GABRG2 encodes the gamma2 subunit of heteromeric GABA-A receptors, membrane channels that conduct chloride in response to GABA. Gamma2 contributes to the channel pore and to the alpha/gamma allosteric interface that confers benzodiazepine sensitivity. Gamma2-containing receptors support fast inhibitory synaptic signaling and, in particular subunit combinations, extrasynaptic signaling. Their synaptic clustering, surface trafficking and pharmacology depend on receptor composition and associated proteins. Alternative splicing produces long, short and an additional inserted-segment protein sequence. Pathogenic variants can impair receptor assembly, trafficking or channel function and cause epilepsy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: The receptor activity can be specified as GABA-A receptor activity. Reason: Human gamma2-containing receptor assemblies mediate GABA responses. The InterPro receptor assertion is biologically sound but is less informative than the supported GABA-A activity, which is an is_a descendant through GABA receptor activity. This refinement does not assign GABA binding to an isolated gamma2 subunit. Proposed replacements: GABA-A receptor activity |
| GO:0004890 GABA-A receptor activity | IDA PMID:30602789 Cryo-EM structure of the human Ξ±1Ξ²3Ξ³2 GABA(A) receptor in a ... | ACCEPT | Summary: Human gamma2L is part of a functional GABA-A receptor. Reason: The genuine Methods specify full-length human gamma2L P18507-2 with a purification tag in alpha1/beta3/gamma2L receptors. Electrophysiology and ligand-binding controls support the receptor activity. An unresolved pocket density and a desensitized structural state do not negate the separately measured function; the UniProt reference-position range does not redefine this construct as the short natural product. |
| GO:0004890 GABA-A receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic assignment matches the human receptor function. Reason: The InterPro and mouse/Ensembl sources converge on the established GABA-A receptor role. Human heteromer expression, structure and functional measurements independently support this activity, so the inference is retained without treating the evidence code itself as proof or assigning gamma2 a separate ligand-binding pocket. |
| GO:0004890 GABA-A receptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse orthology supports gamma2 participation in GABA-A receptor activity. Reason: The mouse P22723 ISS source is consistent with directly studied human gamma2-containing receptors. Gamma2 participates in the receptor architecture and gating; activity belongs to the heteromer, while the literal source qualifier remains unchanged. No independent gamma2 homomer or orthosteric GABA-binding activity is inferred. |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: The ion-channel assignment can be narrowed to GABA-gated chloride conductance. Reason: The broad InterPro channel inference is correct, but gamma2 contributes to a receptor with demonstrated GABA-gated chloride conductance. GO:0022851 is a verified is_a descendant of monoatomic ion channel activity. The refined activity is expressed by the assembled receptor, not an autonomous gamma2 channel. Proposed replacements: GABA-gated chloride ion channel activity |
| GO:0005230 extracellular ligand-gated monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: The extracellular ligand-gated channel can be identified more precisely. Reason: Human gamma2 heteromers respond to GABA and conduct chloride. The specific GABA-gated chloride activity is an is_a descendant of the incoming extracellular ligand-gated channel term. Retain the positive inference while specifying the ligand and transported ion. Proposed replacements: GABA-gated chloride ion channel activity |
| GO:0005254 chloride channel activity | IEA GO_REF:0000107 | MODIFY | Summary: The electronic chloride-channel assignment can specify GABA gating. Reason: Mouse/Ensembl transfer supports a genuine chloride-channel component. Human alpha/beta/gamma2 functional studies establish the more informative GABA-gated activity. Preserve the literal electronic provenance and refine to the supported descendant rather than retain a needlessly broad molecular function. Proposed replacements: GABA-gated chloride ion channel activity |
| GO:0005254 chloride channel activity | ISS GO_REF:0000024 | MODIFY | Summary: The mouse-derived chloride-channel activity has a supported GABA-gated refinement. Reason: The ISS chloride-channel assertion agrees with the human receptor evidence, but its gating mechanism is known. GO:0022851 directly refines chloride channel activity by is_a. This is a specificity correction, not a rejection of the mouse donor or a claim that gamma2 binds GABA independently. Proposed replacements: GABA-gated chloride ion channel activity |
| GO:0005515 protein binding | IPI PMID:27733149 RNA binding protein Nova1 promotes tumor growth in vivo and ... | REMOVE | Summary: NOVA1 and gamma2 associate in human liver-cancer cell experiments. Reason: The original human Huh7 and SMMC-7721 experiments include reciprocal NOVA1/GABAAR-gamma2 co-immunoprecipitation with IgG and buffer controls, supporting association with P51513. Remove this generic protein-binding annotation because it supplies no informative molecular function for gamma2; this does not deny the observed association. The experiment does not establish a purified binary interface or make gamma2 an RNA-processing or transcriptional regulator, and the cancer phenotypes do not substitute for those claims. |
