GABRA1 encodes the alpha1 subunit of heteropentameric GABA-A receptors. Its extracellular domain contributes to GABA-binding interfaces with beta subunits, and its transmembrane helices contribute to the chloride-conducting pore. Alpha1-containing receptors mediate fast postsynaptic GABAergic signaling; other partner combinations support tonic signaling, with gating and pharmacology depending on receptor composition. The direction and electrical effect of chloride movement depend on the ionic gradient. Alpha1-containing receptor assemblies can also promote inhibitory contacts in reduced neuronal co-cultures. Pathogenic GABRA1 variants can impair receptor trafficking or function and cause epilepsy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: The transmembrane receptor is specifically an ionotropic GABA-A receptor subunit. Reason: The InterPro signatures support a membrane receptor, but independent human alpha1 receptor data establish GO:0004890. Official is_a paths connect this descendant through GABA receptor activity to the current broad term. Refinement preserves the positive biological claim and original signatures. Proposed replacements: GABA-A receptor activity |
| GO:0004890 GABA-A receptor activity | IDA PMID:23909897 GABA(A) receptors can initiate the formation of functional i... | ACCEPT | Summary: Alpha1-containing GABA-A receptors support synaptic chloride signaling. Reason: Alpha1/beta2/gamma2-expressing cells show GABA responses and spontaneous and evoked postsynaptic currents in the co-culture assay. These measurements support receptor activity in GABAergic chloride signaling. The HEK host does not independently establish the species of every cloned subunit. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| 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 alpha1/beta3/gamma2L receptors retain ligand-responsive function. Reason: PMID:30602789 uses full-length human P14867 with beta3/gamma2L, purification tags and a megabody. Electrophysiology and ligand-binding assays support receptor activity. The desensitized structural state is not an inactive-protein conclusion, and unresolved pocket densities with GABA docking are not claimed as direct ligand identification. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. Supporting Evidence: PMID:30602789 the reconstituted receptor retains functional properties and allosteric interactions |
| GO:0004890 GABA-A receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Alpha1 forms the complementary ligand-binding surface of GABA-A receptors. Reason: The InterPro-derived activity agrees with human heteromer expression and structures locating the GABA pocket at beta-positive/alpha-negative interfaces. Alpha1 participates in recognition and gating as part of the receptor; it is not assigned an independent soluble GABA-binding or GABA-B activity. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| GO:0004890 GABA-A receptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Rat orthology supports alpha1 GABA-A receptor activity. Reason: Human alpha1 heteromer expression and structural experiments establish GABA-A receptor activity. Conserved receptor architecture in the actual family alignment corroborates the rat P62813 ISS transfer; the original donor and method remain the source of this annotation. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| GO:0004890 GABA-A receptor activity | TAS PMID:2465923 Sequence and expression of human GABAA receptor alpha 1 and ... | ACCEPT | Summary: Cloned human alpha1 and beta1 produce GABA-gated chloride channels. Reason: The authentic PMID:2465923 abstract explicitly names human alpha1/beta1 clones and functional channels in mammalian cells. That directly supports the molecular claim despite unavailable detailed original methods. Later human heteromer structures independently corroborate it. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: The channel transports chloride following GABA activation. Reason: Generic monoatomic-ion channel activity is correct but less informative than the established GABA-gated chloride conductance. Official is_a paths connect GO:0022851 to this parent. Human receptor electrophysiology and pore architecture support the refinement without changing the original InterPro evidence. Proposed replacements: GABA-gated chloride ion channel activity Supporting Evidence: PMID:29950725 application of GABA induced inward currents that were inhibited by bicuculline |
