{"gene":"RPL10L","run_date":"2026-04-28T19:45:45","timeline":{"discoveries":[{"year":2017,"finding":"RPL10L is required for ribosome biogenesis in late-prophase spermatocytes during male meiosis. It compensates for MSCI-mediated transcriptional silencing of RPL10 (its X-linked progenitor) during spermatogenesis. Loss of Rpl10l disrupts ribosome biogenesis and blocks the transition from prophase to metaphase of meiosis I, causing male infertility. Ectopic expression of RPL10L rescues RPL10-deficient somatic cells, and transgenic expression of Rpl10 driven by the Rpl10l promoter in spermatocytes restores spermatogenesis in Rpl10l-null mice.","method":"Knockout mouse model (loss-of-function), transgenic rescue experiments, ectopic expression in RPL10-deficient somatic cells, genetic epistasis","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined cellular phenotype, multiple orthogonal rescue experiments (somatic cell rescue + transgenic spermatocyte rescue), strong evidence","pmids":["28502657"],"is_preprint":false},{"year":2002,"finding":"RPL10L is a functional autosomal retrogene of the X-linked RPL10, generated by retrotransposition (lacks introns in coding region). It shares 89-95% nucleotide and 92-99% amino acid identity with RPL10 and is expressed specifically in testis, suggesting it may compensate for reduced dosage of X-linked RP genes.","method":"Northern blot, PCR, sequence analysis","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 3 — expression characterization with structural genomic evidence (intron-less coding region), single lab","pmids":["12490704"],"is_preprint":false},{"year":2020,"finding":"A homozygous missense variant in RPL10L (c.A257C: p.H86P) co-segregates with severe oligozoospermia in an infertile consanguineous family and decreases RPL10L protein levels in vitro, implicating RPL10L in human male fertility through its role in spermatogenesis.","method":"Whole-exome sequencing, Sanger sequencing, in vitro protein expression assay, in silico damaging prediction","journal":"Fertility and sterility","confidence":"Medium","confidence_rationale":"Tier 2/3 — human genetic evidence with in vitro protein-level validation, single lab","pmids":["32111475"],"is_preprint":false},{"year":2009,"finding":"RPL10L, previously thought to be expressed exclusively in the male testis, is also expressed in normal human ovarian tissue and ovarian cancers, as detected by end-point PCR.","method":"End-point PCR","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 — single method (PCR), expression characterization without mechanistic follow-up","pmids":["19333399"],"is_preprint":false}],"current_model":"RPL10L is a testis-specific autosomal retrogene of the X-linked ribosomal protein RPL10 that is functionally interchangeable with RPL10; during male meiosis it compensates for MSCI-mediated silencing of RPL10 to support ribosome biogenesis in late-prophase spermatocytes, and its loss blocks the prophase-to-metaphase transition of meiosis I, causing male infertility."},"narrative":{"teleology":[{"year":2002,"claim":"Identifying RPL10L as an intronless autosomal retrogene of X-linked RPL10 with testis-restricted expression established the hypothesis that it compensates for X-chromosome gene dosage reduction during spermatogenesis.","evidence":"Northern blot, PCR, and sequence analysis of human RPL10L locus","pmids":["12490704"],"confidence":"Medium","gaps":["No functional evidence that RPL10L protein is incorporated into ribosomes","Compensation hypothesis untested by loss-of-function experiments"]},{"year":2009,"claim":"Detection of RPL10L transcript in ovarian tissue challenged the view that expression is strictly testis-limited, raising questions about broader roles.","evidence":"End-point PCR on normal ovarian and ovarian cancer tissue","pmids":["19333399"],"confidence":"Low","gaps":["Single PCR method without quantification or protein-level validation","No functional consequence of ovarian expression demonstrated","Not independently replicated"]},{"year":2017,"claim":"Knockout and rescue experiments proved that RPL10L is essential for ribosome biogenesis during male meiotic prophase and functionally replaces RPL10 silenced by MSCI, resolving the central mechanistic question of why an autosomal ribosomal protein retrogene is needed for spermatogenesis.","evidence":"Rpl10l knockout mouse, transgenic Rpl10 rescue driven by Rpl10l promoter, ectopic RPL10L expression in RPL10-deficient somatic cells","pmids":["28502657"],"confidence":"High","gaps":["Structural basis for RPL10L incorporation into ribosomes not determined","Whether RPL10L-containing ribosomes have altered translational properties is unknown"]},{"year":2020,"claim":"A human loss-of-function variant in RPL10L co-segregating with oligozoospermia extended the mouse findings to human male infertility, providing genetic evidence for clinical