| GO:0005515 protein binding | IPI PMID:28978485 An Essential Role for the Tetraspanin LHFPL4 in the Cell-Typ... | REMOVE | Summary: LHFPL4 associates with gamma2-containing receptor constructs. Reason: The selected original Results and Figure 1 caption show mouse turboGFP-LHFPL4 co-immunoprecipitating SEP-tagged gamma2 in COS-7 cells. The separate human LHFPL4 experiment tests alpha1 and is not reassigned to gamma2. The receptor association is positive evidence, with gamma2 clone species and detailed constructs not independently resolved from the inspected main text. Remove the uninformative generic protein-binding annotation without denying that association or assigning the accessory protein's clustering activity to gamma2. |
| GO:0005515 protein binding | IPI PMID:9892355 GABA(A)-receptor-associated protein links GABA(A) receptors ... | REMOVE | Summary: GABARAP association is directly supported by the original report. Reason: The authentic PMID:9892355 abstract reports gamma2 interaction with GABARAP in vitro and in vivo and colocalization with synaptic receptors, supporting the O95166-associated context. Detailed construct, species and domain-assay information from the original full text remains inaccessible. Remove the generic protein-binding annotation because it does not identify an informative molecular function of gamma2; this does not deny the reported interaction or transfer GABARAP's cytoskeletal or trafficking activity to its receptor partner. |
| GO:0005515 protein binding | IPI PMID:9892355 GABA(A)-receptor-associated protein links GABA(A) receptors ... | UNDECIDED | Summary: The specific human GABARAPL1 partner context remains unresolved. Reason: The accessible PMID:9892355 abstract explicitly names GABARAP, but the full original experiment establishing the Q9H0R8 GABARAPL1 context was not recovered. A later primary study demonstrates GABARAPL1 binding to a gamma2 intracellular motif using mouse gamma2 and mouse GABARAPL1 constructs; it is corroborating biology, not verification of this human partner record or of the 1999 assay. Preserve the original IPI assertion as unresolved rather than infer a wrong identifier from the abstract. |
| GO:0005886 plasma membrane | EXP PMID:27864268 De novo GABRG2 mutations associated with epileptic encephalo... | ACCEPT | Summary: Human gamma2L surface delivery is directly measured. Reason: The original selected Methods and Results use human gamma2L in alpha1/beta2/gamma2 receptors, including surface biotinylation and immunoblotting alongside electrophysiology. HA insertion and variant-specific retention are experimental details; they do not redefine the wild-type natural product or establish an endoplasmic-reticulum core location. Inconsistent numerical or variant prose is not reused without the underlying figures. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The deep ancestral plasma-membrane placement is supported by human receptor evidence. Reason: The actual target lies below the PTN001054635 IBD and matches the current 475-residue sequence in the retained alignment. The incoming and retained donor sets are distinct source versions, not evidence of biological loss. Human surface biotinylation, receptor currents and the explicit Reactome target chain independently support plasma-membrane activity. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic surface-location assignment is sound. Reason: The SL and mouse/Ensembl sources identify a plasma-membrane receptor component. Human gamma2L surface assays and the exact Reactome P18507 chain corroborate this location, without inferring every engineered or disease-associated product reaches the surface normally. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Rat orthology supports the well-established plasma-membrane location. Reason: The rat P18508 source is consistent with direct human gamma2L surface biotinylation and receptor function. Preserve the literal ISS provenance while using the independent target evidence to support the whole localization claim. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse orthology agrees with human surface receptor measurements. Reason: The P22723 transfer supports a receptor subunit whose plasma-membrane presence is independently established in human gamma2L expression experiments. Mutation-induced intracellular retention in that work is not substituted for the wild-type localization. |
