome clearance defect unknown
    • Relationship to the mitophagy complex not directly tested
  5. 2017 High

    Resolved the biochemical core mechanism: CLEC16A is an E3 ligase generating non-degradative ubiquitin to assemble a stable CLEC16A-Nrdp1-USP8 mitophagy complex.

    Evidence In vitro E3 ligase activity assay, ubiquitination assays, Co-IP of tripartite complex, lenalidomide inhibition in cells and patient samples

    PMID:29180353

    Open questions at the time
    • Direct ubiquitination substrates within the complex not enumerated
    • Structural arrangement of the complex unknown
  6. 2017 Medium

    Reconciled CLEC16A localization and a parallel autophagy-regulatory role, showing nutrient sensing modulates its Golgi clustering and mTOR signaling.

    Evidence siRNA, overexpression, proteomics, mTOR activity assays, LC3 reporter and confocal localization to vesicles/Golgi

    PMID:28223137

    Open questions at the time
    • mTOR activation inferred from activity, no direct binding shown
    • Reconciliation with endosomal localization reports incomplete
  7. 2017 High

    Ortholog work assigned a conserved trafficking mechanism, showing the CLEC16A ortholog activates Rab2 to drive phagosome/endosome maturation.

    Evidence C. elegans genetics, in vitro GDI-displacement/GEF assay on UNC-108/Rab2, live imaging, unc-108 epistasis

    PMID:28424218

    Open questions at the time
    • Whether human CLEC16A acts as a Rab2 GEF not directly demonstrated
    • Connection between GEF activity and E3 ligase activity unresolved
  8. 2018 Medium

    Extended mitophagy regulation to lymphoid lineages and placed CLEC16A upstream of MEK/PI3K signaling in this context.

    Evidence Inducible KO mouse, mitochondrial potential assays in B/T/NK cells, PI3K/MEK inhibitor rescue, NK cytotoxicity assays

    PMID:30226884

    Open questions at the time
    • Mechanistic link to MEK/PI3K not biochemically defined
    • Single-lab pharmacological epistasis
  9. 2019 Medium

    Connected CLEC16A's HOPS interaction to immune receptor regulation via autophagy in NK cells and DCs.

    Evidence Co-IP of Vps16A, overexpression and siRNA with NK cytotoxicity, IFN-γ, DC maturation and surface-receptor readouts

    PMID:30774629

    Open questions at the time
    • Direct effect of HOPS binding on specific receptors not mapped
    • Single-lab study
  10. 2020 Medium

    Defined CLEC16A's role in the BCR-dependent HLA class II antigen presentation pathway in human B cells.

    Evidence Stable shRNA KD in Raji cells with surface HLA-DR/CD74/CLIP, antigen uptake, and MIIC morphology readouts

    PMID:32641384

    Open questions at the time
    • Biochemical mechanism for CLIP/HLA-DR regulation not established
    • Single-lab study
  11. 2021 Medium

    Identified an ER-stress-to-inflammation axis whereby CLEC16A loss drives lipolysis and JAK-STAT-dependent adipose inflammation.

    Evidence Inducible whole-body KO mouse, ER stress and lipolysis markers, cytokine measures, tofacitinib rescue

    PMID:33795715

    Open questions at the time
    • Whether ER stress is a direct or mitophagy-secondary consequence unclear
    • Single-lab study
  12. 2021 Medium

    Localized CLEC16A to recycling endosomes in T cells and linked it to TCR surface levels.

    Evidence Imaging flow cytometry and confocal localization to Rab4a+ endosomes, siRNA KD with TCR surface readout

    PMID:34643957

    Open questions at the time
    • Functional consequence on T cell activation minimal
    • Mechanism of TCR recycling control undefined
  13. 2022 High

    Mapped CLEC16A to early endosomes with retromer/TRIM27, and demonstrated that a disease-associated C-terminal truncation is loss-of-function for both localization and mitophagy.

