{"gene":"TMEM87A","run_date":"2026-06-10T10:51:55","timeline":{"discoveries":[{"year":2015,"finding":"TMEM87A is a Golgi-resident membrane protein involved in endosome-to-TGN retrograde transport; overexpression of TMEM87A in VPS54-KO cells partially restored both endosome-to-TGN retrograde transport and post-Golgi anterograde transport of cell-surface proteins.","method":"Genome-wide screen in human haploid cells, VPS54 knockout rescue assay, overexpression of TMEM87A in KO cells with transport readouts","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic rescue experiment in human cells with functional transport readout, single lab, two complementary approaches (screen + rescue)","pmids":["26157166"],"is_preprint":false},{"year":2020,"finding":"TMEM87A (renamed Elkin1) functions as a mechanically activated ion channel; heterologous expression of TMEM87A in PIEZO1-deficient cells (which have no baseline mechanosensitivity) reconstituted mechanically activated currents, establishing TMEM87A as sufficient for a PIEZO1-independent mechanoelectrical transduction pathway. Elkin1 deletion in melanoma cells caused decreased motility, increased cell-substrate adhesion, and decreased homotypic cell-cell adhesion.","method":"Heterologous expression in PIEZO1-deficient cells, patch-clamp electrophysiology, CRISPR knockout with motility and adhesion assays, organotypic spheroid dissociation assay","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Strong — functional reconstitution of mechanically activated currents in null-background cells combined with loss-of-function phenotype readouts, multiple orthogonal methods","pmids":["32228863"],"is_preprint":false},{"year":2022,"finding":"Cryo-EM structure of human TMEM87A in lipid nanodiscs revealed a GOLD (Golgi-dynamics) domain atop a seven-transmembrane helix domain with a large cavity open to solution and the outer membrane leaflet. Structural analysis placed TMEM87A in a family of GOLD-domain seven-transmembrane helix (GOST) proteins including WLS, a chaperone for lipidated Wnt proteins, and found key structural determinants for WLS/trafficking function are conserved in TMEM87A, suggesting a role in trafficking membrane-associated cargo.","method":"Cryo-EM structure determination in lipid nanodiscs; structural comparison and functional analysis","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution cryo-EM structure with functional domain analysis, rigorous structural validation","pmids":["36373655"],"is_preprint":false},{"year":2022,"finding":"Structural and functional analyses of the cryo-EM structure suggested TMEM87A may NOT function as an ion channel or G-protein coupled receptor, contrasting with prior electrophysiological reports.","method":"Cryo-EM structure analysis and functional characterization","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — structural analysis from a single lab; contradicts electrophysiology data from other labs; negative functional conclusion based on structural inference","pmids":["36373655"],"is_preprint":false},{"year":2024,"finding":"TMEM87A (renamed GolpHCat) is a voltage-dependent cation channel in the Golgi apparatus that regulates Golgi pH; it displays unique voltage-dependent currents potently inhibited by gluconate. Three high-resolution cryo-EM structures of human GolpHCat provided structural insight into ion conduction. GolpHCat-knockout mice exhibited fragmented Golgi morphology, altered protein glycosylation, and impaired hippocampus-dependent spatial memory.","method":"Patch-clamp electrophysiology, gluconate inhibition assay, cryo-EM structure determination, TMEM87A knockout mouse model with Golgi morphology assessment, glycosylation analysis, and spatial memory behavioral testing","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple cryo-EM structures plus in vitro electrophysiology plus in vivo knockout with multiple orthogonal phenotypic readouts","pmids":["38992057"],"is_preprint":false},{"year":2024,"finding":"ELKIN1 (TMEM87A) is necessary for mechanically activated (MA) currents in low-threshold mechanoreceptors; loss of Elkin1 in mice caused touch insensitivity. Reintroduction of Elkin1 into sensory neurons from Elkin1 knockout mice restored MA currents. siRNA knockdown of ELKIN1 in induced human sensory neurons substantially reduced indentation-induced MA currents.","method":"Elkin1 knockout mice, behavioral touch sensitivity assays, patch-clamp electrophysiology in sensory neurons, neuronal rescue by Elkin1 reintroduction, siRNA knockdown in human induced sensory neurons with electrophysiology","journal":"Science (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 / Strong — genetic rescue experiment restoring current in null neurons, replicated in both mouse and human neurons with multiple orthogonal methods","pmids":["38422143"],"is_preprint":false},{"year":2024,"finding":"TMEM87A (GolpHCat/ELKIN1) is mislocalized and degraded upon acute GARP complex disruption (VPS54 mAID-degron rapid depletion), identifying TMEM87A as a Golgi protein whose localization depends on GARP-mediated retrograde vesicle tethering.","method":"mAID degron-mediated rapid VPS54 depletion in human cells; immunofluorescence and protein level analysis of TMEM87A localization","journal":"bioRxiv : the preprint server for biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — acute depletion system with direct localization and protein level readout, single lab, preprint","pmids":["39416116"],"is_preprint":true},{"year":2025,"finding":"TMEM87A localization and protein levels are reduced upon acute GARP complex disruption, confirmed in the peer-reviewed version of the GARP depletion study.","method":"mAID degron-mediated VPS54 depletion in human cells, immunofluorescence, western