GABRB2

Summary: The generic transmembrane receptor mapping can be specified as GABA-A receptor activity.

Reason: The InterPro mappings identify a ligand-gated receptor family but leave the agonist and receptor class unspecified. Human beta2 is a component of GABA-A receptors in cloned-channel studies and alpha1/beta2/gamma2 structures, rather than an unspecified signaling receptor. GO:0004890 expresses the established receptor identity without asserting a new partner or natural product-specific mechanism.

Proposed replacements: GABA-A receptor activity

Summary: GABA-A receptor activity is inherited from the verified GABA-receptor clade.

Reason: The literal GO:0004890 IBD at PTN008566841 lies on the exact P47870 target path in PTHR18945. Current and retained assertion donors agree for this row, and target sequence conservation is established in the actual alignment. Direct human receptor assays corroborate the ancestral assignment. Donor number and self-donor status are not defects, and no target-specific loss is demonstrated. Beta2 supplies binding interfaces and pore structure within assembled receptors; the core records its contribution to this shared activity.

Summary: The GABA-A receptor family mapping agrees with direct human beta2 receptor evidence.

Reason: IPR002289 supports the receptor family assignment, and PMID:8264558 directly reports cloned human beta2 in functional recombinant receptors. The selected human alpha1/beta2/gamma2 structure identifies the GABA-binding interfaces and coupled chloride pore. This is a core receptor function, with receptor behavior determined by the assembled subunit combination. Beta2 supplies binding interfaces and pore structure within the functional receptor assembly.

Summary: Rat beta2 receptor-function transfer is supported independently by human beta2 experiments.

Reason: The exact ISS source P63138 is rat Gabrb2, not beta3. Its receptor annotations and subcellular record support the ortholog relationship; independent human beta2 recombinant electrophysiology and cryo-EM establish GABA-A receptor activity directly. The rat donor is not used to assign a particular human splice product or every pharmacological response. Human receptor assays establish the activity of beta2-containing assemblies, with beta2 contributing to their shared binding interfaces and pore.

Summary: Cloned human beta2 participates in functional GABA-A receptors.

Reason: The authentic PMID:8264558 abstract explicitly compares cloned human beta1, beta2 and beta3 subunits in functional recombinant receptors. It supports beta2 receptor activity without requiring transfer from another named paralog. Historical chromosomal assignment in the article does not replace the current verified HGNC/UniProt identity, and the study does not establish identical pharmacology for all present-day splice products. The measured biological unit is the recombinant receptor assembly, with beta2 contributing to its interfacial binding sites and channel structure.

Summary: The generic ion-channel mapping can be refined to GABA-gated chloride-channel activity.

Reason: The incoming InterPro family mapping is correct but does not specify either the gating ligand or ion. Human alpha1/beta2/gamma2 receptor structures and current measurements establish GABA-gated chloride conduction. The official is_a-only ancestry response places GO:0022851 under GO:0005216. This refinement describes beta2 function in an assembled receptor and does not claim an independently operating native beta2 pore. Beta2 contributes interfacial binding sites and pore structure to that shared channel mechanism.

Proposed replacements: GABA-gated chloride ion channel activity

Summary: The extracellular ligand-gated channel mapping can name the GABA-gated chloride mechanism.

Reason: IPR006202 and IPR036734 identify extracellular ligand-gated channel architecture. Human beta2-containing receptors have the more specific GABA-gated chloride-channel mechanism, supported by actual structural and electrophysiological experiments. Official typed ancestry confirms GO:0022851 is_a GO:0005230. The replacement adds demonstrated ligand and ion specificity, not an untested pharmacological property. The specific activity is supported for the beta2-containing receptor assembly, in which beta2 contributes to binding interfaces and pore structure.

Proposed replacements: GABA-gated chloride ion channel activity

Summary: Rat beta2 chloride-channel similarity can be refined to the established GABA-gated channel function.

Reason: The ISS donor P63138 is the genuine rat beta2 ortholog. Chloride-channel activity is sound but omits the normal gating ligand established independently in human beta2-containing receptors. GO:0022851 is an official is_a descendant of GO:0005254. Retain the original source record and specify the demonstrated receptor mechanism without asserting that every artificial beta2 homomer behaves like the native heteromer. The supported molecular activity is the shared mechanism of the beta2-containing receptor assembly.

