GABRB3

Summary: The broad signaling-receptor assignment can be specified as GABA-A receptor activity.

Reason: The InterPro mapping identifies a neurotransmitter-gated receptor subunit. Human beta3-containing receptors directly bind/respond to GABA and form the chloride-conducting pore. GABA-A receptor activity is the informative supported receptor class, understood at the assembled-complex level; ordinary upstream relationship text is retained literally.

Proposed replacements: GABA-A receptor activity

Summary: The actual PAINT placement supports inherited GABA-A receptor activity.

Reason: Human AN2283/PTN002498409 descends from the retained AN2107/PTN008566841 Eumetazoa IBD carrying this activity, with no target-path loss assertion. The donor mapping and sequence match were checked. Human structural and functional evidence agrees; donor number is not used to weaken this evolutionary assertion.

Summary: The alpha5-receptor source supports a contextual GABA-A receptor assignment.

Reason: PMID:14993607 studies tonic inhibition in mouse hippocampal CA1 neurons. Its exact beta3 assay was not fully recovered, so the receptor-level inference is corroborated by directly studied human beta3-containing receptors. Preserve both literal incoming extension atoms, including the GABAergic context and chloride output (CHEBI:17996); neither is rewritten as a new assay claim.

Summary: Human alpha1/beta3/gamma2 receptor structures and currents directly support receptor activity.

Reason: PMID:30602789 examines full-length human subunits in nanodiscs with electrophysiological and ligand-binding controls. Beta3 participates in the ligand interfaces and channel architecture. The resolved desensitized pore and an incompletely identified density in one pocket do not negate the separately measured receptor currents.

Summary: Electronic receptor-family mappings correctly identify GABA-A receptor activity.

Reason: The incoming InterPro/UniProt mappings are consistent with human beta3-containing GABA-A receptor structures and currents. Beta3 supplies receptor interfaces and pore structure within a pentamer. This is a functional subunit assignment, not a claim that every reported homomer responds to physiological GABA concentrations.

Summary: Wild-type beta3 participates in functional GABA-A receptors in the G32R study.

Reason: PMID:22303015 reports wild-type and G32R beta3-containing heteromers, surface assays and GABA-evoked currents. Selected accessible figure captions distinguish wild-type activity from reduced mutant gating. Full cloning Methods were unavailable during the earlier selected reading. They are now present in the native full-text cache but were not newly inspected, so no current UniProt splice-product suffix is assigned from the host cell alone.

Summary: Rat ortholog transfer supports GABA-A receptor activity.

Reason: The retained P63079 ortholog has the beta3 receptor architecture. Independent human alpha1/beta3/gamma2 studies resolve receptor subunits and GABA-gated currents, supporting the same functional contribution. The incoming ISS source and relationship are preserved; no monomer sufficiency or universal stoichiometry is inferred.

Summary: The cloned human beta3 subunit belongs to the GABA-A receptor.

Reason: PMID:1664410 establishes human beta3 cDNA identity and chromosomal mapping; the original TAS functional assignment is supported independently by later human beta3-containing receptor structures and electrophysiology. The cloning abstract itself is not described as a complete physiological receptor assay.

Summary: The transferred receptor-binding term exceeds the receptor-ligand autoradiography evidence.

Reason: The actual mouse P63080 source chain reaches PMID:12672542, whose inspected abstract reports ligand autoradiography after Gabrb3 deletion. It measures ligand-binding sites on receptor preparations, not beta3 binding to a signaling receptor. Independent human structures establish beta3 contacts with companion receptor subunits, but intra-complex contact alone does not establish the specific signaling-receptor-binding function. Mark this propagated functional interpretation as over-annotated while preserving the positive receptor biology and the uninspected full-text limit; no universal exclusion of receptor-associated proteins or donor-curator error is asserted.

Summary: The general monoatomic-ion channel term can be refined to GABA-gated chloride channel activity.

Reason: The electronic channel mapping is biologically sound, but human beta3-containing receptors directly conduct chloride in response to GABA. The specific channel term captures the demonstrated contribution without inventing a separate channel activity of a beta3 monomer.

Proposed replacements: GABA-gated chloride ion channel activity

Summary: The extracellular-ligand-gated channel assignment can be specified by its GABA ligand and chloride conductance.

Reason: Human receptor measurements and structures establish GABA-gated chloride channel activity for beta3-containing assemblies. The broad ligand-gated mapping is retained as the original object and refined to the supported specific activity.

Proposed replacements: GABA-gated chloride ion channel activity

Summary: The chloride-channel mapping can be refined to the established GABA-gated activity.