blot for TMEM87A","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — acute depletion with direct localization readout, single lab, peer-reviewed confirmation of preprint finding","pmids":["40100055"],"is_preprint":false},{"year":2022,"finding":"TMEM87A is a recycling TGN protein whose staining intensity at the TGN is decreased in Vti1a/b-deficient neurons, linking its TGN localization to Vti1a/b-dependent retrograde trafficking.","method":"Vti1a/b double-knockout neurons, immunofluorescence staining intensity quantification of TMEM87A at the TGN","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single localization measurement in KO neurons, single lab, single method without mechanistic follow-up","pmids":["36460703"],"is_preprint":false},{"year":2025,"finding":"ELKIN1 (TMEM87A) deletion prevented simulated microgravity-induced alterations of cellular structure, focal adhesion changes, and YAP1 transcription factor redistribution. Melanoma cell invasion from organotypic spheroids was reduced in simulated microgravity in an ELKIN1-dependent manner.","method":"ELKIN1 knockout cells in simulated microgravity conditions, immunofluorescence for focal adhesions and YAP1 localization, organotypic spheroid invasion assay","journal":"NPJ microgravity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knockout loss-of-function with multiple cellular phenotype readouts (structure, focal adhesions, YAP1 localization, invasion), single lab","pmids":["40090965"],"is_preprint":false},{"year":2020,"finding":"A TMEM87A-RASGRF1 gene fusion was identified in a lung cancer exceptional responder; the fusion drives RAS activation via RASGRF1 guanine exchange factor activity and activates MAPK signaling, as demonstrated in NIH/3T3 transformation assays and CRISPR-edited PC9 cells expressing the fusion.","method":"RNA-seq identification of fusion, NIH/3T3 oncogenicity assay, CRISPR-Cas9 editing of PC9 cells to express fusion, MAPK pathway activation measurement","journal":"Clinical cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional in vitro oncogenicity assay and MAPK activation in engineered cells, single lab, two orthogonal cell models","pmids":["32312893"],"is_preprint":false},{"year":2026,"finding":"TMEM87A maintains Golgi pH homeostasis and mediates resistance to ferroptosis; depletion of TMEM87A caused Golgi overacidification, which impaired FSP1-mediated reduction of coenzyme Q, thereby sensitizing cells to ferroptosis. TMEM87A ablation suppressed tumor progression in multiple murine models and enhanced antitumor T cell responses.","method":"TMEM87A knockout/depletion, Golgi pH measurement, FSP1 activity assay, coenzyme Q reduction assay, in vivo tumor models (melanoma, colorectal cancer, liver cancer), immune cell analysis","journal":"Nature cancer","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal mechanistic assays (pH, FSP1 activity, CoQ reduction) combined with in vivo validation across multiple tumor models","pmids":["42014864"],"is_preprint":false},{"year":2026,"finding":"CHP1 (calcineurin homologous protein 1) physically interacts with TMEM87A, forming a mechanosensing complex; knockout of either CHP1 or TMEM87A downregulated WNT5A/GPC6 and inhibited WNT5A/Hedgehog pathways. Sodium gluconate disrupted CHP1-TMEM87A binding and inhibited downstream Hedgehog/PTCH1 signaling. In vivo, CHP1 or TMEM87A knockout suppressed orthotopic ovarian tumor growth and metastasis.","method":"Co-immunoprecipitation, CETSA, microscale thermophoresis (MST), surface plasmon resonance (SPR), CRISPR knockout in 3D spheroid models and in vivo NSG mouse orthotopic model, pathway analysis by western blot","journal":"Molecular biomedicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal binding confirmed by multiple biophysical methods (Co-IP, CETSA, MST, SPR) plus in vivo KO, single lab","pmids":["42258092"],"is_preprint":false}],"current_model":"TMEM87A (also known as Elkin1/GolpHCat) is a Golgi-localized seven-transmembrane protein with a GOLD domain that functions as a voltage-dependent cation channel regulating Golgi pH homeostasis; it supports endosome-to-TGN retrograde trafficking in a GARP-dependent manner, acts as a mechanically activated ion channel sufficient to reconstitute MA currents in null cells and necessary for touch sensation in sensory neurons, maintains Golgi pH to buffer against ferroptosis by enabling FSP1-mediated coenzyme Q reduction, and forms a mechanosensing complex with CHP1 that modulates WNT/Hedgehog signaling and cell migration."},"narrative":{"mechanistic_narrative":"TMEM87A is a Golgi-resident, GOLD-domain seven-transmembrane protein that links Golgi physiology to membrane trafficking, mechanotransduction, and tumor cell behavior [PMID:36373655, PMID:38992057]. Its Golgi/TGN localization depends on retrograde tethering: TMEM87A overexpression partially rescues endosome-to-TGN retrograde transport in VPS54-null cells [PMID:26157166], and acute GARP-complex disruption mislocalizes and degrades the protein [PMID:40100055]. A high-resolution cryo-EM structure positions TMEM87A within the GOLD-domain seven-transmembrane (GOST) family alongside the Wnt chaperone WLS, with a large membrane-facing cavity consistent with handling membrane-associated cargo [PMID:36373655]. Functionally, TMEM87A operates as a voltage-dependent cation channel that maintains Golgi pH; its loss causes Golgi overacidification and fragmentation, altered glycosylation, and impaired spatial memory in knockout mice [PMID:38992057]. The same channel activity is mechanically gated: TMEM87A reconstitutes mechanically activated currents in PIEZO1-deficient cells and is required for mechanotransduction in low-threshold mechanoreceptors, with its loss producing touch insensitivity