{"gene":"CATSPERG","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2009,"finding":"CATSPERG is a novel single transmembrane-spanning protein with a large extracellular domain and short intracellular tail that associates with the CATSPER channel complex and co-localizes with CATSPER1-4 and CATSPERB in the sperm principal piece. In CATSPER1-deficient sperm, CATSPERG protein is lost, indicating that CATSPER1 is required for the trafficking and/or assembly of CATSPERG within the CATSPER complex.","method":"Co-immunoprecipitation, immunofluorescence localization in sperm, analysis of CATSPER1-knockout sperm (loss-of-function), and comparison with KCNU1 (K+ channel) as negative control","journal":"Biology of reproduction","confidence":"High","confidence_rationale":"Tier 2 — reciprocal association confirmed by Co-IP and KO model with specific negative control, highly cited foundational paper","pmids":["19516020"],"is_preprint":false}],"current_model":"CATSPERG is a single-pass transmembrane protein that is a component of the CATSPER ion channel complex in the sperm principal piece, where its stable localization and/or assembly depends on CATSPER1, and the complex is required for sperm hyperactivated motility and male fertility."},"narrative":{"teleology":[{"year":2009,"claim":"Identification of CATSPERG as a novel transmembrane subunit of the CATSPER complex established that the channel includes auxiliary single-pass membrane proteins beyond the pore-forming CATSPER1-4 subunits, and revealed a hierarchical assembly mechanism in which CATSPER1 is required for CATSPERG stability.","evidence":"Co-immunoprecipitation from sperm lysates, immunofluorescence co-localization in wild-type vs. CATSPER1-knockout mouse sperm","pmids":["19516020"],"confidence":"High","gaps":["Direct function of CATSPERG within the CATSPER complex (e.g., whether it modulates channel gating or ligand sensing) has not been determined","No CATSPERG-specific knockout model to assess its individual requirement for fertility","Structural basis of CATSPERG interaction with pore-forming CATSPER subunits is unknown"]},{"year":null,"claim":"The specific molecular role of CATSPERG — whether it functions as a ligand-binding accessory subunit, a structural scaffold, or a regulator of CATSPER channel activity — remains unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No CATSPERG-specific loss-of-function model exists","No electrophysiological data on how CATSPERG affects CATSPER current properties","No structural model of the CATSPERG extracellular domain or its binding interface with the complex"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"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":["CATSPER1","CATSPERB"],"other_free_text":[]},"mechanistic_narrative":"CATSPERG is a single-pass transmembrane protein with a large extracellular domain that associates with the CATSPER ion channel complex in the principal piece of sperm flagella [PMID:19516020]. Its stable expression depends on CATSPER1, as CATSPERG protein is lost in CATSPER1-knockout sperm, indicating that CATSPER1 is required for its trafficking and/or assembly into the complex [PMID:19516020]. As a component of the CATSPER complex, CATSPERG contributes to the channel architecture essential for sperm hyperactivated motility and male fertility [PMID:19516020]."},"prefetch_data":{"uniprot":{"accession":"Q6ZRH7","full_name":"Cation channel sperm-associated auxiliary subunit gamma","aliases":[],"length_aa":1159,"mass_kda":133.0,"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","subcellular_location":"Cell projection, cilium, flagellum membrane","url":"https://www.uniprot.org/uniprotkb/Q6ZRH7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CATSPERG","classification":"Not Classified","n_dependent_lines":13,"n_total_lines":1208,"dependency_fraction":0.01076158940397351},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CATSPERG","total_profiled":1310},"omim":[{"mim_id":"613452","title":"CATION CHANNEL, SPERM-ASSOCIATED, AUXILIARY SUBUNIT GAMMA; CATSPERG","url":"https://www.omim.org/entry/613452"},{"mim_id":"611169","title":"CATION CHANNEL, SPERM-ASSOCIATED, AUXILIARY SUBUNIT BETA; CATSPERB","url":"https://www.omim.org/entry/611169"},{"mim_id":"609121","title":"CATION CHANNEL, SPERM-ASSOCIATED, 4; CATSPER4","url":"https://www.omim.org/entry/609121"},{"mim_id":"609120","title":"CATION CHANNEL, SPERM-ASSOCIATED, 3; CATSPER3","url":"https://www.omim.org/entry/609120"},{"mim_id":"607249","title":"CATION CHANNEL, SPERM-ASSOCIATED, 2; CATSPER2","url":"https://www.omim.org/entry/607249"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Mid piece","reliability":"Approved"},{"location":"Principal piece","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":30.6}],"url":"https://www.proteinatlas.org/search/CATSPERG"},"hgnc":{"alias_symbol":["DKFZp434A1022","FLJ46353"],"prev_symbol":["C19orf15"]},"alphafold":{"accession":"Q6ZRH7","domains":[{"cath_id":"-","chopping":"45-205_654-746","consensus_level":"high","plddt":88.3871,"start":45,"end":746},{"cath_id":"2.60.40","chopping":"759-782_793-881","consensus_level":"high","plddt":86.8298,"start":759,"end":881},{"cath_id":"2.60.40","chopping":"887-1067","consensus_level":"high","plddt":88.7548,"start":887,"end":1067}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZRH7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZRH7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZRH7-F1-predicted_aligned_error_v6.png","plddt_mean":83.