EDAR recognizes EDA-A1 and transmits a cytokine signal through a membrane receptor with an intracellular death domain. The death-domain name does not make cell death the primary physiological function. The central evidence supports developmental NF-kappaB signaling; JNK and overexpression-associated death require their experimental context.
PMID:10431241 established the human sequence, expression and disease association. Its receptor–ligand interpretation was a hypothesis at that time. Later positive studies support the modern receptor classification. PMID:12270937 concerns XEDAR experiments but explicitly states the prior EDAR disease and ligand findings; its EDAR TAS is retained without treating XEDAR assays as EDAR assays.
The complete PMID:42308199 notice was read alongside the relevant PMID:27144394 Methods, Results and Fig. 1C caption. The original article remains a preserved source with invalid status. Removing its unreliable source-specific support does not remove the independently verified EDA–EDAR interaction.
The human extracellular-domain screen in PMID:32822567 used multivalent fusion reagents. Its EDAR pairs were recovered from the actual source spreadsheets, not inferred from the main paper's network narrative. The selected EDAR ECD is 27–187, EDA is 63–391 and LILRB1 is 24–461. Binding in both orientations and controlled triplicate retests support the positive pair assertions. The study does not establish physiological LILRB1 activation by EDAR, and EDAR has no entry in the inspected SPR statistics workbook.
Mouse apical localization is a conserved polarized-cell context rather than a universal surface distribution. Current MGI records preserve the donor's positive plasma-membrane and apical IDAs. The source abstract describes lumen/acinar localization, but the unavailable full microscopy methods and images were not reconstructed. The existing PMID:19619491 cache retains its original full-text flag; actual content supplies Introduction and Discussion, with detailed Methods and Results absent.
The literal PAINT nodes, complete target path, actual ARBA conditions and exact Reactome component joins are reproducible from saved inputs. The source tree and current electronic mappings do not replace direct target evidence or imply identical ligand specificity across TNFR-family members.
The configured Falcon research attempt failed with authentication HTTP 403 and its fallback failed with HTTP 401/insufficient quota. These failures are retained; no generated provider report was fabricated. Literature and database examination was performed manually using the documented source routes.
All 23 imported source assertions retain their original term, evidence, reference, partner and qualifier fields. The review has 8 ACCEPT, 10 MODIFY, 4 KEEP_AS_NON_CORE and one source-specific REMOVE; no NEW annotation is proposed. The removed assertion is the binding result from the retracted PMID:27144394. Its source remains visible, while independently supported EDA–EDAR interactions remain positive.
The source guide distinguishes cache availability from separately recovered originals. The executed source audit supplies primary spreadsheet records, sequence checks and literal database joins. The local guide supplies locators, not independent experimental evidence. Publication caches retain their original bytes and availability flags.
The ClinGen project policy retains supported generic binding when a specific replacement is not established. The non-retracted EDAR binding assertions have independently justified cytokine or signaling-receptor partner classes; no claim is removed simply for being generic or lacking a demonstrated native pathway. Receptor binding is distinct from receptor agonism.
The official record describes 448- and 480-residue products. The longer product replaces Ala219 with a 33-residue segment in the cytoplasmic region. Signal-peptide processing does not define a third splice product. Binding experiments using the shared extracellular region do not demonstrate equivalent trafficking or signaling by both complete natural products.
The two broad epidermis-development assertions are now refined to hair follicle placode formation
(GO:0060789). The separately recovered PMID:19619491 original
shows that mouse Edar-null/downless embryos retain early Wnt prepatterns but fail to refine placode
boundaries and maintain focal Wnt activity through E15.5. Constitutive EDAR signaling does not bypass
Wnt. These experiments establish participation in primary hair placode formation; the human genetics
in PMID:10431241 corroborates the conserved appendage role without supplying a human placode assay.
The original TAS in PMID:12270937 remains an EDAR background statement, separate from that paper's
new XEDAR experiments. The current ontology places GO:0060789 beneath epidermis development,
hair follicle development and ectodermal placode development; only the informative child is retained.
The earlier note that the normal PMID:19619491 cache omits Methods and Results remains an accurate
description of that preserved cache, but it no longer describes overall source access. The separate
complete original supplies the Methods and Results used here. Likewise, separately accessed originals
for PMID:10431241, PMID:11035039 and PMID:12270937 support reference-level availability while their
normal abstract-only caches remain unchanged. The source guide gives original
URLs, section locators and the limits of the selected text reads; no figure-pixel inspection is claimed.
EDAR–LILRB1 remains a signaling-receptor-binding refinement. Sequence-authenticated human extracellular
reagents gave control-normalized positive measurements in both orientations and triplicate retests.
That physical-binding evidence plus the independently established receptor class supports the binding
term without requiring receptor agonism or SPR. The absent EDAR SPR entry limits affinity and native
physiology claims; it does not negate the controlled positive screen. This evidence is distinct from
the binding panel specifically questioned in the retracted PMID:27144394.
The complete abstract of PMID:11780064(https://pubmed.ncbi.nlm.nih.gov/11780064/) corroborates the
Edar–Edaradd death-domain association and downstream signaling mechanism in the mouse discovery
context, with human EDARADD disease genetics. It does not establish uninspected human constructs or
a purified binary assay. Its authentic normal cache and reference-only core citation have been added.
The receptor mechanism, both product descriptions and all 23 imported source dictionaries are unchanged.
The resulting actions are 8 ACCEPT, 12 MODIFY, 2 KEEP_AS_NON_CORE and one source-specific REMOVE;
the earlier action-count paragraph records the preceding assessment. No NEW annotation or new
publication excerpt is introduced. Evidence is provided through source references and explicit locators.
The portable replay now uses explicit input-validation errors that remain active under optimized
Python execution. Normal and optimized executions produced the same saved results, and an altered
input was rejected. The 21-input archive, source manifest and derived result bytes remain unchanged.
The initial action-count paragraph above records the assessment before the placode refinements. The current assessment is 8 ACCEPT, 12 MODIFY, 2 KEEP_AS_NON_CORE and one source-specific REMOVE across the same 23 imported assertions. There are no NEW annotations. The later placode follow-up supersedes the initial counts; the earlier notes remain part of the evidence history.
For PMID:10431241, PMID:11035039 and PMID:12270937, the normal publication caches remain abstract-only. Selected original sections were accessed separately, as documented in the reference assessments and the source guide. Their optional reference-level availability flags are omitted to avoid compressing these two distinct access states into a single Boolean. This omission does not withdraw the documented original reads or change the cache flags. PMID:11039935 remains supported at abstract scope, with the full original unavailable.
Support for ligand recognition and downstream signaling remains reference-only. PMID:11035039 supplies the separately inspected ligand-binding and NF-kappaB experiments at their stated construct and conditioned-medium scope; PMID:11039935 supplies the positive abstract-level ligand specificity. The source guide links the original records and identifies the inspected sections. No passage is presented as a quotation or substituted for an unavailable cache passage.
The two hair-placode refinements describe the process resolved in the mouse experiments of PMID:19619491. They do not exhaustively encode the broader tooth and sweat-gland roles described in the biological summary, and they do not add unassayed organ-specific steps. The source identities, evidence codes, actions, receptor core and both natural-product descriptions remain unchanged.