in mice [PMID:32228863, PMID:38422143]. Through its Golgi pH function, TMEM87A confers ferroptosis resistance by enabling FSP1-mediated coenzyme Q reduction, and its ablation suppresses tumor growth while enhancing antitumor T cell responses [PMID:42014864]. TMEM87A further forms a mechanosensing complex with CHP1 that sustains WNT5A and Hedgehog/PTCH1 signaling, and its loss reduces melanoma motility and microgravity-dependent invasion linked to focal adhesion and YAP1 redistribution [PMID:40090965, PMID:42258092].","teleology":[{"year":2015,"claim":"Established TMEM87A as a Golgi protein functionally tied to retrograde membrane trafficking, the first clue to its cellular role.","evidence":"Genome-wide haploid screen plus overexpression rescue of transport in VPS54-knockout human cells","pmids":["26157166"],"confidence":"Medium","gaps":["Did not define molecular mechanism by which TMEM87A supports transport","No direct interaction partners identified","Rescue was partial"]},{"year":2020,"claim":"Showed TMEM87A is sufficient to generate mechanically activated currents independently of PIEZO1, reframing it as a candidate mechanotransduction channel and linking it to cell motility and adhesion.","evidence":"Heterologous expression in PIEZO1-deficient cells with patch-clamp, plus CRISPR knockout motility/adhesion assays in melanoma cells","pmids":["32228863"],"confidence":"High","gaps":["Did not resolve whether TMEM87A is the pore-forming subunit","Gating mechanism unknown","Relationship between channel activity and Golgi trafficking role unresolved"]},{"year":2020,"claim":"Demonstrated an oncogenic TMEM87A-RASGRF1 fusion can transform cells, an event involving the TMEM87A locus rather than its native channel function.","evidence":"RNA-seq fusion detection, NIH/3T3 transformation and CRISPR-edited PC9 cells with MAPK readout","pmids":["32312893"],"confidence":"Medium","gaps":["Oncogenicity driven by RASGRF1 GEF activity, not native TMEM87A function","Contribution of the TMEM87A portion to fusion activity undefined","Single exceptional-responder context"]},{"year":2022,"claim":"Provided the first structure, placing TMEM87A in the GOST family with WLS and supporting a membrane-cargo trafficking role, while structurally arguing against ion-channel/GPCR function.","evidence":"Cryo-EM in lipid nanodiscs with structural and functional comparison to WLS","pmids":["36373655"],"confidence":"High","gaps":["Structural inference against channel function conflicts with electrophysiology","No cargo directly identified","Static structure does not capture gating or conduction"]},{"year":2022,"claim":"Linked TMEM87A TGN residence to Vti1a/b-dependent retrograde trafficking, reinforcing its dependence on retrograde transport machinery for steady-state localization.","evidence":"Immunofluorescence intensity quantification in Vti1a/b double-knockout neurons","pmids":["36460703"],"confidence":"Low","gaps":["Single localization measurement without mechanistic follow-up","No direct interaction with Vti1a/b shown","Functional consequence of mislocalization untested"]},{"year":2024,"claim":"Resolved the channel controversy by demonstrating TMEM87A is a voltage-dependent cation channel that regulates Golgi pH, connecting its molecular activity to Golgi integrity, glycosylation and brain function in vivo.","evidence":"Patch-clamp with gluconate inhibition, multiple cryo-EM structures, and knockout mice with Golgi, glycosylation and memory phenotypes","pmids":["38992057"],"confidence":"High","gaps":["Direct ion selectivity and conduction path not fully resolved","Mechanism coupling Golgi pH to glycosylation unclear","Reconciliation with 2022 structural channel-negative interpretation not fully addressed"]},{"year":2024,"claim":"Established TMEM87A as necessary for touch sensation by genetically restoring mechanically activated currents in null neurons across mouse and human systems.","evidence":"Elkin1 knockout mice, neuronal rescue, behavioral touch assays, and siRNA knockdown in human induced sensory neurons with electrophysiology","pmids":["38422143"],"confidence":"High","gaps":["Whether TMEM87A forms the pore versus an essential subunit unresolved","Force-transmission mechanism to the channel unknown","Link between Golgi channel role and surface mechanotransduction undefined"]},{"year":2025,"claim":"Peer-reviewed confirmation that GARP-mediated retrograde tethering controls TMEM87A localization and stability, solidifying the trafficking dependence first seen in 2015.","evidence":"mAID degron VPS54 depletion with immunofluorescence and western blot","pmids":["40100055"],"confidence":"Medium","gaps":["Direct GARP-TMEM87A contact not demonstrated","Degradation pathway upon mislocalization unidentified","Functional consequence on channel activity untested"]},{"year":2025,"claim":"Connected TMEM87A to mechanically responsive tumor cell behavior, showing its requirement for microgravity-induced cytoskeletal, focal adhesion and YAP1 changes and spheroid invasion.","evidence":"ELKIN1 knockout cells under simulated microgravity with focal adhesion/YAP1 imaging and organotypic invasion assay","pmids":["40090965"],"confidence":"Medium","gaps":["Mechanism linking TMEM87A to YAP1 redistribution unknown","Single-lab phenotypic study","Whether channel activity is required not tested"]},{"year":2026,"claim":"Defined a Golgi pH-dependent role for TMEM87A in ferroptosis resistance and tumor progression, mechanistically coupling its pH-regulating activity to FSP1/coenzyme Q antioxidant defense.","evidence":"Knockout/depletion with Golgi pH, FSP1 activity and CoQ reduction assays plus multiple in vivo tumor models and immune profiling","pmids":["42014864"],"confidence":"High","gaps":["How Golgi pH controls FSP1/CoQ chemistry mechanistically unclear","Direct versus indirect effect on FSP1 unresolved","Contribution of channel versus trafficking activity not separated"]},{"year":2026,"claim":"Identified CHP1 as a direct physical partner forming a TMEM87A mechanosensing complex that drives WNT5A and Hedgehog signaling in tumor growth and metastasis.","evidence":"Co-IP, CETSA, MST, SPR binding assays plus CRISPR knockout in spheroids and orthotopic mouse models with pathway western blots","pmids":["42258092"],"confidence":"Medium","gaps":["Mechanism by which the complex transduces signal to WNT/Hedgehog undefined","Single-lab characterization","Whether complex requires channel/mechanical activity untested"]},{"year":null,"claim":"It remains unresolved how TMEM87A's Golgi pH-regulating channel activity, its plasma-membrane mechanotransduction role, and its GOST-family cargo-trafficking function are mechanistically unified within one protein.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No model reconciling Golgi-channel and surface mechanosensing roles","Pore-forming versus accessory-subunit status not definitively established","Native trafficking cargo not identified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[1,4,5]},{"term_id":"GO:0140299","term_label":"molecular sensor activity","supporting_discovery_ids":[1,5]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,2,4,7]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,5]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,7]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[11]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[12]}],"complexes":[],"partners":["CHP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8NBN3","full_name":"Transmembrane protein 87A","aliases":["Elkin1"],"length_aa":555,"mass_kda":63.4,"function":"Potential monoatomic ion channel gated by mechanical force, implicated in normal touch sensitivity through the generation of mechanically activated currents (PubMed:32228863, PubMed:38422143). However, a direct channel activity is debated and an alternative could be that it functions as a chaperone for an unidentified mechanosensitive ion channel (PubMed:32228863, PubMed:36373655). Could also be involved in cell mechanosensitivity regulating cell adhesion and migration (PubMed:32228863). May also be involved in retrograde transport from endosomes to the trans-Golgi network (TGN) (PubMed:26157166)","subcellular_location":"Cell membrane; Cell projection, ruffle","url":"https://www.uniprot.org/uniprotkb/Q8NBN3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TMEM87A","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000103978","cell_line_id":"CID000805","localizations":[{"compartment":"golgi","grade":3},{"compartment":"vesicles","grade":3}],"interactors":[{"gene":"CANX","stoichiometry":0.2},{"gene":"ARFGEF1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000805","total_profiled":1310},"omim":[{"mim_id":"621342","title":"TRANSMEMBRANE PROTEIN 87A; TMEM87A","url":"https://www.omim.org/entry/621342"},{"mim_id":"618490","title":"G PROTEIN-COUPLED RECEPTOR 107; GPR107","url":"https://www.omim.org/entry/618490"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Golgi apparatus","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TMEM87A"},"hgnc":{"alias_symbol":["DKFZP564G2022","ELKIN1"],"prev_symbol":[]},"alphafold":{"accession":"Q8NBN3","domains":[{"cath_id":"2.60.120,2.60.120","chopping":"42-146_174-194_204-214","consensus_level":"high","plddt":75.4647,"start":42,"end":214},{"cath_id":"1.20.1070,1.20.1070","chopping":"222-461","consensus_level":"high","plddt":87.376,"start":222,"end":461}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NBN3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NBN3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NBN3-F1-predicted_aligned_error_v6.png","plddt_mean":71.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TMEM87A","jax_strain_url":"https://www.jax.org/strain/search?query=TMEM87A"},"sequence":{"accession":"Q8NBN3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8NBN3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8NBN3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NBN3"}},"corpus_meta":[{"pmid":"26157166","id":"PMC_26157166","title":"Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport.","date":"2015","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/26157166","citation_count":86,"is_preprint":false},{"pmid":"32228863","id":"PMC_32228863","title":"TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/32228863","citation_count":51,"is_preprint":false},{"pmid":"33155080","id":"PMC_33155080","title":"Circular RNA TMEM87A promotes cell proliferation and metastasis of gastric cancer by elevating ULK1 via sponging miR-142-5p.","date":"2020","source":"Journal of gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/33155080","citation_count":36,"is_preprint":false},{"pmid":"38556553","id":"PMC_38556553","title":"Transmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles.","date":"2024","source":"Experimental & molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38556553","citation_count":34,"is_preprint":false},{"pmid":"38422143","id":"PMC_38422143","title":"Touch sensation requires the mechanically gated ion channel ELKIN1.","date":"2024","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/38422143","citation_count":24,"is_preprint":false},{"pmid":"32312893","id":"PMC_32312893","title":"Identification of a RAS-activating TMEM87A-RASGRF1 Fusion in an Exceptional Responder to Sunitinib with Non-Small Cell Lung Cancer.","date":"2020","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/32312893","citation_count":20,"is_preprint":false},{"pmid":"36373655","id":"PMC_36373655","title":"Structure of the GOLD-domain seven-transmembrane helix protein family member TMEM87A.