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CATSPERG","jax_strain_url":"https://www.jax.org/strain/search?query=CATSPERG"},"sequence":{"accession":"Q6ZRH7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ZRH7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ZRH7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZRH7"}},"corpus_meta":[{"pmid":"19516020","id":"PMC_19516020","title":"A novel, single, transmembrane protein CATSPERG is associated with CATSPER1 channel protein.","date":"2009","source":"Biology of reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/19516020","citation_count":99,"is_preprint":false},{"pmid":"33285124","id":"PMC_33285124","title":"Comparison of spermatozoal RNA extraction methods in goats.","date":"2020","source":"Analytical biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/33285124","citation_count":14,"is_preprint":false},{"pmid":"33095540","id":"PMC_33095540","title":"Genome-wide association study of high-sensitivity C-reactive protein, D-dimer, and interleukin-6 levels in multiethnic HIV+ cohorts.","date":"2021","source":"AIDS (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/33095540","citation_count":12,"is_preprint":false},{"pmid":"39506588","id":"PMC_39506588","title":"Identification of Potential Biomarkers Associated with Spermatogenesis in Azoospermia.","date":"2024","source":"Clinical laboratory","url":"https://pubmed.ncbi.nlm.nih.gov/39506588","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3498,"output_tokens":370,"usd":0.008022},"stage2":{"model":"claude-opus-4-6","input_tokens":3515,"output_tokens":757,"usd":0.05475},"total_usd":0.062772,"stage1_batch_id":"msgbatch_011kfMfE81o6CTcyhVUqumuW","stage2_batch_id":"msgbatch_01DTputS6WNkH745x1nVSoBo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"CATSPERG is a novel single transmembrane-spanning protein with a large extracellular domain and short intracellular tail that associates with the CATSPER channel complex and co-localizes with CATSPER1-4 and CATSPERB in the sperm principal piece. In CATSPER1-deficient sperm, CATSPERG protein is lost, indicating that CATSPER1 is required for the trafficking and/or assembly of CATSPERG within the CATSPER complex.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence localization in sperm, analysis of CATSPER1-knockout sperm (loss-of-function), and comparison with KCNU1 (K+ channel) as negative control\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal association confirmed by Co-IP and KO model with specific negative control, highly cited foundational paper\",\n      \"pmids\": [\"19516020\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CATSPERG is a single-pass transmembrane protein that is a component of the CATSPER ion channel complex in the sperm principal piece, where its stable localization and/or assembly depends on CATSPER1, and the complex is required for sperm hyperactivated motility and male fertility.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CATSPERG is a single-pass transmembrane protein with a large extracellular domain that associates with the CATSPER ion channel complex in the principal piece of sperm flagella [PMID:19516020]. Its stable expression depends on CATSPER1, as CATSPERG protein is lost in CATSPER1-knockout sperm, indicating that CATSPER1 is required for its trafficking and/or assembly into the complex [PMID:19516020]. As a component of the CATSPER complex, CATSPERG contributes to the channel architecture essential for sperm hyperactivated motility and male fertility [PMID:19516020].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Identification of CATSPERG as a novel transmembrane subunit of the CATSPER complex established that the channel includes auxiliary single-pass membrane proteins beyond the pore-forming CATSPER1-4 subunits, and revealed a hierarchical assembly mechanism in which CATSPER1 is required for CATSPERG stability.\",\n      \"evidence\": \"Co-immunoprecipitation from sperm lysates, immunofluorescence co-localization in wild-type vs. CATSPER1-knockout mouse sperm\",\n      \"pmids\": [\"19516020\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct function of CATSPERG within the CATSPER complex (e.g., whether it modulates channel gating or ligand sensing) has not been determined\",\n        \"No CATSPERG-specific knockout model to assess its individual requirement for fertility\",\n        \"Structural basis of CATSPERG interaction with pore-forming CATSPER subunits is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular role of CATSPERG — whether it functions as a ligand-binding accessory subunit, a structural scaffold, or a regulator of CATSPER channel activity — remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No CATSPERG-specific loss-of-function model exists\",\n        \"No electrophysiological data on how CATSPERG affects CATSPER current properties\",\n        \"No structural model of the CATSPERG extracellular domain or its binding interface with the complex\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005886\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-1474165\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"complexes\": [\n      \"CATSPER channel complex\"\n    ],\n    \"partners\": [\n      \"CATSPER1\",\n      \"CATSPERB\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}