Affinage

TMEM132A

Transmembrane protein 132A · UniProt Q24JP5

Length
1023 aa
Mass
110.1 kDa
Annotated
2026-06-10
11 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TMEM132A is a single-pass transmembrane protein that functions as a positive regulator of canonical Wnt/β-catenin signaling during development and in cancer cells (PMID:33324648, PMID:39385148, PMID:42203132). It supports the pathway at two levels: in signal-sending cells it physically binds the Wnt cargo transporter WLS, stabilizes Wnt ligand, and enhances ligand secretion (PMID:33324648), while in signal-receiving cells it interacts with the co-receptor LRP6, protecting it from lysosomal degradation to sustain downstream β-catenin activation (PMID:39385148). Consistent with this, TMEM132A loss diminishes Wnt/β-catenin signaling and produces developmental malformations resembling Wnt mutant phenotypes in mice (PMID:39385148), and its knockdown in breast cancer cells reduces Wnt3a, β-catenin, c-Myc, and Cyclin D1 levels and lowers nuclear β-catenin accumulation (PMID:42203132). Beyond canonical Wnt, TMEM132A engages the planar cell polarity machinery, interacting with CELSR1 and FZD6 and cooperating genetically with Vangl2 to control neural tube closure (PMID:37390294), and it regulates integrin signaling required for caudal paraxial mesoderm migration in vivo (PMID:35950911). TMEM132A expression is driven transcriptionally by E2F1, linking it to proliferative control in cancer (PMID:39473405).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2020 Medium

    Established a first molecular role for TMEM132A in Wnt biology by showing it acts in signal-sending cells to stabilize and secrete Wnt ligand via the transporter WLS.

    Evidence Co-immunoprecipitation and Wnt ligand stabilization/pathway activation assays

    PMID:33324648

    Open questions at the time
    • Single lab without independent replication
    • Structural basis of the TMEM132A–WLS interaction not defined
    • Whether ligand-side and receptor-side functions occur in the same cell unresolved
  2. 2022 Medium

    Placed TMEM132A in cell migration and morphogenesis by demonstrating it regulates integrins and is required for mesodermal migration and neural tube closure.

    Evidence Tmem132a-null mouse, cell migration assays, integrin pathway readouts

    PMID:35950911

    Open questions at the time
    • Direct biochemical link between TMEM132A and specific integrins not established
    • Relationship between the migration phenotype and Wnt signaling unclear
  3. 2023 Medium

    Extended TMEM132A function to non-canonical signaling by showing physical and genetic links to the planar cell polarity pathway.

    Evidence Co-IP with CELSR1 and FZD6, genetic epistasis with Vangl2 in mouse mutants

    PMID:37390294

    Open questions at the time
    • Mechanism of how TMEM132A modulates PCP complex assembly unknown
    • Single lab
    • How canonical Wnt and PCP roles are coordinated unresolved
  4. 2024 Medium

    Defined a receptor-side mechanism: TMEM132A stabilizes LRP6 by blocking its lysosomal degradation, directly promoting canonical Wnt/β-catenin output.

    Evidence Co-IP, lysosomal degradation assays, knockout mouse and Wnt/β-catenin reporter readouts

    PMID:39385148

    Open questions at the time
    • Trafficking step at which TMEM132A intercepts LRP6 not defined
    • Whether TMEM132A directly competes with a degradation adaptor unknown
  5. 2024 Low

    Identified an upstream transcriptional input, showing E2F1 drives TMEM132A expression and linking it to cancer cell proliferation.

    Evidence Dual-luciferase reporter assay, qPCR, proliferation assays in prostate cancer cells

    PMID:39473405

    Open questions at the time
    • No ChIP confirmation of direct promoter occupancy
    • Functional link to Wnt signaling in this context not tested
    • Single lab, limited mechanistic depth
  6. 2026 Medium

    Confirmed TMEM132A activates canonical Wnt/β-catenin signaling in a cancer setting with pharmacological dependency on Wnt.

    Evidence Knockdown/overexpression with nuclear/cytoplasmic fractionation and C59 Wnt inhibitor rescue in breast cancer lines

    PMID:42203132

    Open questions at the time
    • Whether the LRP6 or WLS axis underlies the cancer effect not distinguished
    • In vivo tumor relevance not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TMEM132A integrates its canonical Wnt, PCP, and integrin-dependent migration roles into a unified molecular mechanism remains unresolved.
  • No structural model of TMEM132A or its complexes
  • Membrane topology and trafficking itinerary not mapped
  • Whether ligand-side WLS and receptor-side LRP6 functions are separable not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140313 molecular sequestering activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2
Partners
CELSR1FZD6LRP6WLS

