{"gene":"KRT84","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2023,"finding":"KRT84 (Keratin 84) protein is ubiquitinated by the E3 ubiquitin ligase RNF187 via lysine 48-linked polyubiquitination, leading to its proteasomal degradation. KRT84 was identified as a direct interactor of RNF187 by co-immunoprecipitation and mass spectrometry. Overexpression of KRT84 attenuated RNF187-driven proliferation and migration of spermatogonia (GC-1 cells), placing KRT84 as a negative regulator of spermatogonial growth downstream of RNF187.","method":"Co-immunoprecipitation, mass spectrometry, lysine 48-linkage polyubiquitination assay, RNF187 knockdown/overexpression with proliferation/migration/apoptosis readouts, KRT84 overexpression rescue experiment","journal":"FASEB journal","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with MS identification, ubiquitination linkage specificity assay, and functional rescue experiment in a single rigorous study","pmids":["37738023"],"is_preprint":false},{"year":2018,"finding":"HOXC13 transcription factor directly upregulates the promoter activity of KRT84 in dermal papilla cells and HEK 293T cells, as demonstrated by dual-luciferase reporter assays using the KRT84 promoter. Two SNPs (c.812A>G and c.929A>C) in the homeodomain of HOXC13 abolish its regulatory function on KRT84 without affecting HOXC13 protein expression.","method":"Dual-luciferase reporter assay with KRT84 promoter, HOXC13 overexpression in HEK 293T and dermal papilla cells, keratin promoter-GFP system, SNP mutagenesis","journal":"BMC genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dual reporter + GFP system + mutagenesis in a single lab study; functional context (hair follicle differentiation) supported","pmids":["30139327"],"is_preprint":false},{"year":2024,"finding":"KRT84 protein is highly expressed in sheep hair follicles including the inner root sheath, outer root sheath, and hair medulla across all developmental ages examined (1–270 days). Polymorphisms (SNPs) in KRT84 exon 1 forming distinct haplotypes are associated with wool fibre traits (fibre curvature, staple length, staple strength, fibre diameter, coefficient of variation of fibre diameter, and comfort factor), implicating KRT84 in determining structural properties of the wool fibre.","method":"Immunofluorescence localization, RT-qPCR expression profiling, PARMS haplotyping, association analysis of haplotypes with wool traits","journal":"Genes","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct immunofluorescence localization with haplotype-trait association; functional mechanism inferred but not reconstituted","pmids":["38397237"],"is_preprint":false},{"year":2011,"finding":"In sheep, KRT84 transcripts are exclusively present in the fibre cuticle compartment of the hair follicle, as determined by zone-specific expression analysis, indicating a cuticle-restricted structural role for KRT84 in wool/hair.","method":"cDNA sequencing, transcriptome analysis, compartment-specific expression profiling of hair follicle zones","journal":"Experimental dermatology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — zone-specific expression in a defined tissue compartment, replicated across multiple KRT genes in the same study","pmids":["21554405"],"is_preprint":false},{"year":2012,"finding":"KRT84 (keratin type II cuticular Hb4) is citrullinated in synovial tissues of rheumatoid arthritis patients. KRT84 immunoprecipitated from synovial tissues showed citrullination by anti-citrulline antibody detection, and high levels of autoantibodies against KRT84 were detected in RA patient blood compared to healthy controls.","method":"2-D Western blot, mass spectrometry identification, immunoprecipitation with anti-citrulline antibody detection, ELISA for autoantibodies","journal":"The Journal of rheumatology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — citrullination confirmed by immunoprecipitation + anticitrulline antibody in a single study; post-translational modification writer not identified","pmids":["23242181"],"is_preprint":false},{"year":2020,"finding":"In Harlequin (Hq) mutant mice, overexpression of an integrated ecotropic provirus from the Aifm1Hq allele in wild-type keratinocyte cell lines led to specific downregulation of hair-follicle-specific Krt84 (and Krtap3-3) without altering Aifm1 or epidermal Krt5 expression, suggesting that Krt84 transcription can be suppressed by retroviral element expression and is regulated independently of general keratin expression programs.","method":"Retroviral construct overexpression in wild-type keratinocyte cell lines, gene expression analysis (Krt84 downregulation as specific readout)","journal":"Mammalian genome","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single transfection experiment in cell lines; indirect regulatory mechanism, no direct mechanistic dissection of the KRT84 regulatory pathway","pmids":["33367954"],"is_preprint":false}],"current_model":"KRT84 is a type II hair (cuticular) keratin expressed specifically in the cuticle compartment of the hair follicle, whose transcription is directly upregulated by HOXC13 (via its homeodomain) and whose protein is targeted for lysine 48-linked polyubiquitination and proteasomal degradation by the E3 ubiquitin ligase RNF187, thereby promoting spermatogonial cell growth; additionally, KRT84 undergoes citrullination in rheumatoid arthritis synovial tissue and elicits autoantibody responses."