{"gene":"ANKRD24","run_date":"2026-06-09T22:02:43","timeline":{"discoveries":[{"year":2022,"finding":"ANKRD24 concentrates at the stereocilia insertion point in hair cells, forming a ring at the junction between the lower and upper rootlets, and surrounds and binds TRIOBP-5 within the lower rootlet, where TRIOBP-5 bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed-TRIOBP-5 restores endogenous ANKRD24 to rootlets, establishing mutual dependence for correct localization.","method":"Superresolution microscopy, knockout mouse models (Ankrd24KO/KO), exogenous rescue with DsRed-TRIOBP-5, co-localization and binding studies","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic dependency demonstrated by KO and rescue experiments with superresolution microscopy, multiple orthogonal methods in a focused mechanistic study","pmids":["35175278"],"is_preprint":false},{"year":2022,"finding":"ANKRD24 bridges the apical plasma membrane with the lower stereocilia rootlet to maintain a normal distribution of TRIOBP-5. Loss of ANKRD24 (Ankrd24KO/KO mice) results in progressive hearing loss, diminished recovery of auditory function after noise damage, and increased susceptibility to overstimulation of the hair bundle.","method":"Knockout mouse model (Ankrd24KO/KO), auditory functional assays, superresolution microscopy","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cellular and functional phenotypes, multiple assays across hearing and mechanical resilience readouts","pmids":["35175278"],"is_preprint":false},{"year":2023,"finding":"ANKRD24 is identified as a transcriptional target of HMGCS2 via RNA sequencing, and silencing of ANKRD24 reduces autophagy markers LAMP1 and LC3-II, alters autophagic vacuole formation, and diminishes HMGCS2-induced autophagic clearance of Tau/pTau, placing ANKRD24 downstream of HMGCS2 in a ketone body-linked autophagic pathway.","method":"RNA sequencing (to identify ANKRD24 as HMGCS2 target), siRNA-mediated silencing of ANKRD24, western blotting for LAMP1/LC3-II, transmission electron microscopy for autophagosomes","journal":"Journal of Alzheimer's disease : JAD","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — pathway placement via gene silencing with multiple readouts (western blot, TEM) in a single lab; no reconstitution or direct protein interaction assay for ANKRD24 itself","pmids":["36442191"],"is_preprint":false},{"year":2025,"finding":"In TPRN (taperin)-deficient mice, TRIOBP-5 and ANKRD24 are progressively lost from mechanosensory stereocilia rows starting postnatally, indicating that TPRN is upstream of ANKRD24 (and TRIOBP-5) localization at the stereocilia rootlet pivot point.","method":"Knockout mouse model (TPRN-deficient), immunofluorescence localization of ANKRD24 and TRIOBP-5","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic epistasis placing ANKRD24 downstream of TPRN via KO localization data, single study","pmids":["40471101"],"is_preprint":false},{"year":2024,"finding":"A homozygous frameshift variant in ANKRD24 (c.1934_1937del; p.Thr645Lysfs*52) segregates with autosomal recessive nonsyndromic sensorineural hearing loss in a consanguineous human family, implicating ANKRD24 for the first time in human hearing loss.","method":"Whole exome sequencing, variant segregation analysis in a consanguineous family","journal":"Clinical genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — human genetic linkage via WES and segregation; no functional rescue or molecular mechanistic assay performed, single family","pmids":["39434538"],"is_preprint":false}],"current_model":"ANKRD24 is an ankyrin-repeat protein that localizes to the stereocilia insertion point and lower rootlet of inner ear hair cells, where it physically associates with TRIOBP-5 to organize rootlet F-actin architecture and bridge the apical plasma membrane to the rootlet; the two proteins are mutually required for each other's correct localization, and loss of ANKRD24 causes progressive hearing loss and increased mechanical vulnerability, while ANKRD24 also participates in autophagy downstream of HMGCS2-ketone body signaling to promote Tau/pTau clearance."