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/36373655","citation_count":19,"is_preprint":false},{"pmid":"32664164","id":"PMC_32664164","title":"Identification of Target Genes in Hypertension and Left Ventricular Remodeling.","date":"2020","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32664164","citation_count":15,"is_preprint":false},{"pmid":"38992057","id":"PMC_38992057","title":"GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38992057","citation_count":9,"is_preprint":false},{"pmid":"36460703","id":"PMC_36460703","title":"Vti1a/b support distinct aspects of TGN and cis-/medial Golgi organization.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/36460703","citation_count":4,"is_preprint":false},{"pmid":"40090965","id":"PMC_40090965","title":"The mechanosensitive channel ELKIN1 regulates cellular adaptations to simulated microgravity.","date":"2025","source":"NPJ microgravity","url":"https://pubmed.ncbi.nlm.nih.gov/40090965","citation_count":3,"is_preprint":false},{"pmid":"39789885","id":"PMC_39789885","title":"Inflammation alters the expression and activity of the mechanosensitive ion channels in periodontal ligament cells.","date":"2024","source":"European journal of orthodontics","url":"https://pubmed.ncbi.nlm.nih.gov/39789885","citation_count":2,"is_preprint":false},{"pmid":"40100055","id":"PMC_40100055","title":"Acute GARP Depletion Disrupts Vesicle Transport, Leading to Severe Defects in Sorting, Secretion and O-Glycosylation.","date":"2025","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/40100055","citation_count":2,"is_preprint":false},{"pmid":"42014864","id":"PMC_42014864","title":"TMEM87A suppresses ferroptosis and increases cancer immunotherapy resistance by maintaining the Golgi apparatus pH homeostasis.","date":"2026","source":"Nature cancer","url":"https://pubmed.ncbi.nlm.nih.gov/42014864","citation_count":1,"is_preprint":false},{"pmid":"39416116","id":"PMC_39416116","title":"Acute GARP depletion disrupts vesicle transport, leading to severe defects in sorting, secretion, and O-glycosylation.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39416116","citation_count":1,"is_preprint":false},{"pmid":"42258092","id":"PMC_42258092","title":"Targeting the Calcineurin Homologous Protein 1 (CHP1)-Transmembrane Protein 87A (TMEM87A) mechanosensing complex: a druggable vulnerability in metastatic ovarian cancer.","date":"2026","source":"Molecular biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/42258092","citation_count":0,"is_preprint":false},{"pmid":"41596760","id":"PMC_41596760","title":"A Decade-Old Atlas of TMEM (Transmembrane) Protein Family in Lung Cancer: Lessons Learnt and Future Directions.","date":"2026","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41596760","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10329,"output_tokens":3338,"usd":0.040529,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10955,"output_tokens":3782,"usd":0.074663,"stage2_stop_reason":"end_turn"},"total_usd":0.115192,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"TMEM87A is a Golgi-resident membrane protein involved in endosome-to-TGN retrograde transport; overexpression of TMEM87A in VPS54-KO cells partially restored both endosome-to-TGN retrograde transport and post-Golgi anterograde transport of cell-surface proteins.\",\n      \"method\": \"Genome-wide screen in human haploid cells, VPS54 knockout rescue assay, overexpression of TMEM87A in KO cells with transport readouts\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic rescue experiment in human cells with functional transport readout, single lab, two complementary approaches (screen + rescue)\",\n      \"pmids\": [\"26157166\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TMEM87A (renamed Elkin1) functions as a mechanically activated ion channel; heterologous expression of TMEM87A in PIEZO1-deficient cells (which have no baseline mechanosensitivity) reconstituted mechanically activated currents, establishing TMEM87A as sufficient for a PIEZO1-independent mechanoelectrical transduction pathway. Elkin1 deletion in melanoma cells caused decreased motility, increased cell-substrate adhesion, and decreased homotypic cell-cell adhesion.\",\n      \"method\": \"Heterologous expression in PIEZO1-deficient cells, patch-clamp electrophysiology, CRISPR knockout with motility and adhesion assays, organotypic spheroid dissociation assay\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — functional reconstitution of mechanically activated currents in null-background cells combined with loss-of-function phenotype readouts, multiple orthogonal methods\",\n      \"pmids\": [\"32228863\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Cryo-EM structure of human TMEM87A in lipid nanodiscs revealed a GOLD (Golgi-dynamics) domain atop a seven-transmembrane helix domain with a large cavity open to solution and the outer membrane leaflet. Structural analysis placed TMEM87A in a family of GOLD-domain seven-transmembrane helix (GOST) proteins including WLS, a chaperone for lipidated Wnt proteins, and found key structural determinants for WLS/trafficking function are conserved in TMEM87A, suggesting a role in trafficking membrane-associated cargo.\",\n      \"method\": \"Cryo-EM structure determination in lipid nanodiscs; structural comparison and functional analysis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution cryo-EM structure with functional domain analysis, rigorous structural validation\",\n      \"pmids\": [\"36373655\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Structural and functional analyses of the cryo-EM structure suggested TMEM87A may NOT function as an ion channel or G-protein coupled receptor, contrasting with prior electrophysiological reports.