| GO:0005886 plasma membrane | TAS PMID:2538761 Importance of a novel GABAA receptor subunit for benzodiazep... | ACCEPT | Summary: Functional receptor expression is consistent with plasma-membrane localization. Reason: The original receptor-expression abstract supports functional gamma2-containing channels, and direct human gamma2L surface biotinylation supplies independent localization evidence. Detailed original species and construct assignments are not inferred solely from the host system. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-975340 | ACCEPT | Summary: The Reactome reaction explicitly contains human gamma2 at the plasma membrane. Reason: The inspected catalyst and receptor-set chain resolves to R-HSA-975350, human UniProt P18507 residues 40β475 in the plasma membrane. This is direct target membership in the curated model, not inference from a pathway title. Set membership does not demonstrate every represented subunit combination in vivo; independent human surface assays support the location. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: The transported ion and membrane crossing are established. Reason: The InterPro monoatomic-ion transport assignment is correct but broad. Human gamma2-containing receptors provide the pore for chloride transmembrane transport, a verified is_a descendant. Gamma2 contributes transport structure rather than an independent pump or transporter cycle. Proposed replacements: chloride transmembrane transport |
| GO:0006821 chloride transport | IEA GO_REF:0000002 | MODIFY | Summary: Chloride transport can be specified as transmembrane transport. Reason: The original electronic chloride-transport assertion agrees with the receptor experiments. Its direct is_a descendant GO:1902476 captures the demonstrated movement across a membrane and is the supported refinement. Proposed replacements: chloride transmembrane transport |
| GO:0007214 gamma-aminobutyric acid signaling pathway | IDA PMID:29950725 Structure of a human synaptic GABA(A) receptor. | ACCEPT | Summary: Human gamma2-containing receptors couple GABA recognition to gating. Reason: The study determines the human alpha1/beta2/gamma2 receptor architecture and assays function. Gamma2 participates in the channel assembly, whereas the orthosteric GABA pockets are beta/alpha interfaces. The loop-modified, tagged gamma2 structural construct is not treated as a distinct natural isoform. |
| GO:0007214 gamma-aminobutyric acid signaling pathway | IDA PMID:30602789 Cryo-EM structure of the human Ξ±1Ξ²3Ξ³2 GABA(A) receptor in a ... | ACCEPT | Summary: Functional human gamma2L heteromers provide direct GABA-signaling evidence. Reason: The full-length human alpha1/beta3/gamma2L receptor is functionally characterized after reconstitution and in expression assays. This establishes receptor-mediated GABA signaling. Neither a desensitized cryo-EM conformation nor unidentified pocket density is used to deny the independently observed function. |
| GO:0007214 gamma-aminobutyric acid signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Gamma2-containing receptors directly execute GABA signaling. Reason: The receptor subunit contributes channel structure that converts extracellular GABA into a change in cellular conductance. This is direct participation in GABA signaling rather than a phenotype caused by an unrelated downstream perturbation. Human structures and currents corroborate the InterPro inference. |
| GO:0007214 gamma-aminobutyric acid signaling pathway | NAS PMID:34417930 GABA(A) receptors: structure, function, pharmacology, and re... | ACCEPT | Summary: The review correctly places gamma2 in GABA-gated receptor signaling. Reason: The inspected original review describes gamma2-containing heteropentamers, the pore and distinct beta/alpha versus alpha/gamma ligand interfaces. This NAS attribution is consistent with the direct human receptor literature. The review is supporting synthesis rather than a new primary experiment. |
| GO:0007214 gamma-aminobutyric acid signaling pathway | NAS PMID:35355020 Differential assembly diversifies GABA(A) receptor structure... | ACCEPT | Summary: The structural study supports gamma2-containing GABA receptor assemblies. Reason: The original work resolves human alpha4/beta3/gamma2 and beta3/gamma2 assemblies using full-length gamma2L with a purification tag. Detailed co-agonist current experiments focus on delta-containing preparations and are not relabeled as gamma2 measurements. Independent human gamma2 receptor currents establish the GABA-signaling claim as a whole. |
| GO:0007214 gamma-aminobutyric acid signaling pathway | TAS PMID:2538761 Importance of a novel GABAA receptor subunit for benzodiazep... | ACCEPT | Summary: The original receptor-expression study supports GABA signal transduction. Reason: Adding gamma2 to expressed alpha/beta receptor combinations changes pharmacology while retaining functional GABA responses. The assembled receptor executes the signaling step. The accessible abstract and independent human receptor studies support the biological claim without inventing details of the original expression constructs. |
| GO:0008503 benzodiazepine receptor activity | TAS PMID:2538761 Importance of a novel GABAA receptor subunit for benzodiazep... | KEEP AS NON CORE | Summary: Gamma2 contributes the benzodiazepine-sensitive allosteric interface. Reason: The original abstract shows that adding gamma2 to alpha1/beta1 receptors produces benzodiazepine pharmacology; later human structures locate the benzodiazepine/flumazenil site at an alpha/gamma interface. This is a supported pharmacological capability of the heteromer and is retained as non-core to endogenous GABA-gated conductance. It is distinct from the beta/alpha GABA-binding interface. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The generic membrane location can be refined to plasma membrane. Reason: Human gamma2L surface measurements and the explicit Reactome target entity establish plasma-membrane localization. GO:0005886 is an is_a descendant of membrane. The InterPro-derived assertion is retained biologically while specifying its best-supported membrane context. Proposed replacements: plasma membrane |
