{"gene":"SPATA17","run_date":"2026-06-10T07:46:39","timeline":{"discoveries":[{"year":2006,"finding":"Mouse Spata17 protein is localized to the cytoplasm of round spermatids and elongating spermatids within seminiferous tubules of the adult testis, and its overexpression in GC-1 spermatogonial cells accelerates cell apoptosis in a dose-dependent manner.","method":"Immunohistochemistry (subcellular localization), flow cytometry and Hoechst 33258 staining (apoptosis assay), transfection of pcDNA3.1(-)/Spata17 into GC-1 cells (overexpression)","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by IHC with functional consequence (apoptosis) measured by two orthogonal methods (flow cytometry + Hoechst staining) in a single lab","pmids":["16395525"],"is_preprint":false},{"year":2010,"finding":"Zebrafish SPATA17 protein contains three calmodulin-binding IQ motifs, is expressed predominantly in testis, and its overexpression in GC-1 cells accelerates apoptosis as measured by flow cytometry and DNA laddering.","method":"Bioinformatic domain analysis (IQ motif identification), multi-tissue RT-PCR/Northern blot (expression), flow cytometry and genomic DNA ladder assay (apoptosis) in GC-1 cells","journal":"Molecular biology reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, IQ motif identification is computational, apoptosis phenotype replicated from prior study but no mechanistic dissection of IQ motif function","pmids":["21108043"],"is_preprint":false},{"year":2012,"finding":"Overexpression of human SPATA17 specifically in spermatocytes of transgenic male mice (driven by the PGK2 promoter) significantly increases apoptotic germ cells without causing gross testicular anatomical defects or infertility.","method":"Transgenic mouse generation with PGK2 promoter-driven SPATA17, histological analysis and apoptosis quantification in testis","journal":"Molecular biology reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo transgenic model with defined cell-type-specific expression and quantified apoptotic phenotype, single lab","pmids":["23079716"],"is_preprint":false},{"year":2009,"finding":"A coding SNP (SNP3) in SPATA17 is significantly elevated in frequency among Japanese patients with meiotic arrest azoospermia compared to Sertoli-cell-only syndrome patients and healthy controls, suggesting SPATA17 has a functional role in meiosis during spermatogenesis.","method":"Sequencing of SPATA17 coding regions in 18 meiotic arrest patients, statistical comparison of SNP allele frequencies across patient and control groups","journal":"Asian journal of andrology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic association (SNP frequency), no direct functional experiment on the variant, single lab, small cohort","pmids":["19483714"],"is_preprint":false},{"year":2024,"finding":"SPATA17 is a component of the C1a projection of the spermatozoal flagellar axoneme; loss-of-function SPAG17 mutations cause disrupted SPATA17 protein expression along the flagella, indicating SPATA17's localization and function depend on SPAG17-mediated axonemal integrity.","method":"Immunofluorescence and Western blot of patient spermatozoa with homozygous SPAG17 mutations; transmission electron microscopy of axoneme cross-sections","journal":"Asian journal of andrology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — immunofluorescence and Western blot in human patient material with defined genetic lesion, two orthogonal methods, single lab; indirect evidence for SPATA17 localization via SPAG17 epistasis","pmids":["39686771"],"is_preprint":false}],"current_model":"SPATA17 is a testis-specific protein localized to the cytoplasm of round and elongating spermatids and to the C1a projection of the spermatozoal flagellar axoneme, where it contributes to spermatogenesis and meiosis; overexpression in germ cells (both in vitro and in transgenic mice) promotes apoptosis in a dose-dependent manner, and its flagellar localization requires intact SPAG17-mediated axonemal structure, while its IQ motifs suggest regulation by calmodulin."},"narrative":{"mechanistic_narrative":"SPATA17 is a testis-enriched protein that functions in spermatogenesis, with roles in germ cell apoptosis regulation and in the structural organization of the spermatozoal flagellum [PMID:16395525, PMID:39686771]. In the adult testis it localizes to the cytoplasm of round and elongating spermatids, and its overexpression in spermatogonial GC-1 cells accelerates apoptosis in a dose-dependent manner [PMID:16395525]; this pro-apoptotic effect is recapitulated in vivo, where spermatocyte-specific overexpression in transgenic mice increases apoptotic germ cells without gross testicular defects [PMID:23079716]. In mature sperm, SPATA17 is a component of the C1a projection of the flagellar axoneme, and