Affinage

GPNMB

Transmembrane glycoprotein NMB · UniProt Q14956

Round 2 corrected
Length
572 aa
Mass
63.9 kDa
Annotated
2026-04-28
130 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPNMB is a heavily glycosylated type I transmembrane protein that functions as a multifunctional regulator of inflammation, melanosome biogenesis, lysosomal activity, and tissue repair, with context-dependent roles in cancer progression and neurodegeneration. Transcriptionally controlled by MITF and related MiT/TFE family members downstream of mTORC1 and PI3K/Akt signaling (PMID:18313864, PMID:24789918, PMID:25889792, PMID:31043488), GPNMB undergoes ADAM10-mediated ectodomain shedding regulated by PKC/Ca²⁺ to generate a soluble form that signals through CD44 (suppressing inflammation in macrophages and astrocytes and activating mesenchymal stromal cells), integrin α5β1/αVβ1 (driving Src/FAK-dependent cancer metastasis via its RGD motif), GPR39 (mediating cardiac repair after myocardial infarction), and glycosylation-dependent binding to mutant EGFR (activating STAT3 in NSCLC) (PMID:20711474, PMID:29519253, PMID:25772243, PMID:39455836, PMID:33706413). Intracellularly, GPNMB is essential for melanosome formation, promotes microglial phagocytosis by wrapping engulfed particles and delivering them to lysosomes through direct interaction with ATP6V1A, mediates α-synuclein fibril internalization in neurons, and relocates to the nucleus under ER stress to enhance BiP pre-mRNA splicing independently of canonical UPR transducers (PMID:22912767, PMID:39992792, PMID:35981040, PMID:28939899). Loss-of-function mutations in GPNMB cause autosomal-recessive amyloidosis cutis dyschromica in humans, characterized by dermal amyloid deposits, melanocyte loss, and macrophage infiltration (PMID:29336782).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 Medium

    The initial identification of GPNMB as a transmembrane glycoprotein enriched in low-metastatic melanoma cells, whose partial overexpression reduced metastatic potential, established the gene as a candidate suppressor of melanoma aggressiveness and linked it to pigmentation biology.

    Evidence Subtractive cDNA library from melanoma cell lines with in vivo xenograft validation

    PMID:7814155

    Open questions at the time
    • Mechanism of metastasis suppression unknown
    • Partial cDNA used; full-length function not tested
    • Single xenograft model
  2. 2007 High

    Demonstration that GPNMB negatively regulates macrophage inflammatory responses — translocating from Golgi to peripheral vesicles upon activation — and that its natural loss-of-function (DBA/2J mice) elevates proinflammatory cytokines, established GPNMB as an intrinsic brake on innate immune activation.

    Evidence Overexpression in RAW264.7 macrophages, Golgi co-localization imaging, cytokine ELISA, DBA/2J Gpnmb-mutant mouse

    PMID:17475886

    Open questions at the time
    • Receptor mediating anti-inflammatory effect not yet identified
    • Mechanism of vesicular translocation not resolved
  3. 2008 High

    Identification of MITF as the direct transcriptional regulator of GPNMB — binding a conserved M-box in the promoter and an enhancer element active in melanoblasts — placed GPNMB within the MiT/TFE transcriptional network governing melanocyte and osteoclast differentiation.

    Evidence EMSA, promoter mutagenesis/reporter assay, transgenic enhancer analysis, Mitf-mutant mice

    PMID:18313864 PMID:18983539

    Open questions at the time
    • Whether additional MiT family members (TFE3/TFEB) regulate GPNMB in non-melanocyte contexts was unknown
    • Upstream signals controlling MITF occupancy at the GPNMB locus not resolved
  4. 2010 High

    Identification of ADAM10 as the sheddase releasing GPNMB's bioactive ectodomain, regulated by PKC/Ca²⁺ signaling, and the finding that GPNMB on tumor cells inhibits T cell activation via syndecan-4, established two key functional modes: paracrine signaling through ectodomain shedding and immune checkpoint activity on cancer cells.

    Evidence siRNA screen of sheddases in breast cancer cells; GPNMB knockdown in B16F10 melanoma with in vivo growth in immunocompetent vs. immunodeficient mice; syndecan-4 blocking

    PMID:20056711 PMID:20570888 PMID:20711474

    Open questions at the time
    • Whether ADAM10 is the sole sheddase in all cell types not established
    • Structural basis of syndecan-4 interaction unknown
  5. 2012 High

    Demonstrating that GPNMB silencing sharply reduced melanosome number and melanosomal protein expression (tyrosinase, Trp1, Pmel17) in an MITF-independent manner revealed a direct structural or regulatory role for GPNMB in organelle biogenesis beyond transcriptional control.

    Evidence siRNA knockdown in melanocytes, transmission electron microscopy for melanosome counting, Western blotting

    PMID:22912767

    Open questions at the time
    • Mechanism by which GPNMB maintains melanosomal proteins is not defined
    • Whether GPNMB acts in melanosome maturation vs. biogenesis not distinguished
  6. 2014 High

    Placing GPNMB downstream of mTORC1 inhibition → MITF nuclear translocation in macrophages during lysosomal stress connected GPNMB induction to the cellular stress-sensing apparatus and explained its upregulation in obese adipose tissue macrophages.

    Evidence shRNA MITF knockdown, mTORC1 inhibition with Torin1/palmitate, nuclear MITF imaging, in vivo obese mouse adipose tissue macrophage isolation

    PMID:24789918

    Open questions at the time
    • Whether mTORC1-independent signals also regulate GPNMB in macrophages not resolved
    • Direct lysosomal stress sensor upstream of mTORC1 not identified
  7. 2015 High

    Structure–function dissection showed that GPNMB's RGD motif mediates integrin α5β1 binding to activate Src/FAK signaling for lung metastasis, while both RGD and the cytoplasmic tail are required for primary tumor growth; separately, PI3K/Akt inhibition→GSK3β→MITF was identified as an alternative pathway activating GPNMB transcription in dendritic cells.

    Evidence RGD motif mutagenesis, Co-IP of integrin complex, Src/FAK signaling assays, in vivo metastasis model; pharmacological epistasis in dendritic cells

    PMID:25772243 PMID:25889792

    Open questions at the time
    • Whether integrin binding and syndecan-4 binding are independent or cooperative not resolved
    • Role of cytoplasmic tail hemITAM in integrin-mediated signaling not dissected
  8. 2017 Medium

    Discovery that GPNMB relocates to the nucleus during ER stress to promote BiP pre-mRNA splicing — independently of IRE1, PERK, and ATF6 — revealed an unexpected non-canonical function as a nuclear RNA-processing factor in the stress response.