Reason: The ARBA assignment is consistent with the transmembrane pore, but omits the receptor-gating mechanism directly established for beta3-containing human heteromers. Use the existing GABA-gated chloride channel term while preserving the original evidence and reference.

Proposed replacements: GABA-gated chloride ion channel activity

Summary: Histamine-evoked oocyte currents support surface insertion of beta3-containing experimental channels.

Reason: PMID:18281286 reports beta3 homomer currents in Xenopus oocytes. This is a positive functional surface-membrane context, although the abstract does not identify the cloned species. Independent human beta3 heteromer surface assays establish the same general location; physiological native homopentamers are not inferred.

Summary: The epilepsy-variant study supports surface functioning of beta3-containing receptors.

Reason: PMID:18514161 describes beta3 N-terminal variants and heteromeric GABA currents in HEK293T cells. Selected Methods distinguish full receptor subunits from a separately truncated translation/translocation construct. Glycosylation or mutant defects are not generalized to all natural products.

Summary: Human alpha1/beta3 receptor membrane preparations support plasma-membrane receptor expression.

Reason: PMID:22243422 uses stably expressed human receptors, purified membrane protein and radioligand/photoaffinity assays. Its historical beta3 variant terminology and glycosylated bands are not automatically equated with present-day UniProt product suffixes. The membrane context agrees with independent human surface measurements.

Summary: The engineered beta3 homomer study supports membrane expression of the experimental receptor.

Reason: PMID:24909990 measures surface-expressed beta3 constructs and resolves a membrane-channel architecture. The intracellular-loop replacement, tag and engineered homopentamer are explicit experimental limits. Independent wild-type human heteromer data corroborate the general plasma-membrane location.

Summary: The actual broad PAINT membrane placement is supported.

Reason: Human beta3 descends from AN7/PTN001054635 carrying the plasma-membrane IBD. The incoming dated donor set is a strict subset of the later retained IBD donor set; that version difference is recorded rather than forced equal. Target self-donor inclusion is legitimate, and extensive direct surface-receptor evidence agrees.

Summary: The human beta3 mutation study directly measures receptor surface expression.

Reason: PMID:26950270 quantifies expressed beta3 with a beta2/3-reactive antibody in controlled transfections, with mock subtraction. The reagent itself is not intrinsically beta3-specific. Several mutants alter gating without reducing surface abundance, so no uniform trafficking deficit is inferred. These positive assays establish the membrane location of the tested receptors.

Summary: The electronic plasma-membrane assignment is correct.

Reason: Human beta3-containing receptors are surface expressed and conduct extracellular-ligand-gated currents. The location is broadly supported independently of the particular electronic mapping, with intracellular biosynthetic and transport pools not excluded.

Summary: The G32R study includes positive wild-type receptor surface expression.

Reason: PMID:22303015 compares wild-type and mutant beta3-containing surface receptors and channel activity. Preserve this positive plasma-membrane context while keeping mutant effects, beta3-alone preparations and heteromeric conditions distinct.

Summary: The original human cloning source is consistent with the established plasma-membrane receptor location.

Reason: PMID:1664410 identifies the beta3 receptor subunit. Its TAS membrane annotation is independently corroborated by direct later human surface assays and current recordings, without attributing those later assays to the cloning abstract.

Summary: The Reactome chloride-influx reaction places beta3 within the membrane receptor set.

Reason: The actual official model traces R-HSA-975340 through catalyst975314, GABA-bound complex975268, receptor set5340318, heteropentamer5357502 and beta-subunit set975288 to GABRB3 entity975244. That entity explicitly references human UniProt P28472 residues 26–473 in plasma membrane. This supports the modeled membrane receptor location, corroborated by human surface assays; set membership does not establish every combinatorial pentamer as an observed native assembly.

Summary: The general ion-transport assertion can be refined to chloride transport.

Reason: Beta3 supplies part of the GABA-A receptor pore through which chloride moves. The electronic ion-transport claim is sound but lacks the transported ion established by human receptor electrophysiology. Chloride transport is already present in the incoming annotations and is a supported refinement.

Proposed replacements: chloride transmembrane transport

Summary: Beta3-containing receptors perform signal transduction at the receiving cell.

Reason: PMID:1664410 identifies the original human beta3 clone; it is not represented as a later receptor-gating assay. Independent human receptor measurements establish that beta3-containing assemblies receive GABA and convert ligand binding into chloride conductance, changing the receiving cell's electrical state. This supports the original signal-transduction assertion. The official QuickGO is_a/part_of check on 2026-11-04 returns GO:0007214 under GO:0007267 cell-cell signaling, with no GO:0007165 in the complete returned ancestor set and zero paths to it. The source-evidence ontology_relationship_checks preserve those actual responses and the positive path. GABA signaling is separately represented, but it does not hierarchically entail this independently supported receiving-cell claim in the queried ontology; retain the original assertion.

