Affinage

SHROOM3

Protein Shroom3 · UniProt Q8TF72

Length
1996 aa
Mass
216.9 kDa
Annotated
2026-06-10
41 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SHROOM3 is an F-actin-binding scaffold protein that drives epithelial apical constriction and cell shape change by recruiting Rho kinases (ROCK1/2) to apical junctions and activating actomyosin contractility, thereby governing morphogenetic processes from neural tube closure to organ invagination (PMID:18339671, PMID:20081189, PMID:25171888). The ROCK interaction is mediated by a defined binding site (ASD2 domain) on SHROOM3 and the RII-C1 region of ROCK; competitive disruption or a point mutation (R1838C) that abolishes ROCK binding renders SHROOM3 non-functional and causes neural tube defects, establishing ROCK as its principal downstream effector (PMID:18339671, PMID:25171888). SHROOM3 concentrates F-actin, myosin II, and Vasp apically to power apical constriction, and this output operates downstream of an upstream regulatory network: it is transcriptionally activated by Pax6 in the lens and by Pitx factors in the gut, positioned downstream of FGF signaling and the Trio–RhoA GEF pathway (RhoA activity being required for SHROOM3 apical localization), and recruited to adherens junctions by p120-catenin (PMID:20081189, PMID:20332151, PMID:22031541, PMID:23136387, PMID:25038041). SHROOM3 also acts within the planar cell polarity pathway, physically interacting with Dishevelled 2 and genetically with Vangl2/Wnt5a to coordinate planar-polarized constriction during neural tube and cardiac morphogenesis (PMID:25596276, PMID:32511952). In the kidney, SHROOM3 serves two genetically separable functions: an ASD2/ROCK-binding arm that drives TGF-β1/Wnt–β-catenin profibrotic signaling in tubular cells, and a distinct FYN-binding (SH3) arm that activates FYN to phosphorylate nephrin and maintain podocyte foot process architecture and the glomerular filtration barrier (PMID:25437874, PMID:30341149, PMID:39605692, PMID:41469391). Loss or actin-binding-domain variants of SHROOM3 cause podocyte foot process effacement, glomerulosclerosis, and proteinuria, while it is also required for epithelial repair after ischemic injury (PMID:25273069, PMID:26940091, PMID:35368578). Coding and noncoding SHROOM3 variants are linked to chronic kidney disease, acting through altered TCF7L2-dependent transcription, 14-3-3/Hippo interaction, and disrupted actin binding (PMID:25437874, PMID:25273069, PMID:29476007).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2008 High

    Established the core effector mechanism: how SHROOM3 converts its scaffold role into actomyosin contractility at apical junctions.

    Evidence Co-IP, dominant-negative RII-C1 fragment, live phospho-myosin imaging and shRNA in neural tube

    PMID:18339671

    Open questions at the time
    • Does not resolve how SHROOM3 itself is recruited to apical junctions
    • Structural basis of the ROCK-binding interface not defined
  2. 2010 High

    Placed SHROOM3 downstream of tissue-specific transcription factors, explaining how its apical-constriction output is deployed in distinct organs.

    Evidence Mouse LOF with apical F-actin/myosin/Vasp localization and Pax6 epistasis (lens); Pitx promoter-reporter and Xenopus gain-of-function (gut)

    PMID:20081189 PMID:20332151

    Open questions at the time
    • Whether Pax6 and Pitx act through shared cis-elements not addressed
    • Post-transcriptional control of SHROOM3 not examined
  3. 2011 High

    Defined the upstream GTPase and junctional inputs that localize and activate SHROOM3 for apical constriction.

    Evidence Dominant-negative/constitutively active RhoA, Trio LOF and MDCK assays (lens); compound heterozygote Shroom3/N-cadherin genetics (gut)

    PMID:21726547 PMID:22031541

    Open questions at the time
    • Direct biochemical link between RhoA and SHROOM3 localization not established
    • N-cadherin/SHROOM3 cooperation mechanism inferred from genetics only
  4. 2012 High

    Generalized SHROOM3 as the central organizer of cell-shape change downstream of FGF signaling in a vertebrate sensory primordium.