| GO:0022851 GABA-gated chloride ion channel activity | IDA PMID:23909897 GABA(A) receptors can initiate the formation of functional i... | ACCEPT | Summary: Receptor-expressing cells support GABA-gated chloride currents. Reason: The original co-culture study measures functional inhibitory contacts and currents in cells expressing alpha1/beta2/gamma2 receptors. Gamma2 contributes to the channel complex; the literal contributes_to relation is retained. The HEK host is not treated as independent proof of the species of every cloned subunit. |
| GO:0022851 GABA-gated chloride ion channel activity | IDA PMID:2538761 Importance of a novel GABAA receptor subunit for benzodiazep... | ACCEPT | Summary: Gamma2-containing assemblies have GABA-gated chloride-channel activity. Reason: The cited original abstract describes functional receptors assembled with alpha1, beta1 and gamma2 and their GABA responses. Later human structural and electrophysiological studies independently substantiate the same channel activity. Preserve the original enables qualifier as provenance while the synthesized core states gamma2 contribution to a heteromer. |
| GO:0022851 GABA-gated chloride ion channel activity | IDA PMID:30602789 Cryo-EM structure of the human Ξ±1Ξ²3Ξ³2 GABA(A) receptor in a ... | ACCEPT | Summary: The human alpha1/beta3/gamma2L receptor supports GABA-gated conductance. Reason: The paper directly studies a functional human heteromer containing the long gamma2 product. Gamma2 supplies part of the transmembrane architecture; the GABA pockets are at beta/alpha interfaces. Purification tags and a megabody are experimental components, and the natural product is not equated with every engineered preparation. |
| GO:0022851 GABA-gated chloride ion channel activity | IEA GO_REF:0000107 | ACCEPT | Summary: Gamma2 contributes pore structure to a GABA-gated chloride channel. Reason: The mouse-derived inference agrees with human alpha/beta/gamma2 receptor structures and GABA-evoked currents. Gamma2 is a constituent of the channel, and the original contributes_to relation accurately avoids assigning a complete autonomous channel to a single subunit. The GABA recognition pockets are principally beta/alpha interfaces, not a gamma2-only GABA-binding site. |
| GO:0030424 axon | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Gamma2 can occur at postsynaptic sites on axonal compartments. Reason: The mouse donor links the axon assignment to PMID:9682826, whose accessible abstract does not resolve the exact axonal panel. Independently, the original PMID:9014159 abstract explicitly reports gamma2 at axo-axonic synapses on axon initial segments. That supports the broader localization as a specialized non-core context, without assigning gamma2 an axonal transport activity or pretending the mouse source panel was read. |
| GO:0030425 dendrite | IEA GO_REF:0000044 | MODIFY | Summary: The dendritic location can specify the receptor-bearing membrane. Reason: The UniProt subcellular-vocabulary assertion is consistent with gamma2 receptor localization on dendritic membranes. The supported refinement is dendrite membrane, which is part_of dendrite rather than an is_a descendant. This specifies the functional membrane-associated receptor pool without denying intracellular trafficking pools. Proposed replacements: dendrite membrane |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The electronic vesicle-membrane mapping agrees with gamma2-specific transport evidence. Reason: SL-0089 projects a cytoplasmic-vesicle membrane context supported by the same gamma2-specific rat source chain as the ISS annotation. The PMID:25172774 abstract names gamma2 receptor transport, unlike a merely paralog-based inference. Retain this ancillary pool with the same full-text and vesicle-assay limits, without assigning gamma2 the delivery function of KIF21B. |
| GO:0030659 cytoplasmic vesicle membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Gamma2-containing receptor transport vesicles are a supported ancillary pool. Reason: The exact rat UniProt evidence block connects this location to PMID:25172774. Its authentic abstract specifically reports gamma2 association and colocalization with KIF21B and supports delivery of gamma2-containing receptor transport vesicles into dendrites. Retain the vesicular receptor pool as non-core, while detailed vesicle-population imaging and the full original Methods remain unverified. Gamma2 is receptor cargo, not the kinesin motor executing transport. |
| GO:0032229 negative regulation of synaptic transmission, GABAergic | NAS PMID:33234346 Regulation of GABA(A)Rs by Transmembrane Accessory Proteins. | REMOVE | Summary: The cited negative regulator is an accessory protein acting on the receptor. Reason: The complete original main text and relevant captions of PMID:33234346 assign reduced receptor forward trafficking and GABAergic transmission to CLPTM1, with other kinetic regulation assigned to SHISA7. Gamma2-containing receptors are the regulated complexes. GO:0032229 denotes reduction of GABAergic transmission, not the normal inhibitory effect of transmitting through a GABA-A receptor. This source-specific NAS attribution does not establish gamma2 as the executor of the negative-regulation step; the original record is retained, without a universal claim that gamma2 can never influence transmission negatively. |