    Evidence MS proteomics, Co-IP of retromer/TRIM27, immunofluorescence, zebrafish CRISPR with WT vs truncated rescue

    PMID:36538041

    Open questions at the time
    • Whether TRIM27 is a substrate or regulator of CLEC16A unresolved
    • Integration of early-endosome sorting with mitophagy complex unclear
  14. 2022 High

    Established that a structurally disordered C-terminal region governs CLEC16A stability and mitophagy-complex assembly through proline-biased composition.

    Evidence Carbon-detect NMR confirming disorder, in vivo IDPR-deletion mouse, ubiquitination and mitophagy assays, GTT and insulin secretion

    PMID:35604110

    Open questions at the time
    • How proline bias is sensed by the degradation machinery unknown
    • Structure of assembled complex still undefined
  15. 2023 High

    Identified a second, internal disordered region as the RNF41 docking site controlling CLEC16A turnover and tripartite complex stability.

    Evidence NMR/CD confirming disorder, Co-IP, ubiquitination/degradation assays, internal-IDPR deletion mutants

    PMID:36822331

    Open questions at the time
    • Structural basis of RNF41 recognition of the IDPR not solved
    • Interplay between internal and C-terminal IDPRs not fully integrated
  16. 2024 Medium

    Characterized the CLEC16A intronic locus as an enhancer regulating distal genes and immune signaling, separating regulatory from coding function.

    Evidence CRISPR deletion in T cell lines, RNA-seq, 4C chromatin conformation, TF complex proteomics, RPPA of AKT pathway

    PMID:38191060

    Open questions at the time
    • Causal contribution of ATF7IP2 regulation to disease unproven
    • Coding vs enhancer contributions to phenotype not disentangled
  17. 2025 High

    Mechanistically tied CLEC16A mitophagy to suppression of innate inflammatory signaling in astrocytes and to neuroinflammatory disease.

    Evidence Genome-wide CRISPR screen, astrocyte-specific KO in EAE, multiomics linking mitochondrial damage to NF-κB/NLRP3/gasdermin D, human MS tissue

    PMID:40033124

    Open questions at the time
    • Identity of mitochondrial products activating NF-κB not specified
    • Whether suppression is direct or purely via mitophagy unclear
  18. 2025 Medium

    Defined how a non-coding risk variant tunes CLEC16A expression via histone marks and transcription-factor binding affecting autophagy.

    Evidence Luciferase reporter, ChIP-qPCR for H3K27ac/H3K4me1/CTCF/GATA3/STAT3, CRISPR and dCas9 editing, TF knockdown, autophagy assays

    PMID:39796169

    Open questions at the time
    • Causal phenotype link to autoimmune disease not demonstrated
    • Cell-type specificity of variant effect limited
  19. 2026 Medium

    Identified ATG5 as a degradation target whose CLEC16A-dependent stabilization is required for hematopoietic stem/progenitor emergence.

    Evidence Zebrafish loss-of-function with EHT phenotype, transcriptomics/proteomics, K48-linkage ubiquitination assays, ROS and mitophagy readouts, HEK293T models

    PMID:41719124

    Open questions at the time
    • Whether CLEC16A directly opposes ATG5 ubiquitination or acts indirectly unclear
    • Single-study finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CLEC16A's E3 ligase activity, putative Rab2 GEF function, endosomal sorting roles, and the dual IDPR-regulated stability program are mechanistically unified into one biochemical model remains unresolved.
  • No high-resolution structure of CLEC16A or its tripartite complex
  • Direct ubiquitination substrates not comprehensively defined
  • Reconciliation of mTOR-activating vs autophagy-promoting roles incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005768 endosome 3 GO:0031410 cytoplasmic vesicle 3 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-9612973 Autophagy 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
PDX1RILPRNF41TRIM27USP8VPS16
Complex memberships
CLEC16A-RNF41(Nrdp1)-USP8 mitophagy complexHOPS complex (Vps16A)retromer

