CHRNB1

Summary: Retain uncertainty about the source-specific membrane-organization interpretation.

Reason: The authentic PMID:8651643 abstract reports a beta gate mutation, prolonged openings, endplate myopathy and extensive postsynaptic membrane remodeling. This is positive structural pathology, but does not by itself resolve an organization step performed by normal beta1 versus secondary excitotoxic remodeling. The full original body remained inaccessible after bounded publisher/search attempts; do not reject the experimental assertion from the abstract or equate every assembly observation with membrane organization.

Summary: Retain the receptor contribution to muscle contraction.

Reason: Acetylcholine-gated current supplies the excitatory neuromuscular step that triggers contraction; beta1 contributes the conducting/gating structure. This does not assign actomyosin ATPase chemistry to beta1. The PAINT node is a curated phylogenetic assertion; rat P25109 is independently identified as Chrnb1.

Summary: Retain the receptor contribution to muscle contraction.

Reason: Acetylcholine-gated current supplies the excitatory neuromuscular step that triggers contraction; beta1 contributes the conducting/gating structure. This does not assign actomyosin ATPase chemistry to beta1. The source is an Ensembl orthology transfer from rat P25109/ENSRNOP00000089285, independently identified as Chrnb1; human receptor experiments corroborate the excitatory step.

Summary: Specify acetylcholine-gated cation channel activity.

Reason: Human reconstitution and structure identify an acetylcholine-gated cation channel contribution, which GO:0022848 specifies more precisely than general transmembrane receptor activity.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Specify acetylcholine-gated cation channel activity.

Reason: The human beta1-containing receptor conducts cations in response to acetylcholine; GO:0022848 specifies both the ligand and permeant class missing from general ion-channel activity.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Specify acetylcholine-gated cation channel activity.

Reason: GO:0022848 specifies acetylcholine and cation selectivity within the extracellular ligand-gated channel class, matching human receptor electrophysiology and the beta1 pore contribution.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: Three literal positive human CHRNB1–ASB6/Q9NWX5 IntAct records under PMID:32296183 describe pooling, array and validated yeast two-hybrid assays, including N-terminal Gal4 DNA-binding and C-terminal activation-domain fusions. The inspected primary text describes repeated pairwise verification and sequence confirmation; dataset-wide orthogonal validation is not a CHRNB1-specific native assay. ASB6 is a probable substrate-recognition subunit of an ECS ubiquitin-ligase complex, not independently established as the catalytic ligase. Neither a native membrane encounter nor CHRNB1 adaptor/ubiquitination activity follows from this pair. Retain generic binding as non-core rather than invent a molecular mechanism. The published ClinGen project curation instruction explicitly retains supported generic binding as KEEP_AS_NON_CORE when no evidence-backed specific replacement is established; this task-specific rule takes precedence over the skill default. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Retain plasma-membrane activity of the assembled receptor.

Reason: The original source maps to membrane localization; the target-specific assembled human channel evidence corroborates applicability. Conserved membrane topology is not evidence for beta1 functioning alone.

Summary: Retain plasma-membrane activity of the assembled receptor.

Reason: The original source maps to membrane localization; the target-specific assembled human channel evidence corroborates applicability. Conserved membrane topology is not evidence for beta1 functioning alone.

Summary: Retain plasma-membrane activity of the assembled receptor.

Reason: Original PMID:8872460 includes patient muscle endplate studies and mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells. Beta V266M changes receptor gating; receptor-level ACh competition measures apparent affinity rather than isolated beta1 ligand binding.

Summary: Retain membership in the acetylcholine-gated channel complex.

Reason: The original ancestral/domain or ortholog annotation is consistent with the independently demonstrated human heteropentamer. The adult complex contains two alpha1 chains and one beta1, delta and epsilon; fetal receptors use gamma in place of epsilon. No physiological beta1 homopentamer or testing of the N-terminally shortened product is asserted.

Summary: Retain membership in the acetylcholine-gated channel complex.

Reason: The original ancestral/domain or ortholog annotation is consistent with the independently demonstrated human heteropentamer. The adult complex contains two alpha1 chains and one beta1, delta and epsilon; fetal receptors use gamma in place of epsilon. No physiological beta1 homopentamer or testing of the N-terminally shortened product is asserted.

Summary: Retain membership in the acetylcholine-gated channel complex.

Reason: Original PMID:8872460 includes patient muscle endplate studies and mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells. Beta V266M changes receptor gating; receptor-level ACh competition measures apparent affinity rather than isolated beta1 ligand binding. The adult complex contains two alpha1 chains and one beta1, delta and epsilon; fetal receptors use gamma in place of epsilon. No physiological beta1 homopentamer or testing of the N-terminally shortened product is asserted.