| GO:0032590 dendrite membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Gamma2 is an inherited component of dendritic receptor membranes. Reason: The actual PTN008360627 placement supports the dendrite-membrane context, with no retained target-path loss. Rat experimental localization and gamma2-containing synaptic receptor function corroborate the anatomical claim. The annotation does not require every gamma2 pool to be restricted to dendrites. |
| GO:0032590 dendrite membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The rat donor supports dendritic membrane-associated gamma2 receptors. Reason: The actual donor GOA links dendrite-membrane IDA to PMID:15620359. Gamma2 junctional labeling on proximal and distal dendrites in the independent PMID:9014159 abstract also supports the localization. The claim concerns receptor location, not assignment of neurexin or neuroligin signaling activity to gamma2. |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: The transmembrane transport process has a known chloride substrate. Reason: The InterPro assignment correctly identifies membrane transport, but human receptor structure and currents specify chloride. GO:1902476 is a verified is_a descendant of monoatomic ion transmembrane transport and provides the appropriate refinement. Proposed replacements: chloride transmembrane transport |
| GO:0034707 chloride channel complex | IPI PMID:9014148 Extensive heterogeneity of recombinant gamma-aminobutyric ac... | ACCEPT | Summary: Gamma2 is a component of a chloride-conducting receptor complex. Reason: The original PMID:9014148 abstract studies rat alpha4/beta3/gamma2 receptor populations in HEK293 cells, not a wholly human preparation. Independent human gamma2 structures corroborate chloride-channel-complex membership. Retain this accurate composition claim. A fresh official ontology query returns no is_a/part_of path from GABA-A receptor complex GO:1902711 to chloride channel complex GO:0034707; replacing this row with the already represented receptor-complex term would discard a true assertion rather than make a supported hierarchical refinement. The possible ontology relationship is raised separately. |
| GO:0045211 postsynaptic membrane | EXP PMID:2538761 Importance of a novel GABAA receptor subunit for benzodiazep... | ACCEPT | Summary: Postsynaptic membrane localization is supported by the combined evidence. Reason: The cited expression study establishes functional gamma2-containing receptors but its accessible abstract does not itself map native synaptic membranes. Original junctional immunolocalization and functional inhibitory-contact experiments independently establish the whole postsynaptic-membrane claim. Preserve the original EXP context without claiming an uninspected localization panel from that paper. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The subcellular-vocabulary mapping matches postsynaptic receptor membranes. Reason: Gamma2 is concentrated at membrane specializations of inhibitory synaptic junctions in original immunolocalization work, and receptor-expressing cells support functional inhibitory contacts. The electronic SL-derived term is therefore supported beyond the vocabulary mapping itself. |
| GO:0051932 synaptic transmission, GABAergic | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited GABAergic-transmission role is well grounded. Reason: The actual target descends from the PTN008360627 IBD, with no loss on the retained target path. Human gamma2 is legitimately included among the experimental descendants; self-donation is not circularity. Receptor currents and synaptic-contact experiments independently support direct participation in GABAergic transmission. |
| GO:0051932 synaptic transmission, GABAergic | ISS GO_REF:0000024 | ACCEPT | Summary: Rat orthology agrees with direct gamma2-containing inhibitory synaptic function. Reason: The rat P18508 transfer is supported by gamma2 localization at GABAergic junctions and by functional contacts formed with gamma2-containing receptors. Gamma2 is part of the receptor that performs neurotransmission, not merely a substrate or downstream marker. |
| GO:0051932 synaptic transmission, GABAergic | NAS PMID:29950725 Structure of a human synaptic GABA(A) receptor. | ACCEPT | Summary: The human synaptic receptor structure supports the established transmission role. Reason: The study characterizes human alpha1/beta2/gamma2 receptors and their GABA-dependent conductance. Its recombinant structural preparation is not itself an intact neuronal synapse, but the same molecular claim is independently established by functional inhibitory-contact assays. Retain the NAS source scope without claiming a new in-vivo transmission measurement. |