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 TMEM132A physically interacts with the Wnt ligand transporting protein Wntless (WLS), stabilizes Wnt ligand, enhances WLS-Wnt ligand interaction, and activates the Wnt signaling pathway in signal-sending cells. Co-immunoprecipitation (physical interaction), functional assays (Wnt ligand stabilization, pathway activation readouts) Frontiers in cell and developmental biology Medium 33324648
2022 TMEM132A regulates several integrins and downstream integrin pathway activation, and is required for lateral migration of the caudal paraxial mesoderm and spinal neural tube closure in mice; loss of TMEM132A in null mice impairs mesodermal cell migration behaviors. Tmem132a-null mouse genetic model, cell migration assays, integrin pathway activation readouts (loss-of-function with defined cellular phenotype) Development (Cambridge, England) Medium 35950911
2023 TMEM132A physically interacts with planar cell polarity (PCP) regulators CELSR1 and FZD6, mediates intercellular interaction, and genetically interacts synergistically with PCP regulator Vangl2 for neural tube closure, placing TMEM132A as a regulator of PCP signaling. Co-immunoprecipitation (physical interaction with CELSR1 and FZD6), genetic epistasis (double mutant with Vangl2), Tmem132a mutant mouse phenotypic analysis Development (Cambridge, England) Medium 37390294
2024 TMEM132A interacts with the Wnt co-receptor LRP6, stabilizes LRP6, and prevents its lysosomal degradation, thereby promoting canonical Wnt/β-catenin signaling; loss of Tmem132a in mice leads to diminished Wnt/β-catenin signaling and developmental malformations resembling Wnt/β-catenin mutant phenotypes. Co-immunoprecipitation (TMEM132A–LRP6 interaction), lysosomal degradation assays, Tmem132a knockout mouse model, knockdown in cultured cells with Wnt/β-catenin reporter readout Cell communication and signaling : CCS Medium 39385148
2024 E2F1 directly regulates TMEM132A expression by binding to the TMEM132A promoter, as demonstrated by dual-luciferase reporter assay; TMEM132A is a transcriptional target of E2F1 and its expression affects prostate cancer cell proliferation. Dual-luciferase reporter assay (E2F1 binding to TMEM132A promoter), qPCR, CCK8 proliferation assay, knockdown/overexpression in cancer cell lines Frontiers in bioscience (Landmark edition) Low 39473405
2026 TMEM132A knockdown in breast cancer cell lines reduces expression of Wnt pathway components (Wnt3a, β-catenin, c-Myc, Cyclin D1) and decreases nuclear accumulation of β-catenin, while TMEM132A overexpression promotes nuclear β-catenin accumulation, establishing that TMEM132A activates canonical Wnt/β-catenin signaling in breast cancer cells. Nuclear/cytoplasmic fractionation assays, knockdown and overexpression in breast cancer cell lines (MDA-MB-231, MCF-7), Wnt inhibitor C59 rescue experiment, proliferation/migration/invasion/apoptosis assays Biochimica et biophysica acta. Molecular cell research Medium 42203132

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 TMEM132A, a Novel Wnt Signaling Pathway Regulator Through Wntless (WLS) Interaction. Frontiers in cell and developmental biology 33 33324648
2022 TMEM132A ensures mouse caudal neural tube closure and regulates integrin-based mesodermal migration. Development (Cambridge, England) 14 35950911
2022 Knockdown of TMEM132A restrains the malignant phenotype of gastric cancer cells via inhibiting Wnt signaling. Nucleosides, nucleotides & nucleic acids 7 36441075
2024 Multidimensional analysis of TMEM132A in pan-cancer: unveiling its potential as a biomarker for treatment response prediction. Journal of Cancer 6 38947398
2024 TMEM132A regulates Wnt/β-catenin signaling through stabilizing LRP6 during mouse embryonic development. Cell communication and signaling : CCS 6 39385148
2024 Study of the Role of E2F1 and TMEM132A in Prostate Cancer Development. Frontiers in bioscience (Landmark edition) 5 39473405
2023 TMEM132A regulates mouse hindgut morphogenesis and caudal development. Development (Cambridge, England) 5 37390294
2026 TMEM132A autoimmunity in patients with suspected autoimmune cerebellar ataxia. Journal of neuroimmunology 0 41564469
2026 TMEM132A is associated with metabolic reprogramming, macrophage-oriented immune remodeling, and breast cancer progression. Clinical and experimental medicine 0 41874757
2026 A pan-cancer analysis of TMEM132A in human tumors. Discover oncology 0 42035383
2026 TMEM132A affects proliferation, invasion, and apoptosis via the β-catenin-dependent Wnt signaling in breast cancer. Biochimica et biophysica acta. Molecular cell research 0 42203132

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