Summary: Retain membership in the acetylcholine-gated channel complex.

Reason: PMID:15701510 is the native Torpedo receptor structure, not a purified human receptor. The authentic author PDF supports the five-subunit complex at that species scope; later human reconstruction independently confirms target membership. The adult complex contains two alpha1 chains and one beta1, delta and epsilon; fetal receptors use gamma in place of epsilon. No physiological beta1 homopentamer or testing of the N-terminally shortened product is asserted.

Summary: Specify monoatomic cation transmembrane transport.

Reason: The channel carries cations across the postsynaptic membrane, making GO:0098655 more precise than unrestricted ion transport or cation transport without the membrane step. Original evidence, source and relation are preserved; this refinement does not turn beta1 into an independently functioning transporter.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Specify monoatomic cation transmembrane transport.

Reason: The channel carries cations across the postsynaptic membrane, making GO:0098655 more precise than unrestricted ion transport or cation transport without the membrane step. Original evidence, source and relation are preserved; this refinement does not turn beta1 into an independently functioning transporter.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Specify monoatomic cation transmembrane transport.

Reason: The channel carries cations across the postsynaptic membrane, making GO:0098655 more precise than unrestricted ion transport or cation transport without the membrane step. Original PMID:8872460 includes patient muscle endplate studies and mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells. Beta V266M changes receptor gating; receptor-level ACh competition measures apparent affinity rather than isolated beta1 ligand binding.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Retain calcium transport by the beta1-containing muscle receptor.

Reason: PMID:16527851 measures fractional calcium current through wild-type human adult alpha/beta/delta/epsilon receptors reconstituted in rat GH4C1 cells; fetal human receptors are additionally examined in human myotubes. Adult receptors carry about 7% of inward current as calcium, versus 2–3% for the fetal receptor. Epsilon strongly influences the adult human–mouse difference; this is not a beta1-only selectivity measurement. These direct target-containing receptor experiments corroborate the IBA without a donor-count or neuronal-donor exclusion argument.

Summary: Retain the receptor contribution to muscle contraction.

Reason: Acetylcholine-gated current supplies the excitatory neuromuscular step that triggers contraction; beta1 contributes the conducting/gating structure. This does not assign actomyosin ATPase chemistry to beta1. The original PMID:8651643 abstract directly links beta1 gate disruption to weakness and altered neuromuscular function, although its complete body was not recovered.

Summary: Specify acetylcholine receptor signaling.

Reason: ACh-evoked current in human beta1-containing receptors (PMID:27375219) identifies acetylcholine receptor signaling, GO:0095500, more precisely than unrestricted signal transduction. The ARBA source is retained; no presynaptic release mechanism is inferred.

Proposed replacements: acetylcholine receptor signaling pathway

Summary: Specify acetylcholine receptor signaling.

Reason: ACh stimulation and altered endplate/channel responses identify GO:0095500 rather than unrestricted signal transduction. Original PMID:8872460 includes patient muscle endplate studies and mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells. Beta V266M changes receptor gating; receptor-level ACh competition measures apparent affinity rather than isolated beta1 ligand binding.

Proposed replacements: acetylcholine receptor signaling pathway

Summary: Retain the core postsynaptic cholinergic transmission role.

Reason: At the neuromuscular junction, beta1 participates in conversion of transmitter occupancy into a cation current; it does not perform presynaptic secretion. The broad original transmission term remains valid coverage of this defining function.

Summary: Retain the core postsynaptic cholinergic transmission role.

Reason: At the neuromuscular junction, beta1 participates in conversion of transmitter occupancy into a cation current; it does not perform presynaptic secretion. The broad original transmission term remains valid coverage of this defining function.

Summary: Retain the core postsynaptic cholinergic transmission role.

Reason: At the neuromuscular junction, beta1 participates in conversion of transmitter occupancy into a cation current; it does not perform presynaptic secretion. Original PMID:8872460 includes patient muscle endplate studies and mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells. Beta V266M changes receptor gating; receptor-level ACh competition measures apparent affinity rather than isolated beta1 ligand binding.

Summary: Retain the core postsynaptic cholinergic transmission role.

Reason: At the neuromuscular junction, beta1 participates in conversion of transmitter occupancy into a cation current; it does not perform presynaptic secretion. The original PMID:8651643 abstract supports disturbed endplate transmission from a beta gate mutation; detailed full-source access remains limited.

Summary: Specify acetylcholine-gated cation channel activity.