    Evidence FGF pathway manipulation and shroom3 gain/loss-of-function with rosette quantification in zebrafish

    PMID:23136387

    Open questions at the time
    • Direct transcriptional link between FGF and shroom3 not mapped
  5. 2014 High

    Proved ROCK binding is the essential output and identified the junctional recruitment receptor, cementing the constriction module.

    Evidence ENU R1838C mutant abolishing ROCK binding (neural tube); p120-catenin compound heterozygote genetics and SHROOM3 localization rescue (lens)

    PMID:25038041 PMID:25171888

    Open questions at the time
    • Whether p120-catenin binds SHROOM3 directly not shown
    • Other recruitment partners at distinct junctions unexplored
  6. 2014 High

    Opened the kidney axis, distinguishing a tubular profibrotic transcriptional/signaling role from a podocyte actin-barrier role.

    Evidence TCF7L2-dependent enhancer reporter, tubule-specific knockdown UUO fibrosis model; zebrafish allele-specific rescue with actin-binding-domain mutant

    PMID:25273069 PMID:25437874

    Open questions at the time
    • How a single gene's distinct cellular roles are coordinated not resolved at this stage
    • Direct SHROOM3 effectors in fibrosis vs. barrier maintenance not yet separated
  7. 2015 Medium

    Extended ROCK-interaction dependence to axon outgrowth and demonstrated druggability of the SHROOM3-ROCK interface.

    Evidence HTS, covalent inhibitor CCG-17444 targeting Cys1816, neurite outgrowth assay placing SHROOM3 downstream of NogoA

    PMID:26077244

    Open questions at the time
    • In vivo relevance of the NogoA-SHROOM3 axis not tested
    • Single lab, biochemical and cell-based only
  8. 2015 High

    Connected SHROOM3 to PCP machinery, showing it acts within planar polarity signaling rather than as an isolated constriction effector.

    Evidence Reciprocal Co-IP with Dishevelled 2, compound heterozygote genetics with Vangl2/Wnt5a, planar polarity marker imaging in neural plate

    PMID:25596276

    Open questions at the time
    • Domain on SHROOM3 binding Dishevelled 2 not mapped
    • Whether PCP input is upstream of or parallel to ROCK recruitment unclear
  9. 2016 High

    Demonstrated SHROOM3 maintains podocyte architecture and drives invagination in additional organs, defining adult kidney disease and developmental roles.

    Evidence Shroom3 KO/heterozygous mice with glomerulosclerosis and actomyosin readouts; gene-trap thyroid bud apical constriction with Cdc42 dependence

    PMID:26772200 PMID:26940091

    Open questions at the time
    • Mechanism linking Cdc42 to SHROOM3 localization not defined
    • How heterozygosity produces adult-onset disease not resolved
  10. 2018 High

    Identified a second, ROCK-independent SHROOM3 signaling arm (FYN/nephrin) and a 14-3-3/Hippo-linked CKD variant, revealing functional modularity.

    Evidence Endogenous SHROOM3-FYN Co-IP, SH3-binding domain mapping, glomerular shRNA mouse with EM/RNA-seq; SHROOM3 P1244L 14-3-3 binding assay and novel PDZ-less isoform cloning

    PMID:29476007 PMID:30341149

    Open questions at the time
    • Direct kinase mechanism of FYN activation by SHROOM3 not fully resolved
    • Functional role of the PDZ-less isoform untested in vivo
  11. 2020 High

    Showed the SHROOM3-Dishevelled2/PCP axis governs cardiomyocyte polarity and cardiac chamber morphogenesis.

    Evidence SHROOM3-Dishevelled 2 Co-IP, Shroom3 gene-trap KO with congenital heart defects and actomyosin/proliferation readouts

    PMID:32511952

    Open questions at the time
    • Whether cardiac defects arise cell-autonomously not fully separated
    • Link between proliferation phenotype and actomyosin role unclear
  12. 2022 Medium

    Refined the cellular logic of constriction, showing SHROOM3 acts both cell-autonomously and non-cell-autonomously across cell neighborhoods.