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CLEC16A is a membrane-associated endosomal protein that interacts with E3 ubiquitin ligase Nrdp1. Loss of Clec16a leads to an increase in the Nrdp1 target Parkin, a master regulator of mitophagy. Pancreas-specific deletion of Clec16a causes abnormal mitochondria with reduced oxygen consumption and ATP concentration, impairing glucose-stimulated insulin release. Co-immunoprecipitation, conditional knockout mouse, mitochondrial function assays (oxygen consumption, ATP measurement), glucose-stimulated insulin secretion assay Cell High 24949970
2017 CLEC16A encodes an E3 ubiquitin ligase that promotes non-degradative ubiquitin conjugates to direct its mitophagy effectors. CLEC16A forms a tripartite complex with E3 ligase Nrdp1 and deubiquitinase USP8, and ubiquitination is essential for assembly and stability of this complex. Inhibition of CLEC16A by lenalidomide impairs β-cell mitophagy, oxygen consumption, and insulin secretion. Co-immunoprecipitation, ubiquitination assays, in vitro E3 ligase activity assay, siRNA knockdown, lenalidomide treatment in cell lines and patients Diabetes High 29180353
2015 Clec16a regulates autophagy in thymic epithelial cells (TECs). Clec16a knockdown in NOD mice protected against autoimmunity through T cell hyporeactivity, secondary to changes in TEC stimuli driving thymocyte selection, implicating Clec16a's role in TEC autophagy as the mechanism. shRNA knockdown mouse model (NOD), T cell functional assays, diabetes incidence monitoring, autophagy assays in thymic epithelial cells Immunity High 25979422
2015 CLEC16A controls HLA class II expression in antigen-presenting cells via regulation of late endosome biogenesis. CLEC16A knockdown in dendritic cells severely impaired cytoplasmic distribution and formation of HLA class II-positive late endosomes. CLEC16A directly binds RILP and the HOPS complex (by co-immunoprecipitation) and participates in dynein motor complex-dependent trafficking of HLA class II-positive late endosomes to perinuclear regions. siRNA knockdown, co-immunoprecipitation, immunofluorescence, electron microscopy, confocal microscopy Brain : a journal of neurology High 25823473
2015 Pdx1 transcriptionally regulates Clec16a expression by binding its chromatin locus. Loss of Pdx1 reduces Clec16a and Nrdp1 expression, impairs autophagosome-lysosome fusion during mitophagy, and causes mitochondrial dysfunction. Restoration of Clec16a after Pdx1 loss rescues mitochondrial trafficking during mitophagy and improves glucose-stimulated insulin release, positioning Clec16a downstream of Pdx1 in a Pdx1-Clec16a-Nrdp1 mitophagy pathway. Chromatin occupancy analysis (ChIP), expression microarray, siRNA knockdown, Clec16a overexpression rescue, mitochondrial trafficking assays, glucose-stimulated insulin secretion assay Diabetes High 26085571
2016 Clec16a is critical for autolysosome function and clearance. Clec16a-mutant mice develop neurodegeneration with Purkinje cell loss and motor impairment. Clec16a-deficient cells show abnormal bulk autophagy with striking accumulation of LC3 and LAMP-1 positive autolysosomes containing undigested cytoplasmic contents, despite unimpaired autophagosome formation. Endocytosis, lysosome, and Golgi functions were normal, pinpointing the defect specifically to autolysosome clearance. Mouse genetic models (two independent Clec16a mutant strains), immunofluorescence, LC3/LAMP-1 staining, p62 accumulation assay, neurological/motor testing, Golgi morphology analysis Scientific reports High 26987296
2017 CLEC16A resides in cytosolic vesicles and the Golgi. Overexpression of CLEC16A inhibits starvation-induced autophagy by activating the mTOR pathway, causing heightened mTOR activity and diminished LC3 autophagic activity following nutrient deprivation. CLEC16A deficiency delays mTOR activity in response to nutrient sensing, resulting in augmented autophagy. Nutrient removal promotes CLEC16A clustering within the Golgi. siRNA silencing, ectopic overexpression, quantitative proteomics, immunoblotting, mTOR activity assays, LC3 autophagy reporter, confocal microscopy for subcellular localization Experimental cell research Medium 28223137