| GO:0005230 extracellular ligand-gated monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Extracellular GABA gates the alpha1-containing chloride channel. Reason: The broad extracellular-ligand-gated channel term is refined to GO:0022851, an official is_a descendant. Direct human heteromer experiments identify both the ligand and transported ion. The substitution does not claim that alpha1 alone forms a functional physiological homopentamer. Proposed replacements: GABA-gated chloride ion channel activity |
| GO:0005886 plasma membrane | EXP PMID:25489750 Inhibitory synapse formation in a co-culture model incorpora... | ACCEPT | Summary: Alpha1 is detected at the surface of receptor-expressing HEK293 cells. Reason: The original PMID:25489750 Methods and Results use antibodies to extracellular subunit epitopes to select and demonstrate surface-expressing receptor cells. Retain the Figure1B beta2/beta3 caption discrepancy and avoid inferring clone species from the host. This positive target surface evidence supports the location independently of the synapse-assembly interpretation. Supporting Evidence: PMID:25489750 cell surface expression of Ξ±1, Ξ²2 and Ξ³2 subunits |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha1 functions in the plasma membrane. Reason: Alpha1-containing receptors function at the plasma membrane in both synaptic and composition-dependent extrasynaptic pools. Human surface-expression and channel experiments support this location, and the actual PAINT plasma-membrane assertion descends to the target without a retained target-path loss. The two dated donor versions are documented separately in the source guide. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: The HPA membrane assignment agrees with direct human receptor evidence. Reason: Cloned human receptor function and surface-labeling assays establish plasma-membrane localization. The HPA immunofluorescence method is consistent with that conclusion, although no particular target image or antibody-specific localization was independently inspected. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined electronic sources agree on the plasma-membrane receptor pool. Reason: Human alpha1 surface-expression and channel measurements support plasma-membrane localization. The mouse/Ensembl and subcellular-location mappings agree with this location; the donor response contains experimental membrane contexts whose primary assays were not independently read. These combined mappings are not counted as separate experiments. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Rat orthology and human experiments support plasma-membrane localization. Reason: Human alpha1 expression and surface-labeling experiments establish plasma-membrane localization. The rat P62813 transfer is consistent with those findings and retains direct membrane EXP contexts in the current donor response; their detailed primary assays were not independently read. |
| GO:0005886 plasma membrane | TAS PMID:2465923 Sequence and expression of human GABAA receptor alpha 1 and ... | ACCEPT | Summary: Human alpha1/beta1 expression produces functional surface channels. Reason: The PMID:2465923 abstract explicitly names human clones and chloride channels in mammalian cells. Detailed localization methods were not recovered, but later surface immunolabeling and functional human receptor work independently support the membrane assignment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-975340 | ACCEPT | Summary: Reactome explicitly places the alpha1-containing channel in the plasma membrane. Reason: Reactome places the alpha1-containing chloride channel in the plasma membrane. The catalyst chain resolves through the heteropentamer and GABRA sets to human P14867 residues 28β456, rather than assigning alpha1 the location of the transported chloride. This is target membership in a curated model, not experimental verification of every modeled component or a universal stoichiometry. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Alpha1 directly contributes to transmembrane chloride movement. Reason: The generic ion-transport parent is refined to the already asserted GO:1902476. The official is_a paths and direct receptor current/pore evidence establish this specificity; the original InterPro signatures remain intact. Proposed replacements: chloride transmembrane transport |
| GO:0006821 chloride transport | IEA GO_REF:0000002 | MODIFY | Summary: The established chloride transport occurs through a transmembrane pore. Reason: GO:1902476 is a direct is_a child of chloride transport and specifies the membrane-crossing event executed by the alpha1-containing channel. This is a refinement of a positive claim, not rejection of the family mapping. 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 alpha1-containing receptors couple GABA binding to channel responses. Reason: PMID:29950725 links the beta/alpha ligand pockets, receptor pore and GABA-evoked bicuculline-sensitive currents. Engineered loop replacements and detergent-dependent conformations are acknowledged; functional comparisons support the native molecular signaling role. |