    Evidence Mosaic CRISPR crispants and tissue-scale time-lapse imaging with regression modeling in Xenopus; regional cranial vs. spinal analysis

    PMID:35244026 PMID:36113571

    Open questions at the time
    • Molecular basis of non-cell-autonomous coupling not identified
    • Regional functional differences not linked to specific partners
  13. 2023 Medium

    Validated SHROOM3's apical-constriction role in human and primate neuroepithelial models and tied it to folate-independent neural tube defect mechanisms.

    Evidence SHROOM3 CRISPR KO in human cortical organoids (lumen/F-actin); KO in cynomolgus monkey neuroepithelial organoids with folate supplementation test

    PMID:37443734 PMID:38287904

    Open questions at the time
    • Single-lab organoid models
    • Does not establish SHROOM3 variants as human NTD causes
  14. 2025 High

    Achieved separation-of-function, dissociating the ROCK-binding (profibrotic) and FYN-binding (antiproteinuric) arms and demonstrating therapeutic targeting of the SHROOM3-ROCK interaction.

    Evidence Domain-deletion transgenic mice (ASD2Δ, FBDM-Sh3), cell-based ROCK activation, UUO/AAN fibrosis models, small-molecule P2Is (BT1137)

    PMID:39605692 PMID:41469391

    Open questions at the time
    • Long-term efficacy and specificity of P2Is in vivo not established
    • How the two arms are differentially deployed across cell types not fully resolved
  15. 2025 High

    Expanded SHROOM3's roles to epithelial fusion, cardiomyocyte ploidy/contractile function, and podocyte focal adhesion regulation.

    Evidence Tissue-specific KO of optic fissure/retina; CM-specific Nkx2-5-Cre deletion with ploidy/echo and actin-variant testing; podocyte-specific KO with focal adhesion/RhoA/calpain readouts

    PMID:40113025 PMID:40558522 PMID:42189988

    Open questions at the time
    • Mechanism linking SHROOM3 to DNA replication genes and ploidy unclear
    • Direct effectors at focal adhesions vs. apical actin not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SHROOM3's distinct molecular arms (ROCK/actomyosin, FYN/nephrin, 14-3-3/Hippo, focal adhesion regulation) are selectively engaged and coordinated within a single cell type remains unresolved.
  • No structural model integrating the multiple binding interfaces
  • Upstream switch determining which arm is active in a given context unknown
  • Direct mechanism by which SHROOM3 alters DNA replication gene expression undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 4
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4
Partners
CTNND1DVL2FYNNRP1RHOAROCK1ROCK2YWHAE

