ARX (UniProt Q96QS3; HGNC:18060) is a paired homeobox transcription factor. The recovered seed contains 48 original assertions and no alternative-product list. The seed, UniProt and GOA are preserved byte-for-byte. Decisions remain prospective until independent annotation/core consultation. No new annotation is currently proposed.
The configured Falcon research attempt with Perplexity-lite fallback failed once after 5.89 seconds with a connection error and produced no report. Sensitive traceback output was discarded after its digest and safe diagnostic signals were recorded. This journal records manual research; it is not a provider report. Normal publication recovery and the quarantined Seed14 auxiliary copies are tracked separately. Existing canonical copies of PMID:21653829 and PMID:28473536 take precedence over differing recovered copies.
The normal record is abstract-only. Separately, I read the author-uploaded original paper: cloning/cell-culture, reporter, EMSA and ChIP Methods; targeted Results and Figures 1–5 captions. The constructs explicitly encode human full-length ARX (1–562) or its 303–431 region. In HEK293T cells, wild-type ARX represses a reporter containing LMO1 TAATTA sites and decreases endogenous LMO1/SHOX2 expression. EMSA competition and antibody supershift support sequence recognition; full-length Myc-ARX ChIP supports occupancy of the two endogenous loci. Wild-type protein is predominantly nuclear. Mutants disrupt binding and repression to differing degrees; P353L is a milder case. These observations establish nuclear, chromatin-associated transcriptional repression. External full-text reading does not turn the normal abstract-only cache into full text.
The canonical-eligible 2019 record contains the complete main Results, Discussion and Methods, which I read. Promoter reporters and ChIP support ARX-mediated KDM5C activation, enhanced with PHF8. The paper explicitly leaves direct ARX–PHF8 contact unresolved. Its embryonic mouse brain, mouse ES-derived neuron and worm experiments are distinct from its cultured-cell promoter experiments. SAHA rescue of downstream chromatin/transcriptional abnormalities does not establish a clinical treatment or assign histone-demethylase chemistry to ARX. Original paper.
For the 2021 paper, I read Methods 2.3–2.5, Results 3.4/3.6 and the relevant Discussion in the recovered XML. Reciprocal endogenous co-immunoprecipitation in SH-SY5Y cells and tagged-protein experiments support ARX–PHF8 association. The paper explicitly identifies the human ARX reference sequence NM_139058.2. PHF8 is a catalytic histone demethylase; enzyme binding is a possible same-source refinement of the existing generic interaction. Co-immunoprecipitation does not establish a purified binary interface, and no demethylase activity is attributed to ARX. Original paper.
For PMID:21653829(https://pmc.ncbi.nlm.nih.gov/articles/PMC3169432/), I read the available canonical main Results/Discussion and original PMC Methods. The screen uses full or partial bait cDNAs and a human brain library; secondary yeast tests and a sampled mammalian affinity assay are reported. I did not recover the supplementary construct/pair table identifying the exact ARX–ACTN1 and ARX–PICK1 experiments. The UniProt interaction list corroborates the named pairs but does not establish each source-local construct or validation route. The inaccessible supplement is an evidence boundary, not proof that either interaction is false.
For PMID:28473536(https://pmc.ncbi.nlm.nih.gov/articles/PMC8009048/), I read the complete available canonical abstract and concluding text and inspected the original article's supplement links. The specific ARX row, reagent and methylation-preference data were not recovered. The existing broad sequence-specific DNA-binding assertion is independently supported by the targeted ARX experiments above; no ARX methyl-CpG preference is inferred from this screen's general conclusions.
The abstract-only PMID:37883554(https://pubmed.ncbi.nlm.nih.gov/37883554/) is not sufficient to assign all five human ARX lineage endpoints. I read targeted institutional original Results; an independent reader also examined pages 1, 6 and 7. In the human ZNF800-null organoid context, ARX overexpression did not reverse the enterochromaffin bias or alter PAX4, and FLAG-ARX ChIP did not bind the tested PAX4 enhancer. These are conditional negatives. The five-lineage discussion draws on earlier mouse literature; the supplementary ARX Methods and panel images remain unread. The human IDA assertions therefore require source-specific adjudication, rather than either automatic acceptance from the pathway model or removal from the title.