| 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: Human alpha1/beta3/gamma2L receptors execute GABA signaling. Reason: Electrophysiology and ligand-binding assays in PMID:30602789 support receptor signaling by the full-length human assembly. GABA docking into uncertain structural density is not substituted for those actual functional measurements. |
| GO:0007214 gamma-aminobutyric acid signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: GABRA1 directly transduces GABA signals through receptor conductance. Reason: Alpha1-containing receptors directly convert GABA binding into channel responses in synaptic and composition-dependent extrasynaptic settings. The checked ontology records GO:0160001 extrasynaptic signaling via GABA as an is_a child of GO:0007214. Restricting this whole claim to that child would omit the supported synaptic setting. GO:0051932 separately encompasses transmitter release and the postsynaptic response; its name alone is not used to assert an is_a relationship. |
| GO:0007214 gamma-aminobutyric acid signaling pathway | NAS PMID:35140402 Mechanisms of inhibition and activation of extrasynaptic Ξ±Ξ² ... | ACCEPT | Summary: Alpha1/beta3 receptors provide a composition-dependent mode of GABA signaling. Reason: PMID:35140402 compares wild-type and engineered human alpha1/beta3 receptors with alpha1/beta3/gamma2 in patch-clamp experiments. Lower opening probability and zinc inhibition are receptor-context properties, not evidence against GABA signaling. Zinc-coordinating beta3 histidines are not assigned to alpha1. |
| GO:0007214 gamma-aminobutyric acid signaling pathway | TAS PMID:2465923 Sequence and expression of human GABAA receptor alpha 1 and ... | ACCEPT | Summary: Human alpha1/beta1 channels directly respond to GABA. Reason: Cloned human alpha1/beta1 channels respond directly to GABA, supporting receptor-mediated signal transduction. The authentic 1989 abstract establishes the human clones and functional channels; detailed methods remain unread. Later human receptor experiments corroborate the molecular role. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The broad membrane assignment is refined to the established plasma-membrane pool. Reason: InterPro membrane architecture and direct human surface-expression measurements support GO:0005886, a verified is_a descendant of membrane. This positive refinement does not assert absence of intracellular trafficking pools, whose specific vesicle evidence is assessed separately. Proposed replacements: plasma membrane Supporting Evidence: PMID:25489750 cell surface expression of Ξ±1, Ξ²2 and Ξ³2 subunits |
| GO:0016917 GABA receptor activity | ISS GO_REF:0000024 | MODIFY | Summary: Alpha1 contributes to the ionotropic GABA-A receptor within a heteropentamer. Reason: Human alpha1/beta1 expression and alpha1-containing receptor structures establish the ionotropic GABA-A subtype. Refine broad GABA receptor activity to its verified is_a descendant GO:0004890 while retaining the original contributes_to relationship and rat P62813 ISS provenance. The activity belongs to the assembled receptor. Proposed replacements: GABA-A receptor activity |
| GO:0022851 GABA-gated chloride ion channel activity | IDA PMID:23909897 GABA(A) receptors can initiate the formation of functional i... | ACCEPT | Summary: Alpha1-containing receptors mediate GABA-evoked currents in the co-culture preparation. Reason: PMID:23909897 records GABA-evoked, zolpidem-sensitive currents from alpha1/beta2/gamma2-expressing HEK293 cells and functional contacts with embryonic rat neurons. This supports the existing subunit contribution to channel activity. HEK host identity does not independently identify every cloned subunit species; direct human structural/functional work corroborates the molecular claim. Supporting Evidence: PMID:23909897 This response was enhanced by zolpidem |
