CNGB3 is the beta subunit of the cone photoreceptor cyclic-nucleotide-gated cation channel. It assembles with CNGA3 in a heterotetramer containing three alpha subunits and one beta subunit. CNGB3 contributes to the ion-conduction pathway, selectivity filter and cyclic-nucleotide-binding machinery, shaping ligand sensitivity and pore gating. Intracellular cGMP controls the cone membrane current during visual transduction. Pathogenic CNGB3 variants can disrupt channel function and cause achromatopsia or related cone disorders.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001750 photoreceptor outer segment | IBA GO_REF:0000033 | ACCEPT | Summary: Accept conserved photoreceptor outer-segment localization. Reason: The mapped mouse Cngb3 donor supports photoreceptor outer-segment localization: PMID:15634774 reports CNGB3 in cone outer segments as data not shown. The other donors include a rod beta subunit and are not relabeled as CNGB3 orthologs. This is an ortholog inference, not direct human outer-segment immunolocalization. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000025740 UNRESOLVED The published PTHR45638 PAINT slice records a positive IBD for this exact node and term, dated 20260828, with an empty taxon value. Its seed set matches the preserved GOA WITH/FROM after separating the PTN. This verifies the recorded ancestral assertion, but the historical tree topology, alignment and placement rationale were not inspected. UNRESOLVED is restricted to that phylogenetic assessment; the positive target-function judgment is recorded separately. UniProtKB:Q9JJZ9 SUPPORTS TRANSFER The mapped mouse Cngb3 donor has a same-term IDA from PMID:15634774. The actual Results report cone outer-segment CNGB3 as data not shown; this is positive ortholog localization, not direct human microscopy. |
| GO:0001750 photoreceptor outer segment | IEA GO_REF:0000107 | ACCEPT | Summary: Accept the mouse-ortholog outer-segment transfer. Reason: Q9JJZ9 is mouse Cngb3, with current direct outer-segment annotation grounded in the inspected mouse retinal study. Human CNGB3 contributes to the cone surface channel. Preserve the original Ensembl transfer while distinguishing endogenous mouse localization from recombinant human membrane experiments. |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine the broad channel mapping to cGMP-gated cation-channel activity. Reason: The InterPro ion-channel domain identifies a real pore-forming component. Human CNGA3/CNGB3 currents and structures establish the cGMP-gated cation-channel contribution more specifically. CNGB3 is not asserted to form a functional autonomous channel. Proposed replacements: intracellularly cGMP-activated cation channel activity |
| GO:0005221 intracellularly cyclic nucleotide-activated monoatomic cation channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine cyclic-nucleotide gating to the principal cGMP-gated activity. Reason: Human heteromeric-channel recordings and cGMP-bound structures support the more specific GO:0005223. This converges on the existing specific channel assertions without merging their distinct sources or adding a NEW annotation. cAMP responsiveness is retained separately as a secondary capability. The original enables qualifier is preserved as source data; the reviewed relation should be contributes_to, because CNGB3 supplies part of the assembled channel activity. Proposed replacements: intracellularly cGMP-activated cation channel activity |
| GO:0005222 intracellularly cAMP-activated cation channel activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inherited cAMP activation as a secondary channel capability. Reason: Wild-type human CNGB3 increases relative cAMP efficacy and apparent affinity in CNGA3/CNGB3 channels compared with CNGA3 homomers. cAMP nevertheless activates the heteromer less effectively than cGMP, consistent with its secondary physiological scope. The target self-donor is legitimate experimental grounding. The original enables qualifier is preserved as source data; the reviewed relation should be contributes_to, because CNGB3 supplies part of the assembled channel activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000025739 UNRESOLVED The published PTHR45638 PAINT slice records a positive IBD for this exact node and term, dated 20240801, with taxon:33213. Its seed set matches the preserved GOA WITH/FROM after separating the PTN. This verifies the recorded ancestral assertion, but the historical tree topology, alignment and placement rationale were not inspected. UNRESOLVED is restricted to that phylogenetic assessment; the positive target-function judgment is recorded separately. UniProtKB:Q9NQW8 SUPPORTS TRANSFER Human CNGB3 itself has same-term IDA from PMID:12815043. Wild-type CNGB3 changes cAMP responsiveness of CNGA3/CNGB3 channels; the target is a legitimate experimental descendant premise, with secondary physiological scope. |
