{"gene":"TMC7","run_date":"2026-06-10T10:51:55","timeline":{"discoveries":[{"year":2024,"finding":"TMC7 physically interacts with the mechanosensitive channel Piezo2 and with cytoskeletal β-actin in somatosensory neurons; genetic deletion of TMC7 in primary sensory ganglia neurons increases the proportion of rapidly adapting (RA) currents conducted by Piezo2 in DRG neurons and accelerates RA deactivation kinetics; in HEK293 cells co-expressing both proteins, TMC7 significantly suppresses Piezo2 current amplitudes, establishing TMC7 as an inhibitory modulator of Piezo2-mediated mechanotransduction.","method":"In vivo conditional knockout in DRG neurons with electrophysiological readout (RA current proportion and kinetics), co-expression in HEK293 cells with whole-cell patch clamp, co-immunoprecipitation / physical interaction assays for TMC7–Piezo2 and TMC7–β-actin","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal physical interaction, in vivo genetic deletion with defined electrophysiological phenotype, and heterologous expression functional assay; multiple orthogonal methods in one study","pmids":["38568807"],"is_preprint":false},{"year":2025,"finding":"Selective deletion of Tmc7 in mice increases nociception across pain modalities and increases pruritogen-evoked itch scratching, demonstrating that TMC7 functions as a suppressor of pain and itch signaling in sensory neurons; however, Tmc7 deletion did not prevent mechanical allodynia in the spared nerve injury (SNI) neuropathic pain model or alter responses in an inflammatory pain setting.","method":"Tmc7 knockout mouse behavioral analysis (mechanical, heat, cold nociception assays; pruritogen-evoked scratching assay; SNI neuropathic pain model); comparison with Tmc3 and Tmc5 knockouts","journal":"The journal of pain","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockout with defined behavioral phenotypes across multiple modalities, single lab, no molecular mechanism identified beyond gene deletion","pmids":["41207409"],"is_preprint":false},{"year":2024,"finding":"TMC7 is required for spermiogenesis; deletion of Tmc7 in mice causes oligoasthenoteratozoospermia (OAT)-like phenotype with abnormal swelling of trans-Golgi network (TGN) vesicles in elongated spermatids, defined by the marker SYPL1; TMC7 is proposed to act as a potential chloride transport channel to regulate TGN vesicle size.","method":"Tmc7 knockout mouse with histological analysis, transmission electron microscopy (TEM), RNA-seq, DIA mass spectrometry of testes, immunofluorescence localization of SYPL1-marked TGN vesicles","journal":"International journal of biological macromolecules","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knockout with defined ultrastructural phenotype and organelle marker, multiple orthogonal methods (TEM, immunofluorescence, proteomics), but chloride channel activity is inferred, not directly measured","pmids":["39732242"],"is_preprint":false},{"year":2023,"finding":"Knockdown of exon 17 of TMC7 (an alternative splicing event upregulated in metastatic pancreatic cancer lesions) significantly inhibited proliferation, invasion, and migration of pancreatic cancer cells in 2D and 3D cell experiments, indicating that this specific TMC7 isoform promotes EMT-associated malignant behaviors.","method":"Exon 17 knockdown in pancreatic cancer cell lines and organoid models; 2D/3D proliferation, invasion, and migration assays; correlation with human tissue and organoid expression data","journal":"Frontiers in immunology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, knockdown of specific exon with phenotypic readout but no defined molecular mechanism or pathway placement for TMC7 protein function","pmids":["36713450"],"is_preprint":false}],"current_model":"TMC7 is a transmembrane channel-like protein expressed in primary somatosensory (DRG) neurons where it physically interacts with the mechanosensitive channel Piezo2 and with β-actin to suppress Piezo2-mediated rapidly adapting mechanocurrents; in the male reproductive tract it localizes to elongated spermatids and is required for normal trans-Golgi network vesicle trafficking during spermiogenesis, likely acting as a chloride transport channel; behavioral genetics in mice further establish TMC7 as a suppressor of nociceptive and itch signaling."