GABRA1 review notes

Manual review and native reconciliation — 2026-11-01

All 66 genuine human P14867 contexts have individual reviewed judgments: 47 ACCEPT, five KEEP_AS_NON_CORE, 11 MODIFY and three UNDECIDED. One core describes alpha1 contribution to heteropentameric GABA-gated chloride channel activity and its directly supported signaling/transport roles. No NEW annotation is added. The source guide records the 36 manual reference assessments, source-specific construct and access limits, actual PAINT placements and Reactome target membership.

The unresolved contexts concern one specific alpha1 spine panel and two vesicle-membrane assertions. The rat P62813 source chain explicitly identifies PMID25172774, but its abstract does not resolve the alpha1-specific assay. Extrasynaptic signaling depends on receptor composition; the positive co-culture synapse-assembly contribution remains non-core. General positive terms are refined through the 11 verified typed paths without asserting biological falsity.

Genuine seeded native acquisition produced 66 untouched annotations and all 16 export columns exactly matching the retained official inputs. The canonical precursor is 456 residues with mature-chain processing at 28–456; no alternative natural products are declared. Raw 0/1/2 contributes_to qualifiers remain exact. Raw 6/native 1 contains a single conjunction of three atoms: part_of GO:0051932, has_input CHEBI:17996 and has_output CHEBI:17996. These atoms were omitted by the parser and are restored literally with verified BFO/RO predicates; original raw and parsed objects remain separate. This is not a biological NEW.

The 29 sources comprise six unchanged existing objects and 23 missing-only native acquisitions. Native availability is recorded independently of the actual manual reading scope. The one 13-word core quotation retains the native cache's line breaks and is an exact substring. All prior lane work, branch tips and Orca links remain preserved; no provider or new environment was used. No pre-existing GABRA1 journal, review or quote archive required migration.

The accepted science is transferred. Native CREATE history and all target checks completed successfully.

Executed checks — 2026-11-01

The genuine CREATE session is 2026-11-01T224938Z-codex-52cafa. Target default validation passed with 18 nonblocking suggestions for direct supporting excerpts on accepted PMID-backed rows. The manually read source contexts and full reasons remain governing; no additional quotation was invented to silence those suggestions. Native row 43 now includes faithful structured term-scope metadata for the verified PTN008360627 ancestry, preserving its exact action and reason. Strict GOA conservation matches all 66 contexts, and native status is DRAFT.

History validation, source and prior-work conservation, scoped whitespace and private HTML rendering passed. Native term validation added exactly two ontology cache rows, GO:0022851 and GO:1902711, with the complete preimage and exact added-row comparison retained. All existing ontology rows, all six immutable source objects and all prior lane work remain exact. No provider or broad test suite was run. The old diagnostic attempts remain private and were resumed only from the incomplete stage.

The native Reactome977443 cache ends with one extra blank line; its exact acquired bytes are retained. Authored content and the ontology companion pass scoped whitespace checks. This source-format exception does not change its biology or source identity.

Biological evidence and review follow-up — 2026-11-01

Alpha1 contributes to the ligand-recognition interfaces and shared pore of GABA-A heteropentamers. The human cloning study establishes GABA-gated chloride channels, and later human structural and functional studies explain receptor assembly and gating PMID:2465923(https://pubmed.ncbi.nlm.nih.gov/2465923/), PMID:29950725(https://pmc.ncbi.nlm.nih.gov/articles/PMC6220708/). The full-length human nanodisc study reports PMID:30602789, "We isolated the full-length human α1β3γ2L receptor". Its ligand-binding and electrophysiological measurements support receptor function alongside the desensitized structural state. Tags, megabodies and engineered loop replacements are assay constructs, not additional natural GABRA1 products.

In the neuron–HEK co-culture preparation, GABA-evoked currents are pharmacologically consistent with alpha1-containing receptors: PMID:23909897, "This response was enhanced by zolpidem". Spontaneous and evoked currents show postsynaptic transmission, while receptor-dependent contacts support a contextual structural contribution to inhibitory synapse assembly. The latter is non-core and does not establish a universal alpha1-only organizing mechanism. The JoVE protocol includes surface staining and contact assays but reuses earlier figures, so it is not independent replication of every earlier measurement PMID:25489750(https://pmc.ncbi.nlm.nih.gov/articles/PMC4354098/).