Reason: Original PMID:8872460 includes patient muscle endplate studies and mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells. Beta V266M changes receptor gating; receptor-level ACh competition measures apparent affinity rather than isolated beta1 ligand binding. The measured ACh-evoked currents identify GO:0022848 more precisely than unrestricted channel activity; beta1 contributes to the heteromeric pore.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Specify acetylcholine-gated cation channel activity.

Reason: GO:0022848 specifies the acetylcholine ligand and cation-selective channel contribution demonstrated by human reconstitution, beyond general ligand gating. The original rat P25109 donor is beta1; the evidence code and source relation are retained.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Specify acetylcholine-gated cation channel activity.

Reason: GO:0022848 specifies the acetylcholine ligand and cation-selective channel contribution demonstrated by human reconstitution, beyond general ligand gating. The original rat P25109 donor is beta1; the evidence code and source relation are retained.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Specify acetylcholine-gated cation channel activity.

Reason: The original PMID:8651643 abstract gives a beta gate mutation and prolonged channel openings; detailed original constructs remain uninspected. The official GO:0015464 usage comment directs ionotropic nicotinic receptors to GO:0022848; independent human channel recordings establish the beta1-containing receptor at that scope.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Specify acetylcholine-gated cation channel activity.

Reason: Original PMID:8872460 includes patient muscle endplate studies and mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells. Beta V266M changes receptor gating; receptor-level ACh competition measures apparent affinity rather than isolated beta1 ligand binding. The official GO:0015464 usage comment directs ionotropic nicotinic receptors to GO:0022848; independent human channel recordings establish the beta1-containing receptor at that scope.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Refine generic membrane location to the postsynaptic membrane.

Reason: The specific physiological compartment is the muscle postsynaptic membrane, supported by patient endplates and receptor structure/function. Domain-based membrane topology alone is broader than this directly substantiated location.

Proposed replacements: postsynaptic membrane

Summary: Retain the specific acetylcholine-gated cation channel function.

Reason: Current mouse P09690, rat P25109 and bovine P04758 identities are beta1 orthologs, where present in the original source. The complete preserved relation is interpreted at subunit scope; the core represents contribution to the heteromeric pore. Canonical ligand-binding sites lie at alpha1–delta/epsilon interfaces, so channel participation is distinct from isolated beta1 acetylcholine binding.

Summary: Retain the specific acetylcholine-gated cation channel function.

Reason: Current mouse P09690, rat P25109 and bovine P04758 identities are beta1 orthologs, where present in the original source. The complete preserved relation is interpreted at subunit scope; the core represents contribution to the heteromeric pore. Canonical ligand-binding sites lie at alpha1–delta/epsilon interfaces, so channel participation is distinct from isolated beta1 acetylcholine binding.

Summary: Retain the specific acetylcholine-gated cation channel function.

Reason: Current mouse P09690, rat P25109 and bovine P04758 identities are beta1 orthologs, where present in the original source. The complete preserved relation is interpreted at subunit scope; the core represents contribution to the heteromeric pore. Canonical ligand-binding sites lie at alpha1–delta/epsilon interfaces, so channel participation is distinct from isolated beta1 acetylcholine binding.

Summary: Retain the specific acetylcholine-gated cation channel function.

Reason: Current mouse P09690, rat P25109 and bovine P04758 identities are beta1 orthologs, where present in the original source. The complete preserved relation is interpreted at subunit scope; the core represents contribution to the heteromeric pore. Canonical ligand-binding sites lie at alpha1–delta/epsilon interfaces, so channel participation is distinct from isolated beta1 acetylcholine binding.

Summary: Retain the neuromuscular-junction compartment.

Reason: Actual original PMID:7531341 pages 758–762 were read as primary page images. Human patient/control endplate recordings are separate from mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells (Methods 759). The causal mutation is epsilon T264P; beta is the wild-type coassembled subunit, not the mutated gene. Receptor-level endplate evidence and human heteropentamer membership support the beta1-containing receptor at this compartment. The original experiment does not provide a beta1-mutant localization assay or prove every alternative product is localized there.

Summary: Retain the neuromuscular-junction compartment.

Reason: The mouse beta1 source is independently identified; receptor-level endplate evidence and human heteropentamer membership support the beta1-containing receptor at this compartment. The original experiment does not provide a beta1-mutant localization assay or prove every alternative product is localized there.

Summary: Retain the neuromuscular-junction compartment.

Reason: Actual original PMID:7531341 pages 758–762 were read as primary page images. Human patient/control endplate recordings are separate from mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells (Methods 759). The causal mutation is epsilon T264P; beta is the wild-type coassembled subunit, not the mutated gene. Receptor-level endplate evidence and human heteropentamer membership support the beta1-containing receptor at this compartment. The original experiment does not provide a beta1-mutant localization assay or prove every alternative product is localized there.