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Shroom3 directly binds ROCK1/2 (Rho kinases) via a defined binding site (RII-C1 on ROCKs) and recruits them to epithelial apical junctions. Expression of the competitive antagonist RII-C1 fragment displaced apically localized ROCKs and blocked neural tube closure, demonstrating that the Shroom3-ROCK interaction is required for apical junction remodeling and neural tube morphogenesis. Co-immunoprecipitation, dominant-negative RII-C1 fragment expression, live imaging of phospho-myosin distribution, shRNA depletion in neural tube Development (Cambridge, England) High 18339671
2010 Shroom3 is required for apical localization of F-actin, myosin II, and Vasp during lens placode invagination. Loss of Shroom3 abolishes apical constriction of lens epithelial cells, and Shroom3 expression in the lens is directly controlled by the transcription factor Pax6. Loss-of-function mouse genetics, immunofluorescence for F-actin/myosin II/Vasp localization, genetic epistasis with Pax6 mutants Development (Cambridge, England) High 20081189
2010 Pitx transcription factors directly activate Shroom3 transcription through Pitx-responsive regulatory elements in the Shroom3 genomic locus. Ectopic Pitx expression is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change in Xenopus gut. Promoter-reporter assays, Pitx gain-of-function in Xenopus, Shroom3 loss-of-function, identification of Pitx-responsive cis-regulatory elements Development (Cambridge, England) High 20332151
2011 A Trio (RhoA-GEF)–RhoA–Shroom3 pathway is required for apical constriction during lens pit invagination. RhoA activity is required for Shroom3 apical localization, and activated apical RhoA is sufficient to induce apical constriction. Trio is required for Shroom3-dependent apical constriction in MDCK cells and in the lens pit. Dominant-negative and constitutively active RhoA constructs, MDCK cell assays, Trio loss-of-function in lens pit, epistasis experiments Development (Cambridge, England) High 22031541
2011 Shroom3 and N-cadherin function cooperatively downstream of Pitx2 to regulate asymmetric epithelial cell shape changes required for gut tube morphogenesis. Genetic interaction shown by compound heterozygous analysis: loss of one allele each of Shroom3 and N-cadherin phenocopies homozygous loss of either gene alone. Mouse genetics, compound heterozygous analysis, morphometric analysis of dorsal mesentery epithelial cells Developmental biology Medium 21726547
2012 Shroom3 expression in the lateral line primordium is downstream of FGF signaling. Shroom3 drives apical constriction and rosette assembly by coordinating Rho kinase recruitment and non-muscle myosin activation. Gain- and loss-of-function experiments in zebrafish demonstrated Shroom3 is the main organizer of cell shape changes during proneuromast assembly. FGF pathway manipulation, shroom3 gain- and loss-of-function in zebrafish, quantitative rosette detection, myosin inhibition Development (Cambridge, England) High 23136387
2014 A point mutation (R1838C) in mouse Shroom3, identified by ENU mutagenesis, abolishes ROCK binding without affecting Shroom3 expression or localization, rendering Shroom3 non-functional for cell morphology regulation and causing neural tube defects. This establishes ROCK as the major downstream effector of Shroom3 in neural tube morphogenesis. ENU mutagenesis, biochemical binding assays, site-directed mutagenesis, neural tube phenotype analysis Biology open High 25171888
2014 p120-catenin recruits Shroom3 to adherens junctions and is required for apical constriction during lens placode morphogenesis. Genetic interaction between p120-catenin and Shroom3 was established; p120-catenin loss phenocopies Shroom3 loss in lens AC. Mouse genetics, genetic interaction analysis (compound heterozygotes), immunolocalization of Shroom3 at junctions, lens cell morphometry Development (Cambridge, England) High 25038041
