{"gene":"SPATA19","run_date":"2026-06-10T07:46:39","timeline":{"discoveries":[{"year":2002,"finding":"Spergen-1 (SPATA19) protein is associated with mitochondria in spermatids and spermatozoa; subcellular fractionation and immunoblot confirmed mitochondrial association, and transfection experiments in COS-7 cells demonstrated that an N-terminal sequence functions as a mitochondria-targeting signal.","method":"Subcellular fractionation + immunoblot; transfection of COS-7 cells with spergen-1 expression constructs","journal":"Biology of reproduction","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — subcellular fractionation plus cell transfection, single lab but two orthogonal methods","pmids":["11967211"],"is_preprint":false},{"year":2002,"finding":"Spergen-1 (SPATA19) localizes to the surface of mitochondria in the middle piece of spermatozoa (confirmed by immunoelectron microscopy), and when expressed in COS-7 cells, induces mitochondrial aggregation; deletion analysis showed that both the N-terminal mitochondria-targeting signal and the C-terminal region are required for mitochondrial aggregation, suggesting a role as an adhesive molecule assembling mitochondria into the mitochondrial sheath.","method":"Immunocytochemistry, immunoelectron microscopy, and transfection of COS-7 cells with spergen-1 deletion/mutant constructs","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — immunoelectron microscopy plus functional mutagenesis in transfected cells, single lab with multiple orthogonal methods","pmids":["12453465"],"is_preprint":false},{"year":2004,"finding":"Mouse spergen-1 (SPATA19) is a sperm mitochondrial protein; Western blot identified a testis-specific ~18 kDa band, and antibody-based localization confirmed the protein resides in sperm mitochondria.","method":"Western blot; immunolocalization with antibodies raised against mouse Spergen-1","journal":"International journal of andrology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunolocalization and Western blot, replicated across species (mouse), single lab","pmids":["15139970"],"is_preprint":false},{"year":2015,"finding":"Spata19 is required for sperm mitochondrial structural organization and function: conditional knockout males (Spata19-cKO, using Stra8-Cre) were infertile, their sperm showed disorganized mitochondrial structure, reduced mitochondrial protein abundance, decreased mitochondrial respiratory chain complex IV activity, and reduced ATP levels; fertility was rescued by intracytoplasmic sperm injection, demonstrating that SPATA19 is specifically required for mitochondrial organization/function supporting sperm motility but not for intrinsic developmental competence of sperm.","method":"Conditional knockout mouse model (Spata19flox/flox; Stra8-Cre); electron microscopy of sperm mitochondria; mitochondrial protein Western blot; complex IV activity assay; ATP measurement; intracytoplasmic sperm injection rescue","journal":"Molecular reproduction and development","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function (cKO) with multiple orthogonal biochemical readouts (complex IV activity, ATP, protein abundance, ultrastructure) and functional rescue experiment","pmids":["26265198"],"is_preprint":false}],"current_model":"SPATA19 (Spergen-1) is a small haploid spermatid/sperm-specific protein that localizes to the outer surface of mitochondria in the sperm midpiece via an N-terminal mitochondria-targeting signal; its C-terminal region enables mitochondrial aggregation, and conditional knockout studies in mice demonstrate it is essential for organizing the mitochondrial sheath around the outer dense fibers and sustaining mitochondrial respiratory chain (complex IV) activity and ATP production, thereby supporting sperm motility and male fertility."},"narrative":{"mechanistic_narrative":"SPATA19 (Spergen-1) is a small haploid spermatid/sperm-specific protein that organizes the mitochondrial sheath of the sperm midpiece and sustains its respiratory function [PMID:11967211, PMID:26265198]. It associates with mitochondria through an N-terminal mitochondria-targeting signal that directs it to the outer mitochondrial surface, while its C-terminal region drives mitochondrial aggregation, allowing the protein to act as an adhesive molecule that assembles mitochondria into the sheath [PMID:11967211, PMID:12453465]. Conditional knockout in mice establishes that this organizing activity is essential for male fertility: loss of SPATA19 produces disorganized sperm mitochondria, reduced mitochondrial protein abundance, decreased respiratory chain complex IV activity, and lowered ATP, with infertility rescued by intracytoplasmic sperm injection — indicating the defect is in mitochondrial organization and motility support rather than in intrinsic developmental competence of sperm [PMID:26265198].","teleology":[{"year":2002,"claim":"Establishing where Spergen-1 acts answered whether this spermatid-specific protein is targeted to a defined organelle, identifying mitochondria as