| GO:0051932 synaptic transmission, GABAergic | NAS PMID:30602789 Cryo-EM structure of the human Ξ±1Ξ²3Ξ³2 GABA(A) receptor in a ... | ACCEPT | Summary: Human gamma2L receptor function corroborates GABAergic transmission. Reason: The full-length human receptor study supports the molecular channel step used in GABAergic transmission. Native synaptic localization and co-culture currents provide complementary cellular context. Reconstituted nanodiscs are not presented as an in-vivo synaptic assay. |
| GO:0060078 regulation of postsynaptic membrane potential | IEA GO_REF:0000108 | ACCEPT | Summary: Channel opening directly changes postsynaptic membrane potential. Reason: The GO_REF:0000108 inference is mechanistically appropriate: a transmitter-gated chloride channel contributes to regulation of postsynaptic potential. This follows from the receptor activity and functional synaptic currents; it is not a separate broad developmental or behavioral role. |
| GO:0071420 cellular response to histamine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The electronic histamine-response transfer reflects heteromer modulation. Reason: The mouse/Ensembl inference is consistent with the positive gamma2-dependent modulation reported in PMID:18281286. Histamine is a modulator of the assayed alpha1/beta2/gamma2 receptor, whereas direct agonism was shown for beta-only channels. Retain the response as non-core and do not convert it into an autonomous histamine receptor molecular function for gamma2. |
| GO:0071420 cellular response to histamine | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Gamma2 modulates the receptor response to histamine. Reason: The exact mouse donor has an experimental PMID:18281286 record. Its authentic abstract distinguishes histamine-gated beta homomers from histamine potentiation of alpha1/beta2/gamma2 GABA responses in a gamma2-controlled manner. This supports a contextual cellular response to histamine, retained as non-core, without assigning gamma2 a histamine-binding site or claiming the original subunit species and detailed Methods were independently resolved. |
| GO:0098794 postsynapse | IBA GO_REF:0000033 | MODIFY | Summary: The broad postsynapse assertion can specify its membrane component. Reason: Gamma2 is a transmembrane receptor subunit with positive junctional-membrane localization. GO:0045211 is part_of the broader postsynapse, not an is_a descendant; this explicit anatomical refinement is supported independently of the valid ancestral placement. Self-donation and the actual PTN008360627 lineage remain legitimate, with no target-loss claim. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008360627 SUPPORTS TRANSFER The actual PTHR18945 IBD at AN1671/PTN008360627 lies above human P18507 at AN1793/PTN002498426. The retained tree and exact 475-residue alignment support descent without target-path loss. Target self-donation is legitimate grounding. The refinement specifies the independently supported postsynaptic membrane, which is part_of the broader postsynapse; it does not assert that ancestral localization or its propagation is false. Proposed replacements: postsynaptic membrane |
| GO:0098982 GABA-ergic synapse | IEA GO_REF:0000107 | ACCEPT | Summary: Gamma2-containing receptors are present at GABAergic synapses. Reason: The mouse/Ensembl inference agrees with gamma2 immunolabeling at inhibitory junctions and functional GABAergic contacts formed by receptor-expressing cells. This is a supported synaptic context; it is not an assertion that all gamma2 receptors are exclusively synaptic. |
| GO:0099634 postsynaptic specialization membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The rat donor directly supports concentration at postsynaptic membrane specializations. Reason: The literal rat donor has IDA records from PMID:9014159 and PMID:9464994. Their authentic abstracts describe gamma2 immunogold labeling at junctional membrane specializations and inhibitory synapses, rather than diffuse cell-surface expression alone. This directly supports the more specific compartment, with detailed image reanalysis outside the present reading scope. |
| GO:0160001 extrasynaptic signaling via GABA | NAS PMID:35355020 Differential assembly diversifies GABA(A) receptor structure... | KEEP AS NON CORE | Summary: Some gamma2-containing receptor combinations can participate in extrasynaptic GABA signaling. Reason: The cited paper characterizes recombinant human alpha4/beta3/gamma2L assemblies, while the detailed new co-agonist current measurements are centered on delta-containing preparations. Independent gamma2 immunogold localization includes extrasynaptic membranes, and functional human gamma2 receptors respond to GABA. These complementary observations support the composition-dependent context as non-core, without claiming a gamma2-specific native tonic-current experiment in this paper or making every gamma2 receptor extrasynaptic. |
| GO:1902476 chloride transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: The ancestral chloride-transport placement agrees with target function. Reason: The verified PTN008360627 origin lies above the exact human target in the actual tree; no retained target-path loss contradicts it. Human experimental self-donation is legitimate grounding. Gamma2 contributes part of the chloride-conducting receptor pore. |