Tracing the mouse donor O35085 identified PMID:22387004(https://pmc.ncbi.nlm.nih.gov/articles/PMC3322318/). I read its original Methods, targeted mouse Results, human Figure 6 Results/caption and Discussion through the indexed official PMC text. WA09 human ES cells received stable ARX shRNA or control and were differentiated into proximal intestinal organoids. At day 68, partial ARX knockdown reduced CCK, secretin and preproglucagon expression while general epithelial, non-endocrine and pan-endocrine markers were maintained. Somatostatin expression did not increase in the human experiment. Mouse conditional deletion reduced several hormone-producing lineages and increased somatostatin cells. Thus the human and mouse D-cell observations must not be collapsed into a positive human D-cell differentiation claim. This source independently supports an ARX role in human endocrine specification; it does not retrospectively change the experiment cited by the 2023 IDA rows.
I read the complete official abstract of PMID:12379852(https://pubmed.ncbi.nlm.nih.gov/12379852/). Mutant embryonic mice show forebrain proliferation and interneuron migration/differentiation defects; human XLAG cases carry loss-of-function variants. Full Methods have not been read. The mouse experimental and human clinical evidence are kept distinct.
For PMID:26633894(https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144100), I read the original human CA1S hESC/ZFN and re-expression Methods, targeted Figures 4–5 Results and Discussion. ARX-deficient endocrine cultures lose most glucagon-positive cells; an examined human XLAG pancreas lacks glucagon and pancreatic-polypeptide cells. Re-expression restores insulin but not glucagon in that protocol. The beta-cell effect in vitro differs from the patient tissue. This supports human pancreatic endocrine specification without claiming universal alpha-cell rescue or a mapped direct target mechanism.
PMID:16301625 is a valid normal record whose complete abstract describes mouse HY antigen/Smcy presentation. Its full assay identity has not been investigated sufficiently to declare an ARX misattribution. The original reference is preserved; the ARX transcription-factor function has independent positive evidence.
PANTHER’s controlled name for PTHR24329 is “HOMEOBOX PROTEIN ARISTALESS”; the separately fetched InterPro metadata displays “Paired Homeobox Transcription Factors.” No complete PAINT topology or target node reconstruction has been inspected. Existing IBA nodes PTN004692309 and PTN001216073 are not rejected on donor counts, and ARX occurring among its own descendant evidence is not circularity.
I inspected all five ARX activity objects in the cached production GO-CAM 69169b7400000113. They connect DNA-binding transcription-factor activity and chromatin with the five intestinal lineage terms. The MF edge cites PMID:16301625, the chromatin edge PMID:22194193 and the lineage edges PMID:37883554. This is a genuine curator model to consider, but it does not resolve the source-specific reading gaps by itself. No missing process assertion is inferred from the model or from necessity alone.
Current official GO pages were read for transcription-factor activity, pancreatic A-cell differentiation, enteroendocrine differentiation and its G-cell child, enzyme binding and alpha-actinin binding. Specific replacement/core terms will be checked before authorship. Broad and narrow DNA-binding assertions can all remain in the original annotation audit, while the synthesized core should avoid redundant parent/child lists.
On 2026-09-28, I read the indexed official reviewed mouse Arx record O35085. Its Gene Ontology table explicitly lists “intestinal type N enteroendocrine cell differentiation” with UniProtKB as the source and two publications. Its function summary links intestinal lineage roles to PMID:22387004 and PMID:22570716. This observation supports the provenance of the existing mouse-to-human electronic N-cell assertion; it is not an independent human neurotensin perturbation result. The human experiments read in PMID:22387004 measured CCK, secretin and preproglucagon, so that paper is not attached as though it directly measured human N cells. The current direct entry renderer returned a JavaScript fallback, while the indexed official record exposed the table and function text. The underlying N-cell experimental panels were not newly read in this donor-record check.
The independent all48 consultation supports 39 ACCEPT, eight UNDECIDED and one same-source enzyme-binding refinement, with no new assertions. The five 2023 human lineage assertions retain their source-specific uncertainty; the mouse N-cell transfer cites the donor-record observation above, not an invented human neurotensin assay. PHF8 association is a cellular co-immunoprecipitation result, not purified binary binding or ARX demethylase activity. The single core combines sequence-specific transcriptional regulation with supported developmental roles. Normal Source54 reference closure is documented below. Original source objects and the absent alternative-product list are preserved.