its site of action.","evidence":"Subcellular fractionation with immunoblot plus targeting-signal mapping by transfection of COS-7 cells","pmids":["11967211"],"confidence":"Medium","gaps":["Targeting demonstrated in a heterologous cell line, not in spermatids in vivo","Functional consequence of mitochondrial association not addressed"]},{"year":2002,"claim":"Resolving the protein's submitochondrial position and the domains required for aggregation defined a candidate mechanism: surface localization with a C-terminal aggregation activity that could glue mitochondria into the sheath.","evidence":"Immunoelectron microscopy of sperm midpiece plus deletion/mutant transfection in COS-7 cells","pmids":["12453465"],"confidence":"Medium","gaps":["Aggregation observed in transfected cells, not shown to mediate sheath assembly in vivo","No molecular partner mediating adhesion identified"]},{"year":2004,"claim":"Cross-species confirmation in mouse showed the sperm mitochondrial localization is conserved, supporting a general role beyond a single species.","evidence":"Western blot of a testis-specific ~18 kDa band and antibody-based immunolocalization in mouse sperm","pmids":["15139970"],"confidence":"Medium","gaps":["Descriptive localization only; no functional perturbation"]},{"year":2015,"claim":"Genetic loss-of-function directly tested whether SPATA19 is required in vivo, demonstrating it is essential for mitochondrial sheath organization and respiratory function underlying sperm motility and fertility.","evidence":"Spata19 conditional knockout mouse (Stra8-Cre) with sperm electron microscopy, mitochondrial Western blot, complex IV activity assay, ATP measurement, and ICSI rescue","pmids":["26265198"],"confidence":"High","gaps":["Whether reduced complex IV activity is a direct effect or secondary to structural disorganization is unresolved","The molecular interactions tethering mitochondria to outer dense fibers are not defined","No biochemical partner or structural model provided"]},{"year":null,"claim":"The direct molecular partners through which SPATA19 mediates mitochondrial adhesion and links the sheath to outer dense fibers remain unidentified.","evidence":"","pmids":[],"confidence":"High","gaps":["No interacting protein identified","No structural basis for C-terminal aggregation activity","Mechanism linking SPATA19 loss to specific complex IV decline unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1,2,3]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[3]}],"complexes":["mitochondrial sheath"],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q7Z5L4","full_name":"Spermatogenesis-associated protein 19, mitochondrial","aliases":["Spermatogenic cell-specific gene 1 protein","Spergen-1"],"length_aa":167,"mass_kda":19.2,"function":"Essential for sperm motility and male fertility (By similarity). Plays an important role in sperm motility by regulating the organization and function of the mitochondria and is also required for correct sperm midpiece assembly (By similarity)","subcellular_location":"Mitochondrion outer membrane; Mitochondrion; Cell projection, cilium, flagellum","url":"https://www.uniprot.org/uniprotkb/Q7Z5L4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SPATA19","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/SPATA19","total_profiled":1310},"omim":[{"mim_id":"613906","title":"ZINC FINGER PROTEIN 641; ZNF641","url":"https://www.omim.org/entry/613906"},{"mim_id":"609805","title":"SPERMATOGENESIS-ASSOCIATED PROTEIN 19; SPATA19","url":"https://www.omim.org/entry/609805"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"testis","ntpm":125.4}],"url":"https://www.proteinatlas.org/search/SPATA19"},"hgnc":{"alias_symbol":["FLJ25851","spergen1","SPAS1","CT132"],"prev_symbol":[]},"alphafold":{"accession":"Q7Z5L4","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z5L4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z5L4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z5L4-F1-predicted_aligned_error_v6.png","plddt_mean":69.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SPATA19","jax_strain_url":"https://www.jax.org/strain/search?query=SPATA19"},"sequence":{"accession":"Q7Z5L4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z5L4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z5L4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z5L4"}},"corpus_meta":[{"pmid":"20682177","id":"PMC_20682177","title":"Expression of two testis-specific genes, SPATA19 and LEMD1, in prostate cancer.","date":"2010","source":"Archives of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/20682177","citation_count":56,"is_preprint":false},{"pmid":"26265198","id":"PMC_26265198","title":"Spata19 is critical for sperm mitochondrial function and male fertility.","date":"2015","source":"Molecular reproduction and development","url":"https://pubmed.ncbi.nlm.nih.gov/26265198","citation_count":54,"is_preprint":false},{"pmid":"18303116","id":"PMC_18303116","title":"SPAS-1 (stimulator of prostatic adenocarcinoma-specific T cells)/SH3GLB2: A prostate tumor antigen identified by CTLA-4 blockade.","date":"2008","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/18303116","citation_count":48,"is_preprint":false},{"pmid":"12453465","id":"PMC_12453465","title":"Spergen-1 might be an adhesive molecule associated with mitochondria in the middle piece of spermatozoa.","date":"2002","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/12453465","citation_count":39,"is_preprint":false},{"pmid":"11967211","id":"PMC_11967211","title":"Complementary DNA cloning and characterization of rat spergen-1, a spermatogenic cell-specific gene-1, containing a mitochondria-targeting signal.","date":"2002","source":"Biology of reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/11967211","citation_count":31,"is_preprint":false},{"pmid":"15139970","id":"PMC_15139970","title":"Cloning and characterization of a mouse spergen-1 localized in sperm mitochondria.","date":"2004","source":"International journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/15139970","citation_count":13,"is_preprint":false},{"pmid":"26989727","id":"PMC_26989727","title":"Identification of Spata-19 new variant with expression beyond meiotic phase of mouse testis development.","date":"2014","source":"Reports of biochemistry & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/26989727","citation_count":8,"is_preprint":false},{"pmid":"28972294","id":"PMC_28972294","title":"Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer.","date":"2017","source":"APMIS : acta pathologica, microbiologica, et immunologica Scandinavica","url":"https://pubmed.ncbi.nlm.nih.gov/28972294","citation_count":7,"is_preprint":false},{"pmid":"22736110","id":"PMC_22736110","title":"Molecular characterization, polymorphism and association of porcine SPATA19 gene.","date":"2012","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/22736110","citation_count":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6338,"output_tokens":1123,"usd":0.01793,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7727,"output_tokens":1617,"usd":0.03953,"stage2_stop_reason":"end_turn"},"total_usd":0.05746,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"Spergen-1 (SPATA19) protein is associated with mitochondria in spermatids and spermatozoa; subcellular fractionation and immunoblot confirmed mitochondrial association, and transfection experiments in COS-7 cells demonstrated that an N-terminal sequence functions as a mitochondria-targeting signal.\",\n      \"method\": \"Subcellular fractionation + immunoblot; transfection of COS-7 cells with spergen-1 expression constructs\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — subcellular fractionation plus cell transfection, single lab but two orthogonal methods\",\n      \"pmids\": [\"11967211\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Spergen-1 (SPATA19) localizes to the surface of mitochondria in the middle piece of spermatozoa (confirmed by immunoelectron microscopy), and when expressed in COS-7 cells, induces mitochondrial aggregation; deletion analysis showed that both the N-terminal mitochondria-targeting signal and the C-terminal region are required for mitochondrial aggregation, suggesting a role as an adhesive molecule assembling mitochondria into the mitochondrial sheath.\",\n      \"method\": \"Immunocytochemistry, immunoelectron microscopy, and transfection of COS-7 cells with spergen-1 deletion/mutant constructs\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — immunoelectron microscopy plus functional mutagenesis in transfected cells, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"12453465\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Mouse spergen-1 (SPATA19) is a sperm mitochondrial protein; Western blot identified a testis-specific ~18 kDa band, and antibody-based localization confirmed the protein resides in sperm mitochondria.\",\n      \"method\": \"Western blot; immunolocalization with antibodies raised against mouse Spergen-1\",\n      \"journal\": \"International journal of andrology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — immunolocalization and Western blot, replicated across species (mouse), single lab\",\n      \"pmids\": [\"15139970\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Spata19 is required for sperm mitochondrial structural organization and function: conditional knockout males (Spata19-cKO, using Stra8-Cre) were infertile, their sperm showed disorganized mitochondrial structure, reduced mitochondrial protein abundance, decreased mitochondrial respiratory chain complex IV activity, and reduced ATP levels; fertility was rescued by intracytoplasmic sperm injection, demonstrating that SPATA19 is specifically required for mitochondrial organization/function supporting sperm motility but not for intrinsic developmental competence of sperm.