Summary: Human alpha1/beta3/gamma2 experiments directly support GABA signaling.

Reason: PMID:30602789 combines actual GABA-response measurements with a full-length human receptor structure. Beta3 executes part of the receptor/channel step, while assembly composition and structural state are retained as experimental context.

Summary: Human beta3-containing receptor assemblies directly transduce GABA.

Reason: PMID:35355020 resolves and functionally examines human alpha4/beta3/delta and related assemblies. Actual recordings distinguish GABA responses from histamine activation and mixed receptor populations. Beta3 participation is supported without assigning a single stoichiometry to every native receptor.

Summary: Beta3 is a receptor component executing GABA signaling.

Reason: The curated electronic mapping matches direct human beta3-containing receptor responses to GABA. The product contributes to ligand recognition, gating and conductance, rather than being merely a downstream expression marker. Synaptic and extrasynaptic contexts depend on companion subunits.

Summary: The beta3 mutation study directly measures the receptor step in GABA signaling.

Reason: PMID:26950270 compares GABA responses in wild-type and variant beta3-containing human receptors. That is direct execution of the signaling step, with diverse mutant kinetic effects. No single mutant phenotype is generalized to every beta3-containing receptor.

Summary: The receptor architecture review supports beta3 participation in GABA signaling.

Reason: PMID:28528665 is a synthesis source, not a new beta3-specific experiment. Its general receptor assertion is independently supported by full-length human beta3 heteromer structural and functional studies, so the biological claim is retained with the NAS provenance unchanged.

Summary: The engineered alpha5/beta3 structure supports the receptor contribution to GABA signaling.

Reason: PMID:30140029 studies an engineered human alpha5/beta3 assembly with shortened intracellular loops and a beta3-directed nanobody. Its unusual one-alpha/four-beta stoichiometry and structural interpretation are not generalized to native receptors. Independent human beta3-containing receptor currents support the underlying GABA signaling role.

Summary: The pharmacology review supports the established GABA signaling role.

Reason: PMID:34417930 provides receptor pharmacology context. The NAS assertion agrees with direct human beta3-containing receptor measurements; it is not treated as a new physiological beta3 experiment or evidence for every natural product.

Summary: Alpha1/beta3 receptor experiments establish signaling despite low opening efficacy.

Reason: PMID:35140402 compares engineered structural constructs with wild-type human alpha1/beta3 receptors and measures GABA currents. The predominantly closed structural pore is compatible with the measured lower opening probability. The BRIL insertion and loop replacements are not mapped onto natural splice products.

Summary: The source also supports the broader GABA signaling synthesis.

Reason: PMID:35355020 connects assembly-dependent GABA responses to receptor signaling. The NAS row is retained separately from its IDA row, with the same underlying biological judgment. Simulation-derived receptor distributions and physiological histamine speculation are not presented as observed native compositions.

Summary: The general chemical-transmission assignment can be refined to GABAergic synaptic transmission.

Reason: Beta3 is a subunit of GABA-A receptors mediating postsynaptic GABA responses. The general electronic mapping can be made informative using the already asserted GABAergic transmission term, supported by mouse inhibitory-current rescue and human receptor studies.

Proposed replacements: synaptic transmission, GABAergic

Summary: Cell-surface exposure is an established property of beta3-containing receptors.

Reason: The incoming GO_REF:0000107 assertion is an Ensembl ortholog transfer from mouse P63080, not a UniProt subcellular-location vocabulary mapping. Independent human beta3 surface-flow assays and extracellular receptor architecture support cell-surface exposure. This does not imply identical surface delivery for every natural product or assembly.

Summary: The nonspecific membrane annotation can be refined to plasma membrane.

Reason: The protein has membrane-spanning pore structure, and direct human surface assays establish plasma-membrane localization. The generic electronic term is sound but less informative. This refinement does not deny intracellular biosynthetic or trafficking pools.

Proposed replacements: plasma membrane

Summary: Full-length human beta3 contributes to the structurally and functionally characterized GABA channel.

Reason: PMID:30602789 combines nanodisc structures with actual electrophysiological controls. Beta3 contributes a pore-lining helix and neurotransmitter interfaces. A static desensitized structural state is distinguished from the ensemble of channel states measured electrically.

Summary: The epsilon-subunit source supplies receptor context; independent beta3 studies establish the channel contribution.

Reason: The authentic PMID:9039914 abstract identifies a human epsilon subunit assembling with alpha and beta subunits and altering anaesthetic sensitivity. It does not identify the beta3 clone or an expression method. Preserve this original IDA and its unresolved partner/construct limit; independent human beta3-containing receptor recordings support ACCEPT for the biological GABA-gated chloride-channel claim.