\",\n      \"method\": \"Cryo-EM structure analysis and functional characterization\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — structural analysis from a single lab; contradicts electrophysiology data from other labs; negative functional conclusion based on structural inference\",\n      \"pmids\": [\"36373655\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TMEM87A (renamed GolpHCat) is a voltage-dependent cation channel in the Golgi apparatus that regulates Golgi pH; it displays unique voltage-dependent currents potently inhibited by gluconate. Three high-resolution cryo-EM structures of human GolpHCat provided structural insight into ion conduction. GolpHCat-knockout mice exhibited fragmented Golgi morphology, altered protein glycosylation, and impaired hippocampus-dependent spatial memory.\",\n      \"method\": \"Patch-clamp electrophysiology, gluconate inhibition assay, cryo-EM structure determination, TMEM87A knockout mouse model with Golgi morphology assessment, glycosylation analysis, and spatial memory behavioral testing\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple cryo-EM structures plus in vitro electrophysiology plus in vivo knockout with multiple orthogonal phenotypic readouts\",\n      \"pmids\": [\"38992057\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ELKIN1 (TMEM87A) is necessary for mechanically activated (MA) currents in low-threshold mechanoreceptors; loss of Elkin1 in mice caused touch insensitivity. Reintroduction of Elkin1 into sensory neurons from Elkin1 knockout mice restored MA currents. siRNA knockdown of ELKIN1 in induced human sensory neurons substantially reduced indentation-induced MA currents.\",\n      \"method\": \"Elkin1 knockout mice, behavioral touch sensitivity assays, patch-clamp electrophysiology in sensory neurons, neuronal rescue by Elkin1 reintroduction, siRNA knockdown in human induced sensory neurons with electrophysiology\",\n      \"journal\": \"Science (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — genetic rescue experiment restoring current in null neurons, replicated in both mouse and human neurons with multiple orthogonal methods\",\n      \"pmids\": [\"38422143\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TMEM87A (GolpHCat/ELKIN1) is mislocalized and degraded upon acute GARP complex disruption (VPS54 mAID-degron rapid depletion), identifying TMEM87A as a Golgi protein whose localization depends on GARP-mediated retrograde vesicle tethering.\",\n      \"method\": \"mAID degron-mediated rapid VPS54 depletion in human cells; immunofluorescence and protein level analysis of TMEM87A localization\",\n      \"journal\": \"bioRxiv : the preprint server for biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — acute depletion system with direct localization and protein level readout, single lab, preprint\",\n      \"pmids\": [\"39416116\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TMEM87A localization and protein levels are reduced upon acute GARP complex disruption, confirmed in the peer-reviewed version of the GARP depletion study.\",\n      \"method\": \"mAID degron-mediated VPS54 depletion in human cells, immunofluorescence, western blot for TMEM87A\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — acute depletion with direct localization readout, single lab, peer-reviewed confirmation of preprint finding\",\n      \"pmids\": [\"40100055\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TMEM87A is a recycling TGN protein whose staining intensity at the TGN is decreased in Vti1a/b-deficient neurons, linking its TGN localization to Vti1a/b-dependent retrograde trafficking.\",\n      \"method\": \"Vti1a/b double-knockout neurons, immunofluorescence staining intensity quantification of TMEM87A at the TGN\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization measurement in KO neurons, single lab, single method without mechanistic follow-up\",\n      \"pmids\": [\"36460703\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ELKIN1 (TMEM87A) deletion prevented simulated microgravity-induced alterations of cellular structure, focal adhesion changes, and YAP1 transcription factor redistribution. Melanoma cell invasion from organotypic spheroids was reduced in simulated microgravity in an ELKIN1-dependent manner.\",\n      \"method\": \"ELKIN1 knockout cells in simulated microgravity conditions, immunofluorescence for focal adhesions and YAP1 localization, organotypic spheroid invasion assay\",\n      \"journal\": \"NPJ microgravity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knockout loss-of-function with multiple cellular phenotype readouts (structure, focal adhesions, YAP1 localization, invasion), single lab\",\n      \"pmids\": [\"40090965\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"A TMEM87A-RASGRF1 gene fusion was identified in a lung cancer exceptional responder; the fusion drives RAS activation via RASGRF1 guanine exchange factor activity and activates MAPK signaling, as demonstrated in NIH/3T3 transformation assays and CRISPR-edited PC9 cells expressing the fusion.\",\n      \"method\": \"RNA-seq identification of fusion, NIH/3T3 oncogenicity assay, CRISPR-Cas9 editing of PC9 cells to express fusion, MAPK pathway activation measurement\",\n      \"journal\": \"Clinical cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional in vitro oncogenicity assay and MAPK activation in engineered cells, single lab, two orthogonal cell models\",\n      \"pmids\": [\"32312893\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TMEM87A maintains Golgi pH homeostasis and mediates resistance to ferroptosis; depletion of TMEM87A caused Golgi overacidification, which impaired FSP1-mediated reduction of coenzyme Q, thereby sensitizing cells to ferroptosis. TMEM87A ablation suppressed tumor progression in multiple murine models and enhanced antitumor T cell responses.