Affinage

ITPR3

Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 · UniProt Q14573

Length
2671 aa
Mass
304.1 kDa
Annotated
2026-06-10
85 papers in source corpus 27 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITPR3 encodes IP3R3, an endoplasmic reticulum-localized inositol 1,4,5-trisphosphate-gated Ca2+ release channel that converts IP3-coupled receptor signaling into cytosolic and mitochondrial Ca2+ flux (PMID:8388391, PMID:28614305). A dominant function of IP3R3 is to deliver Ca2+ from the ER to mitochondria at ER-mitochondria contact sites (MAMs), where it is recruited and tethered through interactions with TOM70, GRP75/VDAC1, Sigma-1 receptor, and Mfn2 to sustain oxidative phosphorylation and, under overload, to drive apoptosis (PMID:29395920, PMID:32916960, PMID:40128893, PMID:40595218). The abundance of IP3R3 is set by a ubiquitin-proteasome axis: the SCF F-box protein FBXL2 binds IP3R3 and targets it for p97- and proteasome-dependent degradation, a reaction antagonized by PTEN (which competes for IP3R3 binding) and by FUNDC1 (which stabilizes FBXL2), and opposed by the ER-localized deubiquitylase BAP1, which removes ubiquitin to stabilize IP3R3 and license genotoxic-stress apoptosis (PMID:28614305, PMID:28614300, PMID:32938669). Through this Ca2+-apoptosis and Ca2+-bioenergetic output, IP3R3 acts as a context-dependent determinant of cell fate, influencing chemotherapy-induced apoptosis, cancer cell survival, invasion and metabolism via NF-κB/RELB, CD44, and cytoskeletal RhoA signaling (PMID:29630900, PMID:34518526, PMID:33573671, PMID:35487218). Its expression is tuned transcriptionally and epigenetically, by KLF4/H3K27ac under pulsatile shear stress in endothelial cells and by SMARCA4/2-dependent chromatin accessibility (PMID:30917677, PMID:34518526). IP3R3-dependent ER Ca2+ release is also required to trigger store-operated Ca2+ entry for NF-κB/NFAT-driven T cell activation, and dominant de novo ITPR3 variants (recurrent p.Arg2524Cys) act through a dominant-negative mechanism to cause a multisystemic disorder comprising combined immunodeficiency, Charcot-Marie-Tooth neuropathy, and ectodermal dysplasia (PMID:39560673, PMID:39270020). In specialized sensory tissue, IP3R3 is specifically required for GPCR-coupled taste transduction (PMID:23859941).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1993 High

    Established the molecular identity of IP3R3 as a distinct IP3-binding ER Ca2+ channel subtype, defining the protein on which all later mechanism rests.

    Evidence Recombinant rat IP3R3 in COS-7 cells with radioligand binding and immunohistochemistry

    PMID:8388391

    Open questions at the time
    • No channel structure or gating mechanism resolved
    • Tissue-specific functions not yet addressed
  2. 2013 High

    Resolved whether IP3R3 is functionally specialized in vivo by showing it is selectively required for GPCR-coupled taste transduction and for injury-induced regenerative signaling in sensory epithelia.

    Evidence Spontaneous Itpr3 deletion in BTBR mice, Itpr3 knockout mice, and behavioral/cellular assays in taste and olfactory tissue

    PMID:23516531 PMID:23859941

    Open questions at the time
    • Downstream effectors of taste-cell Ca2+ release not mapped
    • Subtype specificity over IP3R1/IP3R2 not mechanistically explained
  3. 2017 High

    Defined the post-translational control of IP3R3 abundance as a determinant of Ca2+-driven apoptosis, identifying opposing ubiquitylation (FBXL2, antagonized by PTEN) and deubiquitylation (BAP1) activities.

    Evidence Reciprocal Co-IP, ubiquitination/deubiquitylation assays, FBXL2-insensitive knock-in, BAP1 loss-of-function, and Ca2+ flux

    PMID:28614300 PMID:28614305

    Open questions at the time
    • Degron site within IP3R3 not fully defined
    • Stoichiometry and dynamics of BAP1 vs FBXL2 competition unresolved
  4. 2018 High

    Mapped how IP3R3 is physically recruited to ER-mitochondria contact sites and how its degradation is co-opted, establishing TOM70 and Cav-1 as direct partners and showing viral hijacking of the FBXL2 pathway.

    Evidence Co-IP, colocalization, mutants, and Ca2+/respiration assays for TOM70 and Cav-1; trimeric NS5A-IP3R3-FBXL2 complex with HCV replication readouts

    PMID:19052258 PMID:29395920 PMID:30355490

    Open questions at the time
    • How TOM70 binding alters channel gating not defined
    • Physiological trigger for degron unmasking in non-viral contexts unclear
  5. 2019 High

    Showed IP3R3 expression is epigenetically activated by mechanotransduction, with KLF4 driving chromatin opening and transcription to control endothelial Ca2+ and NO output.