Summary: Beta3 contributes to the GABA-gated chloride channel assembled from receptor subunits.

Reason: The explicit contributes_to flag correctly states a subunit contribution. Mouse P63080 is the literal ortholog source; independently, human beta3-containing heteromers have GABA-evoked chloride currents and beta3 pore-lining helices. This does not assert that an isolated natural beta3 monomer is a complete GABA receptor.

Summary: The G32R study demonstrates wild-type beta3-containing GABA-gated channels.

Reason: PMID:22303015 contrasts wild-type and mutant alpha1/beta3/gamma2L currents and channel openings. Mutant gating defects are evidence about a functioning wild-type receptor, not evidence that all beta3 products lack activity. Accessible abstract/captions support the contribution; exact current-product cloning identity remains unresolved.

Summary: Human beta3-containing receptors directly conduct GABA-activated chloride currents.

Reason: PMID:26950270 compares wild-type and disease-associated beta3 constructs in HEK293T heteromers with whole-cell and single-channel recordings. The chloride solutions, wild-type channel conductance and current controls support the function. Mutant phenotypes vary and do not justify a universal surface-trafficking defect or product-specific annotation.

Summary: The mouse beta3 ortholog supports the same GABA-gated channel contribution.

Reason: The ISS assertion is consistent with mouse Gabrb3-dependent inhibitory currents and with direct human beta3 heteromer electrophysiology. Retain the functional claim at the assembled receptor level, without converting an ortholog source into a human tissue assay.

Summary: The matching electronic vesicle-membrane mapping has the same evidence gap.

Reason: The UniProt location mapping does not resolve the target-specific beta3 vesicle evidence missing from the accessible PMID:25172774 source. Apply the same UNDECIDED judgment as the rat ISS row rather than treating two mappings as independent confirmation of the unresolved claim.

Summary: The rat-source cytoplasmic-vesicle membrane assignment remains unresolved.

Reason: Rat P63079 UniProt cites PMID:25172774 for vesicular transport. The accessible abstract foregrounds gamma2/KIF21B, and the exact beta3-containing vesicle assay was not recovered. Rat postsynaptic membrane labeling is not vesicle evidence. Preserve uncertainty without claiming a paralog misattribution from the title.

Summary: The cited negative regulation is performed by receptor accessory proteins, not established for beta3 itself.

Reason: The complete main text of original review PMID:33234346 was read; it explicitly assigns reduced forward trafficking and GABAergic transmission to CLPTM1, and altered receptor-current decay to SHISA7. Beta3-containing receptors are the regulated complexes. GO:0032229 describes reducing GABAergic transmission, not the ordinary inhibitory effect of transmitting through a GABA receptor. This NAS attribution is therefore not supported by the actual executor described in the source; the original citation and context remain preserved.

Summary: The general transmembrane ion-transport term can be specified as chloride transport.

Reason: Direct beta3-containing human receptor recordings establish chloride movement through the receptor pore. Preserve the broad incoming electronic row and use the ion-specific transport term as its informative replacement.

Proposed replacements: chloride transmembrane transport

Summary: Beta3 participates in experimentally supported chloride channel complexes.

Reason: PMID:9014148 expresses rat alpha4/beta3/gamma2 receptors in HEK293 cells and explicitly recognizes heterogeneous assemblies. This is not a human clone experiment. Independent human beta3 structures and functional recordings establish chloride-conducting receptor complexes, supporting the original chloride-channel-complex claim without asserting a unique native stoichiometry. PMID:35355020 explicitly measures GABA-evoked chloride currents in the human alpha4/beta3/delta expression system. The official QuickGO is_a/part_of check on 2026-11-04 places GO:1902711 under GO:1902710 and GO:0043235 receptor complex; its complete returned ancestor set omits GO:0034707 and the requested path response is empty. The source-evidence ontology_relationship_checks preserve both actual responses and the positive path. GABA-A receptor complex is independently annotated, so preserve both supported assertions rather than invent a hierarchical replacement.

Summary: Beta3 can self-associate in experimentally expressed homomeric channels.

Reason: PMID:16537435 directly studies human beta3 homopentamers in Sf9 cells, including cysteine substitutions and oxidation-dependent cross-linking. PMID:24909990 independently resolves beta3-beta3 interfaces. This is a reproducible secondary assembly property, retained as non-core rather than an assertion that physiological beta3 homopentamers exist. It is not confined to homomer experiments: PMID:35355020 resolves beta3-beta3 interfaces in recombinant alpha4/beta3/delta and alpha4/beta3/gamma2 heteromers. Neither recombinant system establishes the prevalence of these interfaces in native brain receptors.