\",\n      \"method\": \"TMEM87A knockout/depletion, Golgi pH measurement, FSP1 activity assay, coenzyme Q reduction assay, in vivo tumor models (melanoma, colorectal cancer, liver cancer), immune cell analysis\",\n      \"journal\": \"Nature cancer\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal mechanistic assays (pH, FSP1 activity, CoQ reduction) combined with in vivo validation across multiple tumor models\",\n      \"pmids\": [\"42014864\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CHP1 (calcineurin homologous protein 1) physically interacts with TMEM87A, forming a mechanosensing complex; knockout of either CHP1 or TMEM87A downregulated WNT5A/GPC6 and inhibited WNT5A/Hedgehog pathways. Sodium gluconate disrupted CHP1-TMEM87A binding and inhibited downstream Hedgehog/PTCH1 signaling. In vivo, CHP1 or TMEM87A knockout suppressed orthotopic ovarian tumor growth and metastasis.\",\n      \"method\": \"Co-immunoprecipitation, CETSA, microscale thermophoresis (MST), surface plasmon resonance (SPR), CRISPR knockout in 3D spheroid models and in vivo NSG mouse orthotopic model, pathway analysis by western blot\",\n      \"journal\": \"Molecular biomedicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding confirmed by multiple biophysical methods (Co-IP, CETSA, MST, SPR) plus in vivo KO, single lab\",\n      \"pmids\": [\"42258092\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TMEM87A (also known as Elkin1/GolpHCat) is a Golgi-localized seven-transmembrane protein with a GOLD domain that functions as a voltage-dependent cation channel regulating Golgi pH homeostasis; it supports endosome-to-TGN retrograde trafficking in a GARP-dependent manner, acts as a mechanically activated ion channel sufficient to reconstitute MA currents in null cells and necessary for touch sensation in sensory neurons, maintains Golgi pH to buffer against ferroptosis by enabling FSP1-mediated coenzyme Q reduction, and forms a mechanosensing complex with CHP1 that modulates WNT/Hedgehog signaling and cell migration.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TMEM87A is a Golgi-resident, GOLD-domain seven-transmembrane protein that links Golgi physiology to membrane trafficking, mechanotransduction, and tumor cell behavior [#2, #4]. Its Golgi/TGN localization depends on retrograde tethering: TMEM87A overexpression partially rescues endosome-to-TGN retrograde transport in VPS54-null cells [#0], and acute GARP-complex disruption mislocalizes and degrades the protein [#7]. A high-resolution cryo-EM structure positions TMEM87A within the GOLD-domain seven-transmembrane (GOST) family alongside the Wnt chaperone WLS, with a large membrane-facing cavity consistent with handling membrane-associated cargo [#2]. Functionally, TMEM87A operates as a voltage-dependent cation channel that maintains Golgi pH; its loss causes Golgi overacidification and fragmentation, altered glycosylation, and impaired spatial memory in knockout mice [#4]. The same channel activity is mechanically gated: TMEM87A reconstitutes mechanically activated currents in PIEZO1-deficient cells and is required for mechanotransduction in low-threshold mechanoreceptors, with its loss producing touch insensitivity in mice [#1, #5]. Through its Golgi pH function, TMEM87A confers ferroptosis resistance by enabling FSP1-mediated coenzyme Q reduction, and its ablation suppresses tumor growth while enhancing antitumor T cell responses [#11]. TMEM87A further forms a mechanosensing complex with CHP1 that sustains WNT5A and Hedgehog/PTCH1 signaling, and its loss reduces melanoma motility and microgravity-dependent invasion linked to focal adhesion and YAP1 redistribution [#9, #12].\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Established TMEM87A as a Golgi protein functionally tied to retrograde membrane trafficking, the first clue to its cellular role.\",\n      \"evidence\": \"Genome-wide haploid screen plus overexpression rescue of transport in VPS54-knockout human cells\",\n      \"pmids\": [\"26157166\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define molecular mechanism by which TMEM87A supports transport\", \"No direct interaction partners identified\", \"Rescue was partial\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Showed TMEM87A is sufficient to generate mechanically activated currents independently of PIEZO1, reframing it as a candidate mechanotransduction channel and linking it to cell motility and adhesion.\",\n      \"evidence\": \"Heterologous expression in PIEZO1-deficient cells with patch-clamp, plus CRISPR knockout motility/adhesion assays in melanoma cells\",\n      \"pmids\": [\"32228863\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve whether TMEM87A is the pore-forming subunit\", \"Gating mechanism unknown\", \"Relationship between channel activity and Golgi trafficking role unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated an oncogenic TMEM87A-RASGRF1 fusion can transform cells, an event involving the TMEM87A locus rather than its native channel function.\",\n      \"evidence\": \"RNA-seq fusion detection, NIH/3T3 transformation and CRISPR-edited PC9 cells with MAPK readout\",\n      \"pmids\": [\"32312893\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Oncogenicity driven by RASGRF1 GEF activity, not native TMEM87A function\", \"Contribution of the TMEM87A portion to fusion activity undefined\", \"Single exceptional-responder context\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Provided the first structure, placing TMEM87A in the GOST family with WLS and supporting a membrane-cargo trafficking role, while structurally arguing against ion-channel/GPCR function.