},"narrative":{"mechanistic_narrative":"KRT84 is a type II cuticular hair keratin that contributes to the structural architecture of the hair follicle and wool fibre [PMID:21554405, PMID:38397237]. Its transcripts are restricted to the fibre cuticle compartment of the follicle [PMID:21554405], and at the protein level it is detected in the inner root sheath, outer root sheath, and hair medulla across hair follicle development, with exon 1 polymorphisms associating with wool fibre traits such as curvature, diameter, and staple strength [PMID:38397237]. KRT84 transcription is directly activated by the homeodomain transcription factor HOXC13, which engages the KRT84 promoter; homeodomain SNPs abolish this activation without altering HOXC13 levels [PMID:30139327]. Beyond its follicular role, KRT84 protein stability is controlled by the E3 ubiquitin ligase RNF187, which binds KRT84 and directs its K48-linked polyubiquitination and proteasomal degradation; in this context KRT84 acts as a negative regulator of spermatogonial proliferation and migration downstream of RNF187 [PMID:37738023]. KRT84 is also citrullinated in rheumatoid arthritis synovial tissue and elicits autoantibody responses in patients [PMID:23242181].","teleology":[{"year":2011,"claim":"Establishing where KRT84 acts within the hair follicle was the first step in assigning it a structural role; compartment-resolved expression placed it specifically in the fibre cuticle.","evidence":"cDNA sequencing and zone-specific expression profiling of sheep hair follicle compartments","pmids":["21554405"],"confidence":"Medium","gaps":["Does not demonstrate the structural protein function within the cuticle filament","No protein-level localization in this study","Restricted to sheep follicle"]},{"year":2012,"claim":"Whether KRT84 has a role beyond hair structure was addressed by finding it citrullinated and immunogenic in disease tissue, linking it to autoimmune responses.","evidence":"2-D Western blot, mass spectrometry, anti-citrulline immunoprecipitation, and ELISA for autoantibodies in rheumatoid arthritis synovium and patient blood","pmids":["23242181"],"confidence":"Medium","gaps":["The enzyme (writer) responsible for KRT84 citrullination was not identified","Causal role of KRT84 autoantibodies in disease not established","Single-study observation"]},{"year":2018,"claim":"How KRT84 expression is controlled was answered by identifying HOXC13 as a direct transcriptional activator, connecting a hair-follicle master regulator to a cuticle keratin.","evidence":"Dual-luciferase reporter assays of the KRT84 promoter with HOXC13 overexpression and homeodomain SNP mutagenesis in HEK293T and dermal papilla cells","pmids":["30139327"],"confidence":"Medium","gaps":["Direct HOXC13 occupancy of the endogenous KRT84 locus not shown by ChIP","Single-lab reporter-based assay","In vivo consequence of SNP-mediated loss of activation not tested"]},{"year":2020,"claim":"An additional regulatory input was probed by showing retroviral element expression can suppress Krt84 transcription independently of general keratin programs.","evidence":"Retroviral construct overexpression in wild-type keratinocyte cell lines with gene expression readouts in Harlequin mutant context","pmids":["33367954"],"confidence":"Low","gaps":["Single transfection experiment with indirect regulatory inference, no mechanistic dissection","Mechanism of selective Krt84 suppression unknown","Physiological relevance unclear"]},{"year":2023,"claim":"A post-translational control point and an unexpected non-follicular function were established by showing RNF187 ubiquitinates and degrades KRT84, with KRT84 acting as a brake on spermatogonial growth.","evidence":"Reciprocal Co-IP with mass spectrometry, K48-linkage polyubiquitination assay, and KRT84 overexpression rescue in GC-1 spermatogonia with proliferation/migration readouts","pmids":["37738023"],"confidence":"High","gaps":["Ubiquitination site(s) on KRT84 not mapped","How a cuticular hair keratin functions in spermatogonia mechanistically not resolved","In vivo relevance to spermatogenesis not tested"]},{"year":2024,"claim":"Linking