},"narrative":{"mechanistic_narrative":"ANKRD24 is an ankyrin-repeat protein that organizes the stereocilia rootlet architecture of inner ear hair cells, where it is required for normal mechanosensory function and hearing [PMID:35175278]. It concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets, and surrounds and binds TRIOBP-5 within the lower rootlet where TRIOBP-5 bundles rootlet F-actin; the two proteins are mutually dependent for correct localization, as TRIOBP-5 is mislocalized in Ankrd24-null hair cells, ANKRD24 fails to localize to rootlets without TRIOBP-5, and exogenous TRIOBP-5 restores endogenous ANKRD24 to rootlets [PMID:35175278]. By bridging the apical plasma membrane to the lower rootlet, ANKRD24 maintains TRIOBP-5 distribution, and its loss produces progressive hearing loss, impaired recovery after noise damage, and increased mechanical vulnerability of the hair bundle [PMID:35175278]; positioning of ANKRD24 and TRIOBP-5 at this rootlet pivot point depends on the upstream factor TPRN/taperin [PMID:40471101]. A homozygous frameshift variant in ANKRD24 segregates with autosomal recessive nonsyndromic sensorineural hearing loss in a consanguineous family, implicating the gene in human deafness [PMID:39434538]. Independently of its rootlet role, ANKRD24 is a transcriptional target of HMGCS2 and acts in a ketone body-linked autophagic pathway, where its silencing reduces LAMP1 and LC3-II and diminishes HMGCS2-induced autophagic clearance of Tau/pTau [PMID:36442191].","teleology":[{"year":2022,"claim":"Established ANKRD24's core molecular role by showing it occupies the stereocilia rootlet pivot point and is reciprocally dependent with TRIOBP-5 for localization and rootlet F-actin organization.","evidence":"Superresolution microscopy, Ankrd24 knockout mice, and exogenous DsRed-TRIOBP-5 rescue showing mutual localization dependence","pmids":["35175278"],"confidence":"High","gaps":["The direct binding interface and stoichiometry between ANKRD24 and TRIOBP-5 are not defined","Whether ANKRD24 directly contacts F-actin or only TRIOBP-5 is unresolved","No structural model of the rootlet ring assembly"]},{"year":2022,"claim":"Connected the molecular localization to organismal function by demonstrating that ANKRD24 bridges the apical membrane to the rootlet and is required for hearing and mechanical resilience.","evidence":"Ankrd24 knockout mice with auditory functional assays and superresolution microscopy","pmids":["35175278"],"confidence":"High","gaps":["The membrane-anchoring partner ANKRD24 uses to bridge the apical membrane is not identified","Mechanism by which rootlet disorganization causes progressive rather than congenital loss is unclear"]},{"year":2023,"claim":"Placed ANKRD24 in a second pathway, downstream of HMGCS2 ketone-body signaling, where it supports autophagic clearance of Tau/pTau.","evidence":"RNA-seq identification as HMGCS2 target plus siRNA silencing with LAMP1/LC3-II western blots and TEM of autophagosomes","pmids":["36442191"],"confidence":"Medium","gaps":["No direct protein interaction or reconstitution for ANKRD24 in autophagy","Molecular activity of ANKRD24 within the autophagic machinery is undefined","Relationship between the autophagy role and the stereocilia role is unknown"]},{"year":2024,"claim":"Provided the first human disease link, implicating ANKRD24 in recessive nonsyndromic hearing loss.","evidence":"Whole exome sequencing and segregation of a homozygous frameshift variant in a consanguineous family","pmids":["39434538"],"confidence":"Medium","gaps":["No functional rescue or molecular assay of the variant","Single family limits genotype-phenotype generalization"]},{"year":2025,"claim":"Defined the upstream input to ANKRD24 localization, placing it (and TRIOBP-5) downstream of TPRN/taperin at the rootlet.","evidence":"TPRN-deficient mice with immunofluorescence localization of ANKRD24 and TRIOBP-5","pmids":["40471101"],"confidence":"Medium","gaps":["Whether TPRN acts directly or through intermediate factors on ANKRD24 is unknown","Single study without biochemical interaction data"]},{"year":null,"claim":"How ANKRD24 reconciles its structural rootlet role with its autophagy function, and the direct molecular activity it carries out in either context, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined enzymatic or binding activity for ANKRD24 beyond TRIOBP-5 association","No structural data","Tissue-specific basis for dual roles unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[2]},{"term_id":"R-HSA-9709957","term_label":"Sensory Perception","supporting_discovery_ids":[0,1,4]}],"complexes":[],"partners":["TRIOBP","TPRN"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8TF21","full_name":"Ankyrin repeat domain-containing protein 24","aliases":[],"length_aa":1146,"mass_kda":124.2,"function":"Component of the stereocilia rootlet in hair cells of inner ear. Bridges the apical plasma membrane with the lower rootlet and maintains normal distribution of TRIOBP, thereby