Proposed replacements: GABA-gated chloride ion channel activity

Summary: The original splice-variant study directly reports surface expression of beta2 constructs.

Reason: Selected original PMID:19763268 uses human brain-cDNA beta2 forms with tags in HEK cells, with surface staining and receptor currents. It reports beta2S1/S2 constructs of 314/373 residues, whereas current verified UniProt products P47870-3/-4 are 313/372 residues. Preserve both records without silently assigning exact modern isoform identity. The short constructs lack TM4 but still yield currents with alpha1; architecture alone does not establish loss of channel function.

Summary: The deeper membrane-localization ancestor includes the exact beta2 target and is supported directly in humans.

Reason: The actual PTHR18945 target path includes PTN001054635 carrying plasma-membrane localization. The current GOA donor list and later retained IBD list differ in additional donors, which are preserved as dated source contexts rather than merged into a fabricated current record. Target sequence and descent are verified; direct human surface-expression and receptor experiments support this broad location. Target self-donation is legitimate experimental grounding.

Summary: Wild-type human beta2 reaches the surface in the variant-comparison study.

Reason: The original PMID:27789573 abstract and figure legends compare wild-type and Thr287Pro human beta2 receptor surface expression and electrophysiology. A mutant-associated reduction does not negate wild-type plasma-membrane localization. Newly recovered native Methods explicitly use human alpha1, beta2 and gamma2S cDNAs in HEK293T cells and describe expression and electrophysiology assays. Figure images and exact clone-to-current-splice sequence identity were not checked, so no natural product-specific assignment is made.

Summary: The UniProt plasma-membrane mapping agrees with direct beta2 receptor evidence.

Reason: SL-0039 maps the curated subcellular-location statement to plasma membrane. This is a method-derived assertion, not an additional experiment. Human beta2 surface-expression assays and functional receptor assemblies independently establish the location. It is nonexclusive: intracellular receptor trafficking does not contradict a positive plasma-membrane annotation.

Summary: Rat beta2 plasma-membrane transfer is independently supported by human surface assays.

Reason: P63138 is the exact rat beta2 ortholog. The source localization is consistent with human beta2 surface expression in PMID:19763268 and PMID:27789573 and with functional recombinant receptors. Retain the broad membrane location without claiming that every intracellular pool or every natural short product has identical abundance or trafficking.

Summary: Functional recombinant human beta2 supports plasma-membrane receptor deployment.

Reason: PMID:8264558 explicitly includes cloned human beta2 in functional recombinant GABA-A receptors. The incoming TAS membrane location is coherent with that receptor mechanism and is independently supported by later human surface-expression assays. The source is not treated as ultrastructural localization of a particular human neuronal compartment.

Summary: The Reactome GABA-A signaling model places beta2-containing receptors at the plasma membrane.

Reason: The retained official chloride-transport event R-HSA-975340 links catalyst 975314 to GABA-bound complex 975268, receptor set 5340318, heteropentamer 5357502, beta-subunit set 975288 and GABRB2 entity 975381. The last entity explicitly resolves UniProt P47870, residues 26–512, at plasma membrane. This is actual target membership in the modeled receptor rather than inference from a pathway title. Human receptor structures and surface assays independently support the compartment; the model does not make every possible subunit combination a separately observed assembly.

Summary: The broad ion-transport family mapping can be specified as chloride transmembrane transport.

Reason: The InterPro-derived process correctly captures ion movement but does not identify the ion or membrane crossing. Beta2 contributes to the chloride-conducting GABA-A receptor pore in the actual human receptor structure and functional assays. Official is_a-only ancestry places GO:1902476 under GO:0006811. The refinement names the established channel-mediated process without implying beta2 pumps ions or dictates the chloride electrochemical gradient.

Proposed replacements: chloride transmembrane transport

Summary: Human alpha1/beta2/gamma2 structures and currents directly support GABA signaling.

Reason: Selected original PMID:29950725 Results and Methods resolve a human alpha1/beta2/gamma2 receptor and compare receptor function. Beta2 principal faces contribute GABA-binding interfaces with neighboring alpha1 subunits and couple to the channel pore. The structural construct replaces M3–M4 loops with a short linker; its functional comparison supports the mechanism, but no current P47870 splice suffix is inferred from that engineered construct.

