FOXE1 notes

2026-10-31 — source-specific assessment

FOXE1 is a nuclear forkhead transcription factor. Human DNA-binding, promoter-reporter and tagged chromatin-occupancy experiments support sequence-dependent Pol II regulation. Rat Foxe1 represses selected thyroid promoters under defined cofactor conditions, so the synthesis retains one direction-neutral transcription-factor core (PMID:9697705(https://pubmed.ncbi.nlm.nih.gov/9697705/), PMID:21177256(https://pubmed.ncbi.nlm.nih.gov/21177256/), PMID:9214635(https://doi.org/10.1093/emboj/16.11.3185)).

Human variant effects are not uniformly loss of function: S57N retains partial activity, R73S increases reporter output under the tested conditions, and the N132D study does not establish that variant as the cause of dysgenesis. Tagged-cell and endogenous human thyroid co-IP, together with a FOXE1 C-terminal two-hybrid assay, support the specific ELK1 transcription-factor-binding refinement; they do not establish purified binary affinity (PMID:12165566(https://pubmed.ncbi.nlm.nih.gov/12165566/), PMID:24219130(https://pubmed.ncbi.nlm.nih.gov/24219130/), PMID:20094846(https://pubmed.ncbi.nlm.nih.gov/20094846/), PMID:27852061(https://pmc.ncbi.nlm.nih.gov/articles/PMC5349888/)).

Developmental outcomes remain distinct from the molecular core. The thyroid-hormone-generation transfer exceeds the demonstrated participation scope: the mouse donor uses a broader upstream-or-within relation, and the study measures developmental and endocrine consequences. Human thymus and pharynx expression is genuine but does not by itself establish participation in those developmental processes. Mouse loss, mouse overexpression and rat-cDNA rescue in a mouse locus retain their separate assay boundaries (PMID:9697704(https://pubmed.ncbi.nlm.nih.gov/9697704/), PMID:15494458(https://pubmed.ncbi.nlm.nih.gov/15494458/), PMID:15581879(https://pure.mpg.de/rest/items/item_598362_3/component/file_598361/content), PMID:22304410(https://pmc.ncbi.nlm.nih.gov/articles/PMC3823429/)).

The assessment covers 56 original contexts: 28 ACCEPT, 12 KEEP_AS_NON_CORE, 7 UNDECIDED, 7 TOO_GENERAL, 1 MODIFY and 1 MARK_AS_OVER_ANNOTATED. No new annotation or quotation is proposed. There are no original extension groups or prospective key collisions. The official O00358 record has a 373-aa displayed sequence and no alternative-product block; historical construct lengths and allelic repeat variants are not assigned invented isoform identifiers.

The source guide records public original-source URLs, selected assay locators and access limitations. The source evidence preserves all original contexts, original exporter projection, donor source objects and six phylogenetic joins. The genuine seed and its original source fields were subsequently matched one-to-one to all 56 original contexts; the evidence records the exact stored-order mapping.

Source follow-up

Biological questions

2026-10-31 — source acquisition and review

The genuine repository fetch created 56 PENDING annotations. A fresh complete QuickGO response matched all 56 retained original objects exactly, and the genuine TSV matched the recorded exporter projection byte-for-byte. All 20 required normal sources are present: four existing sources were reused unchanged and 16 publications were acquired through repository tooling. The current UniProt sequence is 373 amino acids with no alternative-product block.

The required Falcon attempt failed with an authentication error and produced no research file. The selected manual primary readings and their access limits remain documented in the source guide. The approved 56 decisions, one core and 17 publication assessments were applied with source fields and stored order preserved; the review has 24 references overall. No new annotations or quotations were added. Validation outcomes will be recorded after the checks run.

Local validation

Ordinary schema, ontology-term, reference and best-practice validation passed. Four advisory groups retain the reviewed source-specific differences for GO:0000981, GO:0006357, GO:0009653 and GO:0043565; the computed curation status is DRAFT. Strict GOA matching confirms all 56 stored source contexts, and the status and new-history checks pass. A private HTML preview rendered successfully. Full repository CI and publication have not yet run for this candidate.

An independent final read confirmed the approved decisions, source and assay limits, original-context mapping, reference assessments and public documentation. Source and prior-work preservation checks also pass. No scientific correction was required.

Review follow-up to PR #5784

The same-term granularity review assigns TOO_GENERAL to all eight original sequence-specific DNA-binding rows, while preserving their individual assay and access limits. Independently established gene-level Pol II activities support the two F137S-related functional claims, and independent developmental evidence supports the cloning-paper morphogenesis claim as non-core. Their original papers retain explicit unverified source details. Two directional transcription rows now use Pol II-specific replacement terms. The biological description is rewritten as a standalone summary.

All 56 annotations remain in their original order with source fields unchanged. The single core, references, normal source caches and existing history remain intact; no new annotations or quotations are added. See the source guide for primary locators and the evidence record for exact before/after decisions. The earlier published history is retained as append-only session provenance; the new follow-up history will focus on this curation change. Validation and final peer outcomes will be recorded after authorized application.

Follow-up checks: ordinary validation passed without annotation advisories, strict GOA matching covers all 56 contexts, and the computed status is COMPLETE. Status verification, new-history validation, private rendering and local-link checks passed. Independent review of the exact proposal found no issue. All 20 normal source files, the original source fields/order and the prior history were preserved. Full repository integration and renewed remote approval remain pending.