reinforcing stereocilia insertion points and organizing rootlets for hearing with long-term resilience","subcellular_location":"Cell membrane; Cell projection, stereocilium","url":"https://www.uniprot.org/uniprotkb/Q8TF21/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ANKRD24","classification":"Not Classified","n_dependent_lines":7,"n_total_lines":1208,"dependency_fraction":0.005794701986754967},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ANKRD24","total_profiled":1310},"omim":[{"mim_id":"620234","title":"ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 24; ANKRD24","url":"https://www.omim.org/entry/620234"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Microtubules","reliability":"Uncertain"},{"location":"Cytosol","reliability":"Uncertain"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":32.9},{"tissue":"testis","ntpm":13.7}],"url":"https://www.proteinatlas.org/search/ANKRD24"},"hgnc":{"alias_symbol":["KIAA1981"],"prev_symbol":[]},"alphafold":{"accession":"Q8TF21","domains":[{"cath_id":"1.25.40.20","chopping":"46-174","consensus_level":"medium","plddt":92.8888,"start":46,"end":174},{"cath_id":"1.25.40.20","chopping":"176-259","consensus_level":"medium","plddt":95.3536,"start":176,"end":259},{"cath_id":"4.10.270","chopping":"1083-1146","consensus_level":"medium","plddt":74.4377,"start":1083,"end":1146}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TF21","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TF21-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TF21-F1-predicted_aligned_error_v6.png","plddt_mean":69.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ANKRD24","jax_strain_url":"https://www.jax.org/strain/search?query=ANKRD24"},"sequence":{"accession":"Q8TF21","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8TF21.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8TF21/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TF21"}},"corpus_meta":[{"pmid":"35175278","id":"PMC_35175278","title":"ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points.","date":"2022","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/35175278","citation_count":16,"is_preprint":false},{"pmid":"36442191","id":"PMC_36442191","title":"HMGCS2-Induced Autophagic Degradation of Tau Involves Ketone Body and ANKRD24.","date":"2023","source":"Journal of Alzheimer's disease : JAD","url":"https://pubmed.ncbi.nlm.nih.gov/36442191","citation_count":11,"is_preprint":false},{"pmid":"34745201","id":"PMC_34745201","title":"Development and Validation of a Five-RNA-Based Signature and Identification of Candidate Drugs for Neuroblastoma.","date":"2021","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34745201","citation_count":9,"is_preprint":false},{"pmid":"40428405","id":"PMC_40428405","title":"Genome-Wide Association Studies and Candidate Genes for Egg Production Traits in Layers from an F2 Crossbred Population Produced Using Two Divergently Selected Chicken Breeds, Russian White and Cornish White.","date":"2025","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/40428405","citation_count":6,"is_preprint":false},{"pmid":"40989574","id":"PMC_40989574","title":"Different Contribution of Missense and Loss-of-Function Variants to the Genetic Structure of Familial and Sporadic Meniere Disease.","date":"2025","source":"MedComm","url":"https://pubmed.ncbi.nlm.nih.gov/40989574","citation_count":5,"is_preprint":false},{"pmid":"39434538","id":"PMC_39434538","title":"A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non-Syndromic Hearing Loss.","date":"2024","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39434538","citation_count":1,"is_preprint":false},{"pmid":"40471101","id":"PMC_40471101","title":"Taperin bundles F-actin at stereocilia pivot points enabling optimal lifelong mechanosensitivity.","date":"2025","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/40471101","citation_count":1,"is_preprint":false},{"pmid":"40731354","id":"PMC_40731354","title":"Cost-effective promoter methylation analysis via target long-read bisulfite sequencing: a case study in severe preterm birth.","date":"2025","source":"BMC medical genomics","url":"https://pubmed.ncbi.nlm.nih.gov/40731354","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6403,"output_tokens":1422,"usd":0.020269,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8129,"output_tokens":2213,"usd":0.047985,"stage2_stop_reason":"end_turn"},"total_usd":0.068254,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"ANKRD24 concentrates at the stereocilia insertion point in hair cells, forming a ring at the junction between the lower and upper rootlets, and surrounds and binds TRIOBP-5 within the lower rootlet, where TRIOBP-5 bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed-TRIOBP-5 restores endogenous ANKRD24 to rootlets, establishing mutual dependence for correct localization.