Summary: The ARBA GABA-signaling assignment agrees with the established human receptor mechanism.

Reason: ARBA00084992 is an automated source, not a newly inspected individual experiment. Its GABA-signaling conclusion is independently grounded in cloned human beta2 receptors and human alpha1/beta2/gamma2 structures with functional comparisons. Beta2 contributes to reception of the extracellular GABA signal through an ionotropic receptor; no additional intracellular enzyme cascade is inferred.

Summary: Human beta2 perturbation alters GABA-evoked receptor signaling.

Reason: PMID:27789573 explicitly compares human wild-type and Thr287Pro beta2 in alpha1/gamma2 receptor assemblies. The accessible original figure legends and authentic abstract establish effects on GABAergic currents and surface trafficking. This supports a receptor contribution to GABA signaling rather than a generic inference from clinical seizures alone. Newly recovered native Methods confirm human alpha1, beta2 and gamma2S cDNAs, HEK293T expression and whole-cell recording; figure images and exact current beta2 splice mapping remain outside the verified scope.

Summary: The pharmacology review provides background for an independently established GABA-signaling role.

Reason: PMID:28528665 is a GABA-A receptor pharmacology review; the retained authentic abstract is not a new beta2-specific assay. The incoming NAS attribution is retained as background, while direct human beta2 experiments and structures independently establish participation in GABA signaling. No particular allosteric drug site or clinical effect is assigned from the review abstract.

Summary: Functional cloned human beta2 receptors transmit the GABA signal.

Reason: PMID:8264558 explicitly includes human beta2 among the cloned beta subunits tested in recombinant GABA-A receptors. This directly supports the receptor-level GABA-signaling process. The authentic abstract does not justify transferring every beta1/beta3 pharmacological observation to beta2 or assigning a modern splice accession to the historical clone.

Summary: The generic chemical-synaptic-transmission attribution can specify GABAergic transmission.

Reason: PMID:8264558 establishes functional human GABA-A receptor beta2, and independent human alpha1/beta2/gamma2 evidence identifies the neurotransmitter mechanism. The original chemical-transmission term is valid but broader than the established GABAergic role. Official is_a-only ancestry confirms GO:0051932 beneath GO:0007268. This refinement concerns receptor-mediated transmission, not a claim that beta2 synthesizes or releases GABA.

Proposed replacements: synaptic transmission, GABAergic

Summary: The generic membrane family mapping can specify plasma membrane.

Reason: The InterPro-derived membrane term is correct but broader than the demonstrated location of functional beta2-containing receptors. Human surface assays and recombinant receptor function support plasma membrane, which the official is_a-only ancestry places beneath GO:0016020. This is a positive location refinement, not a claim that beta2 is absent from biosynthetic or trafficking compartments.

Proposed replacements: plasma membrane

Summary: Human beta2 contributes specifically to GABA-A receptor activity.

Reason: PMID:27789573 examines human beta2 Thr287Pro with alpha1 and gamma2, including wild-type, mixed and mutant conditions. The authentic abstract and original figure legends distinguish altered trafficking from current kinetics. This supports the weaker contributes_to claim for receptor activity within the heteromer; it does not assign the mutant phenotype to every natural splice product. Newly recovered native Methods confirm human alpha1/beta2/gamma2S cDNAs and HEK293T expression; figure images and exact mapping to a current beta2 splice sequence remain unverified. The demonstrated receptor class is specifically GABA-A; official is_a ancestry places GO:0004890 beneath GO:0016917. Refine the broad parent while preserving the original contributes_to qualifier and all construct limits.

Proposed replacements: GABA-A receptor activity

Summary: The verified GABA-channel ancestral node includes the exact human beta2 target.

Reason: The actual PTHR18945 tree places the 512-aa P47870-2 target beneath PTN008566841, and the literal IBD matches this GABA-gated chloride-channel assertion. The current target sequence is exact in both the retained cluster and alignment, with no target-path negative assertion. Human alpha1/beta2/gamma2 structures and electrophysiology independently support the channel mechanism. Preserve contributes_to: beta2 contributes binding-site and pore structure to the assembled channel. Target self-evidence in the IBD is legitimate, not circular.

Summary: Beta2-containing receptors support GABAergic currents in a neuron–HEK co-culture.