its proper expression along the flagellum depends on SPAG17-mediated axonemal integrity, since loss-of-function SPAG17 mutations disrupt SPATA17 distribution [PMID:39686771]. The protein carries calmodulin-binding IQ motifs, indicating potential calcium/calmodulin-dependent regulation [PMID:21108043]. Beyond these observations, the molecular activity and direct binding partners of SPATA17 have not been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Establishing where SPATA17 acts and what cellular consequence it produces, the first study placed the protein in spermatid cytoplasm and linked its overexpression to germ cell apoptosis.","evidence":"Immunohistochemistry localization in mouse testis plus flow cytometry and Hoechst staining apoptosis assays following overexpression in GC-1 cells","pmids":["16395525"],"confidence":"Medium","gaps":["Apoptotic pathway and effectors engaged by SPATA17 not identified","No loss-of-function evidence to establish endogenous role","Mechanism connecting localization to apoptosis unknown"]},{"year":2009,"claim":"To test whether SPATA17 contributes to meiosis in humans, a genetic association implicated a SPATA17 coding variant in meiotic arrest azoospermia.","evidence":"Sequencing of SPATA17 coding regions and SNP allele-frequency comparison across azoospermia patients and controls","pmids":["19483714"],"confidence":"Low","gaps":["Genetic association only, no functional test of the variant","Small cohort","Causal link to meiotic arrest unestablished"]},{"year":2010,"claim":"Probing how SPATA17 might be regulated, domain analysis identified calmodulin-binding IQ motifs and confirmed testis-predominant expression and the apoptotic phenotype.","evidence":"Bioinformatic IQ motif identification, multi-tissue RT-PCR/Northern blot, and flow cytometry/DNA ladder apoptosis assays in GC-1 cells (zebrafish ortholog)","pmids":["21108043"],"confidence":"Low","gaps":["IQ motif function not experimentally dissected","Calmodulin binding not demonstrated biochemically","No mechanistic link between IQ motifs and apoptosis"]},{"year":2012,"claim":"Moving from cell lines to a whole-animal context, transgenic overexpression confirmed that elevated SPATA17 drives germ cell apoptosis in vivo.","evidence":"PGK2 promoter-driven SPATA17 transgenic mice with histology and apoptosis quantification in testis","pmids":["23079716"],"confidence":"Medium","gaps":["Overexpression model does not reveal endogenous loss-of-function role","No fertility or structural defect observed, leaving physiological function unclear","Downstream apoptotic mediators not identified"]},{"year":2024,"claim":"Defining a structural role in the mature gamete, SPATA17 was localized to the axonemal C1a projection and shown to depend on SPAG17 for proper flagellar distribution.","evidence":"Immunofluorescence and Western blot of human spermatozoa with homozygous SPAG17 mutations and TEM of axoneme cross-sections","pmids":["39686771"],"confidence":"Medium","gaps":["Direct SPATA17-SPAG17 physical interaction not demonstrated","Functional contribution of SPATA17 to flagellar motility untested","Relationship between axonemal role and earlier apoptotic role unresolved"]},{"year":null,"claim":"The molecular activity of SPATA17 and the mechanism connecting its pro-apoptotic role in spermatids to its structural role in the flagellar axoneme remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical activity or direct binding partner established","Calmodulin regulation predicted but unproven","Endogenous loss-of-function phenotype not characterized"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[4]}],"pathway":[],"complexes":["flagellar axoneme C1a projection"],"partners":["SPAG17"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96L03","full_name":"Spermatogenesis-associated protein 17","aliases":[],"length_aa":361,"mass_kda":43.5,"function":"","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q96L03/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SPATA17","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SPATA17","total_profiled":1310},"omim":[{"mim_id":"611032","title":"SPERMATOGENESIS-ASSOCIATED PROTEIN 17; SPATA17","url":"https://www.omim.org/entry/611032"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Nucleoplasm","reliability":"Uncertain"},{"location":"Nucleoli","reliability":"Uncertain"},{"location":"Cytosol","reliability":"Uncertain"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":9.5}],"url":"https://www.proteinatlas.org/search/SPATA17"},"hgnc":{"alias_symbol":["IQCH","MOT17","FAP305","CFAP305"],"prev_symbol":[]},"alphafold":{"accession":"Q96L03","domains":[{"cath_id":"1.20.5","chopping":"14-112","consensus_level":"high","plddt":96.806,"start":14,"end":112}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96L03","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96L03-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96L03-F1-predicted_aligned_error_v6.png","plddt_mean":81.