    Evidence ChIP-seq, ATAC-seq, CRISPR promoter deletion, and Ca2+/eNOS measurements in endothelial cells

    PMID:30917677

    Open questions at the time
    • Generality of KLF4 control beyond endothelium unknown
    • Link between IP3R3 Ca2+ flux and eNOS activation not fully traced
  6. 2020 Medium

    Connected IP3R3 to mitochondrial bioenergetics and store-operated Ca2+ entry, linking STIM1, FUNDC1, and IP3R3 stability to mitochondrial Ca2+ and ATP synthesis.

    Evidence STIM1 CRISPR KO with ITPR3 rescue, FUNDC1 KO with FBXL2 Co-IP, mitochondrial Ca2+ imaging and respirometry

    PMID:32916960 PMID:32938669

    Open questions at the time
    • Whether STIM1 regulates ITPR3 transcription directly or indirectly unresolved
    • FUNDC1-FBXL2-IP3R3 hierarchy from single lab
  7. 2020 Medium

    Established ITPR3 as a disease gene, with a dominant de novo variant altering Ca2+ transients in patient fibroblasts and associating with Charcot-Marie-Tooth neuropathy.

    Evidence Whole-exome sequencing and Ca2+ imaging in patient-derived fibroblasts

    PMID:32949214

    Open questions at the time
    • Dominant-negative mechanism inferred, not yet demonstrated structurally
    • Neuronal cell-type basis of neuropathy not resolved
  8. 2021 High

    Demonstrated that chromatin remodeler-controlled IP3R3 expression governs chemotherapy sensitivity through ER-to-mitochondria Ca2+ transfer.

    Evidence ATAC-seq, SMARCA4/2 KO, HDAC-inhibitor rescue, and in vivo cisplatin response

    PMID:34518526

    Open questions at the time
    • Whether SMARCA-dependent regulation applies across tumor types unknown
  9. 2022 Medium

    Linked IP3R3-mediated Ca2+ release to NF-κB/RELB transcriptional programs that promote cancer cell survival and metastasis, expanding IP3R3 from channel to fate-decision node.

    Evidence In vivo shRNA screen, ITPR3/RELB knockdown, Ca2+ imaging, and xenograft colonization assays

    PMID:35487218

    Open questions at the time
    • Mechanism coupling cytosolic Ca2+ to RELB induction not detailed
    • Generality beyond colorectal cancer unknown
  10. 2024 High

    Defined the dominant-negative pathophysiology of recurrent ITPR3 variants, showing depletion of ER Ca2+ stores and blunted SOCE drives combined immunodeficiency and a multisystem disorder.

    Evidence WES in multiple patient cohorts, Jurkat CRISPR knock-in, site-directed mutagenesis at Arg2524, and T-cell functional assays

    PMID:39270020 PMID:39560673

    Open questions at the time
    • Tissue-specific basis of the multisystem phenotype not fully explained
    • Structural basis for Arg2524 sensitivity not resolved
  11. 2025 Medium

    Extended the MAM tethering picture with GRP75/VDAC1 and Mfn2 as IP3R3-associated regulators of mitochondrial Ca2+ overload in cardiovascular disease models.

    Evidence Co-IP, GRP75/Mfn2 perturbation, mitochondrial Ca2+ imaging in ischemia-reperfusion and PAH models

    PMID:40128893 PMID:40595218

    Open questions at the time
    • Direct vs indirect nature of Mfn2-IP3R3 reciprocal regulation unclear
    • Complex assembly stoichiometry not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse regulatory inputs (ubiquitin turnover, chromatin/transcriptional control, MAM tethering) are integrated to set IP3R3-dependent Ca2+ output in any single physiological cell type remains unresolved.
  • No unified quantitative model of IP3R3 abundance vs Ca2+ flux
  • Structural basis of partner-dependent gating unknown
  • Cell-type determinants of apoptotic vs bioenergetic outcome undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005739 mitochondrion 2 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
BAP1CAV1FBXL2FUNDC1MFN2PTENSTIM1TOM70
Complex memberships
IP3R3-GRP75-VDAC1 MAM complexSCF(FBXL2) ubiquitin ligase substrate complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 IP3R3 (IP3R-3) was identified as a third inositol 1,4,5-trisphosphate receptor subtype localized to the endoplasmic reticulum that functions as a Ca2+ channel; recombinant rat IP3R3 expressed in COS-7 cells bound IP3, inositol 1,3,4,5-tetrakisphosphate, and inositol hexakisphosphate, and immunohistochemistry confirmed ER localization. Recombinant expression in COS-7 cells, radioligand binding assay, immunohistochemistry, RNA/protein blotting The Journal of biological chemistry High 8388391
2017 BAP1 localizes to the endoplasmic reticulum where it binds, deubiquitylates, and stabilizes IP3R3, thereby modulating Ca2+ release from the ER into the cytosol and mitochondria and promoting apoptosis; reduced BAP1 levels decrease IP3R3 protein levels and Ca2+ flux, impairing apoptosis after genotoxic stress. Co-immunoprecipitation, deubiquitylation assay, subcellular fractionation, Ca2+ imaging, loss-of-function (BAP1 knockdown/knockout), immunofluorescence Nature High 28614305
2017 The F-box protein FBXL2 binds IP3R3 and targets it for ubiquitin-, p97-, and proteasome-mediated degradation, limiting Ca2+ influx into mitochondria and apoptosis; PTEN competes with FBXL2 for IP3R3 binding, and PTEN loss accelerates FBXL2-dependent IP3R3 degradation. Co-immunoprecipitation, ubiquitination assay, proteasome inhibition, FBXL2 knockdown, CRISPR knock-in of FBXL2-insensitive IP3R3 mutant, Ca2+ imaging, xenograft models Nature High 28614300
2018 TOM70, a subunit of the mitochondrial outer membrane translocase, physically interacts with IP3R3 and promotes its functional recruitment to ER-mitochondria contact sites; TOM70 depletion specifically impairs IP3-linked ER-to-mitochondria Ca2+ transfer, dampening mitochondrial respiration and inducing autophagy. Co-immunoprecipitation, confocal microscopy/colocalization, siRNA knockdown, Ca2+ imaging, mitochondrial respiration assay Current biology : CB High 29395920
2018 HCV non-structural protein NS5A forms a trimeric complex with IP3R3 and FBXL2, unmasking IP3R3's degron in the absence of IP3 stimulation and promoting constitutive IP3R3 degradation to limit apoptosis and facilitate viral replication; disruption of this complex stabilizes IP3R3 and suppresses HCV replication. Co-immunoprecipitation, somatic cell genetics (NS5A domain mutants), pharmacologic FBXL2 disruption, Ca2+ flux assay, viral replication assay Cell reports High 30355490
2008 Caveolin-1 scaffold domain (CSD, residues 82–101) directly interacts with both TRPC1 and IP3R3; wild-type Cav-1 but not Cav-1ΔCSD co-immunoprecipitated IP3R3, and Cav-1ΔCSD expression produced a gain-of-function in Ca2+ store-release-induced Ca2+ entry, indicating CSD-mediated interaction suppresses Ca2+ influx. Co-immunoprecipitation, dominant-negative/truncation mutants, Ca2+ imaging, confocal colocalization American journal of physiology. Cell physiology Medium 19052258
2013 A spontaneous 12-bp deletion in Exon 23 of Itpr3 in BTBR mice abolishes GPCR-mediated taste transduction (sweet, umami, bitter, Polycose, calcium tastes); Itpr3 knockout mice phenocopy this taste indifference, establishing IP3R3 as required for GPCR-coupled taste signaling in taste receptor cells. QTL mapping, congenic strain construction, Itpr3 knockout mice, behavioral taste preference assays, Sanger sequencing Physiological genomics High 23859941
2013 IP3R3-expressing microvillous cells in the olfactory epithelium co-express NPY; ATP-evoked NPY release is impaired in IP3R3-/- mice, and these mice show reduced progenitor cell proliferation and a compromised regenerative response to olfactory injury, establishing IP3R3 as required for injury-induced NPY release and tissue homeostasis. IP3R3 knockout mice, extracellular ATP stimulation, NPY ELISA, BrdU proliferation assay, olfactotoxicant and bulbectomy injury models PloS one Medium 23516531
2018 IP3R3 silencing in invasive breast cancer cell lines induces cell rounding, decreased adhesion, reduced ARHGAP18 expression, decreased RhoA activity and Cdc42 expression, reduced FAK Y861 phosphorylation, and profilin cytoskeleton reorganization, acting via the ARHGAP18/RhoA/mDia1/FAK pathway to regulate actin dynamics. siRNA knockdown, RhoA activity assay, western blotting, confocal imaging, wound-healing assay Biochimica et biophysica acta. Molecular cell research Medium 29630900