KRT84 to fibre phenotype, protein-level localization and haplotype-trait association implicated it in determining structural wool fibre properties.","evidence":"Immunofluorescence localization, RT-qPCR profiling, and PARMS haplotype association with wool fibre traits in sheep","pmids":["38397237"],"confidence":"Medium","gaps":["Causal link between specific SNP haplotypes and fibre structure not functionally reconstituted","Molecular basis of trait effects unknown","Restricted to sheep"]},{"year":null,"claim":"How KRT84's canonical structural role as a cuticular keratin reconciles with its degradation-dependent regulation of spermatogonial growth remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of KRT84 within the cuticle keratin filament network","No mechanistic explanation for KRT84 function outside the hair follicle","Direct partners within keratin intermediate filaments not characterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[2,3]}],"localization":[],"pathway":[],"complexes":[],"partners":["RNF187","HOXC13"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NSB2","full_name":"Keratin, type II cuticular Hb4","aliases":["Keratin-84","K84","Type II hair keratin Hb4","Type-II keratin Kb24"],"length_aa":600,"mass_kda":64.8,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9NSB2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KRT84","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KRT84","total_profiled":1310},"omim":[{"mim_id":"602766","title":"KERATIN 84, TYPE II; KRT84","url":"https://www.omim.org/entry/602766"},{"mim_id":"602765","title":"KERATIN 83, TYPE II; KRT83","url":"https://www.omim.org/entry/602765"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":1.4},{"tissue":"skin 1","ntpm":1.7}],"url":"https://www.proteinatlas.org/search/KRT84"},"hgnc":{"alias_symbol":["Hb-4"],"prev_symbol":["KRTHB4"]},"alphafold":{"accession":"Q9NSB2","domains":[{"cath_id":"-","chopping":"219-316_332-475","consensus_level":"medium","plddt":91.011,"start":219,"end":475}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NSB2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NSB2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NSB2-F1-predicted_aligned_error_v6.png","plddt_mean":66.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KRT84","jax_strain_url":"https://www.jax.org/strain/search?query=KRT84"},"sequence":{"accession":"Q9NSB2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NSB2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NSB2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NSB2"}},"corpus_meta":[{"pmid":"12717087","id":"PMC_12717087","title":"A prospective study of the efficacy 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transfuziologiia","url":"https://pubmed.ncbi.nlm.nih.gov/8144012","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":37916,"output_tokens":1749,"usd":0.069991,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8515,"output_tokens":2236,"usd":0.049237,"stage2_stop_reason":"end_turn"},"total_usd":0.119228,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"KRT84 (Keratin 84) protein is ubiquitinated by the E3 ubiquitin ligase RNF187 via lysine 48-linked polyubiquitination, leading to its proteasomal degradation. KRT84 was identified as a direct interactor of RNF187 by co-immunoprecipitation and mass spectrometry. Overexpression of KRT84 attenuated RNF187-driven proliferation and migration of spermatogonia (GC-1 cells), placing KRT84 as a negative regulator of spermatogonial growth downstream of RNF187.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, lysine 48-linkage polyubiquitination assay, RNF187 knockdown/overexpression with proliferation/migration/apoptosis readouts, KRT84 overexpression rescue experiment\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with MS identification, ubiquitination linkage specificity assay, and functional rescue experiment in a single rigorous study\",\n      \"pmids\": [\"37738023\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"HOXC13 transcription factor directly upregulates the promoter activity of KRT84 in dermal papilla cells and HEK 293T cells, as demonstrated by dual-luciferase reporter assays using the KRT84 promoter. Two SNPs (c.812A>G and c.929A>C) in the homeodomain of HOXC13 abolish its regulatory function on KRT84 without affecting HOXC13 protein expression.