    Evidence Thapsigargin-induced ER stress, nuclear fractionation, mRNA splicing analysis, pathway inhibitor exclusion, GPNMB transgenic mouse MCAO model

    PMID:28939899

    Open questions at the time
    • Mechanism of nuclear import unknown
    • RNA-binding or spliceosome interaction partners not identified
    • Not independently replicated
  9. 2018 High

    Genetic proof from CD44-knockout astrocytes that GPNMB's anti-inflammatory signaling requires CD44, and human genetic evidence that GPNMB loss-of-function truncating mutations cause autosomal-recessive amyloidosis cutis dyschromica, together validated CD44 as a bona fide GPNMB receptor and established GPNMB's non-redundant physiological role in skin homeostasis.

    Evidence CD44-KO primary astrocyte assays with recombinant GPNMB; six independent GPNMB truncating alleles in nine ACD patients with histopathological characterization

    PMID:29336782 PMID:29519253

    Open questions at the time
    • Whether CD44 mediates GPNMB signaling in all anti-inflammatory contexts not established
    • Molecular link between GPNMB loss and amyloid deposition not mechanistically defined
  10. 2019 High

    Identification of TFE3 fusion oncoproteins as direct transcriptional activators of GPNMB (paralleling MITF), and demonstration that the kringle-like domain (KLD) in the ectodomain is essential for tumorigenic sphere formation, refined both the transcriptional regulation and the domain architecture required for GPNMB's oncogenic functions.

    Evidence PRCC-TFE3 transgenic mouse, CRISPR TSC2/TFE3/TFEB KO cell lines; KLD deletion mutagenesis with sphere/tumor assays

    PMID:31043488 PMID:31127873

    Open questions at the time
    • KLD binding partner not identified
    • Whether TFE3 and MITF bind the same or distinct GPNMB regulatory elements not resolved
  11. 2021 High

    Convergent genetic approaches (siRNA, CRISPR KO, QTL mapping, congenic strains) established GPNMB as a causal modifier of macrophage lysosome function and the gene underlying the Mlfm1 QTL, directly linking GPNMB to lysosomal competence beyond transcriptional correlation.

    Evidence AKR/J×DBA/2J intercross QTL, CRISPR Gpnmb KO in RAW264.7, siRNA, DBA/2J-Gpnmb+/SjJ congenic comparison

    PMID:33986446

    Open questions at the time
    • Molecular mechanism by which GPNMB enhances lysosome function not identified at this stage
    • Whether GPNMB acts on lysosome biogenesis vs. acidification vs. substrate delivery unclear
  12. 2022 High

    Co-immunoprecipitation of GPNMB with α-synuclein and the finding that GPNMB loss in iPSC-derived neurons abolishes α-synuclein fibril internalization established GPNMB as a receptor/co-receptor for pathological α-synuclein uptake, directly implicating it in Parkinson's disease pathogenesis.

    Evidence Co-IP, co-localization, iPSC-derived neuron GPNMB loss-of-function, α-synuclein fibril internalization assay

    PMID:35981040

    Open questions at the time
    • Whether GPNMB-mediated fibril internalization is protective or pathogenic in vivo not resolved
    • Co-receptor or downstream signaling upon fibril binding not identified
  13. 2024 High

    Identification of GPR39 as a receptor for circulating GPNMB — with GPR39 knockout negating GPNMB's cardioprotective effects after myocardial infarction — added a new receptor-signaling axis and demonstrated that bone-marrow-derived macrophages are the primary source of GPNMB in injured hearts.

    Evidence Lineage tracing, bone-marrow transplantation, GPNMB KO, viral GPNMB delivery, GPR39 KO mice, single-cell transcriptomics

    PMID:39455836

    Open questions at the time
    • GPR39 downstream signaling pathway in cardiomyocytes not fully characterized
    • Whether GPR39 mediates GPNMB signaling in non-cardiac tissues not known
  14. 2025 High

    The discovery that GPNMB wraps phagocytosed particles and delivers them to lysosomes via direct interaction with the V-ATPase subunit ATP6V1A — with ATP6V1A activation rescuing GPNMB-deficiency phenotypes — provided the first mechanistic link between GPNMB's lysosomal and phagocytic functions.

    Evidence Co-IP of GPNMB–ATP6V1A, GPNMB genetic ablation, multi-substrate phagocytosis assays, ATP6V1A activation rescue, in vivo seizure model

    PMID:39992792

    Open questions at the time
    • Structural basis of GPNMB–ATP6V1A interaction not resolved
    • Whether this mechanism operates in non-microglial phagocytes not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how GPNMB's multiple receptor interactions (CD44, integrins, GPR39, EGFR, syndecan-4) are coordinated across tissues; the structural basis and functional consequences of GPNMB's nuclear translocation and RNA-splicing activity; and whether GPNMB-mediated α-synuclein fibril internalization is net protective or pathogenic in neurodegeneration in vivo.
  • No structural model of full-length GPNMB or its receptor complexes
  • In vivo consequence of GPNMB-mediated α-synuclein uptake for disease progression unknown
  • Nuclear RNA-processing mechanism not independently replicated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 4 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005576 extracellular region 5 GO:0005886 plasma membrane 4 GO:0005764 lysosome 3 GO:0005794 Golgi apparatus 2 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-9612973 Autophagy 2
Partners
ADAM10ATP6V1ACD44GPR39ITGA5MITFSNCA