| GO:1902476 chloride transmembrane transport | IDA PMID:29950725 Structure of a human synaptic GABA(A) receptor. | ACCEPT | Summary: The human alpha1/beta2/gamma2 receptor directly supports chloride conductance. Reason: The structural and functional work identifies gamma2 as a transmembrane constituent of the human GABA-gated receptor. Chloride transmembrane transport is the direct channel output. The engineered intracellular-loop segment and purification tag do not define a natural splice product. |
| GO:1902476 chloride transmembrane transport | IDA PMID:30602789 Cryo-EM structure of the human Ξ±1Ξ²3Ξ³2 GABA(A) receptor in a ... | ACCEPT | Summary: Human gamma2L-containing channels carry chloride across membranes. Reason: The human alpha1/beta3/gamma2L study couples a full-length receptor preparation with functional controls. Gamma2 forms part of the channel architecture that supports chloride conductance; the original target annotation is retained with its assay scope. |
| GO:1902476 chloride transmembrane transport | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer correctly identifies chloride movement across the membrane. Reason: The mouse/Ensembl transfer agrees with human receptor currents and structure. Transport is passive through a GABA-gated heteromeric pore, not energy-coupled pumping by a gamma2 monomer. |
| GO:1902476 chloride transmembrane transport | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse-derived transport claim matches the human chloride pore. Reason: Human gamma2-containing heteromers demonstrate chloride conductance and provide a clear molecular basis for chloride transmembrane transport. The mouse ISS source is consistent with this independently established target function. |
| GO:1902711 GABA-A receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited GABA-A receptor-complex placement is sound. Reason: The verified PTN008360627 IBD lies on the actual human target lineage, with exact sequence alignment and no retained negative placement on that path. Human target self-donation reflects legitimate experimental grounding. Human receptor structures independently confirm complex membership. |
| GO:1902711 GABA-A receptor complex | IEA GO_REF:0000107 | ACCEPT | Summary: The electronic complex assignment matches the human structural evidence. Reason: The mouse/Ensembl inference agrees with directly resolved human gamma2-containing receptor assemblies. Retain the precise GABA-A complex term without imposing a single stoichiometry on every receptor composition. |
| GO:1902711 GABA-A receptor complex | IPI PMID:29950725 Structure of a human synaptic GABA(A) receptor. | ACCEPT | Summary: Engineered human gamma2 is directly resolved within a synaptic receptor assembly. Reason: The original human alpha1/beta2/gamma2 structure establishes gamma2 complex membership. The loop substitution and twin-Strep tag are experimental modifications, not a natural short isoform. GABA binds beta/alpha interfaces, whereas the alpha/gamma interface supports benzodiazepine-site pharmacology. |
| GO:1902711 GABA-A receptor complex | IPI PMID:30602789 Cryo-EM structure of the human Ξ±1Ξ²3Ξ³2 GABA(A) receptor in a ... | ACCEPT | Summary: Full-length human gamma2L is directly present in the reconstituted receptor. Reason: The Methods identify the long P18507-2 backbone with a purification tag in alpha1/beta3/gamma2L receptors. This is direct complex evidence. The shorter reference-position metadata in UniProt does not override the explicitly described construct. |
| GO:1902711 GABA-A receptor complex | IPI PMID:35355020 Differential assembly diversifies GABA(A) receptor structure... | ACCEPT | Summary: Human gamma2L forms more than one experimentally resolved receptor assembly. Reason: The original structures include alpha4/beta3/gamma2L and beta3/gamma2 complexes with different subunit arrangements. Full-length human gamma2L bears a purification tag. These are positive membership observations, but they do not prove that every recombinant stoichiometry is abundant in native tissue. |
| GO:1902711 GABA-A receptor complex | IPI PMID:37892178 Extra-Synaptic GABA(A) Receptor Potentiation and Neurosteroi... | ACCEPT | Summary: Human gamma2L-containing receptor combinations are functionally studied. Reason: The authentic original abstract reports human alpha5/beta3/gamma2L and alpha1/beta2/gamma2L receptors in HEK expression assays. That directly supports gamma2 membership in the heteromers. Separate rat behavioral experiments are not converted into human complex-assembly measurements. |
| GO:1902711 GABA-A receptor complex | IPI PMID:39843743 Resolving native GABA(A) receptor structures from the human ... | ACCEPT | Summary: Native human receptor work directly identifies gamma2-containing GABA-A complexes. Reason: The selected original human-brain Results and Methods explicitly identify gamma2 in the main receptor assemblies, including the predominant beta2/alpha1/beta2/alpha1/gamma2 population. Five main maps contain mixtures at other subunit positions. The separate auxiliary-complex map is assigned gamma-x, and its tentative partner contacts are not turned into exact gamma2 interactions. Mass spectrometry reports short gamma2 in one dataset and both short and long forms in the other; it does not assign a natural splice product to every individual map. |