Composition changes receptor properties. The alpha1/beta3 preparation contains PMID:35140402, "two α1 subunits and three β3 subunits", with engineered constructs compared against wild-type recordings. Mouse alpha1/delta tonic-current evidence and alpha1/beta2/delta oocyte experiments support an extrasynaptic context without making every alpha1 receptor extrasynaptic PMID:17159992(https://pubmed.ncbi.nlm.nih.gov/17159992/), PMID:18204487(https://pubmed.ncbi.nlm.nih.gov/18204487/). Native epilepsy-surgery preparations also establish diverse human alpha1-containing complexes; selected Methods/Results were read, while unresolved subunit mixtures and tentative accessory assignments remain qualified PMID:39843743(https://pubmed.ncbi.nlm.nih.gov/39843743/).

The spine and cytoplasmic-vesicle assertions remain unresolved at their specific source scope. Alpha1 surface biotinylation does not by itself place the receptor in a spine; the inspected spine passage concerns a PSD95 control PMID:25025157(https://pmc.ncbi.nlm.nih.gov/articles/PMC4099074/). The rat transport reference identifies gamma2-containing receptor trafficking, but the unrecovered full text does not establish the alpha1-specific vesicle panel PMID:25172774(https://pubmed.ncbi.nlm.nih.gov/25172774/). Neither uncertainty warrants removal. The source guide retains the detailed construct, ontology, phylogenetic and access record.

This follow-up preserves all 66 actions, original machine fields, three extension atoms, product and core. It adds nine short primary-source anchors, with reference-only reuse where repeating an excerpt would exceed the per-paper limit. The new quotation ledger records exact cache offsets, hashes and occurrence counts without duplicating quotation text. Earlier journal entries describe the initial submission and remain unchanged. Native EDIT history and scoped checks have completed for this amendment.

Follow-up checks — 2026-11-01

The native EDIT session is 2026-11-01T232321Z-codex-9b9bc6. Target default validation passed with 10 optional suggestions for additional excerpts, reduced from 18 at the initial submission. Reference-only reuse keeps repeated quotations within the per-paper budget; those suggestions do not identify an unsupported action. Strict GOA conservation passed for all 66 contexts, status remains DRAFT, and history validation, source conservation, scoped whitespace and private rendering passed. The four approved drafts changed only in this factual completion wording and evidence outcomes. All 29 sources, the existing ontology companion and prior CREATE record remain exact. No provider or broad test suite was run.

Receptor assembly and source-relation clarification — 2026-11-02

Alpha1 supplies ligand-contact and pore-forming elements within GABA-A receptor assemblies. Human alpha1-containing receptor expression, channel measurements and structural work support that molecular role PMID:2465923(https://pubmed.ncbi.nlm.nih.gov/2465923/), PMID:29950725(https://pmc.ncbi.nlm.nih.gov/articles/PMC6220708/), PMID:30602789(https://pmc.ncbi.nlm.nih.gov/articles/PMC6364807/). These measurements do not demonstrate an autonomous isolated-alpha1 channel. The ten accepted molecular-function reasons now make that distinction explicit while preserving their original enables relations; the core continues to express contributes_to_molecular_function in the receptor complex.

The source guide explains this interpretation against the official GO relation guidance. No upstream WRONG_QUALIFIER finding is inferred merely from assembly membership. This follow-up changes no action, original machine field, extension, product, core, reference assessment or supporting quotation. Previous journal entries and the immutable source caches remain unchanged. Native EDIT history and scoped checks have completed for this amendment.

Clarification checks — 2026-11-02

The native EDIT session is 2026-11-02T013830Z-codex-fbd4bb. Default validation passed with 10 optional suggestions for additional excerpts; strict GOA conservation passed for all 66 contexts and status remains DRAFT. History validation, source conservation, scoped whitespace and private rendering passed. All 29 sources, all 13 quotation occurrences, the ontology companion and both earlier history records remain exact. No provider or broad local test suite was run.