| GO:0022851 GABA-gated chloride ion channel activity | IDA PMID:2538761 Importance of a novel GABAA receptor subunit for benzodiazep... | ACCEPT | Summary: Alpha1/beta1/gamma2 assemblies have GABA-A channel pharmacology. Reason: Alpha1/beta1/gamma2 assemblies form functional GABA-A receptors with gamma2-dependent benzodiazepine sensitivity. This is explicit in the authentic PMID:2538761 abstract. Exact clone species and complete methods were not read; independent human alpha1 experiments corroborate the channel contribution. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| 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: Full-length human alpha1 participates in a GABA-responsive chloride pore. Reason: The human alpha1/beta3/gamma2L receptor in PMID:30602789 is functionally tested by patch clamp and ligand binding. This supports channel activity independently of whether the purified structure captures a conducting conformation. Gamma2L is the partner product, not a second GABRA1 isoform. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| GO:0022851 GABA-gated chloride ion channel activity | IDA PMID:9039914 Insensitivity to anaesthetic agents conferred by a class of ... | ACCEPT | Summary: Alpha1 channel activity is established across human heteromer preparations. Reason: Direct human alpha1/beta1 and alpha1/beta2/gamma2 experiments establish alpha1 contribution to GABA-gated chloride channels. The original PMID:9039914 abstract describes epsilon assembly with alpha/beta subunits and altered chloride current but does not expose the precise alpha1 construct. That source-specific limit remains explicit. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| GO:0022851 GABA-gated chloride ion channel activity | IEA GO_REF:0000107 | ACCEPT | Summary: Alpha1 contributes to GABA-gated chloride conductance. Reason: Alpha1 contributes to the shared chloride pore of the assembled receptor, as supported by human expression, patch-clamp measurements and M2 pore architecture. These findings corroborate the mouse/Ensembl transfer. The incoming contributes_to qualifier correctly assigns conductance to the receptor assembly. |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | UNDECIDED | Summary: The subcellular-vocabulary vesicle mapping retains an unresolved source detail. Reason: The human UniProt cytoplasmic-vesicle membrane statement is transferred from rat P62813; GO_REF:0000044 and SL-0089 describe its electronic projection. The inspected rat evidence block now identifies PMID:25172774 with ECO:0000269. Its authentic abstract concerns gamma2-containing receptor transport, while full text and any alpha1-specific localization panel remain unverified. Retain uncertainty consistently with the ISS claim; neither lack of recovered full text nor receptor trafficking in general establishes or refutes this specific alpha1 compartment assignment. |
| GO:0030659 cytoplasmic vesicle membrane | ISS GO_REF:0000024 | UNDECIDED | Summary: The original rat-derived cytoplasmic-vesicle membrane detail is not yet independently resolved. Reason: The specific alpha1 cytoplasmic-vesicle membrane localization remains unresolved. Rat P62813 provides the ISS source; its UniProt evidence block links the location to PMID:25172774 with ECO:0000269. The authentic abstract reports gamma2-containing receptor transport and KIF21B perturbation, but full text and an alpha1-specific localization panel or vesicle population were not verified. This access limit neither establishes nor refutes the alpha1 compartment claim. |
| GO:0032590 dendrite membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha1 receptor activity occurs in dendritic membranes. Reason: Alpha1 receptor localization in dendritic membranes is consistent with its neuronal postsynaptic role and the receptor-context evidence. The actual PAINT assertion and literal rat donors support inherited localization on the target lineage. This does not resolve the separate spine-specific panel or imply that every alpha1 pool is dendritic. |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: The receptor carries chloride across the membrane. Reason: The general monoatomic-ion transmembrane process is refined to its verified chloride-specific descendant GO:1902476, supported by direct human receptor experiments. This does not infer a new transporter activity or a role for an unrelated family branch. Proposed replacements: chloride transmembrane transport |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000117 | MODIFY | Summary: GABRA1 is specifically a GABA-A signaling receptor subunit. Reason: Human alpha1 receptor experiments establish GABA-A receptor activity, a verified is_a descendant of broad signaling receptor activity. The ARBA inference is therefore refined to GO:0004890 while its original method and rule identifier remain unchanged. Proposed replacements: GABA-A receptor activity |
| GO:0043197 dendritic spine | IDA PMID:25025157 Palmitoylation of gephyrin controls receptor clustering and ... | UNDECIDED | Summary: The particular alpha1 dendritic-spine localization remains unresolved. Reason: PMID:25025157 genuinely assays alpha1 surface expression after palmitoylation inhibition; it is not dismissed because gephyrin is the main subject. The selected original spine passage concerns PSD95 controls, and the specific alpha1 spine-localization panel behind this annotation has not been recovered or inspected. Surface biotinylation alone does not locate alpha1 in a spine. Preserve the IDA assertion pending that target-specific source check. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt location mapping agrees with postsynaptic receptor function. Reason: Functional postsynaptic contacts and human transmembrane receptor architecture support postsynaptic-membrane localization. The SL-0219 vocabulary mapping agrees with that biological evidence; the underlying bovine-transfer access limit is retained in the reference assessment. |
| GO:0045211 postsynaptic membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Alpha1 is an established postsynaptic membrane receptor despite limited current bovine donor detail. Reason: Functional postsynaptic contacts, human receptor membrane architecture and conserved alpha1 identity support postsynaptic-membrane localization. The original bovine P08219 donor is retained. Its current same-term GOA row is electronic and the underlying UniProt evidence was not inspected, so the target evidence supports the whole claim without claiming that donor assay was read. |
| GO:0051932 synaptic transmission, GABAergic | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited GABAergic transmission role includes the human alpha1 lineage. Reason: Alpha1-containing receptors execute the postsynaptic response in GABAergic transmission, as shown by the original co-culture currents. The actual PAINT assertion descends to human P14867; its target self-donor is legitimate descendant experimental support. Literal donor and date details remain in the source evidence. |
| GO:0051932 synaptic transmission, GABAergic | IDA PMID:23909897 GABA(A) receptors can initiate the formation of functional i... | ACCEPT | Summary: Alpha1-containing postsynaptic receptors support spontaneous and evoked GABAergic currents. Reason: The original co-culture Results include stable active contacts, spontaneous currents and paired or extracellularly evoked responses. Control and mismatched-receptor preparations do not reproduce the contacts. This directly supports receptor participation in transmission while retaining the reduced-system and clone-species limits. Supporting Evidence: PMID:23909897 spontaneous βminiatureβ synaptic events and AP-driven GABA release |
| GO:0051932 synaptic transmission, GABAergic | ISS GO_REF:0000024 | ACCEPT | Summary: Alpha1 is a postsynaptic component of GABAergic transmission. Reason: The rat ISS transfer is independently supported by functional alpha1-containing contacts in neuronal co-culture and human receptor chemistry. The receptor performs the postsynaptic activation/conductance step included in the official process definition; it is not assigned presynaptic GABA synthesis or release. |
| GO:0051932 synaptic transmission, GABAergic | NAS PMID:29950725 Structure of a human synaptic GABA(A) receptor. | ACCEPT | Summary: Alpha1 receptor conductance is a core postsynaptic step of GABAergic transmission. Reason: PMID:29950725 provides human receptor structure and functional responses, rather than a complete neuronal circuit experiment. Combined with direct co-culture transmission, it supports the existing NAS claim without treating an isolated structure as measurement of vesicular release. |
| GO:0051932 synaptic transmission, GABAergic | NAS PMID:30602789 Cryo-EM structure of the human Ξ±1Ξ²3Ξ³2 GABA(A) receptor in a ... | ACCEPT | Summary: Human alpha1-containing receptors mediate the receptor step of inhibitory transmission. Reason: PMID:30602789 establishes the functional human synaptic receptor assembly. Its purified nanodisc structure does not itself reproduce a synapse, but the molecular function and independent co-culture transmission support the whole claim. The alpha1 component does work in the postsynaptic response. |
| GO:0060078 regulation of postsynaptic membrane potential | IEA GO_REF:0000108 | ACCEPT | Summary: Opening the alpha1-containing channel changes postsynaptic membrane potential. Reason: GO_REF:0000108 projects the existing contextual channel activity GO:1904315 through an official inter-ontology relationship. Direct postsynaptic currents independently support the process. Retain the original source GO term and avoid an unconditional claim that chloride flux is always inward or always hyperpolarizing. |