},"narrative":{"mechanistic_narrative":"TMC7 is a transmembrane channel-like protein that functions as a negative modulator of sensory mechanotransduction in primary somatosensory neurons [PMID:38568807]. In dorsal root ganglion neurons it physically associates with the mechanosensitive channel Piezo2 and with cytoskeletal β-actin, and through these interactions it suppresses Piezo2-mediated rapidly adapting mechanocurrents: genetic deletion of TMC7 increases the proportion of rapidly adapting Piezo2 currents and accelerates their deactivation, while co-expression of TMC7 reduces Piezo2 current amplitude in heterologous cells [PMID:38568807]. Consistent with this inhibitory role, selective deletion of Tmc7 in mice heightens nociception across pain modalities and increases pruritogen-evoked itch, establishing TMC7 as a suppressor of pain and itch signaling, though it is dispensable for spared-nerve-injury neuropathic and inflammatory pain [PMID:41207409]. Beyond the somatosensory system, TMC7 is required for spermiogenesis, where its loss produces an oligoasthenoteratozoospermia-like phenotype with abnormally swollen trans-Golgi network vesicles in elongated spermatids, a role attributed to a putative chloride transport activity regulating TGN vesicle size [PMID:39732242]. Direct biophysical demonstration of TMC7 ion-channel activity has not been achieved in the available corpus.","teleology":[{"year":2024,"claim":"Whether TMC7 participates in mechanotransduction was unknown; this work established it as an inhibitory partner of Piezo2 that dampens rapidly adapting mechanocurrents in sensory neurons.","evidence":"Conditional DRG knockout with patch-clamp electrophysiology, HEK293 co-expression functional assays, and co-immunoprecipitation of TMC7 with Piezo2 and β-actin","pmids":["38568807"],"confidence":"High","gaps":["Does not establish whether TMC7 itself conducts ions or acts purely as a regulatory scaffold","Structural basis of the TMC7–Piezo2 and TMC7–β-actin interactions unresolved","Mechanism by which β-actin binding contributes to current suppression not defined"]},{"year":2024,"claim":"It was unclear whether TMC7 had functions outside sensory neurons; this work showed it is required for spermiogenesis and linked it to trans-Golgi network vesicle regulation.","evidence":"Tmc7 knockout mouse with TEM, histology, RNA-seq, DIA proteomics, and SYPL1 immunofluorescence of TGN vesicles","pmids":["39732242"],"confidence":"Medium","gaps":["Chloride transport activity is inferred from phenotype, not directly measured","Molecular link between TMC7 and TGN vesicle size control unknown","Substrate or ion selectivity not determined"]},{"year":2025,"claim":"The organismal consequence of the TMC7–Piezo2 inhibitory relationship was untested; behavioral genetics established TMC7 as a suppressor of pain and itch signaling in vivo.","evidence":"Tmc7 knockout mouse behavioral panel (mechanical, heat, cold nociception, pruritogen scratching, SNI model) with comparison to Tmc3 and Tmc5 knockouts","pmids":["41207409"],"confidence":"Medium","gaps":["No molecular mechanism beyond gene deletion identified in this study","TMC7 is dispensable for SNI neuropathic and inflammatory pain, leaving the modality boundaries unexplained","Cell-type-specific contribution to itch versus pain circuits not dissected"]},{"year":2023,"claim":"A potential disease-associated role was probed by testing an alternatively spliced TMC7 isoform in pancreatic cancer cells.","evidence":"Exon 17 knockdown in pancreatic cancer cell lines and organoids with 2D/3D proliferation, invasion, and migration assays","pmids":["36713450"],"confidence":"Low","gaps":["No defined molecular mechanism or pathway placement for the TMC7 protein in this context","Effect attributed to a specific exon rather than full-length protein function","Single-lab correlative study without in vivo validation"]},{"year":null,"claim":"Whether TMC7 is itself an ion channel and, if so, its conducted species and gating mechanism remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct biophysical measurement of TMC7 ionic current","Chloride selectivity remains inferred from spermatid phenotype","Relationship between the channel-modulator role in neurons and the transport role in spermatids not unified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[2]}],"complexes":[],"partners":["PIEZO2","ACTB"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q7Z402","full_name":"Transmembrane channel-like protein 7","aliases":[],"length_aa":723,"mass_kda":83.5,"function":"Acts as an inhibitory modulator of PIEZO2 mechanosensitive channel in dorsal root ganglion (DRG) neurons through physical interactions or interference with the interaction between PIEZO2 and the cytoskeleton","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q7Z402/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TMC7","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TMC7","total_profiled":1310},"omim":[{"mim_id":"617198","title":"TRANSMEMBRANE CHANNEL-LIKE PROTEIN 7; TMC7","url":"https://www.omim.org/entry/617198"},{"mim_id":"617197","title":"TRANSMEMBRANE