2018 Chlamydia trachomatis inclusion membrane protein MrcA interacts with ITPR3 and recruits it to active Src-family-kinase-rich microdomains on the inclusion membrane; disruption of MrcA by mutagenesis abolished ITPR3 recruitment and reduced chlamydial extrusion; siRNA depletion of ITPR3 or STIM1 similarly inhibited extrusion, and BAPTA-AM Ca2+ chelation reduced myosin regulatory light chain (MLC2) phosphorylation and myosin motor activity required for extrusion. Directed mutagenesis of MrcA, complementation, siRNA knockdown of ITPR3/STIM1, confocal microscopy, Ca2+ chelation (BAPTA-AM), phospho-MLC2 western blot, extrusion quantification PLoS pathogens High 29543918
2019 KLF4 transcription factor binds a specific locus in the ITPR3 promoter under atheroprotective pulsatile shear stress, driving H3K27ac enrichment, chromatin accessibility, and RNA Pol II recruitment to transcriptionally activate ITPR3; CRISPR-Cas9 deletion of this KLF4-binding locus blunted Ca2+ influx, reduced eNOS expression, and diminished nitric oxide bioavailability in endothelial cells. ChIP-seq, ATAC-seq, ChIP-qPCR, ATAC-qPCR, CRISPR-Cas9 promoter deletion, Ca2+ imaging, eNOS/NO measurements Arteriosclerosis, thrombosis, and vascular biology High 30917677
2020 FUNDC1 interacts with FBXL2 (identified by mass spectrometry and co-immunoprecipitation), and FUNDC1 loss accelerates FBXL2 degradation and stabilizes IP3R3, causing mitochondrial Ca2+ overload; the FUNDC1 F-box deletion mutant disrupts FBXL2 binding, confirming the domain requirement. Mass spectrometry, co-immunoprecipitation, truncation mutants, FUNDC1-/- mouse model, Ca2+ imaging, mitochondrial function assays Science advances Medium 32938669
2021 SMARCA4/2 loss restricts chromatin accessibility at the ITPR3 locus, reducing IP3R3 expression and impairing ER-to-mitochondria Ca2+ transfer required for chemotherapy-induced apoptosis; reactivation of SMARCA2 by HDAC inhibitor rescued IP3R3 expression and enhanced cisplatin response in vitro and in vivo. ATAC-seq, SMARCA4/2 KO, IP3R3 expression analysis, Ca2+ imaging, HDAC inhibitor treatment, in vivo xenograft cisplatin response Nature communications High 34518526
2020 STIM1 deficiency in SH-SY5Y cells causes a specific down-regulation of ITPR3 transcript and protein; re-expression of ITPR3 in STIM1-KO cells restores mitochondrial Ca2+ concentration, mitochondrial oxygen consumption rate, and ATP synthesis rate, establishing a STIM1–ITPR3 axis regulating mitochondrial Ca2+ and bioenergetics. CRISPR/Cas9 STIM1 knockout, ectopic ITPR3 re-expression, RT-qPCR, western blot, mitochondrial Ca2+ imaging, Seahorse respirometry International journal of molecular sciences High 32916960
2020 ITPR3 promotes bladder cancer proliferation, EMT-driven invasion/metastasis, and stemness via the NF-κB/CD44 pathway; demethylation of the ITPR3 promoter region was identified as the mechanism driving its overexpression in bladder cancer cells. siRNA knockdown, overexpression, bisulfite sequencing PCR, western blot, transwell assay, xenograft tumor model, tail-vein metastasis model, flow cytometry Journal of experimental & clinical cancer research : CR Medium 33573671
2022 ITPR3-mediated Ca2+ release from the ER induces expression of RELB (a non-canonical NF-κB transcription factor), promoting colorectal cancer cell survival upon substratum detachment or hypoxia; RELB expression was sufficient to drive metastatic colonization downstream of ITPR3. In vivo shRNA screen, genetic validation, ITPR3 knockdown, RELB knockdown/overexpression, Ca2+ imaging, pharmacologic caffeine inhibition, xenograft colonization assays Developmental cell Medium 35487218
2016 IP3R3 is specifically required for nitric oxide-induced cardiomyocyte differentiation of mouse embryonic stem cells; only IP3R3 knockdown (not IP3R1 or IP3R2 knockdown) inhibited NO-induced Ca2+ increases and abolished cardiomyocyte differentiation, and CMs derived from IP3R3-knockdown ES cells showed structural and functional defects. Individual and triple siRNA knockdown of IP3R1/2/3, Ca2+ imaging, EB differentiation assay, structural/functional characterization of derived CMs Experimental cell research Medium 27349290
2020 Dominant de novo ITPR3 variant p.Val615Met causes altered Ca2+ transients in patient-derived fibroblasts, suggesting a dominant-negative effect on IP3R3 channel function, associated with Charcot-Marie-Tooth neuropathy. Whole-exome sequencing, Ca2+ imaging in patient fibroblasts, western blotting, RT-qPCR Annals of clinical and translational neurology Medium 32949214