2014 SHROOM3 facilitates canonical TGF-β1 signaling (increasing COL1A1 expression) in renal tubular cells downstream of a β-catenin/TCF7L2-mediated pathway. The intronic SNP rs17319721 acts as a TCF7L2-dependent enhancer element increasing SHROOM3 transcription. Tubule-specific knockdown of Shroom3 abrogated interstitial fibrosis in a mouse model of ureteric obstruction. Luciferase reporter assay for enhancer function, siRNA knockdown in renal tubular cells, inducible tubular-specific Shroom3 knockdown mouse, unilateral ureteric obstruction model, collagen expression assays The Journal of clinical investigation High 25437874
2014 Variants disrupting the actin-binding domain of SHROOM3 cause podocyte foot process effacement and impairment of the glomerular filtration barrier, as shown in zebrafish rescue experiments where the FHH rat Shroom3 allele (carrying an actin-binding domain mutation) failed to rescue glomerular defects. Zebrafish shroom3 knockdown, allele-specific rescue with wild-type vs. FHH mutant Shroom3, glomerular filtration assays, congenic rat mapping Genome research High 25273069
2015 Shroom3 physically interacts with Dishevelled 2 (a PCP pathway component) and co-distributes with it in cells. Shroom3 and PCP components (Vangl2, Wnt5a) genetically interact during neural tube closure; simultaneous depletion increases NTD liability and CE failure. Multiple Shroom3 pathway components are planar-polarized along mediolateral junctions in the neural plate in a Shroom3- and PCP-dependent manner. Co-immunoprecipitation (Shroom3–Dishevelled 2), compound heterozygous mouse genetics, immunofluorescence for planar polarity markers, neural tube defect scoring Biology open High 25596276
2015 A small molecule (CCG-17444) covalently targets Shroom3 Cys1816 to inhibit the Shroom3-ROCK protein-protein interaction in vitro. Inhibition of the Shroom3-ROCK interaction with CCG-17444 counteracts Nogo66-mediated inhibition and enhances neurite outgrowth, placing Shroom3 downstream of NogoA/Nogo66 in conveying axon outgrowth inhibitory signals. High-throughput screen, in vitro binding assay, covalent mechanism characterization, site-directed mutagenesis (Cys1816), neurite outgrowth assay BMC neuroscience Medium 26077244
2016 Shroom3 null mice exhibit glomerular abnormalities (cystic and collapsing glomeruli), disrupted podocyte arrangement, and altered Rho-kinase/myosin II signaling with loss of apically distributed actin. Heterozygous mice develop adult-onset glomerulosclerosis and proteinuria, establishing Shroom3's role in maintaining podocyte architecture via actomyosin network modulation. Shroom3 gene trap knockout mouse, immunofluorescence for actin and myosin II, renal histology, proteinuria measurement Journal of the American Society of Nephrology : JASN High 26940091
2016 SHROOM3 is required for apical constriction in the thyroid bud epithelium; its subcellular localization is disrupted in Cdc42-deficient embryos. In Shroom3 gene trap mutants, the thyroid bud epithelium lacks apical constriction, causing it to protrude into the foregut lumen rather than invaginating into the mesenchyme. Shroom3 gene trap mouse, Cdc42 conditional knockout, immunofluorescence for SHROOM3 localization, histological analysis of thyroid bud morphogenesis Biology open Medium 26772200
2018 SHROOM3 interacts with FYN (a Src-family kinase) via a critical SH3-binding domain distinct from its ROCK-binding domain. The SHROOM3-FYN interaction is required for FYN kinase activation and downstream nephrin phosphorylation in podocytes. Glomerular-specific Shroom3 knockdown induces albuminuria and foot process effacement, while altering podocyte cytoskeleton, adhesion, and migration. Co-immunoprecipitation of endogenous SHROOM3 with FYN in human podocytes, inducible shRNA knockdown mouse (glomerular vs. tubular), electron microscopy, glomerular RNA-seq, in vitro kinase/nephrin phosphorylation assays Journal of the American Society of Nephrology : JASN High 30341149