CHANNEL-LIKE PROTEIN 5; TMC5","url":"https://www.omim.org/entry/617197"},{"mim_id":"605829","title":"TRANSMEMBRANE CHANNEL-LIKE PROTEIN 8; TMC8","url":"https://www.omim.org/entry/605829"},{"mim_id":"605828","title":"TRANSMEMBRANE CHANNEL-LIKE PROTEIN 6; TMC6","url":"https://www.omim.org/entry/605828"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":12.3},{"tissue":"testis","ntpm":9.0},{"tissue":"urinary bladder","ntpm":7.6}],"url":"https://www.proteinatlas.org/search/TMC7"},"hgnc":{"alias_symbol":["FLJ21240"],"prev_symbol":[]},"alphafold":{"accession":"Q7Z402","domains":[{"cath_id":"-","chopping":"154-300_453-652","consensus_level":"high","plddt":84.7081,"start":154,"end":652},{"cath_id":"1.10.287","chopping":"89-143","consensus_level":"medium","plddt":69.3518,"start":89,"end":143},{"cath_id":"1.20.5","chopping":"665-723","consensus_level":"medium","plddt":88.0173,"start":665,"end":723}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z402","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z402-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z402-F1-predicted_aligned_error_v6.png","plddt_mean":77.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TMC7","jax_strain_url":"https://www.jax.org/strain/search?query=TMC7"},"sequence":{"accession":"Q7Z402","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z402.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z402/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z402"}},"corpus_meta":[{"pmid":"24316942","id":"PMC_24316942","title":"Prediction of response to preoperative chemoradiotherapy in rectal cancer by using reverse transcriptase polymerase chain reaction analysis of four genes.","date":"2014","source":"Diseases of the colon and rectum","url":"https://pubmed.ncbi.nlm.nih.gov/24316942","citation_count":41,"is_preprint":false},{"pmid":"28525603","id":"PMC_28525603","title":"Genome-Wide Association Study of Psychosis Proneness in the Finnish Population.","date":"2017","source":"Schizophrenia bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/28525603","citation_count":30,"is_preprint":false},{"pmid":"38568807","id":"PMC_38568807","title":"TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction.","date":"2024","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/38568807","citation_count":17,"is_preprint":false},{"pmid":"33760127","id":"PMC_33760127","title":"Long non‑coding RNA MIR4713HG aggravates malignant behaviors in oral tongue squamous cell carcinoma via binding with microRNA let‑7c‑5p.","date":"2021","source":"International journal of molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33760127","citation_count":11,"is_preprint":false},{"pmid":"26732326","id":"PMC_26732326","title":"The Prediction of the Expected Current Selection Coefficient of Single Nucleotide Polymorphism Associated with Holstein Milk Yield, Fat and Protein Contents.","date":"2016","source":"Asian-Australasian journal of animal sciences","url":"https://pubmed.ncbi.nlm.nih.gov/26732326","citation_count":10,"is_preprint":false},{"pmid":"34226407","id":"PMC_34226407","title":"Metagenomic Insight into Lignocellulose Degradation of the Thermophilic Microbial Consortium TMC7.","date":"2021","source":"Journal of microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/34226407","citation_count":9,"is_preprint":false},{"pmid":"36713450","id":"PMC_36713450","title":"Identification of EMT-related alternative splicing event of TMC7 to promote invasion and migration of pancreatic cancer.","date":"2023","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36713450","citation_count":7,"is_preprint":false},{"pmid":"35637170","id":"PMC_35637170","title":"Heterologous Expression of a Thermostable α-Galactosidase from Parageobacillus thermoglucosidasius Isolated from the Lignocellulolytic Microbial Consortium TMC7.","date":"2022","source":"Journal of microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/35637170","citation_count":2,"is_preprint":false},{"pmid":"41207409","id":"PMC_41207409","title":"Contribution of transmembrane channel-like (TMC) proteins 3, 5 and 7 to pain and itch processing.","date":"2025","source":"The journal of pain","url":"https://pubmed.ncbi.nlm.nih.gov/41207409","citation_count":2,"is_preprint":false},{"pmid":"39732242","id":"PMC_39732242","title":"TMC7 is required for spermiogenesis and male fertility by regulating TGN-derived vesicles.","date":"2024","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39732242","citation_count":0,"is_preprint":false},{"pmid":"41488927","id":"PMC_41488927","title":"The ion transport, GPCR, and RTK toolkit expression in the human cerebrovascular endothelial cell line, hCMEC/D3: an Omics