{"gene":"TSNAXIP1","run_date":"2026-06-10T10:51:56","timeline":{"discoveries":[{"year":2002,"finding":"TSNAXIP1 (Tsnaxip1) encodes a 709 amino acid protein that physically interacts with TRAX (translin-associated factor X), identified via yeast two-hybrid screen and verified using in vitro synthesized fusion proteins; the protein colocalizes with TRAX by confocal microscopy of GFP fusion proteins in mouse testis germ cells, suggesting a function associated with perinuclear organelles during spermatogenesis.","method":"Yeast two-hybrid screen, in vitro binding with fusion proteins, confocal microscopy of GFP fusion proteins","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid confirmed by in vitro fusion protein binding and colocalization, single lab with two orthogonal methods","pmids":["12036294"],"is_preprint":false},{"year":2023,"finding":"Knockout of Tsnaxip1 in mice (via CRISPR/Cas9) causes reduced male fertility and impaired sperm motility with asymmetric flagellar waveforms; TSNAXIP1 protein localizes to the sperm tail and fractionates with axonemal proteins, indicating a role in regulating sperm flagellar beating patterns distinct from the TSN-TSNAX complex function.","method":"CRISPR/Cas9 knockout mice, fertility assays, sperm motility analysis, subcellular fractionation, protein localization","journal":"Andrology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cellular phenotype, subcellular fractionation linking localization to function, corroborated by independent KO study in same year","pmids":["36598146"],"is_preprint":false},{"year":2023,"finding":"Knockout of Tsnaxip1 in mice (via CRISPR-Cas9) causes sub-fertility in males with smaller testes, lower sperm count, sperm head malformation (unique flower-shaped head), and abnormal anchorage of the sperm neck, establishing a role for TSNAXIP1 in sperm head morphogenesis; no overt spermatogenesis abnormalities were observed, distinguishing its role from that of the TSN-TSNAX complex.","method":"CRISPR-Cas9 knockout mice, fertility assays, histological analysis of testes, sperm morphology analysis","journal":"Reproductive medicine and biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with specific morphological phenotype, corroborated by independent KO study in same year","pmids":["37389156"],"is_preprint":false}],"current_model":"TSNAXIP1 is a testis-expressed protein that physically interacts with TRAX (translin-associated factor X) and localizes to perinuclear organelles and the sperm tail axoneme; loss-of-function in mice causes impaired sperm motility with asymmetric flagellar waveforms and sperm head malformation (flower-shaped heads with abnormal neck anchorage), establishing essential roles in sperm flagellar beating and sperm head morphogenesis required for male fertility."},"narrative":{"mechanistic_narrative":"TSNAXIP1 is a testis-expressed protein essential for male fertility, functioning in sperm flagellar beating and sperm head morphogenesis [PMID:36598146, PMID:37389156]. It was first identified as a physical interactor of TRAX (translin-associated factor X), colocalizing with TRAX at perinuclear organelles in mouse testis germ cells [PMID:12036294]. In mature sperm, TSNAXIP1 localizes to the tail and fractionates with axonemal proteins, and its loss produces asymmetric flagellar waveforms and impaired motility, indicating a role in regulating the flagellar beating pattern that is distinct from the canonical TSN-TSNAX complex function [PMID:36598146]. Independent knockout work establishes a parallel requirement in sperm head morphogenesis: loss causes smaller testes, reduced sperm count, a characteristic flower-shaped head malformation, and abnormal anchorage of the sperm neck, without overt defects in the broader spermatogenic program [PMID:37389156]. Beyond the TRAX interaction and these flagellar and head-shaping roles, no further molecular mechanism for TSNAXIP1 has been characterized in the available corpus.","teleology":[{"year":2002,"claim":"Established the first molecular handle on TSNAXIP1 by identifying it as a TRAX-binding partner that colocalizes with TRAX at perinuclear organelles, placing it in the spermatogenesis machinery.","evidence":"Yeast two-hybrid screen with in vitro fusion-protein binding and confocal colocalization of GFP fusions in mouse testis germ cells","pmids":["12036294"],"confidence":"Medium","gaps":["Interaction shown by Y2H and in vitro binding without endogenous co-IP or stoichiometry","Functional consequence of the TRAX interaction not defined","No loss-of-function or phenotypic data at this stage"]},{"year":2023,"claim":"Demonstrated that TSNAXIP1 is required for normal sperm flagellar beating, linking its axonemal localization to motility control and separating its function from the TSN-TSNAX complex.","evidence":"CRISPR/Cas9 knockout mice with fertility and sperm motility assays plus subcellular fractionation showing axonemal partitioning","pmids":["36598146"],"confidence":"High","gaps":["Molecular mechanism by which TSNAXIP1 shapes flagellar waveform symmetry unknown","No identified axonemal binding partners or substrates","Relationship between the TRAX interaction and axonemal function not resolved"]},{"year":2023,"claim":"Showed an additional, structural role for TSNAXIP1 