date: '2026-09-20' reviewer: codex genes: - gene: 9POAL/NCGR_LOCUS10166 gene_file: genes/9POAL/NCGR_LOCUS10166/NCGR_LOCUS10166-ai-review.yaml scope: full_gene status: awaiting_adjudication all_annotations_reviewed: true original_annotation_count: 17 final_annotation_count: 17 original_source_assertions_preserved: 17 changes: - term_id: GO:0004399 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: The candidate preserves E368/H369 and Q300/H303/D402/H461 and has 460/472 identities across the aligned HDH region. UniProt missing-residue caution cites ARV1 rule RU368065, not HDH. A plausible fusion-model error does not demonstrate catalytic loss; retain the domain-based inference with the gene-model limitation recorded separately. - term_id: GO:0016491 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: This existing InterPro inference is consistent with the strongly conserved HDH domain and retained catalytic residues. A valid broad parent is not an over-annotation simply because a more specific enzyme term coexists. - term_id: GO:0016616 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: The inferred histidinol oxidation chemistry falls within this term. Retained active-site residues and strong sequence conservation support the mapping; no target-specific loss is established. - term_id: GO:0046872 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: Q300/H303/D402/H461 are retained in the candidate and the separate HDH model. Accept metal binding based on the HDH domain; no ARV zinc-binding claim is needed, and broad specificity alone is not false. - term_id: GO:0051287 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: The HDH domain and annotated NAD-binding region are present. This source mapping is compatible with the inferred reaction; it is not invalidated by coexistence of the enzyme annotation or an unproven fusion-model problem. - term_id: GO:0000105 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: Retain the pathway inference attached to conserved HDH catalysis. This product would perform the biosynthetic reaction, rather than merely be its substrate. Localization and whether the fusion model is expressed remain separate uncertainties. - term_id: GO:0006665 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: The previous categorical artifact premise was unproved. The ARV region is substantially conserved but has divergent ends and an ARV-specific feature-propagation caution. PMID:16725371 reports tolerated deletion of the cysteine-rich subdomain, so missing cysteines do not establish inactivity. Full-domain function, model validity and a direct sphingolipid role need adjudication. - term_id: GO:0016125 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: Homolog evidence supports ARV biology; sequence divergence and the fusion-model uncertainty require assessment rather than blanket rejection. The ARV-specific caution does not demonstrate complete functional loss, and the separate chromosome-1 gene does not prove the chromosome-2 model is false. - term_id: GO:0032366 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: Determine whether the candidate retains the ARV role responsible for intracellular sterol trafficking, including the distinction between direct transport and indirect lipid-homeostasis effects. No target transport assay or confirmed model error has been established. - term_id: GO:0097036 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: The target ARV-like region is present, but its full function and localization have not been established. Missing cysteines and different domain destinations are insufficient to establish loss; keep the explicit uncertainty pending focused adjudication. - term_id: GO:0005737 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: Both plastids and the endoplasmic reticulum are cytoplasmic organelles. The previous reasoning wrongly treated cytoplasm as equivalent to cytosol and used unresolved organelle targeting to reject a broad TreeGrafter inference. - term_id: GO:0005783 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: Arabidopsis ARV localization supports this possibility but does not determine targeting of the complete fusion. Conversely, an HDH-like N-terminus does not prove that ER localization is impossible. Model structure, processing and targeting remain unresolved. - term_id: GO:0005789 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: Conserved hydrophobic segments support membrane association. Assignment specifically to ER membrane depends on the full gene product and targeting; chloroplast predictions alone do not refute it. - term_id: GO:0005829 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: The sequence includes a plant HDH-like N-terminus and a hydrophobic ARV-like region. Neither predicted organelle targeting nor possible gene-model fusion proves exclusive localization. The exact TreeGrafter source placement and target processing require adjudication. - term_id: GO:0009507 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: The N-terminus is strongly conserved with a separate predicted plant HDH. A C-terminal membrane region does not categorically preclude plastid import or processing, but no target localization or authentic fusion transcript has been established. - term_id: GO:0009570 