\",\n      \"method\": \"Superresolution microscopy, knockout mouse models (Ankrd24KO/KO), exogenous rescue with DsRed-TRIOBP-5, co-localization and binding studies\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic dependency demonstrated by KO and rescue experiments with superresolution microscopy, multiple orthogonal methods in a focused mechanistic study\",\n      \"pmids\": [\"35175278\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"ANKRD24 bridges the apical plasma membrane with the lower stereocilia rootlet to maintain a normal distribution of TRIOBP-5. Loss of ANKRD24 (Ankrd24KO/KO mice) results in progressive hearing loss, diminished recovery of auditory function after noise damage, and increased susceptibility to overstimulation of the hair bundle.\",\n      \"method\": \"Knockout mouse model (Ankrd24KO/KO), auditory functional assays, superresolution microscopy\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cellular and functional phenotypes, multiple assays across hearing and mechanical resilience readouts\",\n      \"pmids\": [\"35175278\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"ANKRD24 is identified as a transcriptional target of HMGCS2 via RNA sequencing, and silencing of ANKRD24 reduces autophagy markers LAMP1 and LC3-II, alters autophagic vacuole formation, and diminishes HMGCS2-induced autophagic clearance of Tau/pTau, placing ANKRD24 downstream of HMGCS2 in a ketone body-linked autophagic pathway.\",\n      \"method\": \"RNA sequencing (to identify ANKRD24 as HMGCS2 target), siRNA-mediated silencing of ANKRD24, western blotting for LAMP1/LC3-II, transmission electron microscopy for autophagosomes\",\n      \"journal\": \"Journal of Alzheimer's disease : JAD\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — pathway placement via gene silencing with multiple readouts (western blot, TEM) in a single lab; no reconstitution or direct protein interaction assay for ANKRD24 itself\",\n      \"pmids\": [\"36442191\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In TPRN (taperin)-deficient mice, TRIOBP-5 and ANKRD24 are progressively lost from mechanosensory stereocilia rows starting postnatally, indicating that TPRN is upstream of ANKRD24 (and TRIOBP-5) localization at the stereocilia rootlet pivot point.\",\n      \"method\": \"Knockout mouse model (TPRN-deficient), immunofluorescence localization of ANKRD24 and TRIOBP-5\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic epistasis placing ANKRD24 downstream of TPRN via KO localization data, single study\",\n      \"pmids\": [\"40471101\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A homozygous frameshift variant in ANKRD24 (c.1934_1937del; p.Thr645Lysfs*52) segregates with autosomal recessive nonsyndromic sensorineural hearing loss in a consanguineous human family, implicating ANKRD24 for the first time in human hearing loss.\",\n      \"method\": \"Whole exome sequencing, variant segregation analysis in a consanguineous family\",\n      \"journal\": \"Clinical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — human genetic linkage via WES and segregation; no functional rescue or molecular mechanistic assay performed, single family\",\n      \"pmids\": [\"39434538\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ANKRD24 is an ankyrin-repeat protein that localizes to the stereocilia insertion point and lower rootlet of inner ear hair cells, where it physically associates with TRIOBP-5 to organize rootlet F-actin architecture and bridge the apical plasma membrane to the rootlet; the two proteins are mutually required for each other's correct localization, and loss of ANKRD24 causes progressive hearing loss and increased mechanical vulnerability, while ANKRD24 also participates in autophagy downstream of HMGCS2-ketone body signaling to promote Tau/pTau clearance.