in sperm head morphogenesis and neck anchorage, defining a distinct developmental requirement during spermiogenesis.","evidence":"CRISPR-Cas9 knockout mice with histological analysis of testes and sperm morphology","pmids":["37389156"],"confidence":"High","gaps":["Mechanism producing the flower-shaped head and neck anchorage defect not defined","Molecular partners at the head-neck junction unidentified","Whether head and tail phenotypes arise from a single shared molecular activity is unresolved"]},{"year":null,"claim":"How TSNAXIP1 mechanistically couples its TRAX interaction to axonemal beating control and sperm head shaping remains unknown.","evidence":"No mechanistic reconstitution or structural data in the available corpus","pmids":[],"confidence":"Low","gaps":["No structural model of TSNAXIP1","No defined biochemical activity","Functional significance of the TRAX interaction in mature sperm not established"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["TSNAX"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q2TAA8","full_name":"Translin-associated factor X-interacting protein 1","aliases":[],"length_aa":658,"mass_kda":76.8,"function":"Possible role in spermatogenesis","subcellular_location":"Cytoplasm, perinuclear region","url":"https://www.uniprot.org/uniprotkb/Q2TAA8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TSNAXIP1","classification":"Not Classified","n_dependent_lines":27,"n_total_lines":1208,"dependency_fraction":0.022350993377483443},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TSNAXIP1","total_profiled":1310},"omim":[{"mim_id":"607720","title":"TRANSLIN-ASSOCIATED FACTOR X-INTERACTING PROTEIN 1; TSNAXIP1","url":"https://www.omim.org/entry/607720"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"fallopian tube","ntpm":8.1},{"tissue":"testis","ntpm":19.7}],"url":"https://www.proteinatlas.org/search/TSNAXIP1"},"hgnc":{"alias_symbol":["TXI1"],"prev_symbol":[]},"alphafold":{"accession":"Q2TAA8","domains":[{"cath_id":"-","chopping":"366-466","consensus_level":"high","plddt":92.3548,"start":366,"end":466},{"cath_id":"-","chopping":"577-658","consensus_level":"medium","plddt":86.0505,"start":577,"end":658}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q2TAA8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q2TAA8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q2TAA8-F1-predicted_aligned_error_v6.png","plddt_mean":84.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TSNAXIP1","jax_strain_url":"https://www.jax.org/strain/search?query=TSNAXIP1"},"sequence":{"accession":"Q2TAA8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q2TAA8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q2TAA8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q2TAA8"}},"corpus_meta":[{"pmid":"33431810","id":"PMC_33431810","title":"Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality.","date":"2021","source":"Translational psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/33431810","citation_count":21,"is_preprint":false},{"pmid":"12036294","id":"PMC_12036294","title":"Identification and characterization of cDNAs encoding four novel proteins that interact with translin associated factor-X.","date":"2002","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/12036294","citation_count":20,"is_preprint":false},{"pmid":"36598146","id":"PMC_36598146","title":"Testis-specific proteins, TSNAXIP1 and 1700010I14RIK, are important for sperm motility and male fertility in mice.","date":"2023","source":"Andrology","url":"https://pubmed.ncbi.nlm.nih.gov/36598146","citation_count":10,"is_preprint":false},{"pmid":"37389156","id":"PMC_37389156","title":"TSNAXIP1 is required for sperm head formation and male fertility.","date":"2023","source":"Reproductive medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/37389156","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4279,"output_tokens":880,"usd":0.013019,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7342,"output_tokens":1541,"usd":0.037617,"stage2_stop_reason":"end_turn"},"total_usd":0.050636,"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\": 2002,\n      \"finding\": \"TSNAXIP1 (Tsnaxip1) encodes a 709 amino acid protein that physically interacts with TRAX (translin-associated factor X), identified via yeast two-hybrid screen and verified using in vitro synthesized fusion proteins; the protein colocalizes with TRAX by confocal microscopy of GFP fusion proteins in mouse testis germ cells, suggesting a function associated with perinuclear organelles during spermatogenesis.\",\n      \"method\": \"Yeast two-hybrid screen, in vitro binding with fusion proteins, confocal microscopy of GFP fusion proteins\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid confirmed by in vitro fusion protein binding and colocalization, single lab with two orthogonal methods\",\n      \"pmids\": [\"12036294\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Knockout of Tsnaxip1 in mice (via CRISPR/Cas9) causes reduced male fertility and impaired sperm motility with asymmetric flagellar waveforms; TSNAXIP1 protein localizes to the sperm tail and fractionates with axonemal proteins, indicating a role in regulating sperm flagellar beating patterns distinct from the TSN-TSNAX complex function.