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 GPNMB (nmb) was originally identified as a novel gene encoding a putative transmembrane glycoprotein with homology to the pMEL17 melanocyte-specific protein precursor, preferentially expressed in low-metastatic human melanoma cell lines; transfection of partial nmb cDNA into highly metastatic melanoma cells reduced subcutaneous tumor growth and metastatic potential in nude mice. Subtractive cDNA library, transfection/overexpression in vivo xenograft model International journal of cancer Medium 7814155
2007 GPNMB (Osteoactivin) acts as a negative regulator of macrophage inflammatory responses: overexpression in RAW264.7 cells reduced LPS-induced IL-6, IL-12p40, and NO production; upon IFN-γ/LPS activation, GPNMB translocated from the Golgi apparatus (where it co-localized with coat protein beta) to peripheral vesicular compartments; DBA mice with an inactivating Gpnmb point mutation exhibited elevated proinflammatory cytokines in response to LPS. Epitope-tagged overexpression, co-localization imaging (Golgi marker), cytokine ELISA, DBA mutant mouse model Journal of immunology High 17475886
2007 Osteoactivin/GPNMB promotes breast cancer bone metastasis; sustained GPNMB expression is required for invasion, and GPNMB overexpression elevates matrix metalloproteinase-3 (MMP-3) levels, while siRNA depletion of GPNMB reduces MMP-3 expression, identifying MMP-3 as a downstream mediator. siRNA knockdown, forced overexpression, in vivo bone metastasis model (4T1 mammary carcinoma), gene expression profiling Molecular cancer research : MCR High 17951401
2008 GPNMB expression is directly transcriptionally regulated by microphthalmia transcription factor (MITF) via a conserved M-box binding site in the GPNMB promoter; EMSA identified MITF binding to this site, mutation abolished binding and transactivation, and kinetics of GPNMB induction during osteoclastogenesis paralleled known MITF targets acp5 and clcn7; GPNMB co-localized with lysosomal/endocytic marker MAC-3/LAMP-2 in mature macrophages. EMSA, reporter gene assay with promoter mutation, microarray expression profiling, immunofluorescence co-localization Gene High 18313864
2008 Gpnmb is a MITF-dependent melanoblast-expressed gene; a conserved enhancer element (GPNMB-MCS3) containing two MITF consensus sites drives expression in melanoblasts in vivo, and deletion of the 5'-most MITF site dramatically reduces enhancer activity. Whole-genome MITF binding site annotation, luciferase reporter assay, transgenic in vivo enhancer analysis, Mitf mutant mouse expression studies Pigment cell & melanoma research High 18983539
2010 ADAM10 is the sheddase responsible for proteolytic release of the GPNMB ectodomain (ECD) from breast cancer cell surfaces; siRNA-mediated knockdown of ADAM10 specifically blocked GPNMB ECD shedding, and the shed ECD promoted endothelial cell migration in vitro, identifying ectodomain shedding as a mechanism by which GPNMB promotes angiogenesis. Transient siRNA knockdown of candidate sheddases, immunoblot, ELISA, endothelial migration assay PloS one High 20711474
2010 GPNMB (DC-HIL) expressed on melanoma cells inhibits activation of melanoma-reactive T cells by binding syndecan-4 (SD-4) on activated T cells; siRNA knockdown of GPNMB in B16F10 melanoma markedly reduced in vivo tumor growth in immunocompetent but not immunodeficient mice, and DC-HIL-knocked-down cells showed augmented capacity to activate melanoma-reactive T cells; blocking SD-4 enhanced CD8+ T cell reactivity to melanoma antigens. siRNA knockdown, in vivo tumor growth in immunocompetent vs. immunodeficient mice, T cell activation assays, SD-4 blocking experiments Cancer research High 20570888
2010 GPNMB is a melanosomal protein enriched in mature (stage III-IV) melanosomes; it is released as a secreted form by ectodomain shedding from the largely Golgi-modified form, and the PKC and Ca2+ intracellular signaling pathways regulate GPNMB shedding. Subcellular fractionation, immunofluorescence, kinase inhibitor/signaling pathway pharmacology, ELISA for shed form FASEB journal High 20056711
2012 GPNMB silencing by siRNA sharply reduced the total number of melanosomes in melanocytes and attenuated expression of melanosomal proteins tyrosinase, Trp1, Pmel17/gp100, and OA1, demonstrating that GPNMB is critical for melanosome formation; this effect was MITF-independent. UVB radiation upregulated GPNMB expression in melanocytes. siRNA knockdown, transmission electron microscopy (melanosome counting), Western blotting, qPCR, immunofluorescence PloS one High 22912767
2012 GPNMB glycosylation is inhibited by interaction with mutant SOD1(G93A) in motor neurons, increasing their vulnerability; extracellular fragments of GPNMB secreted from activated astrocytes attenuate neurotoxicity of SOD1(G93A) in neural cells, indicating a neuroprotective paracrine role for secreted GPNMB. Co-expression studies in NSC34 cells, glycosylation assays, recombinant GPNMB treatment, neurotoxicity assays Scientific reports Medium 22891158
2013 ET-1 (endothelin-1) triggers melanogenesis via the MITF-regulated GPNMB pathway: ET-1 increases MITF and GPNMB expression; siRNA knockdown of GPNMB reduces total melanosomes and melanin synthesis; siRNA knockdown of MITF suppresses GPNMB expression and ET-1-induced pigmentation, establishing GPNMB downstream of MITF in the ET-1 signaling axis. siRNA knockdown of GPNMB and MITF, melanin quantification, melanosome counting, Western blotting BMB reports Medium 23884103
2013 GPNMB stimulates osteogenesis and angiogenesis via FGFR-1 signaling: recombinant GPNMB dose-dependently induced osteoblast differentiation (ALP, OCN expression) from human bone marrow stromal cells and promoted endothelial proliferation, migration, and tube formation; pretreatment with FGFR-1 siRNA or inhibitor SU5402 abolished these effects; in a rodent cranial defect model, GPNMB-delivering scaffolds increased bone and vessel formation, reversed by combined SU5402. Recombinant protein treatment, siRNA knockdown of FGFR-1, FGFR-1 inhibitor, in vitro differentiation assays, in vivo cranial defect model Journal of cellular biochemistry High 23794283