Summary: Specify monoatomic cation transmembrane transport.

Reason: The channel carries cations across the postsynaptic membrane, making GO:0098655 more precise than unrestricted ion transport or cation transport without the membrane step. Original evidence, source and relation are preserved; this refinement does not turn beta1 into an independently functioning transporter.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Specify monoatomic cation transmembrane transport.

Reason: The channel carries cations across the postsynaptic membrane, making GO:0098655 more precise than unrestricted ion transport or cation transport without the membrane step. Original evidence, source and relation are preserved; this refinement does not turn beta1 into an independently functioning transporter.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Leave the source-specific nicotine-behavior inference unresolved.

Reason: The authentic PMID:16874522 abstract reports SNP/haplotype associations with smoking quantity and dependence scores in 2,037 subjects from 602 families, including significant CHRNB1 signals. Those positive observations must not be erased, but association alone does not establish a beta1-performed behavioral response mechanism. The full original Methods/Results were not recovered after bounded official and author-copy attempts, so the IMP assertion is retained for expert source review rather than removed or treated as a demonstrated neural beta1 receptor experiment.

Summary: Do not equate receptor affinity changes with direct beta1 acetylcholine binding.

Reason: The actual mouse P09690 donor has an experimental IMP/PMID:8872460 acetylcholine-binding annotation. Its Methods measure ACh competition at assembled mouse receptors in HEK cells, and the beta V266M effect on apparent affinity is explained by altered open-state occupancy. This establishes receptor allostery, not an acetylcholine contact made by beta1. Independent human receptor structures in PMID:40203823 place canonical ACh sites at alpha1–delta and alpha1–epsilon interfaces; the beta1-specific mouse gating study PMID:24194945 makes the same functional distinction. GO:0042166 describes binding itself. The source assertion overextends receptor-level affinity evidence to direct beta1 binding; retain the genuine donor record and beta1 channel role, without a universal claim excluding every possible noncanonical ligand interaction.

Summary: Do not equate receptor affinity changes with direct beta1 acetylcholine binding.

Reason: The actual mouse P09690 donor has an experimental IMP/PMID:8872460 acetylcholine-binding annotation. Its Methods measure ACh competition at assembled mouse receptors in HEK cells, and the beta V266M effect on apparent affinity is explained by altered open-state occupancy. This establishes receptor allostery, not an acetylcholine contact made by beta1. Independent human receptor structures in PMID:40203823 place canonical ACh sites at alpha1–delta and alpha1–epsilon interfaces; the beta1-specific mouse gating study PMID:24194945 makes the same functional distinction. GO:0042166 describes binding itself. The source assertion overextends receptor-level affinity evidence to direct beta1 binding; retain the genuine donor record and beta1 channel role, without a universal claim excluding every possible noncanonical ligand interaction.

Summary: Retain the postsynaptic electrical response function.

Reason: Cation permeation through the beta1-containing receptor generates the endplate depolarization and excitatory postsynaptic response. The term applies to the assembled receptor contribution, not a separate voltage-gated beta1 channel or presynaptic transmitter release. The original logical/ortholog/ancestral evidence remains exact.

Summary: Retain the broader synaptic location.

Reason: Original PMID:8872460 includes patient muscle endplate studies and mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells. Beta V266M changes receptor gating; receptor-level ACh competition measures apparent affinity rather than isolated beta1 ligand binding. The neuromuscular postsynapse is a synaptic compartment. A broader correct source component need not be rejected merely because the core also names the more precise postsynaptic membrane.

Summary: Retain the postsynaptic membrane assignment.

Reason: The original nicotinic receptor domain/subcellular-location mapping matches the demonstrated muscle endplate compartment.

Summary: Refine the true broad process to beta1-mediated neuromuscular transmission.

Reason: Human beta1-containing receptors directly perform the postsynaptic receiver step of neuromuscular transmission. The broad nervous-system process is therefore true and can be refined to this already represented mechanism. The original PMID:11104662 full text studies beta2 epilepsy/reconstitution and only compares beta1 sequence; that source mismatch is retained as provenance, not converted into uncertainty about an independently established beta1 function. ARBA is likewise not the evidence for this refinement.

Proposed replacements: neuromuscular synaptic transmission

Summary: Refine the true broad process to beta1-mediated neuromuscular transmission.