relevance.","evidence":"Whole-exome sequencing in consanguineous family, in vitro protein expression assay","pmids":["32111475"],"confidence":"Medium","gaps":["Single family studied; broader allelic spectrum in infertile men unknown","Variant effect on ribosome assembly not tested in spermatocytes"]},{"year":null,"claim":"Whether RPL10L-containing ribosomes have specialized translational activity distinct from RPL10-containing ribosomes, and whether RPL10L functions outside spermatogenesis (e.g., in ovary), remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No ribosome profiling or structural studies of RPL10L-containing ribosomes","Functional significance of ovarian expression not tested","Translational targets specific to RPL10L-ribosomes in spermatocytes unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[0]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[0,2]}],"complexes":["60S ribosomal subunit"],"partners":["RPL10"],"other_free_text":[]},"mechanistic_narrative":"RPL10L is a testis-specific autosomal retrogene of the X-linked ribosomal protein RPL10 that compensates for meiotic sex chromosome inactivation (MSCI)-mediated silencing of RPL10 during male meiosis, thereby sustaining ribosome biogenesis in late-prophase spermatocytes [PMID:28502657, PMID:12490704]. Loss of Rpl10l in mice disrupts ribosome biogenesis and blocks the prophase-to-metaphase transition of meiosis I, causing male infertility; this phenotype is rescued by transgenic expression of Rpl10 from the Rpl10l promoter, establishing functional interchangeability between the two paralogs [PMID:28502657]. A homozygous missense variant in RPL10L (p.H86P) that reduces protein levels co-segregates with severe oligozoospermia in an infertile consanguineous family, linking RPL10L to human male infertility [PMID:32111475]."},"prefetch_data":{"uniprot":{"accession":"Q96L21","full_name":"Ribosomal protein uL16-like","aliases":["60S ribosomal protein L10-like","Large ribosomal subunit protein uL16-like"],"length_aa":214,"mass_kda":24.5,"function":"Testis-specific component of the ribosome, which is required for the transition from prophase to metaphase in male meiosis I (By similarity). Compensates for the inactivated X-linked RPL10 paralog during spermatogenesis (PubMed:12490704). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:25901680, PubMed:32669547). The male germ cell-specific ribosome displays a ribosomal polypeptide exit tunnel of distinct size and charge states compared with the classical ribosome (By similarity). It is responsible for regulating the biosynthesis and folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm (By similarity)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q96L21/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RPL10L","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/RPL10L","total_profiled":1310},"omim":[{"mim_id":"619689","title":"SPERMATOGENIC FAILURE 63; SPGF63","url":"https://www.omim.org/entry/619689"},{"mim_id":"619655","title":"RIBOSOMAL PROTEIN L10-LIKE; RPL10L","url":"https://www.omim.org/entry/619655"},{"mim_id":"602410","title":"BROMODOMAIN- AND PHD FINGER-CONTAINING PROTEIN; BRPF1","url":"https://www.omim.org/entry/602410"},{"mim_id":"258150","title":"SPERMATOGENIC FAILURE 1; SPGF1","url":"https://www.omim.org/entry/258150"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Endoplasmic reticulum","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":91.6}],"url":"https://www.proteinatlas.org/search/RPL10L"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q96L21","domains":[{"cath_id":"3.90.1170.10","chopping":"7-174","consensus_level":"high","plddt":96.1114,"start":7,"end":174},{"cath_id":"3.30.60.300","chopping":"176-214","consensus_level":"medium","plddt":90.8541,"start":176,"end":214}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96L21","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96L21-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96L21-F1-predicted_aligned_error_v6.png","plddt_mean":94.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPL10L","jax_strain_url":"https://www.jax.org/strain/search?query=RPL10L"},"sequence":{"accession":"Q96L21","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96L21.