2024 De novo missense variants in ITPR3 (including recurrent p.Arg2524Cys) cause combined immunodeficiency through a dominant-negative mechanism that depletes ER Ca2+ stores and blunts store-operated Ca2+ entry (SOCE) in T cells, leading to T cell lymphopenia, defective thymic development, and impaired NF-κB/NFAT-mediated T cell activation. Whole-exome sequencing, Ca2+ imaging in patient T cells, CRISPR knock-in (Jurkat), site-directed mutagenesis, lymphocyte functional assays (proliferation, NF-κB/NFAT activation) The Journal of experimental medicine High 39560673
2024 The recurrent dominant ITPR3 p.Arg2524Cys variant acts through a dominant-negative mechanism to cause defective Ca2+ homeostasis, mitochondrial malfunction, CD4+ lymphopenia with near-absence of naïve T cells, and a complex multisystemic disorder including ectodermal dysplasia and CMT; site-directed mutagenesis showed that any amino acid change at Arg2524 disrupts function. Site-directed mutagenesis, CRISPR knock-in (Jurkat), Ca2+ imaging, immunophenotyping, whole-exome sequencing of four unrelated patients Science advances High 39270020
2022 IP3R3 inhibition attenuates TGF-β1-induced endothelial-to-mesenchymal transition (EndMT) and cell migration by reducing Ca2+ levels, ROS production, and restoring mitochondrial membrane potential and respiratory chain complex activities in pulmonary arterial endothelial cells. IP3R3 inhibition (pharmacologic), Ca2+ measurement, ROS assay, mitochondrial membrane potential assay, respiratory complex activity assay, EndMT marker western blot Biochemical and biophysical research communications Medium 35760011
2025 Mfn2 physically interacts with IP3R3 (confirmed by immunoprecipitation); Mfn2 overexpression reduces IP3R3 expression and decreases mitochondrial Ca2+ transport, while IP3R3 inhibition elevates Mfn2 levels, demonstrating reciprocal regulation at ER-mitochondria contact sites that suppresses PASMC proliferation. Co-immunoprecipitation, Mfn2 overexpression/silencing, IP3R3 inhibition, mitochondrial Ca2+ measurement, cell proliferation assay, monocrotaline PAH rat model Journal of translational medicine Medium 40128893
2023 Acrylamide exposure markedly increases ubiquitination and proteasome-mediated degradation of IP3R3 in rat spinal cord, impairing MAM structure and causing aberrant cytoplasmic Ca2+ rise and downstream calpain activation and axon damage; the proteasome inhibitor MG-132 rescued IP3R3 levels, normalized Ca2+, and reduced axon loss. In vivo ACR exposure (rat), ubiquitination assay, proteasome inhibitor rescue (MG-132), calpain inhibitor (ALLN), Ca2+ measurement, axon loss quantification in N2a cells Toxicology letters Medium 37353096
2025 The IP3R3-GRP75-VDAC1 complex at MAMs mediates ER-to-mitochondria Ca2+ transfer; in myocardial ischemia-reperfusion injury, this complex is upregulated, increasing mitochondrial Ca2+ overload, CaM expression, and mitophagy; GRP75 knockdown inhibited CaM and Ca2+ overload but did not affect IP3R3 or VDAC1 levels directly. Co-immunoprecipitation, GRP75/CaM knockdown, mitochondrial Ca2+ imaging, ATP measurement, mitochondrial membrane potential assay, TEM, H/R cell model Scientific reports Medium 40595218
2025 ITPR3-mediated Ca2+ release activates NF-κB which induces LECT2 expression causing hepatocyte apoptosis; ITPR3 siRNA and NF-κB inhibitor both reduced LECT2 and apoptosis, and in vivo ITPR3 silencing attenuated liver fibrosis in a CCl4 mouse model. siRNA knockdown, NF-κB inhibitor, ITPR3 overexpression, Ca2+ measurement, apoptosis assay, in vivo CCl4 fibrosis model Scientific reports Medium 41826410
2024 miR-223-3p directly targets ITPR3 (validated by luciferase reporter assay); high glucose downregulates miR-223-3p, leading to increased ITPR3 expression, elevated intracellular Ca2+, and ferroptosis in glomerular endothelial cells. Luciferase reporter assay, miR-223-3p overexpression/silencing (adenovirus), Ca2+ measurement, ferroptosis marker assays (GPX4, xCT, ACSL4), high-glucose cell model Molecular and cellular endocrinology Medium 39426490
2025 Sigma-1 receptor (S1R) chaperones IP3R3 at the MAM and upon activation increases Ca2+ efflux from the ER into mitochondria; S1R KO reduces mitochondrial activity and glycolysis in neuronal cells. S1R knockout cells and mice, Ca2+ imaging, Seahorse respirometry, PET imaging, GRIM19 knockdown rescue bioRxivpreprint Low
2024 In uveal melanoma, GNAQ/11 oncogenic activation negatively regulates IP3R expression (including IP3R3 downregulation); restoring IP3R3 expression increased spontaneous cell death and sensitized UVM cells to pro-apoptotic stimuli, demonstrating that IP3R3 downregulation by Gαq/11 protects UVM cells from Ca2+-driven apoptosis. IP3R3 re-expression, Gαq/11 inhibition, Ca2+ imaging, cell death assays (staurosporine, BIRD2 peptide) bioRxivpreprint Low
2024 IP3R3 silencing in breast cancer cells reduces pyruvate dehydrogenase (PDH) enzyme activity, with a stronger effect in estrogen-independent MDA-MB-231 cells than estrogen-dependent MCF-7 cells, linking IP3R3-mediated Ca2+ signaling to mitochondrial metabolic enzyme activity. siRNA knockdown, flow cytometry (transfection efficiency), RT-qPCR, western blot, PDH activity assay Advanced biomedical research Low 38808320