\",\n      \"method\": \"Dual-luciferase reporter assay with KRT84 promoter, HOXC13 overexpression in HEK 293T and dermal papilla cells, keratin promoter-GFP system, SNP mutagenesis\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dual reporter + GFP system + mutagenesis in a single lab study; functional context (hair follicle differentiation) supported\",\n      \"pmids\": [\"30139327\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KRT84 protein is highly expressed in sheep hair follicles including the inner root sheath, outer root sheath, and hair medulla across all developmental ages examined (1–270 days). Polymorphisms (SNPs) in KRT84 exon 1 forming distinct haplotypes are associated with wool fibre traits (fibre curvature, staple length, staple strength, fibre diameter, coefficient of variation of fibre diameter, and comfort factor), implicating KRT84 in determining structural properties of the wool fibre.\",\n      \"method\": \"Immunofluorescence localization, RT-qPCR expression profiling, PARMS haplotyping, association analysis of haplotypes with wool traits\",\n      \"journal\": \"Genes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct immunofluorescence localization with haplotype-trait association; functional mechanism inferred but not reconstituted\",\n      \"pmids\": [\"38397237\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"In sheep, KRT84 transcripts are exclusively present in the fibre cuticle compartment of the hair follicle, as determined by zone-specific expression analysis, indicating a cuticle-restricted structural role for KRT84 in wool/hair.\",\n      \"method\": \"cDNA sequencing, transcriptome analysis, compartment-specific expression profiling of hair follicle zones\",\n      \"journal\": \"Experimental dermatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — zone-specific expression in a defined tissue compartment, replicated across multiple KRT genes in the same study\",\n      \"pmids\": [\"21554405\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"KRT84 (keratin type II cuticular Hb4) is citrullinated in synovial tissues of rheumatoid arthritis patients. KRT84 immunoprecipitated from synovial tissues showed citrullination by anti-citrulline antibody detection, and high levels of autoantibodies against KRT84 were detected in RA patient blood compared to healthy controls.\",\n      \"method\": \"2-D Western blot, mass spectrometry identification, immunoprecipitation with anti-citrulline antibody detection, ELISA for autoantibodies\",\n      \"journal\": \"The Journal of rheumatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — citrullination confirmed by immunoprecipitation + anticitrulline antibody in a single study; post-translational modification writer not identified\",\n      \"pmids\": [\"23242181\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In Harlequin (Hq) mutant mice, overexpression of an integrated ecotropic provirus from the Aifm1Hq allele in wild-type keratinocyte cell lines led to specific downregulation of hair-follicle-specific Krt84 (and Krtap3-3) without altering Aifm1 or epidermal Krt5 expression, suggesting that Krt84 transcription can be suppressed by retroviral element expression and is regulated independently of general keratin expression programs.\",\n      \"method\": \"Retroviral construct overexpression in wild-type keratinocyte cell lines, gene expression analysis (Krt84 downregulation as specific readout)\",\n      \"journal\": \"Mammalian genome\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single transfection experiment in cell lines; indirect regulatory mechanism, no direct mechanistic dissection of the KRT84 regulatory pathway\",\n      \"pmids\": [\"33367954\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KRT84 is a type II hair (cuticular) keratin expressed specifically in the cuticle compartment of the hair follicle, whose transcription is directly upregulated by HOXC13 (via its homeodomain) and whose protein is targeted for lysine 48-linked polyubiquitination and proteasomal degradation by the E3 ubiquitin ligase RNF187, thereby promoting spermatogonial cell growth; additionally, KRT84 undergoes citrullination in rheumatoid arthritis synovial tissue and elicits autoantibody responses.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KRT84 is a type II cuticular hair keratin that contributes to the structural architecture of the hair follicle and wool fibre [#3, #2]. Its transcripts are restricted to the fibre cuticle compartment of the follicle [#3], and at the protein level it is detected in the inner root sheath, outer root sheath, and hair medulla across hair follicle development, with exon 1 polymorphisms associating with wool fibre traits such as curvature, diameter, and staple strength [#2]. KRT84 transcription is directly activated by the homeodomain transcription factor HOXC13, which engages the KRT84 promoter; homeodomain SNPs abolish this activation without altering HOXC13 levels [#1]. Beyond its follicular role, KRT84 protein stability is controlled by the E3 ubiquitin ligase RNF187, which binds KRT84 and directs its K48-linked polyubiquitination and proteasomal degradation; in this context KRT84 acts as a negative regulator of spermatogonial proliferation and migration downstream of RNF187 [#0]. KRT84 is also citrullinated in rheumatoid arthritis synovial tissue and elicits autoantibody responses in patients [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Establishing where KRT84 acts within the hair follicle was the first step in assigning it a structural role; compartment-resolved expression placed it specifically in the fibre cuticle.