Summary: The engineered beta3 homopentamer directly demonstrates beta3-beta3 interfaces.

Reason: PMID:24909990 resolves an engineered human beta3 homopentamer with direct beta3-beta3 interfaces. Its intracellular-loop replacement, purification tag and mature-residue numbering remain explicit. Independently, PMID:35355020 resolves beta3-beta3 interfaces within recombinant heteromeric assemblies, so the observed self-association is not solely a homopentamer artifact. Retain this positive secondary assembly property as non-core, without assigning the engineered construct to a natural short product or asserting native physiological homopentamers.

Summary: The source-specific dendritic-spine localization remains unverified.

Reason: The selected full PMID:25025157 text reports beta2/3-combined surface Westerns and gephyrin/synaptic analyses; its explicit dendritic-spine imaging comparator is PSD95. Those observations do not independently identify beta3 on dendritic spines. The exact original beta3 localization support remains unresolved, so retain UNDECIDED rather than infer wrong-gene attribution or absence from spines.

Summary: The broad synapse mapping can be specified as GABA-ergic synapse.

Reason: Beta3-containing receptors are established components of inhibitory GABAergic postsynaptic sites, with extrasynaptic populations also present. The general electronic synapse term can be refined to the already asserted GABA-ergic synapse without claiming all beta3 molecules occupy synapses.

Proposed replacements: GABA-ergic synapse

Summary: The retained postsynaptic-membrane IBD applies to human beta3.

Reason: The target descends from AN2243/PTN008360792 Euteleostomi, which bears the actual postsynaptic-membrane IBD. Rat beta3-specific membrane labeling and human receptor biology agree, with no target-path loss evidence. Donor number and self-inclusion are not objections.

Summary: Beta3 has a supported postsynaptic-membrane location, with source-specific limits.

Reason: PMID:35355020 directly studies recombinant beta3-containing receptor assemblies and discusses synaptic and extrasynaptic receptor diversity; it does not itself image every native beta3 postsynaptic site. Independent beta3-specific rat membrane localization and the actual PAINT placement support the biological location while the incoming IDA provenance is preserved.

Summary: The curated electronic postsynaptic-membrane location is supported.

Reason: Rat beta3-specific immunogold/FRIL labeling directly identifies receptor-containing postsynaptic membrane specializations, and the actual PAINT assignment agrees. The location is not exclusive: extrasynaptic membrane populations are also reported.

Summary: The specific neuron-development inference remains unresolved in the cochlear donor source.

Reason: The actual mouse P63080 source PMID:17021187 is now available as genuine full text. Beta3 nulls have cochlear dysfunction at six weeks and reduced afferent terminals at about 24 weeks. Rare fragile animals constrained the design: no beta3 animal was killed at six weeks for histopathology, and the P10/P21 developmental comparison concerns alpha5/beta2 only. The authors explicitly did not test beta3 progression with age. These positive mature phenotypes do not resolve neuron development versus later maintenance; preserve UNDECIDED without importing beta2 timing. This is accessible but inconclusive evidence for the specified process, not an unresolved access failure.

Summary: The actual PAINT assertion supports an inherited GABAergic transmission role.

Reason: The target descends from AN2107/PTN008566841 carrying the retained GABAergic-transmission IBD, with no intervening target-path loss. Direct receptor and neuronal-current evidence agrees. The ancestral assertion is evaluated by its placement, not donor-list size.

Summary: The tonic-inhibition paper is consistent with a beta3-containing GABAergic receptor role.

Reason: PMID:14993607 addresses alpha5-containing receptors in mouse CA1 neurons. The precise beta3-specific assay was not fully recovered, but independent beta3 neuronal-current and human receptor evidence establishes the biological transmission role. Retain the original IDA provenance without claiming a newly inspected beta3 image or molecular stoichiometry.

Summary: The structural review supports beta3 participation in GABAergic transmission.

Reason: PMID:28528665 synthesizes GABA-A receptor structure and function. Independent human receptor and mouse synaptic-current studies support the same postsynaptic role. The review is contextual evidence, not a direct human synaptic recording.

Summary: The alpha1/beta2/gamma2 structural source supports receptor-family context rather than an exclusive beta3 assay.

Reason: PMID:29950725 foregrounds human alpha1/beta2/gamma2 receptors. That fact alone does not invalidate the NAS beta3 transmission assignment, which is independently supported by direct beta3-containing receptor and neuronal-current evidence. The exact source-specific beta3 comparison is not claimed to have been fully recovered.