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature 334 28614305
1993 Sequence and functional characterization of a third inositol trisphosphate receptor subtype, IP3R-3, expressed in pancreatic islets, kidney, gastrointestinal tract, and other tissues. The Journal of biological chemistry 283 8388391
2017 PTEN counteracts FBXL2 to promote IP3R3- and Ca2+-mediated apoptosis limiting tumour growth. Nature 208 28614300
2018 TOM70 Sustains Cell Bioenergetics by Promoting IP3R3-Mediated ER to Mitochondria Ca2+ Transfer. Current biology : CB 135 29395920
2020 FUNDC1 interacts with FBXL2 to govern mitochondrial integrity and cardiac function through an IP3R3-dependent manner in obesity. Science advances 118 32938669
2008 Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. American journal of physiology. Cell physiology 99 19052258
2021 SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria. Nature communications 69 34518526
2013 Rapamycin improves sociability in the BTBR T(+)Itpr3(tf)/J mouse model of autism spectrum disorders. Brain research bulletin 61 24295733
2018 Resveratrol attenuates pro-inflammatory cytokines and activation of JAK1-STAT3 in BTBR T+ Itpr3tf/J autistic mice. European journal of pharmacology 57 29654783
2019 Atheroprotective Flow Upregulates ITPR3 (Inositol 1,4,5-Trisphosphate Receptor 3) in Vascular Endothelium via KLF4 (Krüppel-Like Factor 4)-Mediated Histone Modifications. Arteriosclerosis, thrombosis, and vascular biology 56 30917677
2017 Adenosine A2A receptor modulates neuroimmune function through Th17/retinoid-related orphan receptor gamma t (RORγt) signaling in a BTBR T+ Itpr3tf/J mouse model of autism. Cellular signalling 55 28438638
2003 Possible involvement of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers. Anticancer research 55 14666665
2018 Chlamydia trachomatis inclusion membrane protein MrcA interacts with the inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) to regulate extrusion formation. PLoS pathogens 51 29543918
2018 Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal Toll-Like Receptors and COX-2 Signaling in BTBR T+ Itpr3tf/J Mice. Neuromolecular medicine 48 29468499
2017 Toll-like receptors, NF-κB, and IL-27 mediate adenosine A2A receptor signaling in BTBR T+ Itpr3tf/J mice. Progress in neuro-psychopharmacology & biological psychiatry 46 28668513
2017 Activation of adenosine A2A receptor signaling regulates the expression of cytokines associated with immunologic dysfunction in BTBR T+ Itpr3tf/J mice. Molecular and cellular neurosciences 36 28465254
2021 ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma. Journal of experimental & clinical cancer research : CR 33 33573671
2018 S3I-201, a selective Stat3 inhibitor, restores neuroimmune function through upregulation of Treg signaling in autistic BTBR T+ Itpr3tf/J mice. Cellular signalling 30 30213685
2015 Neuronal correlates of asocial behavior in a BTBR T (+) Itpr3(tf)/J mouse model of autism. Frontiers in behavioral neuroscience 29 26300749
2013 An IP3R3- and NPY-expressing microvillous cell mediates tissue homeostasis and regeneration in the mouse olfactory epithelium. PloS one 29 23516531
2010 Single nucleotide polymorphism rs2229634 in the ITPR3 gene is associated with the risk of developing coronary artery aneurysm in children with Kawasaki disease. International journal of immunogenetics 29 20618519
2008 A functional SNP in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus in Japanese population. Journal of human genetics 29 18219441
2023 Ketogenic diet ameliorates autism spectrum disorders-like behaviors via reduced inflammatory factors and microbiota remodeling in BTBR T+ Itpr3tf/J mice. Experimental neurology 28 37149279
2020 5-aminoisoquinolinone attenuates social behavior deficits and immune abnormalities in the BTBR T+ Itpr3tf/J mouse model for autism. Pharmacology, biochemistry, and behavior 27 31982447
2018 IP3R3 silencing induced actin cytoskeletal reorganization through ARHGAP18/RhoA/mDia1/FAK pathway in breast cancer cell lines. Biochimica et biophysica acta. Molecular cell research 26 29630900
2018 NS5A Promotes Constitutive Degradation of IP3R3 to Counteract Apoptosis Induced by Hepatitis C Virus. Cell reports 26 30355490
2013 Taste dysfunction in BTBR mice due to a mutation of Itpr3, the inositol triphosphate receptor 3 gene. Physiological genomics 26 23859941
2020 Dominant mutations in ITPR3 cause Charcot-Marie-Tooth disease. Annals of clinical and translational neurology 23 32949214
2022 Lead (Pb) exposure exacerbates behavioral and immune abnormalities by upregulating Th17 and NF-κB-related signaling in BTBR T+ Itpr3tf/J autistic mouse model. Neurotoxicology 22 35760230
2014 Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation. Neurobiology of aging 21 25482245