| GO:0098794 postsynapse | IBA GO_REF:0000033 | MODIFY | Summary: The inherited postsynaptic localization is specifically membrane-associated. Reason: Alpha1 is a pore-forming transmembrane subunit at postsynaptic membranes, so the broad postsynapse location is refined to GO:0045211. The verified relation to postsynapse is part_of, not is_a. The genuine PAINT placement supports the broader location; this anatomical refinement does not imply target loss or a false ancestral assertion. 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 P14867 at AN1963/PTN002498429. The retained tree and exact 456-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 the ancestral localization or its propagation is false. Proposed replacements: postsynaptic membrane |
| GO:0098982 GABA-ergic synapse | IEA GO_REF:0000107 | ACCEPT | Summary: Alpha1 operates at GABAergic synapses. Reason: Functional GABAergic contacts and human alpha1 channel activity support localization at GABAergic synapses without excluding extrasynaptic pools. The mouse P62812 donor response also retains same-term experimental annotations to PMID:12466441 and their anatomical extension; these are curator records, not independently reread primary assays. |
| GO:0099634 postsynaptic specialization membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Alpha1 is concentrated in the membrane specialization of inhibitory postsynapses. Reason: Alpha1 channel function and neuronal receptor-clustering evidence support the specialized postsynaptic membrane role. The rat donor retains IDA9464994 and separate SynGO contexts, whose primary assays were not independently read. LHFPL4-dependent clustering describes an accessory-protein effect rather than an activity performed by alpha1. |
| GO:0160001 extrasynaptic signaling via GABA | NAS PMID:18204487 alpha1beta2delta, a silent GABAA receptor: recruitment by tr... | KEEP AS NON CORE | Summary: Some alpha1-containing receptor combinations support extrasynaptic tonic signaling. Reason: The cited PMID:18204487 abstract assays alpha1/beta2/delta receptors in oocytes and demonstrates low GABA efficacy with modulation; it does not image human extrasynaptic receptors. Independent native mouse alpha1/delta tonic currents and human alpha1/beta3 functional work support the composition-dependent biological context. Retain it as non-core to the general alpha1 channel role, without making all alpha1 assemblies extrasynaptic or treating the oocyte host as subunit species. |
| GO:1902476 chloride transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha1 inherits and directly performs chloride transmembrane transport. Reason: Human alpha1 receptor measurements establish chloride conductance across the membrane. The actual PAINT assertion lies on the target lineage without a retained loss, and human P14867 legitimately contributes descendant experimental evidence to that inference. |
| GO:1902476 chloride transmembrane transport | IDA PMID:29950725 Structure of a human synaptic GABA(A) receptor. | ACCEPT | Summary: The human alpha1-containing pore carries chloride. Reason: PMID:29950725 couples GABA-evoked currents and antagonist inhibition to the heteropentamer structure and pore-lining helices. The engineered structural loops are not natural products, and caution about detergent conformations does not negate the functional current measurements. Supporting Evidence: PMID:29950725 application of GABA induced inward currents that were inhibited by bicuculline |
| GO:1902476 chloride transmembrane transport | IDA PMID:30602789 Cryo-EM structure of the human Ξ±1Ξ²3Ξ³2 GABA(A) receptor in a ... | ACCEPT | Summary: Functionally tested human alpha1/beta3/gamma2L receptors conduct chloride. Reason: PMID:30602789 uses patch-clamp measurements of the full-length human receptor and functional reconstitution. The captured desensitized state is interpreted alongside those recordings rather than as a permanently closed or nonconducting gene product. |
| GO:1902476 chloride transmembrane transport | IDA PMID:9039914 Insensitivity to anaesthetic agents conferred by a class of ... | ACCEPT | Summary: Alpha1 chloride transport is established, with the epsilon-source construct limit retained. Reason: Human alpha1 channel experiments establish chloride transmembrane transport. PMID:9039914 additionally reports altered GABA-evoked chloride-current properties in epsilon-containing alpha/beta assemblies, but its abstract does not identify the exact alpha1 construct. The whole molecular claim is retained with that source-specific limit. |
| GO:1902710 GABA receptor complex | ISS GO_REF:0000024 | MODIFY | Summary: Alpha1 belongs specifically to the GABA-A receptor complex. Reason: Direct human recombinant and native alpha1 assemblies establish membership in the GABA-A receptor complex. Refine the broad GABA receptor complex to its verified is_a child GO:1902711. The rat P62813 ISS source and its donor IDA12930820 context remain provenance; the latter primary paper was not independently read. Proposed replacements: GABA-A receptor complex Supporting Evidence: PMID:39843743 a minimum of 12 distinct Ξ±1-containing GABAA receptor assemblies |
