The ten source annotation objects are retained exactly. The review contains four KEEP_AS_NON_CORE, five MODIFY and one UNDECIDED decisions, one integrated protein-transport core and no NEW annotations. The official human Q96F81 product is 1524 residues; UniProt does not list natural alternative products. RefSeq and Ensembl cross-references, engineered deletions, NNN substitutions and artificial protease sites are not used to invent isoforms.
The broad peptide-transport assertion is refined to directly performed protein secretion. The secretion-regulation assertion is also recast as that performed export step: the two GO terms are linked through regulation, not an is_a relationship, so this is a mechanistic choice rather than a claimed ontology-child refinement. Broad membrane assertions become plasma membrane using human functional evidence. The molecular-carrier assertion becomes protein transporter activity because DISP1 remains membrane-associated while cargo is released. The integrated core does not assign bacterial LolCDE function or transit of the SHH protein across a bilayer.
The human evidence distinguishes transport-active wild-type constructs from the inactive NNN structural material. Mouse sodium-coupling experiments inform mechanism by homology; they do not establish a separate human ion-transport function or a precise human coupling stoichiometry. Cleavage by Furin or an experimental protease activates DISP1 but is not a DISP1 protease activity. See the source guide for exact original locators and experimental boundaries.
Both imported generic-binding assertions are retained as supported, non-core interactions. This follows the explicit ClinGen Mendelian project instruction: a supported interaction is not removed solely because its GO term is generic. LAPTM5 and WFS1 do not have a verified partner class that supplies a narrower molecular-function assertion here. No endogenous complex, stoichiometry or Hedgehog role is inferred from the heterologous interaction assays.
PAINT inheritance was traced to actual IBD nodes and target descent. The small seed list is not a weakness and self-inclusion in a donor list is not circularity. Canine basolateral localization remains a supported polarized-cell context rather than an exclusive human location. The diaphragm annotation remains unresolved after reading the original candidate-gene study: human mosaicism and mouse expression do not resolve a direct DISP1 contribution or the reported variant's effect. No experimental annotation is removed and no clinical pathogenicity determination is made.
The ordinary Falcon research attempt failed authentication and its configured Perplexity fallback failed quota/authentication. No provider report was fabricated. Genuine publication retrieval and independent original reading supply the documented evidence. Existing shared publication and family files are preserved; the larger normal 25416956 XML extraction is research evidence only, while the protected main cache remains unchanged. The 32814053 protected cache remains abstract-only despite separately recovered original Methods.
The existing GO:0007224 annotation is now ACCEPT and is represented in the single export core. This supersedes its earlier non-core classification: ligand delivery is DISP1's central contribution to Hedgehog signaling. The GO definition names events following Smoothened activation, while curated annotations also include ligand-side participants such as SHH. The valid DISP1 PAINT assertion, zebrafish soluble-ShhN rescue (PMID:19948063(https://pmc.ncbi.nlm.nih.gov/articles/PMC2791760/), craniofacial Results), and human DISP1-dependent release (PMID:34845226(https://pmc.ncbi.nlm.nih.gov/articles/PMC8630017/), Figures 1–4 and release Methods) jointly support the performed pathway step. No lateral positive-regulation replacement or NEW process is added. The core substrate now identifies human SHH as UniProtKB:Q15465; the cargo is its lipid-modified N-terminal signaling product, not the unprocessed precursor or C-terminal processing domain.
The biological summary now connects ligand release to embryonic brain and craniofacial patterning and to the human midline-malformation spectrum. PMID:19184110(https://pmc.ncbi.nlm.nih.gov/articles/PMC2774849/), functional-analysis Methods, truncation Results and family descriptions, reports affected daughters with microform craniofacial findings and normal brain imaging, each inheriting a truncation from a clinically unaffected mother. Functional tests modeled the human changes in murine Disp1 in Drosophila cells; wild-type human DISP1 did not function in that assay. The source-limited cohort findings for PMID:38529886(https://doi.org/10.1016/j.gim.2024.101126) are recorded in the review's reference entry. Its full original was not recovered, and the abstract-only flag remains unchanged; no uniform inheritance or severity is inferred.
All ten imported source objects and the other nine review decisions are unchanged. The action totals are one ACCEPT, three KEEP_AS_NON_CORE, five MODIFY and one UNDECIDED. The single core and existing three quotes are retained, with the pathway and cargo fields made explicit. Two genuine normal publication caches are added unchanged; no provider output, new isoform, new annotation or additional quotation is introduced.