2014 In obese adipose tissue macrophages, lysosomal stress (induced by palmitate, chloroquine, or mTORC1 inhibitor Torin1) causes MITF nuclear translocation, which is absolutely required for GPNMB induction; shRNA knockdown of MITF abolished Gpnmb upregulation; in vivo, reduced mTORC1 activity in obese mouse adipose tissue macrophages coincided with increased nuclear MITF and elevated Gpnmb transcription, placing GPNMB downstream of mTORC1-MITF in lysosomal stress response. shRNA knockdown of MITF, mTORC1 inhibition, nuclear MITF localization imaging, gene expression in isolated ATMs Diabetes High 24789918
2014 GPNMB in LPS-activated microglia upregulates MMP-3 expression, which in turn promotes production of proinflammatory mediators (TNF-α, IL-1β, iNOS, NO); siRNA knockdown of GPNMB or MMP-3 inhibitor treatment suppressed these inflammatory mediators, establishing a GPNMB→MMP-3 axis in microglial inflammation. siRNA knockdown, MMP-3 inhibitor, ELISA for cytokines, RT-PCR and Western blotting Journal of molecular neuroscience : MN Medium 24682924
2014 GPNMB neuroprotection in cerebral ischemia-reperfusion injury is associated with phosphorylation of ERK1/2 and Akt; GPNMB transgenic mice showed reduced infarct volume and increased p-ERK1/2 and p-Akt by Western blotting; recombinant GPNMB (extracellular sequence) also decreased infarction volume, indicating the neuroprotective effect is mediated by the extracellular domain. GPNMB transgenic mouse model, middle cerebral artery occlusion, Western blotting for p-ERK1/2/p-Akt, recombinant GPNMB treatment Neuroscience Medium 25010402
2015 GPNMB cooperates with neuropilin-1 (NRP-1) to promote breast cancer tumor growth: GPNMB overexpression increases NRP-1 expression, potentiating VEGF signaling; NRP-1 is required for GPNMB-driven tumor growth but not metastasis. Additionally, GPNMB binds α5β1 integrin through its RGD motif, and this interaction activates Src and FAK signaling; RGD motif mutation impairs lung metastasis formation whereas both RGD motif and cytoplasmic tail are required for primary tumor growth. Forced overexpression, RNAseq, RGD motif mutagenesis, Co-IP/integrin complex pulldown, Src/FAK signaling assays, in vivo mammary tumor and metastasis models Oncogene High 25772243
2015 GPNMB transcription in dendritic cells is regulated by MITF downstream of PI3K/Akt inhibition: IL-10 and BCR-ABL TKIs (imatinib, nilotinib) inhibit PI3K/Akt, activating GSK3β, which leads to MITF phosphorylation and nuclear translocation; a MITF activity inhibitor reduced GPNMB mRNA and protein; PI3K/Akt inhibition-induced GPNMB overexpression reduced moDC stimulatory capacity in MLRs, rescued by adding the GPNMB T cell ligand syndecan-4. Small molecule inhibitors, MITF inhibitor, mRNA/protein quantification, mixed lymphocyte reaction Cell communication and signaling : CCS Medium 25889792
2015 Soluble Gpnmb ameliorated fat accumulation and fibrosis in obese liver in transgenic mice; Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in reduction of oxidative stress. Gpnmb transgenic mouse model (aP2 promoter), co-localization/interaction studies, oxidative stress assays Scientific reports Medium 26581806
2016 Recombinant GPNMB promotes MSC survival, proliferation, and migration via CD44 receptor, activating downstream ERK and AKT signaling pathways; loss-of-function and rescue studies demonstrated that M2 macrophage-secreted GPNMB mediates these MSC responses via CD44. Recombinant GPNMB treatment, loss-of-function (siRNA/antibody blocking), rescue studies, Western blotting for ERK/AKT phosphorylation Journal of cellular biochemistry Medium 26442636
2016 GPNMB promotes brain glioblastoma progression via interaction with Na+/K+-ATPase α subunits, activating PI3K/Akt and MEK/ERK pathways; the interaction was identified in murine glioma models and human GBM tumors; ouabain (Na+/K+-ATPase inhibitor) suppressed GPNMB-driven glioma growth and blocked GPNMB-induced glioma cell migration. Co-immunoprecipitation, transgenic GPNMB overexpression mouse glioma model, pharmacological inhibition with ouabain, migration assays Biochemical and biophysical research communications Medium 27836549
2016 Recombinant GPNMB ameliorates motor neuron cell death induced by mutant TDP-43 (M337V, A315T) and serum-free stress via activation of ERK1/2 and Akt pathways; phosphorylated ERK1/2 and Akt were decreased by stress and rescued by recombinant GPNMB treatment in NSC34 motor neuron cells; GPNMB aggregates co-localize with TDP-43 aggregates in MAP-2-positive neurons in ALS spinal cord. Mutant TDP-43 plasmid transfection, recombinant GPNMB treatment, Western blotting for p-ERK1/2/p-Akt, immunohistochemistry co-localization in ALS patient tissue Journal of neuroscience research Medium 27935101
2016 GPNMB silencing via siRNA inhibits proliferation and metastasis of osteosarcoma cells (MG63, U2OS) by suppressing PI3K/Akt/mTOR signaling; IGF-1 (PI3K/AKT activator) reversed the suppressive effects, placing GPNMB upstream of PI3K/Akt/mTOR. siRNA knockdown, IGF-1 rescue, MTT proliferation and Transwell invasion assays, Western blotting for PI3K/Akt/mTOR pathway Oncology reports Medium 29620278
2016 BRAF and MEK inhibitor treatment of melanoma cells induces GPNMB expression via MITF in a MITF-dependent manner (siRNA knockdown of MITF blocked treatment-induced GPNMB upregulation); GPNMB is expressed at the cell surface in MAPK inhibitor-treated cells and elevated in on-treatment biopsies from patients; combining MAPK inhibitors with CDX-011 (anti-GPNMB ADC) is more effective than MAPK inhibition alone in preclinical models. siRNA knockdown of MITF, RT-qPCR, immunoblot, FACS, serial patient biopsies, in vivo tumor models Clinical cancer research High 27515299