2020 Development, phenotypes of immune cells in BTBR T+Itpr3tf/J mice. Cellular immunology 20 33137646
2022 Functional genetic screen identifies ITPR3/calcium/RELB axis as a driver of colorectal cancer metastatic liver colonization. Developmental cell 19 35487218
2020 Somatosensorimotor and Odor Modification, Along with Serotonergic Processes Underlying the Social Deficits in BTBR T+ Itpr3tf/J and BALB/cJ Mouse Models of Autism. Neuroscience 19 32061779
2021 Potentially functional variants of HBEGF and ITPR3 in GnRH signaling pathway genes predict survival of non-small cell lung cancer patients. Translational research : the journal of laboratory and clinical medicine 18 33400994
2019 Correlation Between Altered DNA Methylation of Intergenic Regions of ITPR3 and Development of Delayed Cerebral Ischemia in Patients with Subarachnoid Hemorrhage. World neurosurgery 18 31247352
2019 The Stat3 inhibitor, S3I-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T+ Itpr3tf/J mouse model of autism. Brain research bulletin 18 31299319
2025 Mfn2 regulates calcium homeostasis and suppresses PASMCs proliferation via interaction with IP3R3 to mitigate pulmonary arterial hypertension. Journal of translational medicine 17 40128893
2017 Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model. Molecular neurobiology 17 28421534
2019 The potent immunomodulatory compound VGX-1027 regulates inflammatory mediators in CD4+ T cells, which are concomitant with the prevention of neuroimmune dysregulation in BTBR T+ Itpr3tf/J mice. Life sciences 16 31610190
2020 STIM1 Deficiency Leads to Specific Down-Regulation of ITPR3 in SH-SY5Y Cells. International journal of molecular sciences 13 32916960
2019 The histamine-4 receptor antagonist JNJ7777120 prevents immune abnormalities by inhibiting RORγt/T-bet transcription factor signaling pathways in BTBR T+ Itpr3tf/J mice exposed to gamma rays. Molecular immunology 13 31522074
2017 ITPR3 gene haplotype is associated with cervical squamous cell carcinoma risk in Taiwanese women. Oncotarget 13 28036301
2008 The association between type 1 diabetes and the ITPR3 gene polymorphism due to linkage disequilibrium with HLA class II. Genes and immunity 13 18340361
2022 Methylmercury chloride exposure exacerbates existing neurobehavioral and immune dysfunctions in the BTBR T+ Itpr3tf/J mouse model of autism. Immunology letters 11 35259423
2022 CXCR2 antagonist SB332235 mitigates deficits in social behavior and dysregulation of Th1/Th22 and T regulatory cell-related transcription factor signaling in male BTBR T+ Itpr3tf/J mouse model of autism. Pharmacology, biochemistry, and behavior 11 35644272
2024 Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency. The Journal of experimental medicine 10 39560673
2021 Involvement of Intestinal Goblet Cells and Changes in Sodium Glucose Transporters Expression: Possible Therapeutic Targets in Autistic BTBR T+Itpr3tf/J Mice. International journal of environmental research and public health 10 34769857
2022 Transcriptional ITPR3 as potential targets and biomarkers for human pancreatic cancer. Aging 8 35580861
2022 Improvements of autism-like behaviors but limited effects on immune cell metabolism after mitochondrial replacement in BTBR T+Itpr3tf/J mice. Journal of neuroimmunology 8 35617718
2022 Inhibition of IP3R3 attenuates endothelial to mesenchymal transition induced by TGF-β1 through restoring mitochondrial function. Biochemical and biophysical research communications 8 35760011
2012 Itpr3 Is responsible for the mouse tufted (tf) locus. The Journal of heredity 8 23100490
2003 [Possible involvement of inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers]. Gan to kagaku ryoho. Cancer & chemotherapy 8 14619519
2024 Dysregulated HPA axis during postnatal developmental stages in the BTBR T+ Itpr3tf/J mouse: A model of autism spectrum disorder. Neuropsychopharmacology reports 7 39610036
2021 Humulus japonicus rescues autistic‑like behaviours in the BTBR T+ Itpr3tf/J mouse model of autism. Molecular medicine reports 7 33880583
2020 BBOX1 promotes triple-negative breast cancer progression by controlling IP3R3 stability. Molecular & cellular oncology 7 33241108
2024 Fullerenols Ameliorate Social Deficiency and Rescue Cognitive Dysfunction of BTBR T+Itpr3tf/J Autistic-Like Mice. International journal of nanomedicine 6 38911505
2021 Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4). Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 6 34798470
2024 High glucose elevates intracellular calcium level and induces ferroptosis in glomerular endothelial cells through the miR-223-3p/ITPR3 pathway. Molecular and cellular endocrinology 5 39426490