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96L21/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96L21"}},"corpus_meta":[{"pmid":"28502657","id":"PMC_28502657","title":"RPL10L Is Required for Male Meiotic Division by Compensating for RPL10 during Meiotic Sex Chromosome Inactivation in Mice.","date":"2017","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/28502657","citation_count":96,"is_preprint":false},{"pmid":"24860015","id":"PMC_24860015","title":"Ribosome-omics of the human ribosome.","date":"2014","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/24860015","citation_count":68,"is_preprint":false},{"pmid":"12490704","id":"PMC_12490704","title":"Functional second genes generated by retrotransposition of the X-linked ribosomal protein genes.","date":"2002","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/12490704","citation_count":43,"is_preprint":false},{"pmid":"19333399","id":"PMC_19333399","title":"Spermatogenesis associated retrogenes are expressed in the human ovary and ovarian cancers.","date":"2009","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19333399","citation_count":24,"is_preprint":false},{"pmid":"30459810","id":"PMC_30459810","title":"A Meta-Analysis Including Pre-selected Sequence Variants Associated With Seven Traits in Three French Dairy Cattle Populations.","date":"2018","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30459810","citation_count":24,"is_preprint":false},{"pmid":"32111475","id":"PMC_32111475","title":"A homozygous RPL10L missense mutation associated with male factor infertility and severe oligozoospermia.","date":"2020","source":"Fertility and sterility","url":"https://pubmed.ncbi.nlm.nih.gov/32111475","citation_count":17,"is_preprint":false},{"pmid":"27220462","id":"PMC_27220462","title":"Effects of TMEM9 gene on cell progression in hepatocellular carcinoma by RNA interference.","date":"2016","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/27220462","citation_count":15,"is_preprint":false},{"pmid":"39380204","id":"PMC_39380204","title":"SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine.","date":"2024","source":"Genomics, proteomics & bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/39380204","citation_count":5,"is_preprint":false},{"pmid":"38304813","id":"PMC_38304813","title":"Transcriptomics analysis reveals distinct mechanism of breast cancer stem cells regulation in mammospheres from MCF-7 and T47D cells.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/38304813","citation_count":5,"is_preprint":false},{"pmid":"39625557","id":"PMC_39625557","title":"Whole-exome sequencing identifies rare recessive variants in azoospermia patients from consanguineous Pakistani families.","date":"2024","source":"Molecular genetics and genomics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/39625557","citation_count":3,"is_preprint":false},{"pmid":"39201790","id":"PMC_39201790","title":"Comprehensive Analysis of Methylome and Transcriptome to Identify Potential Genes Regulating Porcine Testis Development.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39201790","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6964,"output_tokens":1001,"usd":0.017954},"stage2":{"model":"claude-opus-4-6","input_tokens":4200,"output_tokens":1331,"usd":0.081412},"total_usd":0.099366,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"RPL10L is required for ribosome biogenesis in late-prophase spermatocytes during male meiosis. It compensates for MSCI-mediated transcriptional silencing of RPL10 (its X-linked progenitor) during spermatogenesis. Loss of Rpl10l disrupts ribosome biogenesis and blocks the transition from prophase to metaphase of meiosis I, causing male infertility. Ectopic expression of RPL10L rescues RPL10-deficient somatic cells, and transgenic expression of Rpl10 driven by the Rpl10l promoter in spermatocytes restores spermatogenesis in Rpl10l-null mice.\",\n      \"method\": \"Knockout mouse model (loss-of-function), transgenic rescue experiments, ectopic expression in RPL10-deficient somatic cells, genetic epistasis\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular phenotype, multiple orthogonal rescue experiments (somatic cell rescue + transgenic spermatocyte rescue), strong evidence\",\n      \"pmids\": [\"28502657\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"RPL10L is a functional autosomal retrogene of the X-linked RPL10, generated by retrotransposition (lacks introns in coding region). It shares 89-95% nucleotide and 92-99% amino acid identity with RPL10 and is expressed specifically in testis, suggesting it may compensate for reduced dosage of X-linked RP genes.\",\n      \"method\": \"Northern blot, PCR, sequence analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — expression characterization with structural genomic evidence (intron-less coding region), single lab\",\n      \"pmids\": [\"12490704\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"A homozygous missense variant in RPL10L (c.A257C: p.H86P) co-segregates with severe oligozoospermia in an infertile consanguineous family and decreases RPL10L protein levels in vitro, implicating RPL10L in human male fertility through its role in spermatogenesis.\",\n      \"method\": \"Whole-exome sequencing, Sanger sequencing, in vitro protein expression assay, in silico damaging prediction\",\n      \"journal\": \"Fertility and sterility\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — human genetic evidence with in vitro protein-level validation, single lab\",\n      \"pmids\": [\"32111475\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"RPL10L, previously thought to be expressed exclusively in the male testis, is also expressed in normal human ovarian tissue and ovarian cancers, as detected by end-point PCR.\",\n      \"method\": \"End-point PCR\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single method (PCR), expression characterization without mechanistic follow-up\",\n      \"pmids\": [\"19333399\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPL10L is a testis-specific autosomal retrogene of the X-linked ribosomal protein RPL10 that is functionally interchangeable with RPL10; during male meiosis it compensates for MSCI-mediated silencing of RPL10 to support ribosome biogenesis in late-prophase spermatocytes, and its loss blocks the prophase-to-metaphase transition of meiosis I, causing male infertility.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"RPL10L is a testis-specific autosomal retrogene of the X-linked ribosomal protein RPL10 that compensates for meiotic sex chromosome inactivation (MSCI)-mediated silencing of RPL10 during male meiosis, thereby sustaining ribosome biogenesis in late-prophase spermatocytes [PMID:28502657, PMID:12490704]. Loss of Rpl10l in mice disrupts ribosome biogenesis and blocks the prophase-to-metaphase transition of meiosis I, causing male infertility; this phenotype is rescued by transgenic expression of Rpl10 from the Rpl10l promoter, establishing functional interchangeability between the two paralogs [PMID:28502657]. A homozygous missense variant in RPL10L (p.H86P) that reduces protein levels co-segregates with severe oligozoospermia in an infertile consanguineous family, linking RPL10L to human male infertility [PMID:32111475].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Identifying RPL10L as an intronless autosomal retrogene of X-linked RPL10 with testis-restricted expression established the hypothesis that it compensates for X-chromosome gene dosage reduction during spermatogenesis.\",\n      \"evidence\": \"Northern blot, PCR, and sequence analysis of human RPL10L locus\",\n      \"pmids\": [\"12490704\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional evidence that RPL10L protein is incorporated into ribosomes\",\n        \"Compensation hypothesis untested by loss-of-function experiments\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Detection of RPL10L transcript in ovarian tissue challenged the view that expression is strictly testis-limited, raising questions about broader roles.\",\n      \"evidence\": \"End-point PCR on normal ovarian and ovarian cancer tissue\",\n      \"pmids\": [\"19333399\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single PCR method without quantification or protein-level validation\",\n        \"No functional consequence of ovarian expression demonstrated\",\n        \"Not independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Knockout and rescue experiments proved that RPL10L is essential for ribosome biogenesis during male meiotic prophase and functionally replaces RPL10 silenced by MSCI, resolving the central mechanistic question of why an autosomal ribosomal protein retrogene is needed for spermatogenesis.\",\n      \"evidence\": \"Rpl10l knockout mouse, transgenic Rpl10 rescue driven by Rpl10l promoter, ectopic RPL10L expression in RPL10-deficient somatic cells\",\n      \"pmids\": [\"28502657\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis for RPL10L incorporation into ribosomes not determined\",\n        \"Whether RPL10L-containing ribosomes have altered translational properties is unknown\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"A human loss-of-function variant in RPL10L co-segregating with oligozoospermia extended the mouse findings to human male infertility, providing genetic evidence for clinical relevance.\",\n      \"evidence\": \"Whole-exome sequencing in consanguineous family, in vitro protein expression assay\",\n      \"pmids\": [\"32111475\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single family studied; broader allelic spectrum in infertile men unknown\",\n        \"Variant effect on ribosome assembly not tested in spermatocytes\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether RPL10L-containing ribosomes have specialized translational activity distinct from RPL10-containing ribosomes, and whether RPL10L functions outside spermatogenesis (e.g., in ovary), remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No ribosome profiling or structural studies of RPL10L-containing ribosomes\",\n        \"Functional significance of ovarian expression not tested\",\n        \"Translational targets specific to RPL10L-ribosomes in spermatocytes unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"60S ribosomal subunit\"\n    ],\n    \"partners\": [\n      \"RPL10\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}