Reason: The selected original PMID:23909897 uses alpha1/beta2/gamma2 receptors expressed in HEK cells and rat medium spiny neurons, with active synaptic contacts and GABAergic currents. The human host alone does not establish the cloned subunit species or a current splice accession. Nevertheless, beta2 contribution to the reconstituted channel is explicit and agrees with direct human receptor structures and currents. Preserve contributes_to and do not treat beta2 as an autonomous native channel.

Summary: The mouse ortholog transfer supports beta2 contribution to a GABA-gated chloride channel.

Reason: The literal P63137/ENSMUSP00000007797 sources resolve to mouse Gabrb2. Its direct IDA source PMID:27129275 uses mouse subunit cDNAs in HEK receptor assemblies, neuronal co-cultures and electrophysiology; the selected Methods establish the cloned species independently of the host. Independent human alpha1/beta2/gamma2 functional and structural evidence supports transfer of this conserved channel contribution. The incoming contributes_to qualifier is retained.

Summary: The electronic vesicle-membrane mapping inherits the same unresolved beta2-specific evidence.

Reason: SL-0089 maps a curated cytoplasmic-vesicle localization rather than supplying a new assay. The traced rat beta2 source cites PMID:25172774, whose accessed abstract establishes gamma2-containing receptor transport but does not resolve beta2-specific inclusion. Without the relevant original detail, the specific membrane compartment remains undecided; this is not a claim that beta2 cannot undergo vesicular trafficking.

Summary: The rat source names receptor transport vesicles, but beta2-specific support remains unresolved.

Reason: The exact rat beta2 UniProt record cites PMID:25172774 for cytoplasmic-vesicle membrane. Its authentic abstract directly describes gamma2 co-precipitation, co-localization and KIF21B-dependent receptor delivery, without resolving beta2 inclusion or the relevant construct. The full original was not recovered. Preserve the literal rat source and do not infer misattribution from its gamma2 title, but leave this specific human transfer unresolved.

Summary: The cited NAS source assigns negative regulation to accessory proteins acting on beta2-containing receptors.

Reason: GO:0032229 denotes reducing the frequency, rate or extent of GABAergic synaptic transmission. The complete main text of PMID:33234346 and its figure captions/table were read from the original PMC article. Its CLPTM1 section explicitly assigns reduced forward trafficking and GABAergic transmission to CLPTM1, while GABA-A receptors are the regulated cargo. Its SHISA7 section assigns altered decay and surface delivery to SHISA7 acting on alpha1/beta2/gamma2 and alpha2/beta3/gamma2 assemblies. This does not support assigning that negative-regulatory process to beta2 itself. Ordinary receptor-mediated neuronal inhibition is also distinct from reducing GABAergic transmission. Remove this source-specific NAS attribution while preserving the original assertion and citation; this is not a universal claim that beta2 can never influence transmission regulation, and the review's underlying primary experiments were not newly reanalyzed.

Summary: The broad ion-transmembrane-transport mapping can specify chloride transport.

Reason: The ARBA/InterPro mapping correctly identifies transport across a membrane but leaves the ion unspecified. Human beta2-containing GABA-A receptor structures and functional data establish chloride permeation. The official typed ancestry places GO:1902476 under GO:0034220. This source-specific refinement preserves the original electronic context and does not infer active transport or a fixed direction of chloride flow.

Proposed replacements: chloride transmembrane transport

Summary: The accessed gephyrin study does not resolve beta2-specific dendritic-spine localization.

Reason: The actual PMID:25025157 selected original passages report positive surface biotinylation of alpha1/beta2/3/gamma2 and use a beta2/3 cross-reactive antibody. The spine passage concerns a PSD95-GFP control rather than a resolved beta2-specific spine measurement. Figure S1 and images were not inspected. This leaves the precise IDA claim unresolved without asserting that the full paper lacks such evidence or that the curator used the wrong gene.

Summary: The rat ultrastructural source supports postsynaptic receptor localization with a beta2/3 antibody limit.

Reason: The authentic PMID:9464994 abstract reports adult-rat immunogold localization using beta2/3-reactive labeling at GABAergic and extrasynaptic sites, with some glutamatergic contacts. That signal does not uniquely identify beta2 or constitute human imaging. Independent beta2-specific mouse postsynaptic staining and human beta2 receptor evidence support the location, while the original species and cross-reactivity limit are preserved.