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SPATA17","jax_strain_url":"https://www.jax.org/strain/search?query=SPATA17"},"sequence":{"accession":"Q96L03","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96L03.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96L03/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96L03"}},"corpus_meta":[{"pmid":"21679429","id":"PMC_21679429","title":"Application of site and haplotype-frequency based approaches for detecting selection signatures in cattle.","date":"2011","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/21679429","citation_count":115,"is_preprint":false},{"pmid":"19680270","id":"PMC_19680270","title":"Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome-wide association analysis with microsatellite markers.","date":"2009","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19680270","citation_count":49,"is_preprint":false},{"pmid":"23549274","id":"PMC_23549274","title":"De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association.","date":"2013","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/23549274","citation_count":41,"is_preprint":false},{"pmid":"21901812","id":"PMC_21901812","title":"Effects of decabromodiphenyl ether (BDE-209) on mRNA transcription of thyroid hormone pathway and spermatogenesis associated genes in Chinese rare minnow (Gobiocypris rarus).","date":"2011","source":"Environmental toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/21901812","citation_count":39,"is_preprint":false},{"pmid":"19483714","id":"PMC_19483714","title":"A single nucleotide polymorphism in SPATA17 may be a genetic risk factor for Japanese patients with meiotic arrest.","date":"2009","source":"Asian journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/19483714","citation_count":16,"is_preprint":false},{"pmid":"23079716","id":"PMC_23079716","title":"Overexpression of human SPATA17 protein induces germ cell apoptosis in transgenic male mice.","date":"2012","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/23079716","citation_count":15,"is_preprint":false},{"pmid":"32163230","id":"PMC_32163230","title":"Whole exome sequencing identifies multiple novel candidate genes in familial gastroschisis.","date":"2020","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32163230","citation_count":13,"is_preprint":false},{"pmid":"16395525","id":"PMC_16395525","title":"Expression and identification of a novel apoptosis gene Spata17 (MSRG-11) in mouse spermatogenic cells.","date":"2006","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/16395525","citation_count":12,"is_preprint":false},{"pmid":"21108043","id":"PMC_21108043","title":"Overexpression a novel zebra fish spermatogenesis-associated gene 17 (SPATA17) induces apoptosis in GC-1 cells.","date":"2010","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/21108043","citation_count":11,"is_preprint":false},{"pmid":"35384611","id":"PMC_35384611","title":"Comprehensive Transcriptome Analysis of Gonadal and Somatic Tissues for Identification of Sex-Related Genes in the Largemouth Bass Micropterus salmoides.","date":"2022","source":"Marine biotechnology (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/35384611","citation_count":9,"is_preprint":false},{"pmid":"38886667","id":"PMC_38886667","title":"DNA methylation patterns in patients with asthenospermia and oligoasthenospermia.","date":"2024","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/38886667","citation_count":8,"is_preprint":false},{"pmid":"27802063","id":"PMC_27802063","title":"In silico analysis of candidate proteins sharing homology with Streptococcus agalactiae proteins and their role in male infertility.","date":"2016","source":"Systems biology in reproductive medicine","url":"https://pubmed.ncbi.nlm.nih.gov/27802063","citation_count":7,"is_preprint":false},{"pmid":"39686771","id":"PMC_39686771","title":"Novel homozygous SPAG17 variants cause human male infertility through multiple morphological abnormalities of spermatozoal flagella related to axonemal microtubule doublets.","date":"2024","source":"Asian journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/39686771","citation_count":6,"is_preprint":false},{"pmid":"25353171","id":"PMC_25353171","title":"Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25353171","citation_count":3,"is_preprint":false},{"pmid":"38572922","id":"PMC_38572922","title":"Feature Engineering-Assisted Drug Repurposing on Disease-Drug Transcriptome Profiles in Gastric Cancer.","date":"2024","source":"Assay and drug development technologies","url":"https://pubmed.ncbi.nlm.nih.gov/38572922","citation_count":0,"is_preprint":false},{"pmid":"41972556","id":"PMC_41972556","title":"The