2017 GPNMB expression in dendritic cells is regulated by a Takayasu arteritis risk locus (rs2069837) in IL6 through long-range chromatin looping (~520 kb); the risk allele preferentially recruits MEF2-HDAC repressive complex, suppressing GPNMB expression in monocyte-derived macrophages; HDAC inhibition reversed this suppression. EMSA, DNA affinity precipitation + mass spectrometry, luciferase reporter assay, chromosome conformation capture (3C), HDAC inhibitor treatment in primary macrophages Annals of the rheumatic diseases High 31315839
2017 GPNMB induces BiP expression during ER stress by promoting splicing of BiP pre-mRNA; under ER stress, GPNMB relocates to the nucleus and specifically upregulates BiP mRNA through pre-mRNA splicing, acting independently of the three major ER stress transducers (IRE1, PERK, ATF6); GPNMB transgenic mice showed elevated BiP and reduced infarction after MCAO. Thapsigargin-induced ER stress, subcellular fractionation/nuclear localization imaging, mRNA splicing analysis, IRE1/PERK/ATF6 pathway inhibition, GPNMB transgenic mouse MCAO model Scientific reports Medium 28939899
2017 Gpnmb promotes M2 macrophage polarization: siRNA knockdown of Gpnmb in bone marrow-derived macrophages inhibited M2 polarization and anti-inflammatory cytokines IL-10 and TGF-β, while promoting M1 polarization and pro-inflammatory cytokines IL-1β and TNF-α; IL-4-STAT6 pathway was identified as mechanistically involved in Gpnmb-promoted M2 polarization. siRNA knockdown, macrophage polarization assays, cytokine ELISA, STAT6 pathway analysis Cellular immunology Medium 28433199
2018 GPNMB exerts anti-inflammatory effects on astrocytes via CD44: recombinant GPNMB attenuated cytokine-induced iNOS, NO, ROS, and IL-6 in astrocytes; using primary mouse astrocytes from CD44 knockout mice, the anti-inflammatory effects of GPNMB were abolished, demonstrating CD44-mediated signaling. CD44 knockout primary astrocytes, recombinant GPNMB treatment, qPCR, NO and ROS measurement, immunofluorescence Journal of neuroinflammation High 29519253
2018 GPNMB loss-of-function (truncating alleles) causes autosomal-recessive amyloidosis cutis dyschromica in humans; GPNMB is expressed in all epidermal cells with highest staining in melanocytes, and loss of GPNMB is associated with increased amyloid deposits in the dermis, infiltrating macrophages, and loss of melanocytes, implicating GPNMB in melanosome formation, autophagy, and phagocytosis in skin. Human genetics (6 nonsense/frameshift mutations in 9 individuals), immunofluorescence of skin biopsies, histopathology American journal of human genetics High 29336782
2018 Cell surface GPNMB on dormant breast cancer cells induces stem cell-like properties; wild-type GPNMB, but not a mutant lacking tumorigenic activity (YF mutant in hemITAM of cytoplasmic tail), induced CSC-like properties in breast epithelial cells and 3D sphere formation, demonstrating that the hemITAM tyrosine in the intracellular domain is required for GPNMB's tumorigenic function. 3D sphere culture, cell surface protein isolation/flow cytometry, wild-type vs. YF-mutant GPNMB overexpression, sphere-forming frequency assay Cancer research Medium 30224376
2019 GPNMB is a direct transcriptional target of TFE3 fusion oncoproteins in translocation renal cell carcinoma; GPNMB was upregulated in a PRCC-TFE3 transgenic mouse kidney tumor model and confirmed as a direct TFE3 transcriptional target; GPNMB was also upregulated following TSC2 loss in a MiT/TFE- and mTORC1-dependent fashion in renal cell lines. PRCC-TFE3 transgenic mouse model, CRISPR-Cas9 TSC2/TFE3/TFEB knockout cell lines, IHC, transcriptional target validation Molecular cancer research : MCR High 31043488
2019 Hepatic Gpnmb is transcriptionally upregulated when the sterol regulatory element-binding protein (SREBP) pathway is inhibited in the liver; Gpnmb is processed to a secreted form that acts as a liver-WAT cross-talk factor, stimulating lipogenesis in white adipose tissue; Gpnmb inhibition (neutralizing antibody or liver-specific knockdown) improved metabolic parameters and promoted WAT beiging. Liver-specific Gpnmb knockdown, neutralizing antibody, secreted form identification, metabolic phenotyping in diet-induced obesity model Nature metabolism High 32694855
2019 The kringle-like domain (KLD) in the extracellular domain of GPNMB is essential for its tumorigenic potential: a GPNMB(ΔKLD) deletion mutant lacked sphere and tumor formation activity and lost cell migration-promoting activity, despite retaining normal subcellular localization, Src-induced tyrosine phosphorylation, and homo-oligomerization. Domain deletion mutagenesis, 3D sphere/tumor formation assay, migration assay, subcellular localization, Western blotting Cancer science Medium 31127873
2019 Host GPNMB interacts with porcine circovirus type 2 (PCV2) ORF5 protein (demonstrated by GST pull-down, Co-IP, and confocal microscopy) and restricts PCV2 replication; GPNMB overexpression increased Cyclin A expression and reduced S phase, while knockdown had opposite effects, suggesting GPNMB modulates cell cycle to restrict viral replication. GST pull-down, Co-IP, confocal microscopy, lentiviral overexpression/knockdown, viral replication assays, cell cycle analysis Frontiers in microbiology Medium 30671053
2020 Macrophage-derived soluble GPNMB activates tumor cells through the CD44 receptor to express cytokine IL-33 and its receptor IL-1RL1, triggering cancer stem cell sphere formation; recombinant IL-33 alone was sufficient to induce tumor spheroid formation with CSC features, establishing GPNMB→CD44→IL-33/IL-1RL1 paracrine axis. Gpnmb-mutant DBA/2J mouse tumor models, CD44 receptor blocking/use, recombinant IL-33 treatment, sphere formation assays Cellular & molecular immunology High 32728200