Summary: Full-length human beta3 receptor work supports the GABAergic transmission mechanism.

Reason: PMID:30602789 establishes the receptor/channel step of GABA signaling with actual human beta3-containing constructs. The broader synaptic role is consistent with neuronal beta3 knockout/rescue evidence; nanodisc structures themselves are not described as synaptic recordings.

Summary: Assembly-dependent receptor behavior supports the GABAergic transmission role.

Reason: PMID:35355020 directly studies human beta3-containing receptor responses and distinguishes multiple subunit arrangements. Its broader synaptic framing is supported without turning recombinant alpha4/delta behavior into proof of the localization or stoichiometry of every beta3 receptor.

Summary: The parallel electronic palate-development assignment has the same non-core scope.

Reason: The P63080 ortholog source and targeted mouse cleft-palate phenotype support the biological association. Retain it as non-core with the same source-specific interpretation as the ISS row, rather than assigning different actions solely because one transfer is electronic.

Summary: Mouse beta3 loss supports a contextual role in palate development.

Reason: The actual mouse donor P63080 is supported by PMID:9108119, whose original selected text reports cleft palate after targeted Gabrb3 disruption. This is a genuine developmental phenotype but not the defining adult molecular function. Human transfer retains the mouse inference boundary, incomplete penetrance and the absence of an established beta3 morphogenetic effector mechanism.

Summary: Beta3-containing receptors directly contribute to inhibitory postsynaptic responses.

Reason: PMID:12522165 demonstrates altered miniature inhibitory postsynaptic-current decay after mouse Gabrb3 deletion and rescue by beta3 cDNA. This directly supports the receptor contribution to inhibitory postsynaptic signaling; the species, current-versus-potential measurement and dependence on chloride gradients remain explicit.

Summary: The full donor study does not resolve beta3 receptor-cell development versus later degeneration.

Reason: The full original PMID:17021187 reports beta3-associated cochlear dysfunction at six weeks and older hair-cell loss. It lacks an early beta3 histological series distinguishing receptor-cell development from degeneration; the authors state that beta3 progression was not tested. The positive receptor/hair-cell phenotype is preserved, but it does not settle this precise developmental process. Alpha5/beta2 developmental timing is not transferred to beta3. This is accessible but inconclusive evidence for the specified process, not an unresolved access failure.

Summary: Reduced beta3-knockout afferent density does not resolve formation versus maintenance of innervation.

Reason: The full original PMID:17021187 directly shows reduced afferent terminals in two beta3 null ears examined at about 24 weeks. GO:0060384 describes a nerve invading tissue and making functional synaptic connections. No early beta3 innervation series resolves formation versus later loss: P10/P21 comparisons concern other subunits, and beta3 progression was not tested. Preserve the positive beta3 density phenotype and UNDECIDED for the formation claim, without inventing a human assay or importing beta2 timing. This is accessible but inconclusive evidence for the specified process, not an unresolved access failure.

Summary: Histamine responses are measured in artificial beta3-containing receptor contexts.

Reason: PMID:18281286 reports histamine-evoked currents in beta3 homomers expressed in Xenopus oocytes, while heteromeric receptor modulation differs. The cloned species is not stated in the abstract. Later human alpha4/beta3/delta experiments corroborate composition-dependent histamine responses, but do not make histamine the universal physiological beta3 agonist.

Summary: Parent-of-origin regulation of Gabrb3 expression does not establish beta3 as an imprinting effector.

Reason: The actual mouse donor source PMID:15878204 describes sex- and parent-of-origin-dependent beta3 protein abundance and proposes partial imprinting of the Gabrb3 gene. GO:0071514 concerns establishment and propagation of epigenetic imprints. The measured gene-expression phenotype does not demonstrate that the beta3 channel protein performs that process. Mark this propagated executor interpretation as over-annotated, without claiming the expression observation is false or proving that no indirect influence exists.

Summary: The precise cochlear-development inference remains unresolved.

Reason: The full original mouse study PMID:17021187 establishes beta3 cochlear dysfunction and older afferent/hair-cell loss. Experimental constraints left beta3 early histopathology and longitudinal progression untested; the early developmental series is restricted to alpha5/beta2. The authors favor a maintenance interpretation, but the beta3-specific developmental alternative is not directly resolved. Preserve UNDECIDED for cochlea development while retaining the positive mature phenotype. This is accessible but inconclusive evidence for the specified process, not an unresolved access failure.

Summary: The actual GABA-ergic-synapse ancestral assertion is supported.

Reason: The target lies below AN2107/PTN008566841 carrying this retained IBD, without a target-path loss. Direct beta3 membrane localization and functional inhibitory receptor evidence are consistent with the inherited synaptic location, alongside legitimate extrasynaptic populations.