Summary: The automated postsynaptic-membrane assignment is consistent with established beta2 localization.

Reason: ARBA00027496 and SL-0219 represent rule/location mappings, not new direct assays. Beta2-specific mouse synaptic staining and functional human beta2-containing receptors provide independent biological support for the postsynaptic membrane location. No claim is made that the complete ARBA rule was experimentally validated for every target splice product.

Summary: Rat postsynaptic-membrane transfer agrees with independent beta2-specific evidence.

Reason: P63138 is the genuine rat beta2 ortholog. The associated rat ultrastructural literature uses beta2/3-reactive labeling, which is not uniquely beta2, but independent mouse beta2-specific postsynaptic staining and human beta2 receptor evidence support the conserved compartment. Retain the ISS annotation without asserting human tissue imaging or exclusivity to one receptor assembly.

Summary: The mouse beta2 study supports maintenance of established cochlear neurons rather than their developmental progression.

Reason: The exact mouse P63137 donor has a genuine IMP annotation from PMID:17021187. The newly acquired original Methods, Results and Discussion compare null mice with age-matched wild-type littermates. Neural-response deficits progress with age; spiral-ganglion loss accompanies destruction of inner hair cells at about 24 weeks, whereas olivocochlear neuron numbers and dendritic morphology remain normal after peripheral terminals have disappeared. The authors interpret these findings as neuronal and synaptic maintenance. GO:0048666 instead describes progression from neuronal fate commitment to a fully functional differentiated cell. This source supports a real contextual neuronal role but overextends that role to development. MARK_AS_OVER_ANNOTATED is specific to this transfer, not a claim that beta2 can never influence neuronal maturation.

Summary: The verified ancestral GABA-receptor node supports inherited GABAergic transmission.

Reason: PTN008566841 lies on the actual P47870 target path and carries the literal GO:0051932 IBD. The retained and current donor contexts agree for this row, and the exact displayed target sequence is present in the actual alignment. Direct human receptor function is consistent with that placement; no target-specific loss or divergent transmitter mechanism is established.

Summary: Rat beta2 GABAergic-transmission transfer agrees with direct target receptor evidence.

Reason: P63138 is the verified rat beta2 ortholog, and the transferred process is the established physiological role of beta2-containing GABA-A receptors. Human cloned receptor assays and human receptor structures independently support the same neurotransmitter-response mechanism. This does not transfer every rat circuit-specific effect or assign a particular human splice product.

Summary: The human alpha1/beta2/gamma2 receptor mechanism supports GABAergic transmission.

Reason: The selected original PMID:29950725 resolves the human receptor and its GABA-binding/channel mechanism, with functional comparisons of the engineered structural construct. The incoming NAS process attribution expresses the receptor contribution to GABAergic transmission, rather than claiming that this structural study measured whole-circuit neurotransmission in vivo. Preserve that distinction and the unassigned modern splice identity.

Summary: GABAergic transmission is established for beta2, with the cited NAS paper retained as background.

Reason: Selected original PMID:35355020 experiments concern alpha4/beta3/delta or gamma2 combinations; beta2 appears in historical comparisons. The incoming NAS row is not itself an assertion that beta2 was directly assayed there. Independent human beta2 receptor experiments and structures establish GABAergic transmission, so retain the biological annotation while explicitly limiting what this source demonstrates. Do not transfer the beta3 histamine-binding site to beta2.

Summary: The established postsynaptic channel activity supports regulation of postsynaptic membrane potential.

Reason: This electronic annotation is inferred from GO:1904315 rather than an independent experiment. The underlying mouse donor experiment directly records beta2-dependent postsynaptic currents and potentials, and human receptor studies establish the conserved GABA-gated channel mechanism. Beta2 acts through the assembled receptor; the sign and magnitude of its effect depend on the ionic gradient and receptor/cell context.

Summary: The observed beta2 hair-cell phenotype concerns mature-cell function and later degeneration, not demonstrated receptor-cell development.

Reason: The mouse P63137 IMP source PMID:17021187 was now read in its native original Methods, Results and Discussion. Beta2-null mice have outer-hair-cell functional deficits at six weeks, minimal early hair-cell loss outside the extreme base, and extensive basal hair-cell loss by about 24 weeks. The study interprets the progressive phenotype as long-term maintenance of sensory cells. GO:0060119 concerns progression of an inner-ear receptor cell from formation to maturity; neither dysfunction of an already formed cell nor later degeneration demonstrates that process. The source-grounded maintenance phenotype is genuine, but the developmental specificity is over-annotated. This does not establish universal absence of a developmental role.