2021 N-glycosylated GPNMB (specifically at Asn134) binds to the C-terminus of mutated EGFR and activates EGFR independently of its ligand, promoting phosphorylation at Y845 and activating downstream STAT3 signaling; mutation of N134 glycosylation abolished GPNMB-EGFR binding and inhibited downstream signaling and cancer metastasis in NSCLC. Membrane proteomics, Co-IP (GPNMB-EGFR binding), N134 glycosylation site mutagenesis, phosphorylation assays, metastasis models Cancer science High 33706413
2021 GPNMB overexpression in an APP/PS1 Alzheimer's disease mouse model enhanced autophagy and reduced Aβ deposition via suppression of the mTOR signaling pathway; treatment with 3-MA (autophagy inhibitor) abolished the beneficial effect of GPNMB on Aβ clearance, placing GPNMB-mediated autophagy as the mechanistic route for Aβ clearance. Transgenic GPNMB overexpression in APP/PS1 mice, transmission electron microscopy for autophagy, immunofluorescence, Western blotting for mTOR/Beclin-1, pharmacological autophagy inhibition with 3-MA Neuroscience letters Medium 34695452
2021 Gpnmb is a causal modifier of macrophage lysosome function: Gpnmb siRNA knockdown in AKR/J macrophages decreased lysosome function; CRISPR/Cas9 deletion of Gpnmb in RAW 264.7 macrophages similarly impaired lysosome function; the DBA/2J-Gpnmb+/SjJ substrain (with wild-type Gpnmb) showed recovered lysosome function compared to Gpnmb-nonsense DBA/2J, establishing Gpnmb as the causal gene at the Mlfm1 QTL. QTL mapping in AKR/J×DBA/2J intercross, siRNA knockdown, CRISPR/Cas9 knockout, lysosome function assay, congenic substrain comparison Scientific reports High 33986446
2021 Extracellular vesicles from GPNMB-overexpressing BMSCs activate Wnt/β-catenin signaling to stimulate osteogenic differentiation of BMSCs; DKK1 (Wnt/β-catenin inhibitor) blocked GPNMB-EV-induced osteogenesis, establishing Wnt/β-catenin as the downstream pathway. EV isolation from GPNMB-modified BMSCs, DKK1 inhibition of Wnt/β-catenin pathway, osteogenic differentiation assays, OVX rat model Life sciences Medium 33582177
2022 GPNMB directly coimmunoprecipitates and co-localizes with α-synuclein (aSyn) in cells; in iPSC-derived neurons, loss of GPNMB resulted in loss of ability to internalize aSyn fibrils and develop aSyn pathology, linking GPNMB to aSyn fibril internalization as a mechanistic route to Parkinson's disease pathology. Co-immunoprecipitation, co-localization imaging, iPSC-derived neuron loss-of-function, aSyn fibril internalization assay Science High 35981040
2022 Macrophage-derived GPNMB activates aortic adventitial fibroblasts (AAFs) to produce extracellular matrix (ECM) via integrin αVβ1 receptor and downstream Akt and Erk signaling; Co-IP assay demonstrated GPNMB-integrin αVβ1 interaction, and siRNA or integrin inhibitor intervention confirmed this receptor mediates GPNMB's fibrotic effects on AAFs. Co-IP, siRNA knockdown, integrin inhibitor, Western blotting for Akt/Erk, in vitro AAF activation assays, GPNMB overexpression in macrophages Translational research : the journal of laboratory and clinical medicine Medium 36566014
2023 Macrophage-derived GPNMB trapped by fibrotic ECM activates resident fibroblasts; the CD44/Serpinb2 pathway is activated in fibroblasts by GPNMB, promoting pulmonary fibrosis progression; GPNMB-neutralizing antibodies or macrophage deletion alleviated fibroblast activation in fibrotic ECM from silica-instilled mice. Fibrotic ECM fractionation/proteomics, GPNMB-neutralizing antibody, macrophage depletion, gene expression analysis (Serpinb2, CD44) in fibroblasts, silica-instilled mouse model Communications biology Medium 36732560
2023 CCN3 activates Wnt signaling (ligand-dependent or -independent) in TNBC, which increases MITF protein, which in turn transcriptionally induces GPNMB expression; GPNMB then activates the EGFR/MAPK pathway; CCN3 knockdown reduced GPNMB expression and EGFR activity, and GPNMB overexpression rescued the anti-cancer effects of CCN3 knockdown, establishing the CCN3→Wnt→MITF→GPNMB→EGFR/MAPK axis. siRNA knockdown, overexpression rescue, transcriptome profiling, Western blotting for pathway components, TCGA dataset validation Cell death & disease Medium 36737605
2023 GPNMB ameliorates neuroinflammation after subarachnoid hemorrhage via the AMPK/NFκB signaling pathway: recombinant GPNMB increased p-AMPK and suppressed p-NFκB and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α); AMPK inhibitor (dorsomorphin) reversed the effects of rGPNMB on p-AMPK and p-NFκB, establishing AMPK as the downstream mediator. SAH mouse model, intracerebroventricular rGPNMB injection, AMPK inhibitor epistasis, Western blotting, ELISA, BBB integrity and behavior assays Journal of neuroimmune pharmacology Medium 37919457
2024 Bone-marrow-derived macrophages are the primary source of GPNMB in injured hearts after myocardial infarction (established by lineage tracing and bone-marrow transplantation); GPNMB deficiency increases mortality and cardiac rupture while viral delivery of circulating GPNMB improves heart function; GPR39 was identified as a receptor for circulating GPNMB, and GPR39 absence negated the beneficial effects of GPNMB on cardiac repair. Lineage tracing, bone-marrow transplantation, genetic loss-of-function (GPNMB KO), viral GPNMB delivery, single-cell transcriptomics, GPR39 knockout mice Nature cardiovascular research High 39455836
2025 GPNMB functions in microglial phagocytosis by wrapping engulfed pathogenic particles and presenting them to lysosomes through direct interaction with lysosomal vacuolar-type proton ATPase catalytic subunit A (ATP6V1A); genetic ablation of GPNMB impaired both phagocytic engulfment and degradation; activating ATP6V1A rescued GPNMB-deficiency-caused phagocytosis impairment. GPNMB genetic ablation, Co-immunoprecipitation (GPNMB-ATP6V1A interaction), phagocytosis assays (multiple substrates), ATP6V1A activation rescue, in vivo seizure/epilepsy model Cell reports High 39992792