2023 Aflatoxin B1 Exposure Aggravates Neurobehavioral Deficits and Immune Dysfunctions of Th1, Th9, Th17, Th22, and T Regulatory Cell-Related Transcription Factor Signaling in the BTBR T+Itpr3tf/J Mouse Model of Autism. Brain sciences 5 38002479
2022 Altered meningeal immunity contributing to the autism-like behavior of BTBR T Itpr3 /J mice. Brain, behavior, & immunity - health 5 36439055
2016 Requirement of IP3 receptor 3 (IP3R3) in nitric oxide induced cardiomyocyte differentiation of mouse embryonic stem cells. Experimental cell research 5 27349290
2025 MPTP mediated Ox-mtDNA release inducing macrophage pyroptosis and exacerbating MCD-induced MASH via promoting the ITPR3/Ca2+/NLRP3 pathway. Journal of translational medicine 4 41239426
2024 A pleiotropic recurrent dominant ITPR3 variant causes a complex multisystemic disease. Science advances 4 39270020
2023 Cadmium exposure exacerbates immunological abnormalities in a BTBR T+ Itpr3tf/J autistic mouse model by upregulating inflammatory mediators in CD45R-expressing cells. Journal of neuroimmunology 4 38064869
2024 Aflatoxin B1 exposure deteriorates immune abnormalities in a BTBR T+ Itpr3tf/J mouse model of autism by increasing inflammatory mediators' production in CD19-expressing cells. Journal of neuroimmunology 3 38723577
2024 Vasostatin-1 restores autistic disorders in an idiopathic autism model (BTBR T+ Itpr3tf/J mice) by decreasing hippocampal neuroinflammation. Progress in neuro-psychopharmacology & biological psychiatry 3 39209101
2024 ITPR3-associated neuropathy: Report of a further family with adult onset intermediate Charcot-Marie-Tooth disease. European journal of neurology 3 39287469
2023 Increased IP3R-3 degradation induced by acrylamide promoted Ca2+-dependent calpain activation and axon damage in rats. Toxicology letters 3 37353096
2022 Multiple exposure to methylmercury aggravates DNA damage in the BTBR T + Itpr3 tf/J autistic mouse model: The role of DNA repair efficiency. Toxicology 3 35914580
2008 Apoptotic effects of inositol hexaphosphate on biomarker Itpr3 in induced colon rat carcinogenesis. Acta cirurgica brasileira 3 18372961
2025 A recurrent missense variant in ITPR3 causes demyelinating Charcot-Marie-Tooth with variable severity. Brain : a journal of neurology 2 38938188
2025 A computational perception of BBOX1-IP3R3 interaction uncovers inhibitors for dysregulated calcium signalling in triple negative breast cancer. SAR and QSAR in environmental research 2 40366709
2024 Melatonin Attenuates Ferritinophagy/Ferroptosis by Acting on Autophagy in the Liver of an Autistic Mouse Model BTBR T+Itpr3tf/J. International journal of molecular sciences 2 39684310
2025 Zhizichi decoction alleviates depressive-like behaviors through modulating mitochondria-associated membrane via the IP3R3-GRP75-VDAC1 complex. Journal of ethnopharmacology 1 40074101
2025 Impact of static magnetic field exposure on Stim1 and Itpr3 expression in hepatic cells of obese mice. Journal of advanced veterinary and animal research 1 40568493
2025 Two cases of combined immunodeficiency with ITPR3 mutations presenting with life-threatening severe EBV-associated hemophagocytic lymphohistiocytosis. Frontiers in immunology 1 41019080
2024 Aflatoxin B1 exposure exacerbates chemokine receptor expression in the BTBR T+ Itpr3tf/J Mouse Model, unveiling insights into autism spectrum disorder: A focus on brain and spleen. Reproductive toxicology (Elmsford, N.Y.) 1 38679149
2026 Genomic and AI-driven discovery in chronic prostatitis: Causal role of ITPR3 and therapeutic repurposing of raloxifene. European journal of pharmacology 0 41581718
2026 ITPR3 promotes liver fibrosis by damaging hepatocytes via the Ca2+/NF-B/LECT2 pathway. Scientific reports 0 41826410
2026 Drynaria roosii-derived exosome-like nanovesicles promote alveolar socket healing via activation of ITPR3-mediated calcium flux. Journal of nanobiotechnology 0 42163262
2025 Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism. Molecular neurobiology 0 40172818
2025 CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complex. Scientific reports 0 40595218
2025 Ursolic acid enhances social behavior and modulates Th1, Th17, and T regulatory cell-related transcription factor signaling in the BTBR T+ Itpr3tf/J mouse model of autism. Journal of neuroimmunology 0 41275565
2024 [Immunophenotyping by spectral cytometry reveals a profile of lymphopenia associated with deregulation with an increase in effector memory lymphocytes in a patient with a mutation in the ITPR3 gene]. Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993) 0 38683077
2024 Evaluation of IP3R3 Gene Silencing Effect on Pyruvate Dehydrogenase (PDH) Enzyme Activity in Breast Cancer Cells with and Without Estrogen Receptor. Advanced biomedical research 0 38808320

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