Molecular Characterization and Functional Analysis of Pomacea canaliculata Boule: A Central Player in Spermatogenesis and Male Fertility.","date":"2026","source":"Biology","url":"https://pubmed.ncbi.nlm.nih.gov/41972556","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11373,"output_tokens":1312,"usd":0.026899,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7934,"output_tokens":1956,"usd":0.044285,"stage2_stop_reason":"end_turn"},"total_usd":0.071184,"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\": 2006,\n      \"finding\": \"Mouse Spata17 protein is localized to the cytoplasm of round spermatids and elongating spermatids within seminiferous tubules of the adult testis, and its overexpression in GC-1 spermatogonial cells accelerates cell apoptosis in a dose-dependent manner.\",\n      \"method\": \"Immunohistochemistry (subcellular localization), flow cytometry and Hoechst 33258 staining (apoptosis assay), transfection of pcDNA3.1(-)/Spata17 into GC-1 cells (overexpression)\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by IHC with functional consequence (apoptosis) measured by two orthogonal methods (flow cytometry + Hoechst staining) in a single lab\",\n      \"pmids\": [\"16395525\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Zebrafish SPATA17 protein contains three calmodulin-binding IQ motifs, is expressed predominantly in testis, and its overexpression in GC-1 cells accelerates apoptosis as measured by flow cytometry and DNA laddering.\",\n      \"method\": \"Bioinformatic domain analysis (IQ motif identification), multi-tissue RT-PCR/Northern blot (expression), flow cytometry and genomic DNA ladder assay (apoptosis) in GC-1 cells\",\n      \"journal\": \"Molecular biology reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, IQ motif identification is computational, apoptosis phenotype replicated from prior study but no mechanistic dissection of IQ motif function\",\n      \"pmids\": [\"21108043\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Overexpression of human SPATA17 specifically in spermatocytes of transgenic male mice (driven by the PGK2 promoter) significantly increases apoptotic germ cells without causing gross testicular anatomical defects or infertility.\",\n      \"method\": \"Transgenic mouse generation with PGK2 promoter-driven SPATA17, histological analysis and apoptosis quantification in testis\",\n      \"journal\": \"Molecular biology reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo transgenic model with defined cell-type-specific expression and quantified apoptotic phenotype, single lab\",\n      \"pmids\": [\"23079716\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"A coding SNP (SNP3) in SPATA17 is significantly elevated in frequency among Japanese patients with meiotic arrest azoospermia compared to Sertoli-cell-only syndrome patients and healthy controls, suggesting SPATA17 has a functional role in meiosis during spermatogenesis.\",\n      \"method\": \"Sequencing of SPATA17 coding regions in 18 meiotic arrest patients, statistical comparison of SNP allele frequencies across patient and control groups\",\n      \"journal\": \"Asian journal of andrology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic association (SNP frequency), no direct functional experiment on the variant, single lab, small cohort\",\n      \"pmids\": [\"19483714\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SPATA17 is a component of the C1a projection of the spermatozoal flagellar axoneme; loss-of-function SPAG17 mutations cause disrupted SPATA17 protein expression along the flagella, indicating SPATA17's localization and function depend on SPAG17-mediated axonemal integrity.\",\n      \"method\": \"Immunofluorescence and Western blot of patient spermatozoa with homozygous SPAG17 mutations; transmission electron microscopy of axoneme cross-sections\",\n      \"journal\": \"Asian journal of andrology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — immunofluorescence and Western blot in human patient material with defined genetic lesion, two orthogonal methods, single lab; indirect evidence for SPATA17 localization via SPAG17 epistasis\",\n      \"pmids\": [\"39686771\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SPATA17 is a testis-specific protein localized to the cytoplasm of round and elongating spermatids and to the C1a projection of the spermatozoal flagellar axoneme, where it contributes to spermatogenesis and meiosis; overexpression in germ cells (both in vitro and in transgenic mice) promotes apoptosis in a dose-dependent manner, and its flagellar localization requires intact SPAG17-mediated axonemal structure, while its IQ motifs suggest regulation by calmodulin.