| GO:1902711 GABA-A receptor complex | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse orthology agrees with direct human GABA-A complex membership. Reason: Gamma2 is physically present in human alpha/beta/gamma2 heteropentamers. The mouse ISS transfer is independently corroborated by the human structural preparations and is not accepted merely from a family label. |
| GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | IBA GO_REF:0000033 | ACCEPT | Summary: Ancestral channel activity is consistent with gamma2 postsynaptic function. Reason: The actual PTHR18945 tree places human gamma2 below the verified PTN008360627 IBD, with exact target-sequence alignment and no retained loss annotation on its path. Human receptor currents and inhibitory-contact assays support transmitter-gated regulation of postsynaptic potential. The inference is assessed by the ancestral placement and target biology, not donor number. |
| GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse-derived activity matches postsynaptic receptor conductance. Reason: Gamma2-containing GABA-A receptors convert transmitter binding into chloride conductance that alters postsynaptic membrane potential. Human receptor function corroborates the mouse/Ensembl inference. The sign of the voltage change depends on the chloride gradient, so this activity is not restated as obligatory hyperpolarization in every cell. |
| GO:1904862 inhibitory synapse assembly | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Ancestral synapse-assembly participation is supported in a reduced receptor-contact model. Reason: The genuine PTN008360627 IBD is ancestral to the target, including legitimate human experimental grounding. Gamma2-containing receptor assemblies promote stable functional inhibitory contacts in co-culture; gamma2 is necessary within the combination but is not sufficient alone. The receptor provides a structural contribution to assembly, retained as non-core without asserting a gamma2-only adhesion function or universal in-vivo necessity. |
| GO:1904862 inhibitory synapse assembly | IDA PMID:23909897 GABA(A) receptors can initiate the formation of functional i... | KEEP AS NON CORE | Summary: Alpha1/beta2/gamma2 receptors promote functional inhibitory contacts. Reason: The original co-culture study measures stable contacts and synaptic currents in receptor-expressing cells. Gamma2 alone is not sufficient, but it participates in the receptor assembly whose extracellular presentation supports recognition. Retain this reduced-system structural contribution as non-core, without assigning an independently established gamma2 adhesion ligand or an intact-brain assembly mechanism. |
| GO:1904862 inhibitory synapse assembly | IDA PMID:25489750 Inhibitory synapse formation in a co-culture model incorpora... | KEEP AS NON CORE | Summary: The protocol supports the receptor-dependent contact model with defined reuse limits. Reason: The selected original protocol describes alpha1/beta3/gamma2 assays and reuses some earlier alpha1/beta2/gamma2 figures. Its Figure 1B caption repeats beta2 despite the beta3 context; this is retained as a source inconsistency, not silently repaired or counted as independent replication. The supported inhibitory-contact context remains non-core. |
| GO:1904862 inhibitory synapse assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse-derived assembly inference agrees with positive receptor-contact experiments. Reason: The inferred process is supported by comparisons of receptor-expressing cells with controls in the original contact model. This is more than a downstream perturbation phenotype: the receptor-bearing membrane participates in contact formation. Mixed preparations and receptor-composition dependence limit generalization, so the process is retained as non-core. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which original experiment supports the human GABRG2βGABARAPL1 partner context attributed to PMID:9892355, and how does it relate to the later mouse motif-binding study?
Q: How are the three verified natural gamma2 products distributed among native receptor assemblies and neuronal compartments, especially the 515-residue product?
Q: Which native human gamma2-containing receptor combinations mediate extrasynaptic currents or histamine modulation, beyond the recombinant and ortholog evidence?
Q: Should GO:1902711 GABA-A receptor complex have an ontology relationship to GO:0034707 chloride channel complex, consistent with the established chloride-conducting assembly? The current ontology has no is_a/part_of path between them.
Experiment: Compare the three sequence-verified human gamma2 products in matched alpha/beta backgrounds using surface quantification and electrophysiology, retaining tags and loop substitutions as separate experimental variables.
Hypothesis: Natural product differences may alter trafficking or receptor function in a composition-dependent manner.
Experiment: Test sequence-defined human gamma2 and human GABARAPL1 with full-length association and purified intracellular-segment binding assays, including the mouse constructs and earlier peptide as explicit comparators.
Hypothesis: The conserved interaction mechanism may support the human partner context, but species and construct effects require direct resolution.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)