Summary: Mouse-to-human mapping supports beta3 membership in GABA-ergic synapses.

Reason: The P63080 donor role is independently supported by knockout/rescue effects on inhibitory postsynaptic currents. This agrees with rat localization and the human beta3 receptor mechanism; it does not imply exclusively synaptic localization.

Summary: The rat donor directly supports postsynaptic-specialization membrane localization.

Reason: PMID:21073549 uses beta3-specific labeling validated with expressed rat cDNA and knockout controls, resolving membrane receptor clusters at inhibitory postsynaptic specializations. Its cytoplasmic-face fracture label describes the plasma membrane, not cytoplasmic vesicles. Transfer to human retains the ortholog inference boundary.

Summary: Beta3 participates in extrasynaptic GABA signaling through appropriate receptor assemblies.

Reason: PMID:35355020 directly establishes functional human alpha4/beta3/delta assemblies in the source-defined extrasynaptic receptor class. Independently, native rat beta3-specific membrane labeling in PMID:21073549 establishes an extrasynaptic compartment alongside synaptic clusters. The latter explicitly leaves tonic-current mediation unresolved; it is not a direct ambient-GABA response assay. ACCEPT is a synthesis of receptor capability, known subunit context and native compartment evidence, not a claim that the imaging paper proves extrasynaptic signaling or that recombinant stoichiometry is universal.

Summary: The actual ancestral chloride-transport assertion reaches human beta3.

Reason: The target lies below AN2107/PTN008566841, where the retained IBD places chloride transport. All target/donor mappings were checked, with no target-path loss assertion. Human receptor conductance supports the same inherited role.

Summary: Full-length human receptor experiments directly support chloride transport.

Reason: PMID:30602789 resolves beta3 pore contributions and includes electrophysiological controls. Transport is an activity of the assembled receptor channel; desensitized structural snapshots do not mean the receptor never conducts.

Summary: Human beta3-containing assemblies directly mediate chloride currents.

Reason: PMID:35355020 measures GABA-A receptor-mediated chloride currents with defined recording solutions and multiple subunit combinations. Histamine modulation and mixed populations are treated as context, not a substitute for the measured transport claim.

Summary: The chloride-transport claim is supported independently while the original epsilon-study partner limit is retained.

Reason: PMID:9039914 describes a human epsilon receptor subunit that assembles with alpha and beta subunits and changes chloride-current modulation. The accessible abstract does not resolve the beta3-specific clone. Direct human beta3 heteromer recordings independently establish chloride transport; no expression platform or complete construct identity is invented for the original source.

Summary: The electronic chloride-transport mapping is consistent with direct receptor conductance.

Reason: Human beta3-containing GABA-A receptors conduct chloride upon activation. This is a structural channel contribution within the pentamer, not an independent pump or catalytic transporter activity.

Summary: Wild-type beta3-containing channels in the G32R study support chloride transport.

Reason: PMID:22303015 reports functional alpha1/beta3/gamma2L assemblies and altered currents/openings for G32R. The accessible source distinguishes wild-type channel function from mutant gating effects. Full cloning Methods and exact current product identity remain unverified.

Summary: The mouse ortholog transfer agrees with the established chloride-conducting receptor contribution.

Reason: Beta3-containing GABA-A receptors contribute pore-lining structure to chloride conductance. The original mouse ISS source is retained; independent human currents corroborate the functional assertion without changing species provenance.

Summary: The receptor review supports the established chloride-transport role.

Reason: PMID:28528665 provides family-level structural context for a claim directly corroborated by human beta3 receptor currents. Preserve its NAS evidence type and do not describe it as a new transport measurement.

Summary: The actual PAINT complex-membership placement is supported.

Reason: The target descends from AN2107/PTN008566841 carrying the retained GABA-A receptor-complex IBD, with no target-path loss. Direct human beta3-containing structures validate the biological claim independently of donor-list length.

Summary: Human beta3-containing heteromers are directly characterized in the variant study.

Reason: PMID:26950270 coexpresses wild-type and mutant human beta3 with alpha1/gamma2L and measures receptor currents and surface abundance. The complex claim is supported without confusing experimental expression ratios with individual natural pentamer stoichiometry.

Summary: Independent structures establish beta3 complex membership; the epsilon-study partner assignment remains source limited.

Reason: The authentic PMID:9039914 abstract describes human epsilon assembly with alpha and beta subunits, without specifying beta3 clone identity. The original beta3 IDA is preserved, and direct human beta3 receptor structures independently support complex membership. No expression method, particular epsilon-containing stoichiometry or current beta3 product is inferred from that abstract.