\",\n      \"method\": \"Conditional knockout mouse model (Spata19flox/flox; Stra8-Cre); electron microscopy of sperm mitochondria; mitochondrial protein Western blot; complex IV activity assay; ATP measurement; intracytoplasmic sperm injection rescue\",\n      \"journal\": \"Molecular reproduction and development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function (cKO) with multiple orthogonal biochemical readouts (complex IV activity, ATP, protein abundance, ultrastructure) and functional rescue experiment\",\n      \"pmids\": [\"26265198\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SPATA19 (Spergen-1) is a small haploid spermatid/sperm-specific protein that localizes to the outer surface of mitochondria in the sperm midpiece via an N-terminal mitochondria-targeting signal; its C-terminal region enables mitochondrial aggregation, and conditional knockout studies in mice demonstrate it is essential for organizing the mitochondrial sheath around the outer dense fibers and sustaining mitochondrial respiratory chain (complex IV) activity and ATP production, thereby supporting sperm motility and male fertility.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SPATA19 (Spergen-1) is a small haploid spermatid/sperm-specific protein that organizes the mitochondrial sheath of the sperm midpiece and sustains its respiratory function [#0, #3]. It associates with mitochondria through an N-terminal mitochondria-targeting signal that directs it to the outer mitochondrial surface, while its C-terminal region drives mitochondrial aggregation, allowing the protein to act as an adhesive molecule that assembles mitochondria into the sheath [#0, #1]. Conditional knockout in mice establishes that this organizing activity is essential for male fertility: loss of SPATA19 produces disorganized sperm mitochondria, reduced mitochondrial protein abundance, decreased respiratory chain complex IV activity, and lowered ATP, with infertility rescued by intracytoplasmic sperm injection — indicating the defect is in mitochondrial organization and motility support rather than in intrinsic developmental competence of sperm [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Establishing where Spergen-1 acts answered whether this spermatid-specific protein is targeted to a defined organelle, identifying mitochondria as its site of action.\",\n      \"evidence\": \"Subcellular fractionation with immunoblot plus targeting-signal mapping by transfection of COS-7 cells\",\n      \"pmids\": [\"11967211\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Targeting demonstrated in a heterologous cell line, not in spermatids in vivo\", \"Functional consequence of mitochondrial association not addressed\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Resolving the protein's submitochondrial position and the domains required for aggregation defined a candidate mechanism: surface localization with a C-terminal aggregation activity that could glue mitochondria into the sheath.\",\n      \"evidence\": \"Immunoelectron microscopy of sperm midpiece plus deletion/mutant transfection in COS-7 cells\",\n      \"pmids\": [\"12453465\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Aggregation observed in transfected cells, not shown to mediate sheath assembly in vivo\", \"No molecular partner mediating adhesion identified\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Cross-species confirmation in mouse showed the sperm mitochondrial localization is conserved, supporting a general role beyond a single species.\",\n      \"evidence\": \"Western blot of a testis-specific ~18 kDa band and antibody-based immunolocalization in mouse sperm\",\n      \"pmids\": [\"15139970\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Descriptive localization only; no functional perturbation\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Genetic loss-of-function directly tested whether SPATA19 is required in vivo, demonstrating it is essential for mitochondrial sheath organization and respiratory function underlying sperm motility and fertility.\",\n      \"evidence\": \"Spata19 conditional knockout mouse (Stra8-Cre) with sperm electron microscopy, mitochondrial Western blot, complex IV activity assay, ATP measurement, and ICSI rescue\",\n      \"pmids\": [\"26265198\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether reduced complex IV activity is a direct effect or secondary to structural disorganization is unresolved\", \"The molecular interactions tethering mitochondria to outer dense fibers are not defined\", \"No biochemical partner or structural model provided\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular partners through which SPATA19 mediates mitochondrial adhesion and links the sheath to outer dense fibers remain unidentified.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No interacting protein identified\", \"No structural basis for C-terminal aggregation activity\", \"Mechanism linking SPATA19 loss to specific complex IV decline unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1, 2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\"mitochondrial sheath\"],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}