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ANKRD24 is an ankyrin-repeat protein that organizes the stereocilia rootlet architecture of inner ear hair cells, where it is required for normal mechanosensory function and hearing [#0, #1]. It concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets, and surrounds and binds TRIOBP-5 within the lower rootlet where TRIOBP-5 bundles rootlet F-actin; the two proteins are mutually dependent for correct localization, as TRIOBP-5 is mislocalized in Ankrd24-null hair cells, ANKRD24 fails to localize to rootlets without TRIOBP-5, and exogenous TRIOBP-5 restores endogenous ANKRD24 to rootlets [#0]. By bridging the apical plasma membrane to the lower rootlet, ANKRD24 maintains TRIOBP-5 distribution, and its loss produces progressive hearing loss, impaired recovery after noise damage, and increased mechanical vulnerability of the hair bundle [#1]; positioning of ANKRD24 and TRIOBP-5 at this rootlet pivot point depends on the upstream factor TPRN/taperin [#3]. A homozygous frameshift variant in ANKRD24 segregates with autosomal recessive nonsyndromic sensorineural hearing loss in a consanguineous family, implicating the gene in human deafness [#4]. Independently of its rootlet role, ANKRD24 is a transcriptional target of HMGCS2 and acts in a ketone body-linked autophagic pathway, where its silencing reduces LAMP1 and LC3-II and diminishes HMGCS2-induced autophagic clearance of Tau/pTau [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Established ANKRD24's core molecular role by showing it occupies the stereocilia rootlet pivot point and is reciprocally dependent with TRIOBP-5 for localization and rootlet F-actin organization.\",\n      \"evidence\": \"Superresolution microscopy, Ankrd24 knockout mice, and exogenous DsRed-TRIOBP-5 rescue showing mutual localization dependence\",\n      \"pmids\": [\"35175278\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The direct binding interface and stoichiometry between ANKRD24 and TRIOBP-5 are not defined\", \"Whether ANKRD24 directly contacts F-actin or only TRIOBP-5 is unresolved\", \"No structural model of the rootlet ring assembly\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected the molecular localization to organismal function by demonstrating that ANKRD24 bridges the apical membrane to the rootlet and is required for hearing and mechanical resilience.\",\n      \"evidence\": \"Ankrd24 knockout mice with auditory functional assays and superresolution microscopy\",\n      \"pmids\": [\"35175278\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The membrane-anchoring partner ANKRD24 uses to bridge the apical membrane is not identified\", \"Mechanism by which rootlet disorganization causes progressive rather than congenital loss is unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Placed ANKRD24 in a second pathway, downstream of HMGCS2 ketone-body signaling, where it supports autophagic clearance of Tau/pTau.\",\n      \"evidence\": \"RNA-seq identification as HMGCS2 target plus siRNA silencing with LAMP1/LC3-II western blots and TEM of autophagosomes\",\n      \"pmids\": [\"36442191\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct protein interaction or reconstitution for ANKRD24 in autophagy\", \"Molecular activity of ANKRD24 within the autophagic machinery is undefined\", \"Relationship between the autophagy role and the stereocilia role is unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided the first human disease link, implicating ANKRD24 in recessive nonsyndromic hearing loss.\",\n      \"evidence\": \"Whole exome sequencing and segregation of a homozygous frameshift variant in a consanguineous family\",\n      \"pmids\": [\"39434538\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional rescue or molecular assay of the variant\", \"Single family limits genotype-phenotype generalization\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined the upstream input to ANKRD24 localization, placing it (and TRIOBP-5) downstream of TPRN/taperin at the rootlet.\",\n      \"evidence\": \"TPRN-deficient mice with immunofluorescence localization of ANKRD24 and TRIOBP-5\",\n      \"pmids\": [\"40471101\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether TPRN acts directly or through intermediate factors on ANKRD24 is unknown\", \"Single study without biochemical interaction data\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ANKRD24 reconciles its structural rootlet role with its autophagy function, and the direct molecular activity it carries out in either context, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No defined enzymatic or binding activity for ANKRD24 beyond TRIOBP-5 association\", \"No structural data\", \"Tissue-specific basis for dual roles unexplored\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-9709957\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TRIOBP\", \"TPRN\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":5,"faith_total":5,"faith_pct":100.0}}