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: UNDECIDED reason: The strong HDH-like N-terminus supports the ancestral localization, while the fused membrane region raises a real targeting question. Rejecting stroma solely because another domain predicts ER localization assumed exclusivity and model error without evidence. - term_id: GO:0016020 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: Broad membrane association is supported by the actual candidate sequence. It is not an over-annotation merely because specific membranes were also predicted; exact ER versus plastid targeting remains unresolved. notes_file: genes/9POAL/NCGR_LOCUS10166/NCGR_LOCUS10166-notes.md validation: command: just validate 9POAL NCGR_LOCUS10166 result: PASS warnings: - Available old research report not used as supporting evidence; superseded by checked sources. history_record: history/genes/9POAL/NCGR_LOCUS10166/2026-09-21T032520Z-codex-f90bb5.yaml adjudication: slug: fusion-model-arv-function-and-targeting status: waiting_for_submission_slot history_validation: PASS - gene: ANOGA/TOLL9 gene_file: genes/ANOGA/TOLL9/TOLL9-ai-review.yaml scope: full_gene status: awaiting_adjudication all_annotations_reviewed: true original_annotation_count: 9 final_annotation_count: 8 original_source_assertions_preserved: 8 changes: - term_id: GO:0006954 evidence: IBA old_action: REMOVE new_action: REMOVE reason: QuickGO GO:0006954 complete response specifies only_in_taxon Vertebrata (7742), which excludes Anopheles. The frozen annotation propagated from ancestral PTN000687652; current IBD instead places this term on PTN002808115 outside the target lineage, and current QuickGO no longer returns the row. Preserve the source row and retain REMOVE for this concrete taxonomic incompatibility. Lack of adaptive immunity is not the rationale, and insect innate defense remains biologically valid. - term_id: GO:0007165 evidence: IBA old_action: MODIFY new_action: ACCEPT reason: The target leaf descends from the current positive PTN002808045 for this term, and the TIR-domain mapping independently agrees. The previous specific replacement presumed an AGAP006974 Spaetzle–Myd88–Tube–Pelle mechanism from other receptors and pathway-wide experiments. Retain the supported broad assertion while ligand and pathway specificity are adjudicated. - term_id: GO:0038023 evidence: IBA old_action: MODIFY new_action: ACCEPT reason: Current PTN002808045 supports this target. The previous replacement with pattern recognition receptor activity was justified by processed host Spaetzle, which is not a microbial PAMP. Bombyx Toll9 has genuine LPS/MD-2-like recognition evidence, so PRR capacity is a serious separate hypothesis; it is not established for this receptor by the prior rationale. - term_id: GO:0005886 evidence: IBA old_action: ACCEPT new_action: ACCEPT reason: Retain the ancestral plasma-membrane annotation from PTN002808045. The LRR–membrane–TIR architecture is consistent, and no target-specific loss or alternative exclusive localization has been established. The UniProt prediction also includes a hydrophobic N-terminal segment; it is not an experimental map of mature topology. - term_id: GO:0002376 evidence: IEA old_action: ACCEPT new_action: ACCEPT reason: The existing keyword inference is supported by Toll9 immune activity in Bombyx and immune-associated target expression in PMID:38191283. That study perturbs mosGILT rather than TOLL9 and does not itself prove receptor-specific antiparasite work. Drosophila Toll9 knockout results are context-specific and do not establish loss in Anopheles. - term_id: GO:0007165 evidence: IEA old_action: MODIFY new_action: ACCEPT reason: The target leaf descends from the current positive PTN002808045 for this term, and the TIR-domain mapping independently agrees. The previous specific replacement presumed an AGAP006974 Spaetzle–Myd88–Tube–Pelle mechanism from other receptors and pathway-wide experiments. Retain the supported broad assertion while ligand and pathway specificity are adjudicated. - term_id: GO:0016020 evidence: IEA old_action: MARK_AS_OVER_ANNOTATED new_action: ACCEPT reason: The broad membrane annotation is true and independently supported by the deposited sequence and subcellular-location mapping. Coexistence with plasma membrane does not make an existing broad annotation an over-annotation. - term_id: GO:0045087 evidence: IEA old_action: ACCEPT new_action: ACCEPT reason: Retain the existing family-based keyword inference. Bombyx Toll9 has positive LPS-responsive immune signaling, while target AGAP006974 is upregulated in mosGILT-null mosquitoes. These are not direct Anopheles TOLL9 ligand or loss-of-function assays. Drosophila Toll9 loss-of-function lacks defects in tested antibacterial responses but does not refute every ancestral or mosquito immune role; a focused report will assess the transfer scope. notes_file: genes/ANOGA/TOLL9/TOLL9-notes.md validation: command: just validate ANOGA TOLL9 result: PASS warnings: - Available old research report not used as supporting evidence; superseded by checked sources. history_record: history/genes/ANOGA/TOLL9/2026-09-21T032520Z-codex-c04682.yaml adjudication: slug: toll9-ligand-and-immune-pathway-specificity status: waiting_for_submission_slot history_validation: PASS