{"gene":"CATSPERZ","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2017,"finding":"CATSPERZ (encoded by Tex40) is a novel subunit of the 9-subunit CatSper ion channel complex in sperm. Targeted disruption of CatSperζ reduces CatSper current and disrupts the linear quadrilateral nanodomain organization of the CatSper complex along the flagellum at ~0.8 μm intervals, rendering the proximal flagellum inflexible and altering the 3D flagellar envelope, resulting in severe male subfertility due to impaired rheotaxis and in vivo migration.","method":"Targeted gene disruption (knockout mouse), electrophysiology (CatSper current measurement), super-resolution fluorescence imaging (STORM), sperm motility and rheotaxis assays, in vitro fertilization","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cellular phenotype, electrophysiological functional readout, nanoscale structural imaging, multiple orthogonal methods in a single rigorous study","pmids":["28226241"],"is_preprint":false},{"year":2018,"finding":"Lower expression of TEX40 (CATSPERZ) protein in spermatozoa from asthenozoospermic males correlates with reduced calcium ion entry, consistent with its role as a component of the CatSper channel complex required for normal sperm motility.","method":"2D-DIGE proteomics, mass spectrometry, western blotting, ELISA, qRT-PCR","journal":"Life sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — correlative proteomics without direct functional manipulation of CATSPERZ; no mechanistic experiment performed on the protein itself","pmids":["30550884"],"is_preprint":false}],"current_model":"CATSPERZ (TEX40/C11orf20) encodes a subunit of the nine-subunit CatSper sperm calcium channel complex; it is required for maintaining the structural continuity of the linear quadrilateral CatSper nanodomains along the sperm flagellum, supporting CatSper current amplitude, flagellar flexibility, and rheotaxis-dependent fertilization in vivo."},"narrative":{"mechanistic_narrative":"CATSPERZ (encoded by Tex40, also C11orf20) is a subunit of the nine-subunit CatSper calcium channel complex of the sperm flagellum, where it organizes the channel's spatial architecture rather than forming the pore itself [PMID:28226241]. Targeted disruption of CatSperζ reduces CatSper current and disrupts the linear quadrilateral nanodomain organization of the complex along the flagellum, leaving the proximal flagellum inflexible and altering the three-dimensional flagellar envelope [PMID:28226241]. The consequence is severe male subfertility driven by impaired rheotaxis and in vivo sperm migration, establishing CATSPERZ as a structural organizer required to maintain CatSper nanodomain continuity and the flagellar mechanics needed for fertilization [PMID:28226241]. Beyond this knockout characterization, no further mechanistic detail on CATSPERZ has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Established that CATSPERZ is a bona fide subunit of the CatSper complex and defined its role in organizing the channel's nanodomain architecture rather than carrying the pore.","evidence":"Knockout mouse with CatSper current electrophysiology, STORM super-resolution imaging of flagellar nanodomains, and rheotaxis/IVF assays","pmids":["28226241"],"confidence":"High","gaps":["Molecular mechanism by which CATSPERZ enforces the ~0.8 μm quadrilateral nanodomain spacing is unresolved","Direct physical interactions with specific CatSper subunits not mapped","No structural model of how CATSPERZ integrates into the channel complex"]},{"year":2018,"claim":"Asked whether reduced CATSPERZ levels associate with human sperm dysfunction, linking the protein's abundance to calcium entry and motility defects.","evidence":"2D-DIGE proteomics, mass spectrometry, western blot and ELISA on asthenozoospermic patient spermatozoa","pmids":["30550884"],"confidence":"Low","gaps":["Correlative only; no functional manipulation of CATSPERZ was performed","Causality between lowered TEX40 protein and reduced calcium influx not established","Does not confirm the structural role observed in mouse applies in human sperm"]},{"year":null,"claim":"How CATSPERZ molecularly directs nanodomain assembly and which subunit contacts mediate its organizing function remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No interaction map or structural data for CATSPERZ within the CatSper complex","Mechanism coupling nanodomain integrity to flagellar flexibility undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[0]}],"complexes":["CatSper channel complex"],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NTU4","full_name":"Cation channel sperm-associated auxiliary subunit zeta","aliases":["Testis-expressed protein 40"],"length_aa":200,"mass_kda":22.8,"function":"Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation. Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization. Required for a distribution of the CatSper complex in linear quadrilateral nanodomains along the flagellum, maximizing fertilization inside the mammalian female reproductive tract. Together with EFCAB9, associates with the CatSper channel pore and is required for the two-row structure of each single CatSper channel","subcellular_location":"Cell projection, cilium, flagellum membrane","url":"https://www.uniprot.org/uniprotkb/Q9NTU4/entry"},"depmap":{"release":"DepMap","has_data":false,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CATSPERZ"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CATSPERZ","total_profiled":1310},"omim":[{"mim_id":"618520","title":"EF-HAND CALCIUM-BINDING DOMAIN-CONTAINING PROTEIN 9; EFCAB9","url":"https://www.omim.org/entry/618520"},{"mim_id":"617511","title":"CATION CHANNEL, SPERM-ASSOCIATED, AUXILIARY SUBUNIT ZETA; CATSPERZ","url":"https://www.omim.org/entry/617511"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Primary cilium tip","reliability":"Approved"},{"location":"Mid piece","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":544.5}],"url":"https://www.proteinatlas.org/search/CATSPERZ"},"hgnc":{"alias_symbol":["DKFZP566E164"],"prev_symbol":["C11orf20","TEX40"]},"alphafold":{"accession":"Q9NTU4","domains":[{"cath_id":"1.10.287","chopping":"147-200","consensus_level":"medium","plddt":91.8207,"start":147,"end":200}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NTU4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NTU4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NTU4-F1-predicted_aligned_error_v6.png","plddt_mean":62.