perspective.","date":"2025","source":"Frontiers in physiology","url":"https://pubmed.ncbi.nlm.nih.gov/41488927","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8509,"output_tokens":1300,"usd":0.022513,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7995,"output_tokens":2090,"usd":0.046113,"stage2_stop_reason":"end_turn"},"total_usd":0.068626,"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\": 2024,\n      \"finding\": \"TMC7 physically interacts with the mechanosensitive channel Piezo2 and with cytoskeletal β-actin in somatosensory neurons; genetic deletion of TMC7 in primary sensory ganglia neurons increases the proportion of rapidly adapting (RA) currents conducted by Piezo2 in DRG neurons and accelerates RA deactivation kinetics; in HEK293 cells co-expressing both proteins, TMC7 significantly suppresses Piezo2 current amplitudes, establishing TMC7 as an inhibitory modulator of Piezo2-mediated mechanotransduction.\",\n      \"method\": \"In vivo conditional knockout in DRG neurons with electrophysiological readout (RA current proportion and kinetics), co-expression in HEK293 cells with whole-cell patch clamp, co-immunoprecipitation / physical interaction assays for TMC7–Piezo2 and TMC7–β-actin\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal physical interaction, in vivo genetic deletion with defined electrophysiological phenotype, and heterologous expression functional assay; multiple orthogonal methods in one study\",\n      \"pmids\": [\"38568807\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Selective deletion of Tmc7 in mice increases nociception across pain modalities and increases pruritogen-evoked itch scratching, demonstrating that TMC7 functions as a suppressor of pain and itch signaling in sensory neurons; however, Tmc7 deletion did not prevent mechanical allodynia in the spared nerve injury (SNI) neuropathic pain model or alter responses in an inflammatory pain setting.\",\n      \"method\": \"Tmc7 knockout mouse behavioral analysis (mechanical, heat, cold nociception assays; pruritogen-evoked scratching assay; SNI neuropathic pain model); comparison with Tmc3 and Tmc5 knockouts\",\n      \"journal\": \"The journal of pain\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with defined behavioral phenotypes across multiple modalities, single lab, no molecular mechanism identified beyond gene deletion\",\n      \"pmids\": [\"41207409\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TMC7 is required for spermiogenesis; deletion of Tmc7 in mice causes oligoasthenoteratozoospermia (OAT)-like phenotype with abnormal swelling of trans-Golgi network (TGN) vesicles in elongated spermatids, defined by the marker SYPL1; TMC7 is proposed to act as a potential chloride transport channel to regulate TGN vesicle size.\",\n      \"method\": \"Tmc7 knockout mouse with histological analysis, transmission electron microscopy (TEM), RNA-seq, DIA mass spectrometry of testes, immunofluorescence localization of SYPL1-marked TGN vesicles\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knockout with defined ultrastructural phenotype and organelle marker, multiple orthogonal methods (TEM, immunofluorescence, proteomics), but chloride channel activity is inferred, not directly measured\",\n      \"pmids\": [\"39732242\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Knockdown of exon 17 of TMC7 (an alternative splicing event upregulated in metastatic pancreatic cancer lesions) significantly inhibited proliferation, invasion, and migration of pancreatic cancer cells in 2D and 3D cell experiments, indicating that this specific TMC7 isoform promotes EMT-associated malignant behaviors.\",\n      \"method\": \"Exon 17 knockdown in pancreatic cancer cell lines and organoid models; 2D/3D proliferation, invasion, and migration assays; correlation with human tissue and organoid expression data\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, knockdown of specific exon with phenotypic readout but no defined molecular mechanism or pathway placement for TMC7 protein function\",\n      \"pmids\": [\"36713450\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TMC7 is a transmembrane channel-like protein expressed in primary somatosensory (DRG) neurons where it physically interacts with the mechanosensitive channel Piezo2 and with β-actin to suppress Piezo2-mediated rapidly adapting mechanocurrents; in the male reproductive tract it localizes to elongated spermatids and is required for normal trans-Golgi network vesicle trafficking during spermiogenesis, likely acting as a chloride transport channel; behavioral genetics in mice further establish TMC7 as a suppressor of nociceptive and itch signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TMC7 