| GO:0005222 intracellularly cAMP-activated cation channel activity | IDA PMID:12815043 Achromatopsia-associated mutation in the human cone photorec... | KEEP AS NON CORE | Summary: Retain direct cAMP activation of the assembled human channel. Reason: The actual human retinal CNGB3/oocyte study compares wild-type heteromers with CNGA3 homomers: CNGB3 enhances relative cAMP efficacy and apparent affinity, while CNGB3 alone produces no functional channel in the reported experiment. The null T383fsX construct behaves like the alpha homomer when coexpressed, and S435F effects are separate from wild type. Purified human channel reconstitution independently gives open probabilities of 0.004 with cAMP and 0.28 with cGMP at 10 micromolar; these preparation-specific values are not native-cone response estimates or binding constants. The original enables qualifier is preserved as source data; the reviewed relation should be contributes_to, because CNGB3 supplies part of the assembled channel activity. |
| GO:0005222 intracellularly cAMP-activated cation channel activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the automated cAMP-channel assertion at secondary scope. Reason: The mapped capability agrees with direct cAMP activation of human CNGA3/CNGB3. The relevant functional unit is the assembled channel. cGMP remains the physiological cone agonist; no independent reconstruction of the ARBA rule is claimed. The original enables qualifier is preserved as source data; the reviewed relation should be contributes_to, because CNGB3 supplies part of the assembled channel activity. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited cGMP-gated channel contribution. Reason: Direct human heteromeric-channel recordings and purified-channel reconstitution establish cGMP gating. CNGB3 changes pore and activation properties relative to CNGA3 homomers; its target self-donor is legitimate experimental grounding. The original enables qualifier is preserved as source data; the reviewed relation should be contributes_to, because CNGB3 supplies part of the assembled channel activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000811708 UNRESOLVED The published PTHR45638 PAINT slice records a positive IBD for this exact node and term, dated 20240801, with taxon:6072. Its seed set matches the preserved GOA WITH/FROM after separating the PTN. This verifies the recorded ancestral assertion, but the historical tree topology, alignment and placement rationale were not inspected. UNRESOLVED is restricted to that phylogenetic assessment; the positive target-function judgment is recorded separately. UniProtKB:Q9NQW8 SUPPORTS TRANSFER Human CNGB3 itself has same-term IDAs from PMID:12815043 and PMID:24164424. These human heteromeric-channel experiments provide legitimate target experimental grounding, not evidence of beta3-only current. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IDA PMID:12815043 Achromatopsia-associated mutation in the human cone photorec... | ACCEPT | Summary: Accept direct human cGMP-gated channel contribution. Reason: Human wild-type CNGB3 coexpressed with CNGA3 changes the properties of cGMP-activated currents relative to CNGA3 homomers. The original human retinal CNGB3 clone, oocyte expression and wild-type/mutant controls were inspected in the external full text. This is an assembled-channel activity, not beta3 homomer function. The original enables qualifier is preserved as source data; the reviewed relation should be contributes_to, because CNGB3 supplies part of the assembled channel activity. Supporting Evidence: |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IDA PMID:24164424 Cyclic nucleotide-gated channel subunit glycosylation regula... | ACCEPT | Summary: Accept cGMP activation measured in human heteromeric channels. Reason: The source explicitly uses human retinal CNGB3 with human CNGA3 in Xenopus oocytes and measures inside-out cGMP-dependent currents. The MMP and glycosylation manipulations concern channel regulation; proteolysis is not assigned to CNGB3. Functional activation is distinguished from an isolated ligand-binding assay. The original enables qualifier is preserved as source data; the reviewed relation should be contributes_to, because CNGB3 supplies part of the assembled channel activity. Supporting Evidence: |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IEA GO_REF:0000120 | ACCEPT | Summary: Accept the combined automated cGMP-channel inference. Reason: The mouse Cngb3 ortholog and channel-family mapping agree with direct human CNGA3/CNGB3 cGMP-gated currents and reconstituted channel activity. The exact historical ARBA/Ensembl derivation is not reconstructed, and no unsupported activity is assigned to a beta3 homomer. The original enables qualifier is preserved as source data; the reviewed relation should be contributes_to, because CNGB3 supplies part of the assembled channel activity. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited plasma-membrane activity. Reason: Human CNGB3 has direct target membrane evidence: coexpression with CNGA3 enhances surface localization of tagged CNGB3 in oocytes and yields membrane-patch currents. This supports inherited plasma-membrane activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000811708 UNRESOLVED The published PTHR45638 PAINT slice records a positive IBD for this exact node and term, dated 20260828, with taxon:6072. Its seed set differs from the preserved GOA WITH/FROM: GOA-only RGD:621809. This verifies the recorded ancestral assertion, but the historical tree topology, alignment and placement rationale were not inspected. UNRESOLVED is restricted to that phylogenetic assessment; the positive target-function judgment is recorded separately. UniProtKB:Q9NQW8 SUPPORTS TRANSFER Human CNGB3 has same-term IDA from PMID:12815043, with enhanced surface localization on coexpression with CNGA3 and functional membrane currents. This supports the target premise independently of the ancestral placement. |