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CATSPERZ","jax_strain_url":"https://www.jax.org/strain/search?query=CATSPERZ"},"sequence":{"accession":"Q9NTU4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NTU4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NTU4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NTU4"}},"corpus_meta":[{"pmid":"28226241","id":"PMC_28226241","title":"CatSperζ regulates the structural continuity of sperm Ca2+ signaling domains and is required for normal fertility.","date":"2017","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/28226241","citation_count":129,"is_preprint":false},{"pmid":"30239785","id":"PMC_30239785","title":"Homozygous in-frame deletion in CATSPERE in a man producing spermatozoa with loss of CatSper function and compromised fertilizing capacity.","date":"2018","source":"Human reproduction (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/30239785","citation_count":46,"is_preprint":false},{"pmid":"21949640","id":"PMC_21949640","title":"ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma.","date":"2011","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/21949640","citation_count":43,"is_preprint":false},{"pmid":"30550884","id":"PMC_30550884","title":"Proteomic analyses reveal lower expression of TEX40 and ATP6V0A2 proteins related to calcium ion entry and acrosomal acidification in asthenozoospermic males.","date":"2018","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30550884","citation_count":17,"is_preprint":false},{"pmid":"24504521","id":"PMC_24504521","title":"Low frequency of ESRRA-C11orf20 fusion gene in ovarian carcinomas.","date":"2014","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/24504521","citation_count":10,"is_preprint":false},{"pmid":"37874861","id":"PMC_37874861","title":"Integrated single cell transcriptome sequencing analysis reveals species-specific genes and molecular pathways for pig spermiogenesis.","date":"2023","source":"Reproduction in domestic animals = Zuchthygiene","url":"https://pubmed.ncbi.nlm.nih.gov/37874861","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5483,"output_tokens":612,"usd":0.012814,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6969,"output_tokens":1265,"usd":0.033235,"stage2_stop_reason":"end_turn"},"total_usd":0.046049,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"CATSPERZ (encoded by Tex40) is a novel subunit of the 9-subunit CatSper ion channel complex in sperm. Targeted disruption of CatSperζ reduces CatSper current and disrupts the linear quadrilateral nanodomain organization of the CatSper complex along the flagellum at ~0.8 μm intervals, rendering the proximal flagellum inflexible and altering the 3D flagellar envelope, resulting in severe male subfertility due to impaired rheotaxis and in vivo migration.\",\n      \"method\": \"Targeted gene disruption (knockout mouse), electrophysiology (CatSper current measurement), super-resolution fluorescence imaging (STORM), sperm motility and rheotaxis assays, in vitro fertilization\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cellular phenotype, electrophysiological functional readout, nanoscale structural imaging, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"28226241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Lower expression of TEX40 (CATSPERZ) protein in spermatozoa from asthenozoospermic males correlates with reduced calcium ion entry, consistent with its role as a component of the CatSper channel complex required for normal sperm motility.\",\n      \"method\": \"2D-DIGE proteomics, mass spectrometry, western blotting, ELISA, qRT-PCR\",\n      \"journal\": \"Life sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — correlative proteomics without direct functional manipulation of CATSPERZ; no mechanistic experiment performed on the protein itself\",\n      \"pmids\": [\"30550884\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CATSPERZ (TEX40/C11orf20) encodes a subunit of the nine-subunit CatSper sperm calcium channel complex; it is required for maintaining the structural continuity of the linear quadrilateral CatSper nanodomains along the sperm flagellum, supporting CatSper current amplitude, flagellar flexibility, and rheotaxis-dependent fertilization in vivo.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CATSPERZ (encoded by Tex40, also C11orf20) is a subunit of the nine-subunit CatSper calcium channel complex of the sperm flagellum, where it organizes the channel's spatial architecture rather than forming the pore itself [#0]. Targeted disruption of CatSperζ reduces CatSper current and disrupts the linear quadrilateral nanodomain organization of the complex along the flagellum, leaving the proximal flagellum inflexible and altering the three-dimensional flagellar envelope [#0]. The consequence is severe male subfertility driven by impaired rheotaxis and in vivo sperm migration, establishing CATSPERZ as a structural organizer required to maintain CatSper nanodomain continuity and the flagellar mechanics needed for fertilization [#0]. Beyond this knockout characterization, no further mechanistic detail on CATSPERZ has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established that CATSPERZ is a bona fide subunit of the CatSper complex and defined its role in organizing the channel's nanodomain architecture rather than carrying the pore.\",\n      \"evidence\": \"Knockout mouse with CatSper current electrophysiology, STORM super-resolution imaging of flagellar nanodomains, and rheotaxis/IVF assays\",\n      \"pmids\": [\"28226241\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism by which CATSPERZ enforces the ~0.8 μm quadrilateral nanodomain spacing is unresolved\",\n        \"Direct physical interactions with specific CatSper subunits not mapped\",\n        \"No structural model of how CATSPERZ integrates into the channel complex\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Asked whether reduced CATSPERZ levels associate with human sperm dysfunction, linking the protein's abundance to calcium entry and motility defects.\",\n      \"evidence\": \"2D-DIGE proteomics, mass spectrometry, western blot and ELISA on asthenozoospermic patient spermatozoa\",\n      \"pmids\": [\"30550884\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Correlative only; no functional manipulation of CATSPERZ was performed\",\n        \"Causality between lowered TEX40 protein and reduced calcium influx not established\",\n        \"Does not confirm the structural role observed in mouse applies in human sperm\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CATSPERZ molecularly directs nanodomain assembly and which subunit contacts mediate its organizing function remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No interaction map or structural data for CATSPERZ within the CatSper complex\",\n        \"Mechanism coupling nanodomain integrity to flagellar flexibility undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"CatSper channel complex\"],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}