is a transmembrane channel-like protein that functions as a negative modulator of sensory mechanotransduction in primary somatosensory neurons [#0]. In dorsal root ganglion neurons it physically associates with the mechanosensitive channel Piezo2 and with cytoskeletal \\u03b2-actin, and through these interactions it suppresses Piezo2-mediated rapidly adapting mechanocurrents: genetic deletion of TMC7 increases the proportion of rapidly adapting Piezo2 currents and accelerates their deactivation, while co-expression of TMC7 reduces Piezo2 current amplitude in heterologous cells [#0]. Consistent with this inhibitory role, selective deletion of Tmc7 in mice heightens nociception across pain modalities and increases pruritogen-evoked itch, establishing TMC7 as a suppressor of pain and itch signaling, though it is dispensable for spared-nerve-injury neuropathic and inflammatory pain [#1]. Beyond the somatosensory system, TMC7 is required for spermiogenesis, where its loss produces an oligoasthenoteratozoospermia-like phenotype with abnormally swollen trans-Golgi network vesicles in elongated spermatids, a role attributed to a putative chloride transport activity regulating TGN vesicle size [#2]. Direct biophysical demonstration of TMC7 ion-channel activity has not been achieved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether TMC7 participates in mechanotransduction was unknown; this work established it as an inhibitory partner of Piezo2 that dampens rapidly adapting mechanocurrents in sensory neurons.\",\n      \"evidence\": \"Conditional DRG knockout with patch-clamp electrophysiology, HEK293 co-expression functional assays, and co-immunoprecipitation of TMC7 with Piezo2 and \\u03b2-actin\",\n      \"pmids\": [\"38568807\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not establish whether TMC7 itself conducts ions or acts purely as a regulatory scaffold\", \"Structural basis of the TMC7\\u2013Piezo2 and TMC7\\u2013\\u03b2-actin interactions unresolved\", \"Mechanism by which \\u03b2-actin binding contributes to current suppression not defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unclear whether TMC7 had functions outside sensory neurons; this work showed it is required for spermiogenesis and linked it to trans-Golgi network vesicle regulation.\",\n      \"evidence\": \"Tmc7 knockout mouse with TEM, histology, RNA-seq, DIA proteomics, and SYPL1 immunofluorescence of TGN vesicles\",\n      \"pmids\": [\"39732242\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Chloride transport activity is inferred from phenotype, not directly measured\", \"Molecular link between TMC7 and TGN vesicle size control unknown\", \"Substrate or ion selectivity not determined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The organismal consequence of the TMC7\\u2013Piezo2 inhibitory relationship was untested; behavioral genetics established TMC7 as a suppressor of pain and itch signaling in vivo.\",\n      \"evidence\": \"Tmc7 knockout mouse behavioral panel (mechanical, heat, cold nociception, pruritogen scratching, SNI model) with comparison to Tmc3 and Tmc5 knockouts\",\n      \"pmids\": [\"41207409\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular mechanism beyond gene deletion identified in this study\", \"TMC7 is dispensable for SNI neuropathic and inflammatory pain, leaving the modality boundaries unexplained\", \"Cell-type-specific contribution to itch versus pain circuits not dissected\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"A potential disease-associated role was probed by testing an alternatively spliced TMC7 isoform in pancreatic cancer cells.\",\n      \"evidence\": \"Exon 17 knockdown in pancreatic cancer cell lines and organoids with 2D/3D proliferation, invasion, and migration assays\",\n      \"pmids\": [\"36713450\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No defined molecular mechanism or pathway placement for the TMC7 protein in this context\", \"Effect attributed to a specific exon rather than full-length protein function\", \"Single-lab correlative study without in vivo validation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether TMC7 is itself an ion channel and, if so, its conducted species and gating mechanism remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct biophysical measurement of TMC7 ionic current\", \"Chloride selectivity remains inferred from spermatid phenotype\", \"Relationship between the channel-modulator role in neurons and the transport role in spermatids not unified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PIEZO2\", \"ACTB\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":4,"faith_total":4,"faith_pct":100.0}}