2018 A SHROOM3 coding variant P1244L (associated with CKD) attenuates the interaction of SHROOM3 with 14-3-3 proteins, suggesting involvement of the Hippo pathway. A novel SHROOM3 isoform lacking the PDZ domain was identified, regulated by an alternative transcription start site controlled by the noncoding CKD-risk variant rs17319721, which disrupts TCF7L2 binding in podocyte nuclear extracts. Biophysical binding assays (SHROOM3-14-3-3 interaction), allele-specific transcription factor binding (TCF7L2 binding disruption), CRISPR/Cas9 editing, molecular cloning of novel isoform, nuclear extract pulldown Journal of the American Society of Nephrology : JASN Medium 29476007
2020 SHROOM3 physically and genetically interacts with Dishevelled 2 downstream of PCP signaling during cardiac development. Loss of Shroom3 in mice causes congenital heart defects (VSDs, DORV, thin LV myocardium) with disrupted actomyosin cytoskeleton, cardiomyocyte polarity, organization, proliferation, and morphology, phenocopying PCP disruption. Co-immunoprecipitation (SHROOM3-Dishevelled 2), Shroom3 gene trap KO mouse, cardiac histology, immunofluorescence for PCP/actomyosin components, proliferation assays Developmental biology High 32511952
2021 Shroom3 is required for epithelial repair and redifferentiation after ischemic AKI. Shroom3 heterozygous null mice show increased mortality, worse kidney function, and impaired epithelial redifferentiation after ischemia, associated with disrupted Rho-kinase/myosin signaling and disorganized apical F-actin. MDCK cell experiments showed Shroom3 levels directly correlate with apical organization of actin and actomyosin regulators. Bilateral ischemia in Shroom3 heterozygous mice, renal histology, apoptosis/proliferation assays, immunofluorescence for actomyosin regulators, MDCK cell knockdown Kidney360 Medium 35368578
2022 Medial actin accumulation drives apical constriction non-cell-autonomously in neighborhoods of cells during neural tube closure. Mosaic crispant analysis of Shroom3 in Xenopus revealed both cell-autonomous and non-cell-autonomous effects on apical constriction. Tissue-scale time-lapse imaging, mosaic CRISPR crispant embryos in Xenopus, multivariate regression modeling of cell behavior Developmental biology Medium 36113571
2022 Regional differences exist in Shroom3 function during cranial vs. spinal neural tube closure in Xenopus. Mosaic shroom3 mutations reveal distinct cell biological requirements in anterior versus posterior neural tube closure. CRISPR mosaic mutagenesis in Xenopus, high-resolution tissue-level time-lapse microscopy, regional analysis of actin and N-cadherin dynamics eLife Medium 35244026
2023 SHROOM3 knockout in a human brain organoid model causes expansion of the apical lumen and reduced F-actin polarization, with increased apical cell surface area due to reduced apical constriction. This phenocopies valproic acid treatment, establishing impaired apical constriction as a shared mechanism. SHROOM3 CRISPR/Cas9 knockout in self-organizing single-rosette cortical organoids, high-throughput imaging, F-actin immunostaining, lumen size quantification Cells Medium 37443734
2024 Loss of SHROOM3 in cynomolgus monkey neuroepithelial organoids results in shorter cells with smaller nuclei due to insufficient apical recruitment of F-actin, myosin II, and phospho-myosin light chain. These defects are not rescued by folate supplementation. SHROOM3 knockout in cynomolgus monkey neuroepithelial organoids, immunofluorescence for F-actin/myosin II/pMLC, RNA sequencing, folate supplementation experiment Zoological research Medium 38287904
2024 NRP1 physically interacts with SHROOM3 via protein-protein interaction, and this interaction depends on glycosaminoglycan (GAG) modification of NRP1 at Ser612. Shroom3 knockdown inhibits osteo/odontogenic differentiation of dental pulp stem cells, placing Shroom3 downstream of NRP1 in this pathway. Co-immunoprecipitation (NRP1-SHROOM3), protein docking, confocal co-localization, NRP1 S612A mutant (non-GAG-modified), shroom3 siRNA knockdown, ALP/mineralization assays Biochimica et biophysica acta. Molecular cell research Medium 39033931