Reason: Human beta1-containing receptors directly perform the postsynaptic receiver step of neuromuscular transmission. The broad nervous-system process is therefore true and can be refined to this already represented mechanism. The original PMID:11104662 full text studies beta2 epilepsy/reconstitution and only compares beta1 sequence; that source mismatch is retained as provenance, not converted into uncertainty about an independently established beta1 function. ARBA is likewise not the evidence for this refinement.

Proposed replacements: neuromuscular synaptic transmission

Summary: Retain the postsynaptic electrical response function.

Reason: Cation permeation through the beta1-containing receptor generates the endplate depolarization and excitatory postsynaptic response. The term applies to the assembled receptor contribution, not a separate voltage-gated beta1 channel or presynaptic transmitter release. The original logical/ortholog/ancestral evidence remains exact.

Summary: Separate muscle development from beta-channel excitotoxic pathology.

Reason: PMID:8651643 positively reports severe endplate myopathy and membrane remodeling from a beta gate mutation, but its accessible abstract does not establish progression of muscle cells to mature structure as defined by GO:0055001. The original full body remained inaccessible, so the experimental developmental assertion is unresolved rather than categorically rejected. Normal receptor excitation and secondary muscle damage are distinguished from a demonstrated developmental step.

Summary: Retain the postsynaptic electrical response function.

Reason: Cation permeation through the beta1-containing receptor generates the endplate depolarization and excitatory postsynaptic response. The term applies to the assembled receptor contribution, not a separate voltage-gated beta1 channel or presynaptic transmitter release. The original logical/ortholog/ancestral evidence remains exact.

Summary: Retain the postsynaptic electrical response function.

Reason: Cation permeation through the beta1-containing receptor generates the endplate depolarization and excitatory postsynaptic response. The term applies to the assembled receptor contribution, not a separate voltage-gated beta1 channel or presynaptic transmitter release. The original logical/ortholog/ancestral evidence remains exact.

Summary: Retain acetylcholine-triggered receptor signaling.

Reason: ACh-evoked opening of the beta1-containing human receptor converts transmitter binding into postsynaptic cation current. This directly corroborates acetylcholine receptor signaling; the PAINT node remains a curated ancestral assertion rather than a pairwise neuronal-donor transfer.

Summary: Retain acetylcholine-triggered receptor signaling.

Reason: Original PMID:21480901 explicitly uses Torpedo receptors transplanted into Xenopus oocytes and measures ACh currents/lidocaine inhibition. Its unchanged normal cache is abstract-only; no direct human beta1 construct or detailed full-body assay is invented. Independent human experiments establish the same receptor-signaling role.

Summary: Retain the postsynaptic electrical response function.

Reason: Cation permeation through the beta1-containing receptor generates the endplate depolarization and excitatory postsynaptic response. The term applies to the assembled receptor contribution, not a separate voltage-gated beta1 channel or presynaptic transmitter release. The original logical/ortholog/ancestral evidence remains exact.

Summary: Retain the postsynaptic specialization membrane compartment.

Reason: The muscle endplate membrane is a postsynaptic specialization. Family/ortholog sources are retained with the exact target relation; no unsupported presynaptic pool is inferred.

Summary: Retain the postsynaptic specialization membrane compartment.

Reason: The muscle endplate membrane is a postsynaptic specialization. Family/ortholog sources are retained with the exact target relation; no unsupported presynaptic pool is inferred.

Summary: Specify acetylcholine-gated cation channel activity.

Reason: Actual original PMID:7531341 pages 758–762 were read as primary page images. Human patient/control endplate recordings are separate from mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells (Methods 759). The causal mutation is epsilon T264P; beta is the wild-type coassembled subunit, not the mutated gene. GO:0022848 is a typed descendant of GO:1904315 and adds acetylcholine and cation specificity while retaining the postsynaptic-potential role. Human beta1 reconstitution independently corroborates the channel contribution.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Specify acetylcholine-gated cation channel activity.

Reason: GO:0022848 is a typed descendant of GO:1904315 and adds acetylcholine and cation specificity while retaining the postsynaptic-potential role. Human beta1 reconstitution independently corroborates the channel contribution.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Specify acetylcholine-gated cation channel activity.

Reason: Actual original PMID:7531341 pages 758–762 were read as primary page images. Human patient/control endplate recordings are separate from mouse alpha/beta/delta/epsilon cDNA reconstitution in HEK cells (Methods 759). The causal mutation is epsilon T264P; beta is the wild-type coassembled subunit, not the mutated gene. GO:0022848 is a typed descendant of GO:1904315 and adds acetylcholine and cation specificity while retaining the postsynaptic-potential role. Human beta1 reconstitution independently corroborates the channel contribution.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity