{"gene":"DRC8","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2019,"finding":"EFCAB2 (DRC8) is a calcium-binding protein expressed exclusively in mouse testis and localized specifically to the principal piece of the sperm flagellum. The protein contains two EF-hand motifs (one N-terminal, one C-terminal) and seven α-helices. In vitro assays (Stains-all, ruthenium red staining, and autoradiography) confirmed Ca2+ binding activity of recombinant EFCAB2.","method":"Northern blot, western blot, in situ hybridization, immunohistochemistry, 3D structural modeling, in vitro Ca2+-binding assays (Stains-all, ruthenium red, autoradiography) with recombinant protein","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal biochemical methods in a single study confirming Ca2+ binding and localization, but single lab with no functional genetic validation","pmids":["30933994"],"is_preprint":false},{"year":2018,"finding":"siRNA-mediated knockdown of Efcab2 in mouse osteoblastic MC3T3-E1 cells reduced osteoblastic cell differentiation (assessed by ALP production and bone mineralization markers), indicating that EFCAB2 enhances osteoblast differentiation.","method":"siRNA knockdown in MC3T3-E1 cells, osteoblast differentiation assays (ALP, bone mineralization, marker expression), validated by qPCR","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function with specific cellular phenotype readout, but single lab, single method, no pathway placement","pmids":["29459627"],"is_preprint":false}],"current_model":"EFCAB2 (DRC8) is a calcium-binding protein containing two EF-hand motifs that localizes to the principal piece of the sperm flagellum in mouse testis and binds Ca2+ in vitro; it also promotes osteoblast differentiation in cell-based models, but its precise molecular mechanism and pathway context remain undefined."},"narrative":{"mechanistic_narrative":"EFCAB2 (DRC8) is a calcium-binding protein defined by two EF-hand motifs that binds Ca2+ in vitro and is expressed exclusively in mouse testis, where it localizes specifically to the principal piece of the sperm flagellum [PMID:30933994]. Independent loss-of-function work assigns it a role in osteoblast biology, as siRNA knockdown in MC3T3-E1 cells reduces osteoblast differentiation markers, indicating EFCAB2 promotes differentiation [PMID:29459627]. Beyond its Ca2+-binding capacity and these two cellular contexts, the molecular mechanism, binding partners, and pathway placement of EFCAB2 have not been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Whether EFCAB2 has any cellular function was unknown; knockdown established a role in promoting osteoblast differentiation.","evidence":"siRNA knockdown in mouse MC3T3-E1 osteoblastic cells with ALP, mineralization, and marker readouts validated by qPCR","pmids":["29459627"],"confidence":"Medium","gaps":["single lab, single loss-of-function method without rescue","no molecular mechanism or pathway linking EFCAB2 to differentiation","no identified binding partners or downstream effectors"]},{"year":2019,"claim":"The biochemical identity and tissue context of EFCAB2 were undefined; characterization established it as a testis-specific Ca2+-binding protein localized to the sperm flagellum principal piece.","evidence":"Northern/western blot, in situ hybridization, immunohistochemistry, structural modeling, and in vitro Ca2+-binding assays with recombinant protein in mouse","pmids":["30933994"],"confidence":"Medium","gaps":["no functional genetic validation of a role in sperm or flagellar function","Ca2+-binding partners and effector pathway in the flagellum unknown","relationship between testis localization and the osteoblast phenotype unexplained"]},{"year":null,"claim":"How EFCAB2 Ca2+ binding is mechanistically coupled to flagellar function and to osteoblast differentiation, and whether these reflect a single shared molecular activity, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no direct binding partners identified","no in vivo genetic model of sperm phenotype","no pathway placement for either context"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q5VUJ9","full_name":"Dynein regulatory complex protein 8","aliases":["EF-hand calcium-binding domain-containing protein 2"],"length_aa":269,"mass_kda":29.7,"function":"Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes","subcellular_location":"Cytoplasm, cytoskeleton, flagellum axoneme","url":"https://www.uniprot.org/uniprotkb/Q5VUJ9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"EFCAB2","url":"https://depmap.org/portal/gene/EFCAB2","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DRC8","total_profiled":1310},"omim":[{"mim_id":"619617","title":"EF-HAND CALCIUM-BINDING DOMAIN-CONTAINING PROTEIN 2; EFCAB2","url":"https://www.omim.org/entry/619617"}],"hpa":{"profiled":true,"resolved_as":"EFCAB2","reliability":"Approved","locations":[{"location":"Plasma membrane","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Mid piece","reliability":"Approved"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/EFCAB2"},"hgnc":{"alias_symbol":["MGC12458","DRC8","CFAP200"],"prev_symbol":["EFCAB2"]},"alphafold":{"accession":"Q5VUJ9","domains":[{"cath_id":"1.10.238.10","chopping":"120-228","consensus_level":"high","plddt":83.7097,"start":120,"end":228},{"cath_id":"-","chopping":"231-259","consensus_level":"medium","plddt":84.2848,"start":231,"end":259}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5VUJ9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5VUJ9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5VUJ9-F1-predicted_aligned_error_v6.png","plddt_mean":64.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DRC8","jax_strain_url":"https://www.jax.org/strain/search?query=DRC8"},"sequence":{"accession":"Q5VUJ9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5VUJ9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5VUJ9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5VUJ9"}},"corpus_meta":[{"pmid":"30529582","id":"PMC_30529582","title":"Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.","date":"2018","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/30529582","citation_count":130,"is_preprint":false},{"pmid":"20382278","id":"PMC_20382278","title":"Four patients with speech delay, seizures and variable corpus callosum thickness sharing a 0.440 Mb deletion in region 1q44 containing the HNRPU gene.","date":"2010","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20382278","citation_count":72,"is_preprint":false},{"pmid":"30259364","id":"PMC_30259364","title":"Emerging Role of Circular RNAs as Potential Biomarkers for the Diagnosis of Human Diseases.","date":"2018","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/30259364","citation_count":64,"is_preprint":false},{"pmid":"29428937","id":"PMC_29428937","title":"High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy.","date":"2018","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29428937","citation_count":45,"is_preprint":false},{"pmid":"28938569","id":"PMC_28938569","title":"Evaluation of autoantibody signatures in meningioma patients using human proteome arrays.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/28938569","citation_count":19,"is_preprint":false},{"pmid":"29459627","id":"PMC_29459627","title":"Understanding the functional role of genistein in the bone differentiation in mouse osteoblastic cell line MC3T3-E1 by RNA-seq analysis.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29459627","citation_count":17,"is_preprint":false},{"pmid":"23263656","id":"PMC_23263656","title":"Identification of gender-specific candidate genes that influence bone microarchitecture in chromosome 1.","date":"2012","source":"Calcified tissue international","url":"https://pubmed.ncbi.nlm.nih.gov/23263656","citation_count":12,"is_preprint":false},{"pmid":"30933994","id":"PMC_30933994","title":"EFCAB2 is a novel calcium-binding protein in mouse testis and sperm.","date":"2019","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30933994","citation_count":10,"is_preprint":false},{"pmid":"29636822","id":"PMC_29636822","title":"Maternal interchromosomal insertional translocation leading to 1q43-q44 deletion and duplication in two siblings.","date":"2018","source":"Molecular cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/29636822","citation_count":10,"is_preprint":false},{"pmid":"34334530","id":"PMC_34334530","title":"Identification of key carcinogenic genes in Wilms' tumor.","date":"2021","source":"Genes & genetic 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cohort","date":"2024-11-26","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.25.24317869","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9116,"output_tokens":604,"usd":0.018204,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6944,"output_tokens":1060,"usd":0.03061,"stage2_stop_reason":"end_turn"},"total_usd":0.048814,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"EFCAB2 (DRC8) is a calcium-binding protein expressed exclusively in mouse testis and localized specifically to the principal piece of the sperm flagellum. The protein contains two EF-hand motifs (one N-terminal, one C-terminal) and seven α-helices. In vitro assays (Stains-all, ruthenium red staining, and autoradiography) confirmed Ca2+ binding activity of recombinant EFCAB2.\",\n      \"method\": \"Northern blot, western blot, in situ hybridization, immunohistochemistry, 3D structural modeling, in vitro Ca2+-binding assays (Stains-all, ruthenium red, autoradiography) with recombinant protein\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal biochemical methods in a single study confirming Ca2+ binding and localization, but single lab with no functional genetic validation\",\n      \"pmids\": [\"30933994\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"siRNA-mediated knockdown of Efcab2 in mouse osteoblastic MC3T3-E1 cells reduced osteoblastic cell differentiation (assessed by ALP production and bone mineralization markers), indicating that EFCAB2 enhances osteoblast differentiation.\",\n      \"method\": \"siRNA knockdown in MC3T3-E1 cells, osteoblast differentiation assays (ALP, bone mineralization, marker expression), validated by qPCR\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function with specific cellular phenotype readout, but single lab, single method, no pathway placement\",\n      \"pmids\": [\"29459627\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EFCAB2 (DRC8) is a calcium-binding protein containing two EF-hand motifs that localizes to the principal piece of the sperm flagellum in mouse testis and binds Ca2+ in vitro; it also promotes osteoblast differentiation in cell-based models, but its precise molecular mechanism and pathway context remain undefined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EFCAB2 (DRC8) is a calcium-binding protein defined by two EF-hand motifs that binds Ca2+ in vitro and is expressed exclusively in mouse testis, where it localizes specifically to the principal piece of the sperm flagellum [#0]. Independent loss-of-function work assigns it a role in osteoblast biology, as siRNA knockdown in MC3T3-E1 cells reduces osteoblast differentiation markers, indicating EFCAB2 promotes differentiation [#1]. Beyond its Ca2+-binding capacity and these two cellular contexts, the molecular mechanism, binding partners, and pathway placement of EFCAB2 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether EFCAB2 has any cellular function was unknown; knockdown established a role in promoting osteoblast differentiation.\",\n      \"evidence\": \"siRNA knockdown in mouse MC3T3-E1 osteoblastic cells with ALP, mineralization, and marker readouts validated by qPCR\",\n      \"pmids\": [\"29459627\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"single lab, single loss-of-function method without rescue\",\n        \"no molecular mechanism or pathway linking EFCAB2 to differentiation\",\n        \"no identified binding partners or downstream effectors\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"The biochemical identity and tissue context of EFCAB2 were undefined; characterization established it as a testis-specific Ca2+-binding protein localized to the sperm flagellum principal piece.\",\n      \"evidence\": \"Northern/western blot, in situ hybridization, immunohistochemistry, structural modeling, and in vitro Ca2+-binding assays with recombinant protein in mouse\",\n      \"pmids\": [\"30933994\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no functional genetic validation of a role in sperm or flagellar function\",\n        \"Ca2+-binding partners and effector pathway in the flagellum unknown\",\n        \"relationship between testis localization and the osteoblast phenotype unexplained\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How EFCAB2 Ca2+ binding is mechanistically coupled to flagellar function and to osteoblast differentiation, and whether these reflect a single shared molecular activity, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no direct binding partners identified\",\n        \"no in vivo genetic model of sperm phenotype\",\n        \"no pathway placement for either context\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"loss","faith_supported":2,"faith_total":2,"faith_pct":100.0}}