\",\n      \"evidence\": \"cDNA sequencing and zone-specific expression profiling of sheep hair follicle compartments\",\n      \"pmids\": [\"21554405\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not demonstrate the structural protein function within the cuticle filament\",\n        \"No protein-level localization in this study\",\n        \"Restricted to sheep follicle\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Whether KRT84 has a role beyond hair structure was addressed by finding it citrullinated and immunogenic in disease tissue, linking it to autoimmune responses.\",\n      \"evidence\": \"2-D Western blot, mass spectrometry, anti-citrulline immunoprecipitation, and ELISA for autoantibodies in rheumatoid arthritis synovium and patient blood\",\n      \"pmids\": [\"23242181\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The enzyme (writer) responsible for KRT84 citrullination was not identified\",\n        \"Causal role of KRT84 autoantibodies in disease not established\",\n        \"Single-study observation\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"How KRT84 expression is controlled was answered by identifying HOXC13 as a direct transcriptional activator, connecting a hair-follicle master regulator to a cuticle keratin.\",\n      \"evidence\": \"Dual-luciferase reporter assays of the KRT84 promoter with HOXC13 overexpression and homeodomain SNP mutagenesis in HEK293T and dermal papilla cells\",\n      \"pmids\": [\"30139327\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct HOXC13 occupancy of the endogenous KRT84 locus not shown by ChIP\",\n        \"Single-lab reporter-based assay\",\n        \"In vivo consequence of SNP-mediated loss of activation not tested\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"An additional regulatory input was probed by showing retroviral element expression can suppress Krt84 transcription independently of general keratin programs.\",\n      \"evidence\": \"Retroviral construct overexpression in wild-type keratinocyte cell lines with gene expression readouts in Harlequin mutant context\",\n      \"pmids\": [\"33367954\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single transfection experiment with indirect regulatory inference, no mechanistic dissection\",\n        \"Mechanism of selective Krt84 suppression unknown\",\n        \"Physiological relevance unclear\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"A post-translational control point and an unexpected non-follicular function were established by showing RNF187 ubiquitinates and degrades KRT84, with KRT84 acting as a brake on spermatogonial growth.\",\n      \"evidence\": \"Reciprocal Co-IP with mass spectrometry, K48-linkage polyubiquitination assay, and KRT84 overexpression rescue in GC-1 spermatogonia with proliferation/migration readouts\",\n      \"pmids\": [\"37738023\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Ubiquitination site(s) on KRT84 not mapped\",\n        \"How a cuticular hair keratin functions in spermatogonia mechanistically not resolved\",\n        \"In vivo relevance to spermatogenesis not tested\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linking KRT84 to fibre phenotype, protein-level localization and haplotype-trait association implicated it in determining structural wool fibre properties.\",\n      \"evidence\": \"Immunofluorescence localization, RT-qPCR profiling, and PARMS haplotype association with wool fibre traits in sheep\",\n      \"pmids\": [\"38397237\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Causal link between specific SNP haplotypes and fibre structure not functionally reconstituted\",\n        \"Molecular basis of trait effects unknown\",\n        \"Restricted to sheep\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KRT84's canonical structural role as a cuticular keratin reconciles with its degradation-dependent regulation of spermatogonial growth remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of KRT84 within the cuticle keratin filament network\",\n        \"No mechanistic explanation for KRT84 function outside the hair follicle\",\n        \"Direct partners within keratin intermediate filaments not characterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"RNF187\", \"HOXC13\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":5,"faith_total":5,"faith_pct":100.0}}