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SPATA17 is a testis-enriched protein that functions in spermatogenesis, with roles in germ cell apoptosis regulation and in the structural organization of the spermatozoal flagellum [#0, #4]. In the adult testis it localizes to the cytoplasm of round and elongating spermatids, and its overexpression in spermatogonial GC-1 cells accelerates apoptosis in a dose-dependent manner [#0]; this pro-apoptotic effect is recapitulated in vivo, where spermatocyte-specific overexpression in transgenic mice increases apoptotic germ cells without gross testicular defects [#2]. In mature sperm, SPATA17 is a component of the C1a projection of the flagellar axoneme, and its proper expression along the flagellum depends on SPAG17-mediated axonemal integrity, since loss-of-function SPAG17 mutations disrupt SPATA17 distribution [#4]. The protein carries calmodulin-binding IQ motifs, indicating potential calcium/calmodulin-dependent regulation [#1]. Beyond these observations, the molecular activity and direct binding partners of SPATA17 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing where SPATA17 acts and what cellular consequence it produces, the first study placed the protein in spermatid cytoplasm and linked its overexpression to germ cell apoptosis.\",\n      \"evidence\": \"Immunohistochemistry localization in mouse testis plus flow cytometry and Hoechst staining apoptosis assays following overexpression in GC-1 cells\",\n      \"pmids\": [\"16395525\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Apoptotic pathway and effectors engaged by SPATA17 not identified\", \"No loss-of-function evidence to establish endogenous role\", \"Mechanism connecting localization to apoptosis unknown\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"To test whether SPATA17 contributes to meiosis in humans, a genetic association implicated a SPATA17 coding variant in meiotic arrest azoospermia.\",\n      \"evidence\": \"Sequencing of SPATA17 coding regions and SNP allele-frequency comparison across azoospermia patients and controls\",\n      \"pmids\": [\"19483714\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Genetic association only, no functional test of the variant\", \"Small cohort\", \"Causal link to meiotic arrest unestablished\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Probing how SPATA17 might be regulated, domain analysis identified calmodulin-binding IQ motifs and confirmed testis-predominant expression and the apoptotic phenotype.\",\n      \"evidence\": \"Bioinformatic IQ motif identification, multi-tissue RT-PCR/Northern blot, and flow cytometry/DNA ladder apoptosis assays in GC-1 cells (zebrafish ortholog)\",\n      \"pmids\": [\"21108043\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"IQ motif function not experimentally dissected\", \"Calmodulin binding not demonstrated biochemically\", \"No mechanistic link between IQ motifs and apoptosis\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Moving from cell lines to a whole-animal context, transgenic overexpression confirmed that elevated SPATA17 drives germ cell apoptosis in vivo.\",\n      \"evidence\": \"PGK2 promoter-driven SPATA17 transgenic mice with histology and apoptosis quantification in testis\",\n      \"pmids\": [\"23079716\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Overexpression model does not reveal endogenous loss-of-function role\", \"No fertility or structural defect observed, leaving physiological function unclear\", \"Downstream apoptotic mediators not identified\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defining a structural role in the mature gamete, SPATA17 was localized to the axonemal C1a projection and shown to depend on SPAG17 for proper flagellar distribution.\",\n      \"evidence\": \"Immunofluorescence and Western blot of human spermatozoa with homozygous SPAG17 mutations and TEM of axoneme cross-sections\",\n      \"pmids\": [\"39686771\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct SPATA17-SPAG17 physical interaction not demonstrated\", \"Functional contribution of SPATA17 to flagellar motility untested\", \"Relationship between axonemal role and earlier apoptotic role unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity of SPATA17 and the mechanism connecting its pro-apoptotic role in spermatids to its structural role in the flagellar axoneme remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No biochemical activity or direct binding partner established\", \"Calmodulin regulation predicted but unproven\", \"Endogenous loss-of-function phenotype not characterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"flagellar axoneme C1a projection\"],\n    \"partners\": [\"SPAG17\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}