| GO:0005886 plasma membrane | IDA PMID:12815043 Achromatopsia-associated mutation in the human cone photorec... | ACCEPT | Summary: Accept the demonstrated human plasma-membrane localization. Reason: Actual Figure 2 caption and Results describe GFP-human CNGB3 in oocytes. CNGA3 promotes its surface localization; beta3 expressed alone has only low surface fluorescence. Tagged overexpression and partner dependence are explicit, without treating those measurements as native human retinal imaging. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Accept the UniProt plasma-membrane mapping. Reason: SL-0039 agrees with direct human CNGB3 surface-localization and excised-patch experiments. Cone outer-segment membrane localization is retained in its separate source assertions. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Refine ion transport to cation transmembrane transport. Reason: Human CNGA3/CNGB3 membrane-patch currents and the pore structure establish movement of cations across a membrane. This specifies the performed channel step beyond the broad InterPro ion-transport mapping. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0006812 monoatomic cation transport | IDA PMID:24164424 Cyclic nucleotide-gated channel subunit glycosylation regula... | MODIFY | Summary: Specify the membrane-crossing cation-transport step. Reason: The source measures human CNGA3/CNGB3 currents in inside-out membrane patches under defined predominantly sodium solutions. The demonstrated transport crosses the membrane; this does not convert calcium used for MMP activity into a calcium-permeability experiment. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0007165 signal transduction | NAS PMID:10888875 Genetic basis of total colourblindness among the Pingelapese... | MODIFY | Summary: Refine broad signaling to phototransduction. Reason: The original human family and partial-cDNA study links CNGB3 to cone vision but does not itself express a full-length channel. Independent human channel experiments demonstrate that CNGB3 contributes to the cGMP-controlled pore that converts the cone signaling cascade into membrane current. This performed visual-transduction step is more specific than generic signal transduction. Proposed replacements: phototransduction |
| GO:0007601 visual perception | IEA GO_REF:0000117 | ACCEPT | Summary: Accept the electronically inferred visual role. Reason: The cone-channel role is independently established by human CNGB3 disease genetics and direct channel function. The ARBA mapping is retained without inferring its historical rule execution. |
| GO:0007601 visual perception | IMP PMID:10958649 Mutations in the CNGB3 gene encoding the beta-subunit of the... | ACCEPT | Summary: Accept the human genetic evidence for visual function. Reason: The original positional-cloning study identifies an 809-residue human CNGB3 coding sequence and segregating mutations in achromatopsia families, with clinical visual and ERG assessment. Direct later channel experiments establish the pore contribution underlying this visual role; no channel-expression assay is attributed to the genetic paper. |
| GO:0007601 visual perception | IMP PMID:11536077 CNGA3 mutations in hereditary cone photoreceptor disorders. | ACCEPT | Summary: Retain visual perception with the source-specific citation limitation explicit. Reason: The full original Methods and Results screen CNGA3, while CNGB3 appears as cited prior work and unpublished preliminary prevalence. It does not supply the direct CNGB3 IMP experiment attributed to this row, so that reference relationship is adjudicated as miscited. Independent CNGB3 patient genetics and human channel measurements support the unchanged visual function. Supporting Evidence: PMID:11536077 Exons and flanking intron sequences of the CNGA3 gene |
| GO:0007601 visual perception | IMP PMID:15712225 Cone cGMP-gated channel mutations and clinical findings in p... | ACCEPT | Summary: Accept the explicitly reported CNGB3 visual phenotype. Reason: The complete abstract directly reports CNGB3 mutations in achromatopsia and other cone-dysfunction cohorts, with visual and ERG findings. Full Methods and patient tables were not recovered. The positive source claim and independently established CNGB3 cone-channel mechanism support visual perception without extending individual variant interpretations. |