All three recovered normal records now match their exact archived bytes. PMID:12379852 remains abstract-only; PMID:22387004 and PMID:26633894 have XML full text. Complete abstracts and the bounded Methods/Results scopes recorded in the actual primary assessment were read. No source cache was edited. The 2012 human WA09 organoid experiment supports CCK, Secretin and Preproglucagon transcript outcomes, while the N-cell transfer remains grounded in the separately observed mouse donor annotation. Human somatostatin was not increased after partial knockdown; this does not prove absence of a D-cell role. The 2015 timed rescue increased C-peptide release without restoring glucagon release in that comparison, although a small glucagon transcript increase was reported. Those endpoint qualifications refine prose, not the consulted 39 ACCEPT, eight UNDECIDED and one MODIFY decisions or the single core.
The initial decision counts above remain a historical account. This follow-up accepts the existing I- and L-cell IDA assertions on independent biological support and defers the original 2023 assay provenance to the curator. The resulting totals are 41 ACCEPT, six UNDECIDED and one MODIFY, with all 48 original source objects, the absent product list, the single existing core and no NEW annotations preserved.
I reread the normal full-text PMID:22387004(https://pmc.ncbi.nlm.nih.gov/articles/PMC3322318/) human organoid Methods and Figure 6 Results, plus the endocrine-progenitor mouse Results and relevant Discussion. WA09 cells carried stable ARX shRNA TRCN0000016333 or non-targeting SHC002, were maintained under selection and differentiated to proximal intestinal organoids. At day 68, ARX mRNA was reduced by 50–60%; CCK, secretin and preproglucagon transcripts fell by 60–80%, while CDX2 epithelium and general non-endocrine/pan-endocrine markers were maintained. These are human developmental marker endpoints, not a counted mature-cell census. Conditional deletion in mouse endocrine progenitors separately reduced CCK-, glucagon- and GLP-1-positive cell populations. Together with ARX's established transcription-factor role and the original curated assertions, this supports acceptance of the existing I- and L-cell functions. It does not identify the unread positive assay in the original 2023 reference or reassign its IDA evidence to the 2012 experiment.
The current official I-cell and L-cell definitions concern acquisition of specialized cell features; both are children of enteroendocrine and intestinal epithelial cell differentiation. The proximal human model and transcript endpoints remain explicit limits, especially for mature distal L-cell features. G- and N-cell source-local human evidence remains unresolved, and the D-cell perturbation/direction uncertainty remains unchanged. The proposed organoid experiment separates lineage abundance from hormone expression and compares anatomical contexts rather than presuming that one protocol settles all subtypes.
The full main-text cache of PMID:21653829(https://pmc.ncbi.nlm.nih.gov/articles/PMC3169432/) does not contain the unread Table S2 pair/construct entries. I reread its screen Results: candidate interactions passed secondary yeast testing, and 44 of 52 sampled pairs validated by mammalian GST affinity co-purification. These aggregate results neither identify whether either ARX pair was sampled nor establish that either pair is false. Both original ARX–ACTN1 and ARX–PICK1 assertions remain UNDECIDED. No specific actinin-binding or adaptor activity is invented. Under the user's ActionEnum and source-access rule, genericity alone is not biological evidence that an experimental assertion is unlikely correct; the lower-priority generic-binding removal recommendation does not override this instruction.
The authoritative local PANTHER ontology identifies PTHR24329 as HOMEOBOX PROTEIN ARISTALESS. The InterPro-fetched metadata for this PANTHER entry is integrated with IPR050649 and displays “Paired Homeobox Transcription Factors”; its descriptive metadata carries LLM/unreviewed flags. That display text must not be substituted for PANTHER's own controlled family name. No new family identifier or PAINT node-placement claim is made.
I enumerated the cached GO-CAM 69169b7400000113 again. It has exactly five ARX/Q96QS3 activity objects, attached to the G-, I-, L-, N- and D-cell terms. Its additional enterochromaffin differentiation node (GO:7770020, activity 69169b7400000164) is enabled by PAX4/O43316, not ARX. Thus the earlier count of five ARX objects was correct, but the notes needed to distinguish that count from the model's broader endocrine content. The curator model is considered evidence context; it neither supplies the unread experimental supplement nor justifies a new ARX enterochromaffin assertion.