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nature genetics 1512 25064009
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2019 Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma. Cell 1200 31675496
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2016 The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer. Nature cell biology 466 26751287
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proceedings of the National Academy of Sciences of the United States of America 357 16247014
2015 Glioma-associated microglia/macrophages display an expression profile different from M1 and M2 polarization and highly express Gpnmb and Spp1. PloS one 335 25658639
2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome research 285 12975309
2004 Functional proteomics mapping of a human signaling pathway. Genome research 247 15231748
2013 Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein. Proceedings of the National Academy of Sciences of the United States of America 235 23898208
1995 nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts. International journal of cancer 232 7814155
2007 Gpnmb is induced in macrophages by IFN-gamma and lipopolysaccharide and acts as a feedback regulator of proinflammatory responses. Journal of immunology (Baltimore, Md. : 1950) 193 17475886
2003 The DNA sequence of human chromosome 7. Nature 188 12853948
2010 ADAM10 releases a soluble form of the GPNMB/Osteoactivin extracellular domain with angiogenic properties. PloS one 175 20711474
2010 Glycoprotein nonmetastatic B is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 160 20215530
2003 Human chromosome 7: DNA sequence and biology. Science (New York, N.Y.) 154 12690205
2006 Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. Journal of proteome research 150 17081065
2018 Identification of phagocytosis regulators using magnetic genome-wide CRISPR screens. Nature genetics 146 30397336
2015 EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 146 25847941
2006 Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme. Clinical cancer research : an official journal of the American Association for Cancer Research 143 16609006
2007 Osteoactivin promotes breast cancer metastasis to bone. Molecular cancer research : MCR 141 17951401
2018 The glycoprotein GPNMB attenuates astrocyte inflammatory responses through the CD44 receptor. Journal of neuroinflammation 136 29519253
2018 Glycoprotein NMB: a novel Alzheimer's disease associated marker expressed in a subset of activated microglia. Acta neuropathologica communications 123 30340518
2003 Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. Journal of proteome research 121 12643545
2019 A Human Organotypic Microfluidic Tumor Model Permits Investigation of the Interplay between Patient-Derived Fibroblasts and Breast Cancer Cells. Cancer research 120 30992322
2022 GPNMB confers risk for Parkinson's disease through interaction with α-synuclein. Science (New York, N.Y.) 118 35981040
2012 The potential of GPNMB as novel neuroprotective factor in amyotrophic lateral sclerosis. Scientific reports 112 22891158
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2020 The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33. Cellular & molecular immunology 105 32728200
2010 Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specific and proteolytically released protein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 99 20056711
2002 Identification of the genes differentially expressed in human dendritic cell subsets by cDNA subtraction and microarray analysis. Blood 96 12176896
2019 Proteomics in cerebrospinal fluid and spinal cord suggests UCHL1, MAP2 and GPNMB as biomarkers and underpins importance of transcriptional pathways in amyotrophic lateral sclerosis. Acta neuropathologica 95 31701227
2018 The glycoprotein GPNMB is selectively elevated in the substantia nigra of Parkinson's disease patients and increases after lysosomal stress. Neurobiology of disease 92 30149180
2017 Glycoprotein non-metastatic melanoma protein b (Gpnmb) is highly expressed in macrophages of acute injured kidney and promotes M2 macrophages polarization. Cellular immunology 92 28433199
2022 GPNMB expression identifies TSC1/2/mTOR-associated and MiT family translocation-driven renal neoplasms. The Journal of pathology 90 35072947
2017 Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) and Cancer: A Novel Potential Therapeutic Target. Steroids 89 29097143
2019 Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance. Nature metabolism 80 32694855
2008 Microphthalmia transcription factor regulates the expression of the novel osteoclast factor GPNMB. Gene 77 18313864
2019 The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis. Nature communications 74 31586073
2016 Macrophage-Associated Osteoactivin/GPNMB Mediates Mesenchymal Stem Cell Survival, Proliferation, and Migration Via a CD44-Dependent Mechanism. Journal of cellular biochemistry 74 26442636
2019 TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease. Molecular cancer research : MCR 72 31043488
2017 Targeting GPNMB with glembatumumab vedotin: Current developments and future opportunities for the treatment of cancer. Pharmacology & therapeutics 72 28546082
2015 Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis. Scientific reports 71 26581806
2022 Integrated single-cell transcriptomic analyses reveal that GPNMB-high macrophages promote PN-MES transition and impede T cell activation in GBM. EBioMedicine 70 36054938
2010 DC-HIL/glycoprotein Nmb promotes growth of melanoma in mice by inhibiting the activation of tumor-reactive T cells. Cancer research 67 20570888
2015 GPNMB cooperates with neuropilin-1 to promote mammary tumor growth and engages integrin α5β1 for efficient breast cancer metastasis. Oncogene 65 25772243
2017 Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson's disease on chromosome 7p15.3. Neurogenetics 60 28391543
2008 Gpnmb is a melanoblast-expressed, MITF-dependent gene. Pigment cell & melanoma research 60 18983539
2014 Lysosomal stress in obese adipose tissue macrophages contributes to MITF-dependent Gpnmb induction. Diabetes 59 24789918
2014 Glycoprotein nonmetastatic melanoma protein B (GPNMB) as a novel neuroprotective factor in cerebral ischemia-reperfusion injury. Neuroscience 56 25010402
2013 GPNMB enhances bone regeneration by promoting angiogenesis and osteogenesis: potential role for tissue engineering bone. Journal of cellular biochemistry 55 23794283
2019 A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma. Cancer 54 30690710
2022 GPNMB: a potent inducer of immunosuppression in cancer. Oncogene 52 36050467
2016 Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease. Blood cells, molecules & diseases 50 28003098
2015 The transcription factor MITF is a critical regulator of GPNMB expression in dendritic cells. Cell communication and signaling : CCS 49 25889792
2009 Upregulation of monocyte/macrophage HGFIN (Gpnmb/Osteoactivin) expression in end-stage renal disease. Clinical journal of the American Society of Nephrology : CJASN 47 19833906
2018 Glycoprotein nmb Is Exposed on the Surface of Dormant Breast Cancer Cells and Induces Stem Cell-like Properties. Cancer research 46 30224376
2015 Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma. Pediatric blood & cancer 46 26305408
2006 Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer 177Lu-AMBA. European journal of nuclear medicine and molecular imaging 44 16909223
2016 Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo. Journal of cellular physiology 43 25899717
2018 Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans. American journal of human genetics 42 29336782
2016 MAPK Pathway Inhibitors Sensitize BRAF-Mutant Melanoma to an Antibody-Drug Conjugate Targeting GPNMB. Clinical cancer research : an official journal of the American Association for Cancer Research 42 27515299
2022 Tumor endothelial cell-induced CD8+ T-cell exhaustion via GPNMB in hepatocellular carcinoma. Cancer science 41 35289033
2021 Extracellular vesicles from GPNMB-modified bone marrow mesenchymal stem cells attenuate bone loss in an ovariectomized rat model. Life sciences 40 33582177
1992 Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific carcinogen, by rabbit nasal microsomes and cytochrome P450s NMa and NMb. Carcinogenesis 40 1423886
2019 Microglia express GPNMB in the brains of Alzheimer's disease and Nasu-Hakola disease. Intractable & rare diseases research 39 31218162
2009 Characterization of putative GRP- and NMB-receptor antagonist's interaction with human receptors. Peptides 38 19463875
2012 Silencing of GPNMB by siRNA inhibits the formation of melanosomes in melanocytes in a MITF-independent fashion. PloS one 37 22912767