Summary: Age-resolved beta2-null analysis directly separates normal initial innervation from subsequent terminal degeneration.

Reason: The genuine mouse P63137 IMP chain reaches PMID:17021187. Its Results explicitly test developmental failure versus postdevelopmental degeneration: beta2-null efferent terminals appear normally around P10 and are fully developed by P21, then show reduced density by six weeks. Olivocochlear somata remain present after the peripheral terminals disappear. GO:0060384 describes nerve invasion and establishment of functional synaptic connections, whereas the measured beta2 phenotype concerns maintenance of established connections. The developmental interpretation therefore exceeds this source-specific evidence. Preserve the exact experimentally grounded donor record while marking the transferred innervation claim as over-annotated; do not infer loss of all developmental capacity.

Summary: A urinary-vesicle proteomics fraction contains a historical GABRB2 protein assignment.

Reason: The authentic expanded NHLBI table has GABRB2 at row 443, NP_068711, historical beta2 isoform 1, one peptide and reference 2 corresponding to PMID:19056867. No actual peptide sequence was recovered, so the hit cannot distinguish current P47870 products or establish vesicle topology, biogenesis or a defining secreted function. Retain the non-core occurrence and the original part_of urine extension exactly. Imported GO columns in that database are not independent experimental evidence.

Summary: Histamine modulates beta2-containing recombinant channels in a composition-dependent manner.

Reason: The exact rat beta2 donor chain cites PMID:18281286. Its authentic abstract reports histamine-evoked currents in artificial beta2 homomers with an EC50 of 212 micromolar and potentiation of GABA responses, rather than direct histamine agonism, in alpha1/beta2(/gamma2) heteromers. These positive assays support a contextual cellular response to histamine; they do not make histamine the defining physiological agonist of human beta2 receptors. Clone species and detailed Methods were not recovered from the full original, so no finer species, splice or native homomer claim is made.

Summary: Progressive beta2-null cochlear degeneration does not establish a role in forming and maturing the cochlea.

Reason: The exact P63137 IMP source PMID:17021187 contains genuine beta2 functional and histological experiments. Newly read original Results show progressive hearing deficits, later hair-cell and fibrocyte degeneration, and normal initial efferent innervation followed by loss of peripheral terminals. The Discussion emphasizes the mature ear and long-term maintenance. GO:0090102 describes progression of the cochlea from formation to its mature structure. The available age-resolved maintenance results do not establish that developmental process, so the transferred developmental specificity is over-annotated. No wrong-gene, evolutionary-loss or universal developmental-absence claim is made.

Summary: The verified GABA-receptor ancestor supports localization at GABAergic synapses.

Reason: The actual target lies beneath PTN008566841 with a literal GO:0098982 IBD; the current and retained donors agree for this row. Beta2-specific mouse postsynaptic clusters appose VGAT-positive terminals, and human beta2-containing receptors have the expected GABA-gated mechanism. This supports conserved GABAergic-synapse localization without asserting exclusivity or excluding extrasynaptic receptors.

Summary: The mouse donor has direct beta2-specific GABAergic-synapse evidence.

Reason: The literal P63137/Ensembl source is mouse Gabrb2. Selected PMID:26179122 staining uses beta2-specific antibodies, gephyrin/gamma2 markers and VGAT apposition, together with beta2-dependent postsynaptic currents. This provides experimental grounding for the conserved synaptic location, rather than treating a same-term electronic donor as an independent assay. Human receptor evidence is consistent with transfer.

Summary: Mouse beta2 postsynaptic localization supports the specialized membrane compartment.

Reason: The source resolves to genuine mouse beta2. Beta2-specific clustered staining and postsynaptic recordings in PMID:26179122 establish placement of this membrane receptor at postsynaptic specializations. Human receptor structures and functional assemblies corroborate the conserved membrane mechanism. The inference does not extend every mouse circuit or synapse subtype to all human cells.

Summary: The rat transfer to postsynaptic-specialization membrane is supported by conserved receptor localization.