\",\n      \"evidence\": \"Cryo-EM in lipid nanodiscs with structural and functional comparison to WLS\",\n      \"pmids\": [\"36373655\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural inference against channel function conflicts with electrophysiology\", \"No cargo directly identified\", \"Static structure does not capture gating or conduction\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked TMEM87A TGN residence to Vti1a/b-dependent retrograde trafficking, reinforcing its dependence on retrograde transport machinery for steady-state localization.\",\n      \"evidence\": \"Immunofluorescence intensity quantification in Vti1a/b double-knockout neurons\",\n      \"pmids\": [\"36460703\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single localization measurement without mechanistic follow-up\", \"No direct interaction with Vti1a/b shown\", \"Functional consequence of mislocalization untested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Resolved the channel controversy by demonstrating TMEM87A is a voltage-dependent cation channel that regulates Golgi pH, connecting its molecular activity to Golgi integrity, glycosylation and brain function in vivo.\",\n      \"evidence\": \"Patch-clamp with gluconate inhibition, multiple cryo-EM structures, and knockout mice with Golgi, glycosylation and memory phenotypes\",\n      \"pmids\": [\"38992057\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct ion selectivity and conduction path not fully resolved\", \"Mechanism coupling Golgi pH to glycosylation unclear\", \"Reconciliation with 2022 structural channel-negative interpretation not fully addressed\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established TMEM87A as necessary for touch sensation by genetically restoring mechanically activated currents in null neurons across mouse and human systems.\",\n      \"evidence\": \"Elkin1 knockout mice, neuronal rescue, behavioral touch assays, and siRNA knockdown in human induced sensory neurons with electrophysiology\",\n      \"pmids\": [\"38422143\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether TMEM87A forms the pore versus an essential subunit unresolved\", \"Force-transmission mechanism to the channel unknown\", \"Link between Golgi channel role and surface mechanotransduction undefined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Peer-reviewed confirmation that GARP-mediated retrograde tethering controls TMEM87A localization and stability, solidifying the trafficking dependence first seen in 2015.\",\n      \"evidence\": \"mAID degron VPS54 depletion with immunofluorescence and western blot\",\n      \"pmids\": [\"40100055\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct GARP-TMEM87A contact not demonstrated\", \"Degradation pathway upon mislocalization unidentified\", \"Functional consequence on channel activity untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected TMEM87A to mechanically responsive tumor cell behavior, showing its requirement for microgravity-induced cytoskeletal, focal adhesion and YAP1 changes and spheroid invasion.\",\n      \"evidence\": \"ELKIN1 knockout cells under simulated microgravity with focal adhesion/YAP1 imaging and organotypic invasion assay\",\n      \"pmids\": [\"40090965\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking TMEM87A to YAP1 redistribution unknown\", \"Single-lab phenotypic study\", \"Whether channel activity is required not tested\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defined a Golgi pH-dependent role for TMEM87A in ferroptosis resistance and tumor progression, mechanistically coupling its pH-regulating activity to FSP1/coenzyme Q antioxidant defense.\",\n      \"evidence\": \"Knockout/depletion with Golgi pH, FSP1 activity and CoQ reduction assays plus multiple in vivo tumor models and immune profiling\",\n      \"pmids\": [\"42014864\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How Golgi pH controls FSP1/CoQ chemistry mechanistically unclear\", \"Direct versus indirect effect on FSP1 unresolved\", \"Contribution of channel versus trafficking activity not separated\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identified CHP1 as a direct physical partner forming a TMEM87A mechanosensing complex that drives WNT5A and Hedgehog signaling in tumor growth and metastasis.\",\n      \"evidence\": \"Co-IP, CETSA, MST, SPR binding assays plus CRISPR knockout in spheroids and orthotopic mouse models with pathway western blots\",\n      \"pmids\": [\"42258092\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which the complex transduces signal to WNT/Hedgehog undefined\", \"Single-lab characterization\", \"Whether complex requires channel/mechanical activity untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how TMEM87A's Golgi pH-regulating channel activity, its plasma-membrane mechanotransduction role, and its GOST-family cargo-trafficking function are mechanistically unified within one protein.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No model reconciling Golgi-channel and surface mechanosensing roles\", \"Pore-forming versus accessory-subunit status not definitively established\", \"Native trafficking cargo not identified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [1, 4, 5]},\n      {\"term_id\": \"GO:0140299\", \"supporting_discovery_ids\": [1, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 2, 4, 7]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [11]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [12]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CHP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}