\",\n      \"method\": \"CRISPR/Cas9 knockout mice, fertility assays, sperm motility analysis, subcellular fractionation, protein localization\",\n      \"journal\": \"Andrology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cellular phenotype, subcellular fractionation linking localization to function, corroborated by independent KO study in same year\",\n      \"pmids\": [\"36598146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Knockout of Tsnaxip1 in mice (via CRISPR-Cas9) causes sub-fertility in males with smaller testes, lower sperm count, sperm head malformation (unique flower-shaped head), and abnormal anchorage of the sperm neck, establishing a role for TSNAXIP1 in sperm head morphogenesis; no overt spermatogenesis abnormalities were observed, distinguishing its role from that of the TSN-TSNAX complex.\",\n      \"method\": \"CRISPR-Cas9 knockout mice, fertility assays, histological analysis of testes, sperm morphology analysis\",\n      \"journal\": \"Reproductive medicine and biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with specific morphological phenotype, corroborated by independent KO study in same year\",\n      \"pmids\": [\"37389156\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TSNAXIP1 is a testis-expressed protein that physically interacts with TRAX (translin-associated factor X) and localizes to perinuclear organelles and the sperm tail axoneme; loss-of-function in mice causes impaired sperm motility with asymmetric flagellar waveforms and sperm head malformation (flower-shaped heads with abnormal neck anchorage), establishing essential roles in sperm flagellar beating and sperm head morphogenesis required for male fertility.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TSNAXIP1 is a testis-expressed protein essential for male fertility, functioning in sperm flagellar beating and sperm head morphogenesis [#1, #2]. It was first identified as a physical interactor of TRAX (translin-associated factor X), colocalizing with TRAX at perinuclear organelles in mouse testis germ cells [#0]. In mature sperm, TSNAXIP1 localizes to the tail and fractionates with axonemal proteins, and its loss produces asymmetric flagellar waveforms and impaired motility, indicating a role in regulating the flagellar beating pattern that is distinct from the canonical TSN-TSNAX complex function [#1]. Independent knockout work establishes a parallel requirement in sperm head morphogenesis: loss causes smaller testes, reduced sperm count, a characteristic flower-shaped head malformation, and abnormal anchorage of the sperm neck, without overt defects in the broader spermatogenic program [#2]. Beyond the TRAX interaction and these flagellar and head-shaping roles, no further molecular mechanism for TSNAXIP1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established the first molecular handle on TSNAXIP1 by identifying it as a TRAX-binding partner that colocalizes with TRAX at perinuclear organelles, placing it in the spermatogenesis machinery.\",\n      \"evidence\": \"Yeast two-hybrid screen with in vitro fusion-protein binding and confocal colocalization of GFP fusions in mouse testis germ cells\",\n      \"pmids\": [\"12036294\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction shown by Y2H and in vitro binding without endogenous co-IP or stoichiometry\", \"Functional consequence of the TRAX interaction not defined\", \"No loss-of-function or phenotypic data at this stage\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrated that TSNAXIP1 is required for normal sperm flagellar beating, linking its axonemal localization to motility control and separating its function from the TSN-TSNAX complex.\",\n      \"evidence\": \"CRISPR/Cas9 knockout mice with fertility and sperm motility assays plus subcellular fractionation showing axonemal partitioning\",\n      \"pmids\": [\"36598146\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which TSNAXIP1 shapes flagellar waveform symmetry unknown\", \"No identified axonemal binding partners or substrates\", \"Relationship between the TRAX interaction and axonemal function not resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed an additional, structural role for TSNAXIP1 in sperm head morphogenesis and neck anchorage, defining a distinct developmental requirement during spermiogenesis.\",\n      \"evidence\": \"CRISPR-Cas9 knockout mice with histological analysis of testes and sperm morphology\",\n      \"pmids\": [\"37389156\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism producing the flower-shaped head and neck anchorage defect not defined\", \"Molecular partners at the head-neck junction unidentified\", \"Whether head and tail phenotypes arise from a single shared molecular activity is unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TSNAXIP1 mechanistically couples its TRAX interaction to axonemal beating control and sperm head shaping remains unknown.\",\n      \"evidence\": \"No mechanistic reconstitution or structural data in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of TSNAXIP1\", \"No defined biochemical activity\", \"Functional significance of the TRAX interaction in mature sperm not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TSNAX\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}