Reason: The exact P63138 donor is rat beta2. Independent beta2-specific mouse postsynaptic staining and human beta2-containing receptor function support residence in the membrane of a postsynaptic specialization. The original donor context remains intact; this is not a claim that every beta2 receptor is synaptic or that rat antibody labeling was uniquely beta2.

Summary: Beta2-containing delta receptors have an extrasynaptic signaling context, with experimental limits.

Reason: PMID:18204487 reports functional alpha1/beta2/delta receptors in Xenopus oocytes, including low GABA efficacy and enhancement by modulators. That directly supports the receptor combination but does not by itself localize it in human tissue or measure tonic responses to ambient GABA in vivo. Retain the incoming NAS extrasynaptic context as a non-core receptor deployment, without assigning it uniformly to all beta2-containing assemblies or natural products. Independently, PMID:9464994 reports adult-rat beta2/3-reactive immunogold signal at extrasynaptic membrane, and the rat beta2 UniProt record cites it for this context. That supports receptor-family deployment but does not resolve beta2 alone or directly establish ambient-GABA signaling in human tissue.

Summary: The extrasynaptic NAS context is retained without transferring beta3-specific experiments to beta2.

Reason: The selected original PMID:35355020 experimentally studies alpha4/beta3/delta or gamma2 assemblies and discusses beta2-containing receptors historically. Independent alpha1/beta2/delta recombinant evidence supports a contextual extrasynaptic receptor class, but the cited beta3 structural and histamine results are not beta2 assays. Keep the broad NAS deployment as non-core, not a universal localization or newly demonstrated beta2 drug-binding mechanism. Independently, PMID:9464994 reports adult-rat beta2/3-reactive immunogold signal at extrasynaptic membrane, and the rat beta2 UniProt record cites it for this context. That supports receptor-family deployment but does not resolve beta2 alone or directly establish ambient-GABA signaling in human tissue.

Summary: The verified ancestral channel clade supports inherited chloride transport.

Reason: The literal GO:1902476 IBD at PTN008566841 is on the exact P47870 target path, with matching current and retained donor contexts and exact displayed sequence in the alignment. The human receptor pore and functional data independently corroborate chloride transport. No loss or divergent ion specificity is demonstrated for the target.

Summary: The human beta2-containing receptor directly supports chloride transmembrane transport.

Reason: Selected original PMID:29950725 structures and functional comparisons establish the ligand-gated anion pore of human alpha1/beta2/gamma2 receptors. Beta2 contributes to the multimeric pore and gating architecture; it does not independently set the chloride gradient or act as an ATP-driven transporter. The engineered structural loops are disclosed and no specific current splice product is inferred.

Summary: Rat beta2 chloride-transport transfer matches the human receptor pore mechanism.

Reason: The source P63138 is verified rat Gabrb2. Chloride transmembrane transport is independently supported by the human beta2-containing GABA-A receptor structure and electrophysiology, rather than inferred merely from membrane localization. Retain the ortholog transfer while leaving the net ion-flow direction dependent on the electrochemical conditions.

Summary: The actual ancestral GABA-receptor node supports beta2 complex membership.

Reason: PTN008566841 lies on the exact P47870 path and carries the literal GO:1902711 IBD. Current and retained donor contexts match for this row, and the target sequence is exact in the family alignment. Direct human structures corroborate receptor-complex membership. No target-specific loss is established, and neither donor count nor target self-evidence invalidates the ancestral placement.

Summary: Cryo-EM directly resolves human beta2 in a GABA-A receptor complex.

Reason: The selected original PMID:29950725 resolves human alpha1/beta2/gamma2 receptor architecture with functional comparisons. The structural construct replaces the large intracellular M3–M4 loops with a short linker, so its identity is not assigned to a current natural splice accession. That construct qualification does not undermine the directly observed beta2-containing heteromer.

Summary: The neurosteroid study uses a human alpha1/beta2/gamma2L receptor assembly.

Reason: The authentic PMID:37892178 abstract and selected original introduction describe human alpha1/beta2/gamma2L receptor currents alongside alpha5/beta3/gamma2L comparisons. This supports the beta2-containing complex, while the separate rat behavioral experiments are not human beta2-specific evidence. Full Methods/Results were not recovered, so precise clone sequence and current splice identity remain unassigned.

Summary: Native human brain structures directly include beta2-containing GABA-A receptors.