2017 C. elegans GOP-1 (the CLEC16A ortholog) promotes apoptotic cell degradation by activating the small GTPase UNC-108/Rab2. GOP-1 transiently associates with cell corpse-containing phagosomes, disrupts GDI-UNC-108 complexes, and promotes activation and membrane recruitment of UNC-108/Rab2 in vitro. Loss of gop-1 impairs phagosome maturation through the RAB-5-positive stage, causing defects in phagosome acidification and phagolysosome formation, and also causes defects in endosome and dense core vesicle maturation. C. elegans genetics, in vitro GEF/GDI displacement assay, live imaging, epistasis analysis with unc-108 The Journal of cell biology High 28424218
2018 In Clec16a knockout mice, mitochondrial potential is lowered in splenocyte B, T, and NK cells, resulting in aggregation of unhealthy mitochondria. Disrupted mitophagy in splenic B and T cells is attenuated by PI3K and/or MEK inhibition, placing CLEC16A in a pathway upstream of MEK signaling in mitophagy regulation. NK cells from KO mice show increased cytotoxicity. Inducible knockout mouse, mitochondrial potential assays, flow cytometry, PI3K/MEK inhibitor treatment, NK cell cytotoxicity assays PloS one Medium 30226884
2019 CLEC16A is a cytosolic protein that associates with Vps16A, a subunit of the class C Vps-HOPS complex. CLEC16A overexpression in YTS NK cells reduces NK cell cytotoxicity and IFN-γ release, delays DC maturation, decreases conjugate formation, downregulates cell-surface receptors, and increases autophagy. CLEC16A knockdown has opposite effects and disrupts mitophagy. Subcellular localization studies place CLEC16A at cytosolic vesicles modulating receptor expression via autophagy. Overexpression, siRNA knockdown, Co-immunoprecipitation (Vps16A interaction), NK cytotoxicity assays, flow cytometry, confocal/subcellular localization studies Frontiers in immunology Medium 30774629
2020 CLEC16A participates in the BCR-dependent HLA class II pathway in human B cells. Stable knockdown of CLEC16A in EBV-positive Raji B cells resulted in upregulation of surface HLA-DR and CD74 (invariant chain), reduction of surface CLIP, decreased IgM-mediated antigen uptake, and less clustered MIICs (MHC class II compartments). CLEC16A was coexpressed with surface CLIP in EBV-positive B cell lines. Stable shRNA knockdown, flow cytometry, immunofluorescence, antigen uptake assay, primary B cell expression analysis Journal of immunology Medium 32641384
2021 Loss of CLEC16A triggers ER stress that activates hormone-sensitive lipase (HSL)-mediated lipolysis, contributing to adipose inflammation via activation of JAK-STAT, ERK1/2, P38, and JNK signaling and release of proinflammatory mediators. Treatment with a JAK-STAT inhibitor (tofacitinib) partially rescued the inflammatory lipodystrophic phenotype and improved survival in Clec16a KO mice. Inducible whole-body KO mouse (Clec16aΔUBC), metabolic analysis, cytokine measurements, JAK-STAT inhibitor treatment, ER stress markers, lipolysis assays Scientific reports Medium 33795715
2022 CLEC16A localizes to early endosomes in HEK293T cells and interacts with retromer complex subunits and the endosomal E3 ubiquitin ligase TRIM27 (identified by mass spectrometry). CLEC16A knockdown increased TRIM27 adhesion to early endosomes and abnormal accumulation of endosomal F-actin, indicating disrupted vesicle sorting. A disease-associated C-terminal truncation of CLEC16A abolishes both its endosomal localization and interaction with TRIM27. In zebrafish, clec16a CRISPR mutagenesis caused accumulated acidic/phagolysosome compartments and dysregulated mitophagy, rescued by wild-type but not truncated human CLEC16A. Mass spectrometry proteomics, Co-immunoprecipitation, immunofluorescence, CRISPR-Cas9 zebrafish mutagenesis, rescue experiments with WT vs. truncated CLEC16A Human genetics High 36538041