| GO:1902711 GABA-A receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: The human alpha1 lineage inherits GABA-A receptor-complex membership. Reason: Human alpha1-containing structures directly establish membership in GABA-A receptor complexes. The actual PAINT complex assertion descends to the target, with P14867 legitimately included among its experimental descendants. |
| GO:1902711 GABA-A receptor complex | IDA PMID:30266951 Structural basis of neurosteroid anesthetic action on GABA(A... | ACCEPT | Summary: Alpha1 complex membership is established independently of the ELIC chimera. Reason: Independent human heteropentamer and native brain studies establish alpha1 membership in GABA-A receptor complexes. The original PMID:30266951 experiment instead uses an ELIC extracellular domain fused to engineered human alpha1 transmembrane sequence. Its propylamine/steroid responses cannot alone establish native alpha1 orthosteric recognition or a physiological alpha1 homopentamer. |
| GO:1902711 GABA-A receptor complex | IDA PMID:9039914 Insensitivity to anaesthetic agents conferred by a class of ... | ACCEPT | Summary: The alpha1 complex claim is supported without inferring details hidden in the epsilon abstract. Reason: Human alpha1 structures and native brain complexes establish GABA-A receptor membership. The original PMID:9039914 abstract supports epsilon assembly with alpha/beta subunits but does not name the precise alpha1 construct. That limitation is retained without replacing the curator-supplied IDA source. |
| GO:1902711 GABA-A receptor complex | IPI PMID:29950725 Structure of a human synaptic GABA(A) receptor. | ACCEPT | Summary: Human alpha1 is directly resolved in alpha1/beta2/gamma2 heteropentamers. Reason: PMID:29950725 identifies the human subunits, engineered loop replacements, receptor architecture and functional comparisons. The artificial loops are construct features, not natural products; the human alpha1 complex membership is directly supported. |
| 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 alpha1 is a component of alpha1/beta3/gamma2L complexes. Reason: PMID:30602789 specifies human P14867 in a purified tagged heteropentamer reconstituted into nanodiscs. The gamma2L product, megabody and minor alpha1 proteolysis do not define alternative natural GABRA1 proteins. Complex membership is supported irrespective of the captured desensitized conformation. Supporting Evidence: PMID:30602789 We isolated the full-length human Ξ±1Ξ²3Ξ³2L receptor |
| GO:1902711 GABA-A receptor complex | IPI PMID:35140402 Mechanisms of inhibition and activation of extrasynaptic Ξ±Ξ² ... | ACCEPT | Summary: Alpha1/beta3 forms a functional GABA-A receptor assembly without gamma. Reason: PMID:35140402 resolves two alpha1 and three beta3 subunits and compares engineered structures with wild-type receptor recordings. This supports alpha1 complex membership and composition-dependent behavior, not a fixed five-chain subtype or universal extrasynaptic localization. Supporting Evidence: PMID:35140402 two Ξ±1 subunits and three Ξ²3 subunits |
| GO:1902711 GABA-A receptor complex | IPI PMID:39843743 Resolving native GABA(A) receptor structures from the human ... | ACCEPT | Summary: Native alpha1-containing receptor complexes were isolated from human brain. Reason: Anti-alpha1 purification and structural analysis identify native alpha1-containing GABA-A receptor assemblies in human epilepsy-surgery tissue. The authentic abstract and selected native Methods/Results support complex membership, including beta2- and beta3-containing assemblies. Mixed subunit assignments, tentative accessory interfaces and preparation abundances are not generalized to fixed stoichiometries, specific direct partner interactions or healthy tissue. Supporting Evidence: PMID:39843743 a minimum of 12 distinct Ξ±1-containing GABAA receptor assemblies |
| GO:1902711 GABA-A receptor complex | NAS PMID:17159992 A new naturally occurring GABA(A) receptor subunit partnersh... | ACCEPT | Summary: Alpha1 can partner with delta in native GABA-A receptor assemblies. Reason: The PMID:17159992 abstract explicitly describes mouse hippocampal alpha1/delta colocalization and tonic currents with genetic comparisons. It is not a direct human imaging experiment, but it demonstrates genuine composition diversity. Independent human alpha1 receptor complexes establish the whole membership claim without restricting all alpha1 assemblies to gamma2. |
| GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha1 channel activity regulates postsynaptic membrane potential. Reason: GABA activation of alpha1-containing receptors changes postsynaptic conductance and thereby regulates membrane potential, as supported by co-culture currents and human channel measurements. The contextual transmitter-gated activity is inherited through the verified PAINT placement. The electrical effect depends on the ionic gradient. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse orthology supports a transmitter-gated postsynaptic channel activity. Reason: The P62812/Ensembl projection agrees with the observed function of alpha1-containing receptors. GABA activation changes postsynaptic conductance; the sign and size of the voltage response depend on the ionic gradient, so the annotation is not recast as unconditional hyperpolarization. The retained enables relation is interpreted as receptor function attributable to alpha1 within the assembled receptor, where alpha1 supplies ligand-contact and pore-forming elements; it is not evidence for an autonomous isolated-alpha1 channel. The core states this assembly-level contribution explicitly. |
| GO:1904862 inhibitory synapse assembly | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Alpha1-containing receptors can help organize inhibitory synaptic contacts. Reason: Receptor-expressing cells promote active inhibitory contacts in the original co-culture model, supporting a structural contribution to synapse assembly. This reduced-system contribution is retained as non-core without assigning a unique alpha1 adhesion interface or universal in-vivo requirement. The actual PAINT placement and legitimate target experimental descendants corroborate the inherited process assertion. |
| 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 formation of functional inhibitory contacts in co-culture. Reason: PMID:23909897 compares receptor-expressing HEK293 cells with control and mismatched-receptor cells and measures stable, active contacts and synaptic currents. The assembly contributes structural recognition rather than merely being required for a downstream phenotype. Its reduced-model scope supports non-core retention, not a universal alpha1-only synapse-organizing mechanism. Supporting Evidence: PMID:23909897 formation of functional GABAergic synapses |
| GO:1904862 inhibitory synapse assembly | IDA PMID:25489750 Inhibitory synapse formation in a co-culture model incorpora... | KEEP AS NON CORE | Summary: The protocol extends the receptor-dependent inhibitory-contact model. Reason: PMID:25489750 describes surface-expression and contact assays with alpha1/beta3/gamma2 cells while reusing some 2013 alpha1/beta2/gamma2 figures. Figure1B repeats beta2 in its caption despite the beta3 context; that source inconsistency is retained without silently fixing the panel. The positive assembly context is non-core and is not counted as an independent replication of every earlier measurement. |
| GO:1904862 inhibitory synapse assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse-derived synapse-assembly inference agrees with positive target-context evidence. Reason: Receptor-dependent contact formation in co-culture supports a contextual contribution to inhibitory synapse assembly. High expression, mixed cellular preparations and disrupted native connectivity limit generalization, so the mouse/Ensembl inference is retained as non-core rather than an alpha1-specific adhesion molecular function. |
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Download this section (compressed HTML)Q: Which original alpha1-specific localization image or assay supports the PMID25025157 dendritic-spine annotation?
Suggested experts: GABA-A receptor localization specialists
Q: Which alpha1-specific measurements, if any, support the rat cytoplasmic-vesicle membrane assignment linked to PMID:25172774, and which vesicle population was measured?
Q: Which alpha1 extracellular contacts contribute to synapse assembly in native neurons independently of receptor abundance and channel conductance?
Q: How do native human alpha1 partner compositions and cellular chloride gradients determine synaptic versus tonic signaling?
Experiment: Compare wild-type alpha1-containing assemblies with defined channel-silent and extracellular-interface variants in neuronal contact assays, controlling surface abundance and partner stoichiometry.
Experiment: Trace endogenous alpha1 in defined endosomal/vesicular compartments and dendritic spines using validated target labeling, compartment markers and surface-versus-internal controls.
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