| GO:0007601 visual perception | TAS PMID:10888875 Genetic basis of total colourblindness among the Pingelapese... | ACCEPT | Summary: Accept the original human visual-function association. Reason: The inspected original partial-cDNA and family study identifies CNGB3 variation associated with total colorblindness and loss of cone ERG responses. Its historical inferred stoichiometry and partial numbering are not treated as modern channel measurements. Later human functional work independently establishes the performed channel role. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Refine broad membrane location to plasma membrane. Reason: The InterPro membrane-channel topology is consistent with the direct human surface-localization and membrane-patch evidence. Plasma membrane is a supported, more informative replacement for the unrestricted membrane term. Proposed replacements: plasma membrane |
| GO:0017071 intracellular cyclic nucleotide activated cation channel complex | IBA GO_REF:0000033 | ACCEPT | Summary: Accept membership in the cyclic-nucleotide-activated channel complex. Reason: Direct human structural and functional evidence establishes a CNGA3/CNGB3 tetramer with three alpha and one beta subunit. The recorded ancestral complex assertion and current experimental premises are distinguished in the propagation assessment. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000811708 UNRESOLVED The published PTHR45638 PAINT slice records a positive IBD for this exact node and term, dated 20260828, with taxon:6072. Its seed set differs from the preserved GOA WITH/FROM: IBD-only UniProtKB:Q16281, UniProtKB:Q9NQW8. This verifies the recorded ancestral assertion, but the historical tree topology, alignment and placement rationale were not inspected. UNRESOLVED is restricted to that phylogenetic assessment; the positive target-function judgment is recorded separately. UniProtKB:Q9NQW8 SUPPORTS TRANSFER The current IBD adds human CNGB3 among its seeds although it is absent from the original GOA WITH/FROM. Current same-term IMP from PMID:12815043 and independent human channel structures support complex membership; neither is substituted into the preserved original source fields. |
| GO:0017071 intracellular cyclic nucleotide activated cation channel complex | IMP PMID:12815043 Achromatopsia-associated mutation in the human cone photorec... | ACCEPT | Summary: Accept functional assembly into the cone CNG-channel complex. Reason: The original human coexpression study distinguishes wild-type heteromers from CNGA3 homomers by ligand responses, pore properties and partner-dependent targeting. Mutant controls assess assembly-related behavior. The precise 3:1 stoichiometry comes from later structures, not the mRNA injection ratio. |
| GO:0030553 cGMP binding | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited cGMP binding. Reason: Human CNGB3 itself has a resolved cGMP-binding pocket in the assembled channel. Natural isoform 2 has a five-residue deletion across part of this pocket and was not tested separately; no equal ligand-binding capacity is assumed for that product. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000025739 UNRESOLVED The published PTHR45638 PAINT slice records a positive IBD for this exact node and term, dated 20260828, with taxon:33213. Its seed set differs from the preserved GOA WITH/FROM: GOA-only RGD:621809. This verifies the recorded ancestral assertion, but the historical tree topology, alignment and placement rationale were not inspected. UNRESOLVED is restricted to that phylogenetic assessment; the positive target-function judgment is recorded separately. UniProtKB:Q9NQW8 SUPPORTS TRANSFER Human CNGB3 has same-term IDA from PMID:37463923, where cGMP density occupies the beta-subunit pocket in the assembled channel. This supports target binding; it does not establish equivalent activity of the untested natural five-residue-deletion product. |
| GO:0030553 cGMP binding | IDA PMID:24164424 Cyclic nucleotide-gated channel subunit glycosylation regula... | ACCEPT | Summary: Retain cGMP binding with the source-assay distinction explicit. Reason: The original paper measures ligand-dependent activation of human CNGA3/CNGB3, not isolated beta3 affinity. Direct later structures independently resolve cGMP in the CNGB3 pocket. Together they support the binding capability while preserving the original annotation and avoiding a claim that a functional half-activation concentration is a binding constant. |
| GO:0030553 cGMP binding | IDA PMID:37463923 Conformational trajectory of allosteric gating of the human ... | ACCEPT | Summary: Accept direct structural cGMP binding by CNGB3. Reason: The human channel structures resolve cGMP in all four subunits, including beta3. Full-length detergent preparations and engineered CNGB3 79–809 nanodisc preparations are distinguished. Some fully occupied channels remain closed; ligand occupancy does not by itself establish pore opening. The natural five-residue-deletion product is not independently tested. Supporting Evidence: PMID:37463923 cGMP is bound to all four subunits |
| GO:0030553 cGMP binding | IEA GO_REF:0000117 | ACCEPT | Summary: Accept the automated cGMP-binding inference. Reason: The domain-based capability is directly corroborated by the human ligand-bound structures. This is an integrated part of the channel mechanism, not a separate enzyme activity or evidence that both natural products have identical binding. |