2022 A C-terminal intrinsically disordered protein region (IDPR) of CLEC16A, confirmed by carbon-detect NMR to lack secondary structure, is critical for mitochondrial quality control. Loss of the C-terminal IDPR increases CLEC16A ubiquitination and degradation, impairs assembly of the mitophagy regulatory machinery, and causes impaired mitophagy, mitochondrial dysfunction, glucose-stimulated insulin secretion defects, and glucose intolerance in vivo. Proline bias within the IDPR (not sequence order or charge) determines CLEC16A stability. Carbon-detect NMR (structural validation of IDPR), in vivo mouse models with IDPR deletion, ubiquitination assays, mitophagy assays, metabolic tests (GTT), insulin secretion assays, mutagenesis Autophagy High 35604110
2023 CLEC16A contains an internal intrinsically disordered protein region (IDPR), confirmed by NMR and CD spectroscopy. This internal IDPR is crucial for CLEC16A degradation and turnover: RNF41 binds and acts upon the internal IDPR to destabilize CLEC16A. Loss of the internal IDPR also destabilizes the ubiquitin-dependent tripartite CLEC16A-RNF41-USP8 mitophagy complex. NMR spectroscopy, CD spectroscopy, Co-immunoprecipitation, ubiquitination/degradation assays, IDPR deletion mutants The Journal of biological chemistry High 36822331
2021 CLEC16A expression in T cells is located in Rab4a-positive recycling endosomes (demonstrated by imaging flow cytometry and confocal microscopy). CLEC16A knockdown in Jurkat cells lowered cell-surface expression of the T cell receptor, though this did not significantly impact T cell activation in vitro. Imaging flow cytometry, confocal microscopy, siRNA knockdown, flow cytometry for TCR surface expression Scandinavian journal of immunology Medium 34643957
2025 In astrocytes, CLEC16A promotes mitophagy and suppresses NF-κB signaling. CLEC16A deficiency leads to mitochondrial dysfunction and accumulation of mitochondrial products that activate NF-κB, the NLRP3 inflammasome, and gasdermin D. Astrocyte-specific Clec16a inactivation worsened experimental autoimmune encephalomyelitis in mice, and disrupted mitophagic capacity and gasdermin D activation were detected in astrocytes from MS patient samples. Genome-wide CRISPR forward genetic screen, astrocyte-specific conditional KO mouse (EAE model), small-molecule perturbation, multiomic analyses, human MS tissue analysis Nature neuroscience High 40033124
2026 Clec16a (E3 ubiquitin ligase) is enriched in hemogenic endothelium and regulates embryonic hematopoietic stem and progenitor cell (HSPC) emergence via mitophagy. Clec16a deficiency promotes aberrant K48-linked ubiquitination and proteasomal degradation of ATG5, leading to impaired mitophagy, mitochondrial dysfunction, elevated reactive oxygen species, disrupted arterial identity, and impaired endothelial-to-hematopoietic transition (EHT) in zebrafish. Zebrafish loss-of-function, transcriptomic and proteomic analyses, ubiquitination assays (K48-linkage specific), mitophagy assays, ROS measurements, HEK293T cell models Cell reports Medium 41719124
2024 The CLEC16A intronic locus (intron 19) functions as an enhancer regulating multiple target genes including the distant gene ATF7IP2 through chromatin interactions. Distinct transcription factor complexes mediate allele-specific chromatin interactions. Disruption of this locus affects the AKT signaling pathway and molecular response of CD4+ T cells to immune stimulation. CRISPR-Cas9 deletion of candidate SNP in T cell lines, RNA-sequencing, circular chromosome conformation capture (4C), proteomics of transcription factor complexes, reverse phase protein array The Journal of allergy and clinical immunology Medium 38191060
2025 The non-coding intronic variant rs17673553 in CLEC16A acts as an enhancer; the risk allele increases binding of H3K27ac and H3K4me1 histone marks, CTCF, GATA3, and STAT3. Knockdown of GATA3 and STAT3 decreases CLEC16A expression. CRISPR KO of CLEC16A reduces starvation-induced autophagy compared to wild-type cells. Luciferase reporter assay, ChIP-qPCR, CRISPR genome editing, CRISPR-dCas9 epigenetic activation/silencing, siRNA knockdown of transcription factors, autophagy assays International journal of molecular sciences Medium 39796169