2024 The ASD2 domain of Shroom3 (ROCK-binding domain) is the specific profibrotic motif mediating tubulo-interstitial fibrosis. Transgenic mice overexpressing ASD2-deleted Shroom3 (ASD2Δ-Sh3) show reduced ROCK activation (phospho-MYPT1), reduced profibrotic/pro-inflammatory transcripts, and reduced fibrosis in UUO and aristolochic acid nephropathy models compared to WT-Sh3 overexpressors. A distinct FYN-binding motif of Shroom3, separate from ASD2, is required for its anti-albuminuric function. ASD2 domain deletion transgenic mice, in vitro ROCK activation assays, in vivo fibrosis models (UUO, AAN), transcriptome analysis, albuminuria measurement, Fyn-binding domain mutant bioRxiv (preprint)preprint Medium 39605692
2025 The ASD2-domain deletion of Shroom3 (ASD2Δ-Sh3) abolishes ROCK binding and prevents TGFβ1/Wnt/Ctnnb1 profibrotic signaling in tubular cells and fibroblasts. In vivo, tubular-specific (but not fibroblast-specific) ASD2Δ-Sh3 overexpression mitigates tubulo-interstitial fibrosis. A distinct Fyn-binding deficient mutant Shroom3 (FBDM-Sh3) induces albuminuria, dissociating the profibrotic (ROCK-binding ASD2) from the antiproteinuric (FYN-binding) function of Shroom3. Small molecule P2Is (including BT1137) targeting the Shroom3-ROCK interaction inhibit ROCK activation and mitigate fibrosis in WT-Sh3 mice. Transgenic overexpression (WT-Sh3, ASD2Δ-Sh3, FBDM-Sh3), cell-based ROCK activation assays, in vivo conditional (tubular/fibroblast-specific) overexpression, fibrosis models (UUO, AAN), small molecule P2I development and testing Nature communications High 41469391
2025 Shroom3 is apically localized in neural retina and retinal pigmented epithelium. Shroom3 deficiency increases apical surface area of neural retina and RPE cells and disrupts optic fissure alignment. Neural retina-specific ablation showed that Shroom3 function in RPE is sufficient for tissue alignment but the fusion process fails due to inability of neural tissue to re-establish apical-basal polarity. Shroom3 deficiency also impairs other polarity-dependent epithelial fusion events (lens vesicle separation, eyelid formation, palate closure). Conditional/tissue-specific Shroom3 knockout mouse, immunofluorescence for apical localization, histological analysis of optic fissure and lens vesicle, quantification of apical cell areas Developmental biology Medium 40113025
2025 VANGL2 and its downstream effector SHROOM3 control bilateral symmetry of the splanchnic mesoderm caudal to the venous pole during heart tube morphogenesis. Apically localized VANGL2 acts through SHROOM3 to regulate this process. Quantitative 3D heart geometry analysis, cell labeling in chick, genetic manipulation of Vangl2 and Shroom3 in mouse, immunolocalization bioRxiv (preprint)preprint Low bio_10.1101_2025.09.05.674213
2025 Shroom3 is specifically expressed in cardiomyocytes of the developing and adult mouse heart. CM-specific deletion of Shroom3 (using Nkx2-5-Cre) causes increased cardiomyocyte hyperpolyploidization and left ventricular dilation with reduced ejection fraction. Functional characterization identified two SHROOM3 coding variants that disrupt SHROOM3-ACTIN interaction and alter expression of DNA replication genes. Genome-wide association mapping in Hybrid Rat Diversity Panel, CM-specific Cre-lox Shroom3 deletion, ploidy assays, echocardiography, functional variant characterization (SHROOM3-actin interaction assay), transcriptome analysis Proceedings of the National Academy of Sciences of the United States of America High 42189988
2025 SHROOM3 deficiency in podocytes exacerbates adriamycin-induced nephropathy. In vitro, SHROOM3 deficiency impairs podocyte size and adhesion with downregulation of focal adhesion molecules (talin1, vinculin, paxillin) and stress fiber regulators (synaptopodin and RhoA), as well as calpain activation and RhoA inactivation. Podocyte-specific SHROOM3 knockout mice, adriamycin nephropathy model, immunofluorescence for focal adhesion and stress fiber components, RhoA activity assay, calpain activity assay Cells Medium 40558522