| GO:0042622 photoreceptor outer segment membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Accept the conserved cone outer-segment membrane location. Reason: MGI:1341818 identifies mouse Cnga3, the alpha partner rather than a beta3 ortholog. Actual mouse Cnga3 immunoelectron microscopy localizes the channel to cone outer-segment membrane folds; mouse Cngb3 is independently reported in cone outer segments. Together with direct human beta3 membrane-channel assembly, this supports the family/complex localization transfer without calling it native human imaging. |
| GO:0042622 photoreceptor outer segment membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Accept the conserved cone outer-segment membrane location. Reason: Q9JJZ8 identifies mouse Cnga3, the alpha partner rather than a beta3 ortholog. Actual mouse Cnga3 immunoelectron microscopy localizes the channel to cone outer-segment membrane folds; mouse Cngb3 is independently reported in cone outer segments. Together with direct human beta3 membrane-channel assembly, this supports the family/complex localization transfer without calling it native human imaging. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Refine transmembrane transport to cation transmembrane transport. Reason: The channel-family mapping is supported by human heteromeric membrane currents and monovalent-cation permeability experiments. The transported class is cations, and CNGB3 contributes to the conducting pore. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0098655 monoatomic cation transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited cation transmembrane transport. Reason: Direct human CNGA3/CNGB3 recordings demonstrate membrane-crossing cation current and beta3-dependent pore properties. These experiments support the inherited transport assertion; the incomplete mapping of two worm source identifiers is not evidence against it. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000811708 UNRESOLVED The published PTHR45638 PAINT slice records a positive IBD for this exact node and term, dated 20240801, with taxon:6072. Its seed set matches the preserved GOA WITH/FROM after separating the PTN. This verifies the recorded ancestral assertion, but the historical tree topology, alignment and placement rationale were not inspected. UNRESOLVED is restricted to that phylogenetic assessment; the positive target-function judgment is recorded separately. |
| GO:0120201 cone photoreceptor disc membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Accept the cone disc-membrane transfer at family/complex scope. Reason: MGI:1341818 is mouse Cnga3. Its actual immunoelectron microscopy places the alpha subunit on the membrane folds forming cone discs; the official cone-disc definition states that these membranes remain contiguous with the ciliary membrane. This is not rod closed-disc localization. Mouse beta3 outer-segment expression and human alpha/beta assembly support the conserved channel compartment, while direct human beta3 ultrastructural imaging is not claimed. |
| GO:1902495 transmembrane transporter complex | IDA PMID:24164424 Cyclic nucleotide-gated channel subunit glycosylation regula... | MODIFY | Summary: Specify the cyclic-nucleotide-activated cation-channel complex. Reason: Human CNGA3/CNGB3 coexpression and currents identify the particular CNG-channel complex. Later direct structures resolve its 3:1 assembly. The specific complex term is more informative than an unrestricted transmembrane transporter complex. Proposed replacements: intracellular cyclic nucleotide activated cation channel complex |
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Download this section (compressed HTML)Q: Does natural CNGB3 isoform 2 retain cGMP binding and channel contribution despite deletion of residues 590–594 across part of the resolved nucleotide-binding pocket?
Suggested experts: Cone-channel structural biologists and electrophysiologists
Q: How closely do native human cone subunit stoichiometry and membrane distribution match recombinant 3:1 CNGA3/CNGB3 preparations and mouse localization?
Suggested experts: Retinal cell biologists
Q: What conditions permit the secondary cAMP response to influence native cone currents?
Suggested experts: Photoreceptor electrophysiologists
Experiment: Sequence-verify both natural CNGB3 products and express each with matched CNGA3. Compare surface abundance, subunit assembly, cGMP and cAMP concentration-response curves, and single-channel behavior; include full-length canonical and engineered truncation controls. Distinguish activation from direct binding using an independent ligand-binding measurement.
Hypothesis: The five-residue deletion in natural CNGB3 isoform 2 changes ligand recognition or assembly independently of surface abundance.
Type: Product-resolved assembly, binding and electrophysiology
Experiment: Combine validated endogenous CNGB3 labeling with membrane-resolved imaging and cone patch recordings in an appropriate retinal model, separating alpha-partner colocalization from direct beta3 membrane localization.
Hypothesis: Native cone membrane organization constrains the channel behavior measured in heterologous preparations.
Type: Native localization and channel physiology
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