Summary: Electronic complex mapping agrees with direct human receptor structures.

Reason: Human beta3 is repeatedly resolved within assembled GABA-A receptor pentamers. This supports the complex-membership claim while leaving natural product-specific assembly and partner stoichiometry open.

Summary: The G32R study supports beta3 membership in tested GABA-A receptor assemblies.

Reason: PMID:22303015 compares alpha1/beta3/gamma2L and beta3-alone conditions. Its current and surface evidence supports receptor participation; modeled shifts toward homomeric or binary assemblies are not treated as directly determined native stoichiometry.

Summary: The engineered alpha5/beta3 structure establishes a receptor assembly.

Reason: PMID:30140029 resolves an engineered human alpha5/beta3 complex with a beta3-binding nanobody. The shortened intracellular loops and unusual one-alpha/four-beta arrangement are documented; they support complex membership without proving that arrangement is a universal native receptor or a natural short beta3 product.

Summary: Full-length human beta3 is directly resolved within an alpha1/beta3/gamma2 receptor.

Reason: PMID:30602789 uses full-length human subunits and resolves the heteromer in nanodiscs. Tags and stabilizing antibody context are retained, and unresolved intracellular density is not interpreted as a naturally deleted sequence.

Summary: The alpha1/beta3 structural study directly demonstrates the receptor complex.

Reason: PMID:35140402 resolves engineered alpha1/beta3 pentamers and compares their behavior with wild-type receptors. BRIL/loop replacements, stabilizing binders and low gating efficacy are explicit limits; the positive complex membership does not depend on interpreting the static pore as open.

Summary: Human beta3-containing complexes with multiple companion subunits are directly resolved.

Reason: PMID:35355020 identifies alpha4/beta3/delta, beta3/delta and related assemblies in recombinant preparations. The study establishes context-dependent assembly, not one universal native composition. Functional receptor mixtures are distinguished from individual structural classes.

Summary: Native human receptor purification directly supports beta3 complex membership.

Reason: PMID:39843743 resolves alpha1-containing receptors purified from pooled human surgical tissue, including beta3 and mixed beta2/beta3 arrangements. Native membership is strong evidence, but it does not establish a unique beta3 splice product, a fixed stoichiometry in every cell, or direct beta3 binding to all nearby accessory densities.

Summary: The mouse ortholog supports membership in the GABA-A receptor complex.

Reason: Beta3 is a structural subunit of GABA-A receptor pentamers. The original mouse ISS source is corroborated by direct human receptor structures, while companion subunits and stoichiometry remain context dependent.

Summary: Homologous-complex transfer supports GABA-A receptor membership.

Reason: The exact CPX-280 source is a rat alpha4/beta3/delta complex, not a direct human preparation. The GO_REF homologous-complex transfer is consistent with human full-length beta3-containing receptor structures. Preserve the source identity and avoid treating all modeled set combinations as experimentally observed.

Summary: The receptor pharmacology review supports established complex membership.

Reason: PMID:34417930 supplies receptor-family context, while independent human beta3 structures directly establish the complex claim. Keep NAS provenance distinct from primary structural evidence.

Summary: Beta3 contributes to transmitter-gated postsynaptic membrane-potential changes.

Reason: The mouse donor study PMID:12522165 measures Gabrb3-dependent inhibitory postsynaptic currents and rescue by beta3 cDNA. Together with direct human receptor conductance, this supports a postsynaptic channel contribution. Current kinetics and potential change are related roles; the mouse recording is not mislabeled as a human current-clamp experiment. The current, nonobsolete GO:1904315 definition explicitly combines transmitter-gated channel activity with its postsynaptic-potential role; this precomposed annotation is retained deliberately because the cited donor experiment supports the combined contribution.

Summary: Beta3-containing receptors directly promote inhibitory contacts in the coculture experiment.

Reason: PMID:25489750 Figure 4 reports more synapsin-positive contacts on alpha1/beta3/gamma2-expressing HEK cells than controls. This is positive structural participation in assembly, not merely a knockout necessity inference. Functional vesicle-release validation in the same paper is beta2-specific and is not silently assigned to beta3; the presynaptic ligand and in-vivo generality remain unresolved.

Summary: Beta3-containing receptors can participate structurally in inhibitory contact assembly.

Reason: The mouse ortholog chain cites PMID:27129275, which tests receptor extracellular-domain contributions in neuron-HEK cocultures. Its beta2-domain competition is not relabeled as a beta3-domain assay. Independently, PMID:25489750 directly reports beta3-containing receptor-induced inhibitory contacts. Retain the broader structural association as non-core and distinguish contact induction from an identified presynaptic ligand or universal in-vivo sufficiency.