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling. Development (Cambridge, England) 245 18339671
2010 Pax6-dependent Shroom3 expression regulates apical constriction during lens placode invagination. Development (Cambridge, England) 104 20081189
2011 A Trio-RhoA-Shroom3 pathway is required for apical constriction and epithelial invagination. Development (Cambridge, England) 99 22031541
2014 Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis. The Journal of clinical investigation 71 25437874
2015 Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure. Biology open 70 25596276
2014 Shroom3 contributes to the maintenance of the glomerular filtration barrier integrity. Genome research 66 25273069
2012 Shroom3 is required downstream of FGF signalling to mediate proneuromast assembly in zebrafish. Development (Cambridge, England) 55 23136387
2011 SHROOM3 is a novel candidate for heterotaxy identified by whole exome sequencing. Genome biology 54 21936905
2016 Developmental Origins for Kidney Disease Due to Shroom3 Deficiency. Journal of the American Society of Nephrology : JASN 52 26940091
2014 p120-catenin-dependent junctional recruitment of Shroom3 is required for apical constriction during lens pit morphogenesis. Development (Cambridge, England) 51 25038041
2011 Shroom3 and a Pitx2-N-cadherin pathway function cooperatively to generate asymmetric cell shape changes during gut morphogenesis. Developmental biology 50 21726547
2018 Characterization of Coding/Noncoding Variants for SHROOM3 in Patients with CKD. Journal of the American Society of Nephrology : JASN 47 29476007
2010 Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut. Development (Cambridge, England) 47 20332151
2014 The interaction between Shroom3 and Rho-kinase is required for neural tube morphogenesis in mice. Biology open 36 25171888
2020 SHROOM3 is downstream of the planar cell polarity pathway and loss-of-function results in congenital heart defects. Developmental biology 25 32511952
2018 SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts. Journal of the American Society of Nephrology : JASN 22 30341149
2020 SHROOM3, the gene associated with chronic kidney disease, affects the podocyte structure. Scientific reports 18 33273487
2023 A Shared Pathogenic Mechanism for Valproic Acid and SHROOM3 Knockout in a Brain Organoid Model of Neural Tube Defects. Cells 17 37443734
2022 Global analysis of cell behavior and protein dynamics reveals region-specific roles for Shroom3 and N-cadherin during neural tube closure. eLife 17 35244026
2022 Cardiac Cx43 Signaling Is Enhanced and TGF-β1/SMAD2/3 Suppressed in Response to Cold Acclimation and Modulated by Thyroid Status in Hairless SHRM. Biomedicines 13 35885012
2016 Thyroid bud morphogenesis requires CDC42- and SHROOM3-dependent apical constriction. Biology open 11 26772200
2015 Targeted inhibition of the Shroom3-Rho kinase protein-protein interaction circumvents Nogo66 to promote axon outgrowth. BMC neuroscience 11 26077244
2021 Shroom3, a Gene Associated with CKD, Modulates Epithelial Recovery after AKI. Kidney360 10 35368578
2017 The influence of living donor SHROOM3 and ABCB1 genetic variants on renal function after kidney transplantation. Pharmacogenetics and genomics 10 27779570
2023 The Good and the Bad of SHROOM3 in Kidney Development and Disease: A Narrative Review. Canadian journal of kidney health and disease 8 38107159
2023 Minimal Kidney Disease Phenotype in Shroom3 Heterozygous Null Mice. Canadian journal of kidney health and disease 7 37313360
2022 In vivo high-content imaging and regression analysis reveal non-cell autonomous functions of Shroom3 during neural tube closure. Developmental biology 6 36113571
2024 Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids. Zoological research 4 38287904
2025 Shroom3 facilitates optic fissure closure via tissue alignment and reestablishment of apical-basal polarity during epithelial fusion. Developmental biology 3 40113025
2025 Common cis-regulatory variation modifies the penetrance of pathogenic SHROOM3 variants in craniofacial microsomia. Genome research 3 40234029
2025 Clinical and Metabolic Signatures of FAM47E-SHROOM3 Haplotypes in a General Population Sample. Kidney international reports 3 40485680
2025 Understanding the role of Shroom3 in the developing mouse myocardium. PloS one 2 40920782
2024 Shroom3-Rock interaction and profibrotic function: Resolving mechanism of an intronic CKD risk allele. bioRxiv : the preprint server for biology 2 39605692
2025 Pathogenic variants in SHROOM3 associated with hemifacial microsomia. Journal of human genetics 1 39875538
2025 SHROOM3 Deficiency Aggravates Adriamycin-Induced Nephropathy Accompanied by Focal Adhesion Disassembly and Stress Fiber Disorganization. Cells 1 40558522
2024 NRP1 promotes osteo/odontogenic differentiation via shroom3 in dental pulp stem cells. Biochimica et biophysica acta. Molecular cell research 1 39033931
2023 A Shared Pathogenic Mechanism for Valproic Acid and SHROOM3 Knockout in a Brain Organoid Model of Neural Tube Defects. bioRxiv : the preprint server for biology 1 37090564
2026 Genome-wide association mapping and targeted loss of function studies identify Shroom3 as a driver of hyperpolyploidy and ventricular dilation. Proceedings of the National Academy of Sciences of the United States of America 0 42189988
2025 Mapping Shroom3 expression across the adult mouse. Gene expression patterns : GEP 0 41101717
2025 Design of precision therapeutics for a CKD risk allele by targeting Shroom3-Rock interaction. Nature communications 0 41469391
2025 A non-coding signature in SHROOM3 is associated with kidney disease progression in Fabry disease. Molecular genetics and metabolism 0 41483748

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