Reason: Selected original PMID:39843743 Results and Methods analyze alpha1-selected receptors from pooled brain tissue outside epileptic foci. They resolve predominant beta2-containing and mixed beta2/beta3 assemblies, with several positions remaining mixed or unresolved. This establishes native beta2 complex membership without assigning a current splice suffix, a complete all-brain composition census, a direct beta2–neuroligin contact or an established beta2/beta2 lamotrigine site.

Summary: Rat beta2 complex-membership transfer agrees with direct human assemblies.

Reason: P63138 is the rat beta2 ortholog. Human alpha1/beta2/gamma2 structures and native human alpha1-selected assemblies independently establish beta2 as a GABA-A receptor-complex component. The general complex term does not specify one universal stoichiometry or equate the donor’s particular assembly with every human splice product.

Summary: The homologous ComplexPortal assembly supports a broad inference, while human beta2 membership is independently demonstrated.

Reason: The exact official CPX-280 record is rat alpha4/beta3/delta, with participants P28471, P63079 and P18506; it is not a directly observed beta2 complex. The incoming ISS assertion uses homologous complex context. Broad GABA-A receptor-complex membership is independently established for human beta2 by recombinant and native human structures, so retain the biological annotation while preserving that source distinction. Do not rewrite CPX-280 as alpha1/beta2/gamma2 or label the inference wrong-gene merely because the source contains beta3.

Summary: The broad complex claim is sound, with the mouse tonic-inhibition source kept within its accessible scope.

Reason: The authentic PMID:17159992 abstract foregrounds mouse alpha1/delta colocalization and tonic inhibition, rather than a resolved beta2-specific biochemical assembly. The incoming NAS claim is therefore retained as contextual attribution, not recast as a direct beta2 assay. Independent human beta2-containing receptor structures establish GABA-A receptor-complex membership. Absence of beta2 detail from the abstract is not evidence of a wrong-gene annotation.

Summary: Mouse beta2 directly contributes to channels producing postsynaptic currents.

Reason: The actual mouse donor chain reaches PMID:26179122 IDA/IMP records. Selected original Results, Figures 3–5 and Methods show beta2-specific postsynaptic staining, reduced basket-cell–Purkinje-cell currents in beta2-knockout mice and loss of rebound potentiation; beta3 does not compensate in that context. Those experiments support the channel activity involved in postsynaptic membrane-potential regulation, together with independent human GABA-A receptor function. They do not establish the same input-specific plasticity in every human neuron. GO:1904315 precomposes the channel activity with its postsynaptic process context; the current term is retained while the project-wide precomposition question remains separate from this supported receptor claim.

Summary: Beta2-containing receptor assemblies support synaptic-contact formation in co-culture.

Reason: The selected original PMID:23909897 establishes contacts and functional GABAergic transmission between receptor-expressing HEK cells and rat medium spiny neurons. The beta2-containing receptor assembly participates in this model, but the assay does not isolate a beta2-only adhesive mechanism or establish universal in-vivo synaptogenesis. Later mouse beta2 extracellular-domain competition provides a more specific structural contribution. Retain the process with these contextual limits.

Summary: The protocol’s beta2-related synapse-assembly evidence is retained with its reused-data limitation.

Reason: PMID:25489750 describes a neuron–HEK co-culture protocol. Its detailed preparation uses alpha1/beta3/gamma2 while selected figures reuse earlier alpha1/beta2/gamma2 observations; this is not an independent beta2 replication, and the caption inconsistency is retained explicitly. The earlier receptor co-culture and later beta2-domain competition independently support contextual inhibitory synapse assembly. No wrong-gene conclusion or novel universal adhesive function is inferred.

Summary: The mouse ortholog and ARBA sources support contextual synapse assembly by receptor structure.

Reason: The actual mouse beta2 source reaches PMID:27129275. Its selected Methods use mouse subunits and mouse neurons; beta2 extracellular-domain competition reduces VGAT-positive presynaptic contacts in receptor-expressing HEK co-cultures, while the bicuculline control showed no statistically significant difference in contact numbers. This supports a structural contribution beyond a knockout-only necessity argument. The precise ligand and in-vivo sufficiency remain unresolved, so retain inhibitory synapse assembly as a contextual non-core role rather than a universal beta2 organizing activity. Receptor activity was established in separate co-culture experiments, not measured in that extracellular-domain competition arm.