Source papers

Stage 0 corpus · 55 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 422 17632545
2014 The diabetes susceptibility gene Clec16a regulates mitophagy. Cell 177 24949970
2008 Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes and immunity 106 18650830
2008 Polymorphisms in CLEC16A and CIITA at 16p13 are associated with primary adrenal insufficiency. The Journal of clinical endocrinology and metabolism 94 18593762
2015 The Autoimmunity-Associated Gene CLEC16A Modulates Thymic Epithelial Cell Autophagy and Alters T Cell Selection. Immunity 89 25979422
2020 Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways. Cell death & disease 73 32312970
2015 Diabetes Susceptibility Genes Pdx1 and Clec16a Function in a Pathway Regulating Mitophagy in β-Cells. Diabetes 71 26085571
2012 Association of primary biliary cirrhosis with variants in the CLEC16A, SOCS1, SPIB and SIAE immunomodulatory genes. Genes and immunity 68 22257840
2008 Variation within the CLEC16A gene shows consistent disease association with both multiple sclerosis and type 1 diabetes in Sardinia. Genes and immunity 65 18946483
2017 Clec16a, Nrdp1, and USP8 Form a Ubiquitin-Dependent Tripartite Complex That Regulates β-Cell Mitophagy. Diabetes 60 29180353
2015 Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells. Nature communications 56 25891430
2016 Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency. Nature genetics 55 27723758
2015 Multiple sclerosis-associated CLEC16A controls HLA class II expression via late endosome biogenesis. Brain : a journal of neurology 46 25823473
2009 Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15(-) Crohn's disease patients. European journal of human genetics : EJHG 44 19337309
2011 Interrogating the complex role of chromosome 16p13.13 in multiple sclerosis susceptibility: independent genetic signals in the CIITA-CLEC16A-SOCS1 gene complex. Human molecular genetics 43 21653641
2013 From Identification to Characterization of the Multiple Sclerosis Susceptibility Gene CLEC16A. International journal of molecular sciences 37 23439554
2010 Exploring the CLEC16A gene reveals a MS-associated variant with correlation to the relative expression of CLEC16A isoforms in thymus. Genes and immunity 35 21179112
2012 Multiple sclerosis-associated single-nucleotide polymorphisms in CLEC16A correlate with reduced SOCS1 and DEXI expression in the thymus. Genes and immunity 33 23151489
2016 Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival. Scientific reports 30 26987296
2017 Human CLEC16A regulates autophagy through modulating mTOR activity. Experimental cell research 29 28223137
2023 CLEC16A-An Emerging Master Regulator of Autoimmunity and Neurodegeneration. International journal of molecular sciences 24 37175930
2018 CLEC16A regulates splenocyte and NK cell function in part through MEK signaling. PloS one 20 30226884
2011 Involvement of CLEC16A in activation of astrocytes after LPS treated. Neurochemical research 20 22002632
2010 More CLEC16A gene variants associated with multiple sclerosis. Acta neurologica Scandinavica 20 20849399
2020 The Role of Autoimmunity-Related Gene CLEC16A in the B Cell Receptor-Mediated HLA Class II Pathway. Journal of immunology (Baltimore, Md. : 1950) 17 32641384
2017 GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in C. elegans. The Journal of cell biology 17 28424218
2008 Intron polymorphism in the KIAA0350 gene is reproducibly associated with susceptibility to type 1 diabetes (T1D) in the Han Chinese population. Clinical endocrinology 17 19178520
2025 CLEC16A in astrocytes promotes mitophagy and limits pathology in a multiple sclerosis mouse model. Nature neuroscience 16 40033124
2019 The Autoimmune Disorder Susceptibility Gene CLEC16A Restrains NK Cell Function in YTS NK Cell Line and Clec16a Knockout Mice. Frontiers in immunology 16 30774629