1994 Desensitization of neuromedin B receptors (NMB-R) on native and NMB-R-transfected cells involves down-regulation and internalization. The Journal of biological chemistry 36 8163469
2017 Glycoprotein NMB: an Emerging Role in Neurodegenerative Disease. Molecular neurobiology 34 28856541
2016 Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells. Oncotarget 34 26883195
2023 Positive GPNMB Immunostaining Differentiates Renal Cell Carcinoma With Fibromyomatous Stroma Associated With TSC1/2/MTOR Alterations From Others. The American journal of surgical pathology 33 37661807
2021 GPNMB mitigates Alzheimer's disease and enhances autophagy via suppressing the mTOR signal. Neuroscience letters 33 34695452
2018 GPNMB silencing suppresses the proliferation and metastasis of osteosarcoma cells by blocking the PI3K/Akt/mTOR signaling pathway. Oncology reports 33 29620278
2020 Transgenic Overexpression of GPNMB Protects Against MPTP-Induced Neurodegeneration. Molecular neurobiology 32 32436108
2023 Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis. Communications biology 31 36732560
2016 GPNMB ameliorates mutant TDP-43-induced motor neuron cell death. Journal of neuroscience research 31 27935101
2013 Endothelin-1 enhances the melanogenesis via MITF-GPNMB pathway. BMB reports 31 23884103
2019 CSE1L silence inhibits the growth and metastasis in gastric cancer by repressing GPNMB via positively regulating transcription factor MITF. Journal of cellular physiology 30 31347172
2014 Induction of matrix metalloproteinase-3 (MMP-3) expression in the microglia by lipopolysaccharide (LPS) via upregulation of glycoprotein nonmetastatic melanoma B (GPNMB) expression. Journal of molecular neuroscience : MN 30 24682924
2010 C57BL/6J, DBA/2J, and DBA/2J.Gpnmb mice have different visual signal processing in the inner retina. Molecular vision 29 21203347
2007 Role of human HGFIN/nmb in breast cancer. Breast cancer research : BCR 29 17845721
2024 Gpnmb and Spp1 mark a conserved macrophage injury response masking fibrosis-specific programming in the lung. JCI insight 27 39509324
2017 Characterization of NMB, GRP and their receptors (BRS3, NMBR and GRPR) in chickens. Journal of molecular endocrinology 27 28500250
2021 Anti-inflammatory role of Gpnmb in adipose tissue of mice. Scientific reports 26 34608215
2002 Restraint stress impaired maternal behavior in female mice lacking the neuromedin B receptor (NMB-R) gene. Neuroscience letters 26 12231437
1992 Cytochromes P450 NMa, NMb (2G1), and LM4 (1A2) are differentially expressed during development in rabbit olfactory mucosa and liver. Molecular pharmacology 25 1282662
2019 DC-HIL/Gpnmb Is a Negative Regulator of Tumor Response to Immune Checkpoint Inhibitors. Clinical cancer research : an official journal of the American Association for Cancer Research 24 31822499
2019 Takayasu arteritis risk locus in IL6 represses the anti-inflammatory gene GPNMB through chromatin looping and recruiting MEF2-HDAC complex. Annals of the rheumatic diseases 23 31315839
2023 CCN3/NOV promotes metastasis and tumor progression via GPNMB-induced EGFR activation in triple-negative breast cancer. Cell death & disease 22 36737605
2011 Hematopoietic growth factor inducible neurokinin-1 (Gpnmb/Osteoactivin) is a biomarker of progressive renal injury across species. Kidney international 22 21389974
2010 Affinity-matured anti-glycoprotein NMB recombinant immunotoxins targeting malignant gliomas and melanomas. International journal of cancer 22 20824708
2021 BNP facilitates NMB-encoded histaminergic itch via NPRC-NMBR crosstalk. eLife 21 34919054
2016 Glycoprotein nonmetastatic melanoma protein B (GPNMB) promotes the progression of brain glioblastoma via Na+/K+-ATPase. Biochemical and biophysical research communications 21 27836549
2011 Genetic dissection of the Gpnmb network in the eye. Investigative ophthalmology & visual science 21 21398278
1996 Alanine scan and N-methyl amide derivatives of Ac-bombesin[7-14]. Development of a proposed binding conformation at the neuromedin B (NMB) and gastrin releasing peptide (GRP) receptors. International journal of peptide and protein research 21 8985785
2021 N-glycosylated GPNMB ligand independently activates mutated EGFR signaling and promotes metastasis in NSCLC. Cancer science 20 33706413
2022 miR-532-3p suppresses proliferation and invasion of ovarian cancer cells via GPNMB/HIF-1α/HK2 axis. Pathology, research and practice 19 35914373
2017 DLG2, but not TMEM229B, GPNMB, and ITGA8 polymorphism, is associated with Parkinson's disease in a Taiwanese population. Neurobiology of aging 19 29290481
2003 The msbB mutant of Neisseria meningitidis strain NMB has a defect in lipooligosaccharide assembly and transport to the outer membrane. Infection and immunity 19 12540541
2019 Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer. Journal of cellular physiology 18 31498430
2024 Bone-marrow macrophage-derived GPNMB protein binds to orphan receptor GPR39 and plays a critical role in cardiac repair. Nature cardiovascular research 17 39455836
2019 Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Ameliorates the Inflammatory Response in Periodontal Disease. Inflammation 17 30793225
2024 Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma. Acta neuropathologica communications 16 38566120
2005 Cloning and characterization of the 5' flanking region of the HGFIN gene indicate a cooperative role among p53 and cytokine-mediated transcription factors: relevance to cell cycle regulation. Cell cycle (Georgetown, Tex.) 16 15684612
2023 GPNMB Ameliorates Neuroinflammation Via the Modulation of AMPK/NFκB Signaling Pathway After SAH in Mice. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 15 37919457
2023 Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease. Journal of neuroinflammation 15 38037070
2023 PCSK9 inhibitor protects against ischemic cerebral injury by attenuating inflammation via the GPNMB/CD44 pathway. International immunopharmacology 15 38048667
2022 A novel molecular mechanism of vascular fibrosis in Takayasu arteritis: macrophage-derived GPNMB promoting adventitial fibroblast extracellular matrix production in the aorta. Translational research : the journal of laboratory and clinical medicine 15 36566014
1994 Characterization of a triple opioid system in the human neuroblastoma NMB cell line. Brain research 15 7882024
2022 TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma. Cancers 14 35158847
2021 Evaluation of cerebrospinal fluid glycoprotein NMB (GPNMB) as a potential biomarker for Alzheimer's disease. Alzheimer's research & therapy 14 33947460
2021 Quantitative trait locus mapping identifies the Gpnmb gene as a modifier of mouse macrophage lysosome function. Scientific reports 14 33986446
2019 Role of the kringle-like domain in glycoprotein NMB for its tumorigenic potential. Cancer science 14 31127873
2017 GPNMB Induces BiP Expression by Enhancing Splicing of BiP Pre-mRNA during the Endoplasmic Reticulum Stress Response. Scientific reports 14 28939899
2024 Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Immunohistochemistry Can Be a Useful Ancillary Tool to Identify Perivascular Epithelioid Cell Tumor. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 13 38219952
2021 Genetic ablation of Gpnmb does not alter synuclein-related pathology. Neurobiology of disease 13 34464706
2021 Adaptive resistance in tumors to anti-PD-1 therapy through re-immunosuppression by upregulation of GPNMB expression. International immunopharmacology 13 34673297
2021 Proteomic analysis of alcohol-associated hepatitis reveals glycoprotein NMB (GPNMB) as a novel hepatic and serum biomarker. Alcohol (Fayetteville, N.Y.) 13 34923085
2019 A Host Factor GPNMB Restricts Porcine Circovirus Type 2 (PCV2) Replication and Interacts With PCV2 ORF5 Protein. Frontiers in microbiology 13 30671053
2018 Overexpression of GPNMB predicts an unfavorable outcome of epithelial ovarian cancer. Archives of gynecology and obstetrics 13 29428978
2024 Roles of Activin A and Gpnmb in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Diabetes 12 37934943
2014 Differential expression of glycoprotein non-metastatic melanoma protein B (GPNMB) involved in trichostatin A-induced apoptosis in gastric cancer. International journal of clinical and experimental medicine 12 25663982
2025 GPNMB and ATP6V1A interact to mediate microglia phagocytosis of multiple types of pathological particles. Cell reports 11 39992792
2021 Functional Domains and Evolutionary History of the PMEL and GPNMB Family Proteins. Molecules (Basel, Switzerland) 11 34207849
2017 The laminin-derived peptide C16 regulates GPNMB expression and function in breast cancer. Experimental cell research 11 28689015
2016 Effects of MC4R, FTO, and NMB gene variants to obesity, physical activity, and eating behavior phenotypes. IUBMB life 11 27634552