2015 Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells. PloS one 16 26203907
2022 CLEC16A interacts with retromer and TRIM27, and its loss impairs endosomal trafficking and neurodevelopment. Human genetics 14 36538041
2012 Polymorphisms in the inflammatory genes CIITA, CLEC16A and IFNG influence BMD, bone loss and fracture in elderly women. PloS one 14 23133532
2021 JAK/STAT inhibitor therapy partially rescues the lipodystrophic autoimmune phenotype in Clec16a KO mice. Scientific reports 12 33795715
2015 Systemic Lupus Erythematosus Patients Exhibit Reduced Expression of CLEC16A Isoforms in Peripheral Leukocytes. International journal of molecular sciences 11 26121298
2022 Autoimmune Disease Associated CLEC16A Variants Convey Risk of Parkinson's Disease in Han Chinese. Frontiers in genetics 10 35432448
2021 Inducible knockout of Clec16a in mice results in sensory neurodegeneration. Scientific reports 10 33927318
2019 Variants in the BACH2 and CLEC16A gene might be associated with susceptibility to insulin-triggered type 1 diabetes. Journal of diabetes investigation 10 30970177
2014 Polymorphisms of CLEC16A region and autoimmune thyroid diseases. G3 (Bethesda, Md.) 10 24646814
2022 An intrinsically disordered protein region encoded by the human disease gene CLEC16A regulates mitophagy. Autophagy 9 35604110
2021 Exploring the role of the multiple sclerosis susceptibility gene CLEC16A in T cells. Scandinavian journal of immunology 9 34643957
2019 Clarifying the function of genes at the chromosome 16p13 locus in type 1 diabetes: CLEC16A and DEXI. Genes and immunity 9 31570815
2012 The Correlation between the CLEC16A Gene and Genetic Susceptibility to Type 1 Diabetes in Chinese Children. International journal of endocrinology 7 22778732
2015 A variant of CLEC16A gene confers protection for Vogt-Koyanagi-Harada syndrome but not for Behcet's disease in a Chinese Han population. Experimental eye research 5 25576669
2023 Reciprocal regulatory balance within the CLEC16A-RNF41 mitophagy complex depends on an intrinsically disordered protein region. The Journal of biological chemistry 4 36822331
2009 Autoimmune disease association signals in CIITA and KIAA0350 are not involved in celiac disease susceptibility. Tissue antigens 4 19317741
2025 Defining Mechanistic Links Between the Non-Coding Variant rs17673553 in CLEC16A and Lupus Susceptibility. International journal of molecular sciences 3 39796169
2024 Target genes regulated by CLEC16A intronic region associated with common variable immunodeficiency. The Journal of allergy and clinical immunology 3 38191060
2024 Prevalence of Selected Polymorphisms of Il7R, CD226, CAPSL, and CLEC16A Genes in Children and Adolescents with Autoimmune Thyroid Diseases. International journal of molecular sciences 3 38612837
2010 A candidate gene study of CLEC16A does not provide evidence of association with risk for anti-CCP-positive rheumatoid arthritis. Genes and immunity 3 20220768
2017 GOP-1: Helping phagosomes pass the acid test. The Journal of cell biology 1 28539387
2014 Association of the C-type lectin-like domain family-16A (CLEC16A) gene polymorphisms with acute coronary syndrome in Mexican patients. Immunology letters 1 25447402
2026 Single-cell multi-omic analyses highlight the essential role of NKX2.2-CLEC16A/endosomal pathway for human pancreatic differentiation and function. Cell reports 0 41689803
2026 Clec16a maintains definitive hematopoietic stem and progenitor cells via mitophagy. Cell reports 0 41719124
2026 The Role of CD44, CALCOCO2, ALDH4A1, and CLEC16A in the Cross-Talk Model of Epilepsy and Thyroid Cancer Progression. Molecular carcinogenesis 0 41950359
2024 [Durable remission of T-cell prolymphocytic leukemia with CLEC16A::IL2 after allogeneic hematopoietic stem cell transplantation]. [Rinsho ketsueki] The Japanese journal of clinical hematology 0 38311387

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