Connexin-30 is a four-pass membrane protein of gap junctions in cochlear non-sensory cells, epidermal keratinocytes and astrocytes. Its channels connect neighboring cytoplasms, supporting electrical coupling and small-solute exchange. Human connexin-30 can form homomeric channels and combine with connexin-26 in heteromeric connexons and heterotypic channels. GJB6 variants cause Clouston syndrome, affecting hair, nails and skin. GJB6 also lies in the DFNB1 hearing-loss locus; large deletions spanning this region can impair neighboring GJB2 regulation, complicating attribution to connexin-30 protein alone.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003163 sinoatrial node development | NAS PMID:26786210 The formation and function of the cardiac conduction system. | UNDECIDED | Summary: Gjb6 is included in a mouse sinoatrial-node gene program. Reason: The inspected Figure 3B in the author-hosted version of PMID:26786210 explicitly names Gjb6, so this is not a wrong-gene inference from an empty text search. That diagram establishes program membership, while the selected text concerns developmental regulators. Direct participation by GJB6 in sinoatrial-node development remains unresolved; an expression-program label alone does not adjudicate the full process claim. Supporting Evidence: |
| GO:0005243 gap junction channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: Connexin-30 enables gap-junction channel activity. Reason: Human GJB6 lies below the experimentally informed AN0/PTN008334405 assertion in the actual PTHR11984 tree. The target retains the four membrane-spanning regions inspected in the alignment, and its experimentally supported channel role is consistent with this placement. No target-specific functional loss is indicated. GJB6 itself is a legitimate experimental descendant source; its appearance in the donor set is not circular evidence. |
| GO:0005243 gap junction channel activity | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Human connexin-30 forms functional intercellular channels. Reason: PMID:12767933 measured human Cx30-EYFP dye transfer and Cx30 conductance. These results support channel activity. The construct and HeLa host limits remain explicit; untagged protein and physiological tissue conditions are not assumed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and A2RU14. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and O75396. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and P26715. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and Q15125. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and Q3KNW5. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and Q5J8X5. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and Q8TAF8. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and Q96IW7. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and Q9BZJ8. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI detected an interaction between GJB6 and Q9H2L4. Reason: Generic protein binding is uninformative for GJB6. Retain the interaction observation in the summary; no specific physiological function follows from partner identity alone. Supporting Evidence: |
| GO:0005884 actin filament | IMP PMID:19285977 The role of the cytoskeleton in the formation of gap junctio... | UNDECIDED | Summary: Actin-filament component assignment remains unresolved. Reason: Positive cortical association does not settle filament residence; actin-associated proteins can qualify, so membrane topology alone is not exclusionary. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Connexin-30 is a membrane-spanning gap-junction protein. Reason: The UniProt cell-membrane mapping is consistent with the four predicted transmembrane segments and the established gap-junction channel role. Plasma membrane identifies the membrane environment of GJB6, while gap junction and connexin complex identify more specific structural contexts. This location remains core without treating predicted segment boundaries as a newly measured human topology. |
| GO:0005921 gap junction | IEA GO_REF:0000120 | ACCEPT | Summary: Connexin-30 is located at gap junctions. Reason: The combined mapping cites mouse P70689, the recorded Ensembl protein and UniProt gap-junction location. Independent human evidence agrees. Preserve the actual source identifiers and distinguish ortholog annotation from a separate human assay. |
| GO:0005921 gap junction | IMP PMID:19285977 The role of the cytoskeleton in the formation of gap junctio... | ACCEPT | Summary: Connexin-30 localizes to gap-junction structures. Reason: Independent human evidence supports gap-junction localization (PMID:12767933). PMID:19285977 also describes junction targeting in HeLa cells. Preserve the location without claiming complete construct-sequence verification or verification of every cytoskeletal interaction. |
| GO:0005921 gap junction | NAS PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Human connexin-30 accumulates in junctional plaques. Reason: Human Cx30-EYFP localized to plaques in HeLa cells (PMID:12767933). Neither the host nor fluorescent fusion is converted into a claim of endogenous localization in every tissue. Supporting Evidence: |
| GO:0005922 connexin complex | IBA GO_REF:0000033 | ACCEPT | Summary: Connexin-30 inherits the connexin-complex structural role. Reason: The actual AN0/PTN008334405 complex-membership assertion is ancestral to GJB6; the literal experimental donor records and target sequence are conserved in the retained tree and alignment. The connexin architecture and target channel function fit that placement. This supports membership in the channel complex without converting reconstructed ancestral sequences into experiments or extending the claim to an untested heteromeric composition. |
| GO:0005922 connexin complex | IEA GO_REF:0000002 | ACCEPT | Summary: Connexin-30 is a subunit of connexin channel complexes. Reason: The connexin-family mapping supports the structural role of GJB6 within a connexon. The current UniProt subunit statement is explicitly by similarity, while channel formation provides compatible target evidence. Retain complex membership without claiming an independent human stoichiometric measurement, a particular mixed-subunit composition, or a new trafficking mechanism. |
| GO:0007154 cell communication | IEA GO_REF:0000002 | TOO GENERAL | Summary: Connexin-30 mediates communication between adjacent cells. Reason: The InterPro mapping correctly identifies a communication role, but GO:0007154 also covers interactions with the extracellular matrix and other surroundings. The more informative cell-cell signaling and electrical-coupling annotations already present describe GJB6 directly. Current ontology places these within cell communication; retain the source assertion while marking its specificity as too general, without adding a duplicate replacement. |
| GO:0007267 cell-cell signaling | IBA GO_REF:0000033 | ACCEPT | Summary: Connexin-30 provides a direct route for intercellular signaling. Reason: The actual AN0/PTN008334405 cell-cell signaling assertion is ancestral to GJB6, with the recorded experimental donors mapping inside that clade. The current definition explicitly includes signaling through gap junctions. The target channel architecture and electrical-coupling evidence support retention; neither a small donor subset nor lack of target self-evidence in this particular donor set would invalidate the placement. |
| GO:0007605 sensory perception of sound | TAS PMID:10610709 Human connexin 30 (GJB6), a candidate gene for nonsyndromic ... | UNDECIDED | Summary: Positive auditory evidence is substantial but does not isolate the human connexin-30 contribution. Reason: Cochlear coexpression (PMID:10610709), UniProt DFNA3B/DFNB1B disease records and the human deletion association (PMID:11807148) support auditory relevance. Teubner’s Gjb6-null mice had severe hearing loss and absent endocochlear potential (PMID:12490528). However, Boulay’s deletion preserving more Cx26 produced normal ABR and otoacoustic emissions (PMID:23303923), exposing a neighboring-gene confound. This does not disprove every auditory role or dominant variant effect. The original human TAS article and full dominant-variant study remain unavailable; retain uncertainty after weighing the positive evidence, rather than inferring absence of function. |
| GO:0008017 microtubule binding | IDA PMID:19285977 The role of the cytoskeleton in the formation of gap junctio... | KEEP AS NON CORE | Summary: Retain the reported microtubule interaction. Reason: The positive association and ZO-1 control support retaining the curator’s IDA claim. Partner-specific assay details remain inaccessible; this contextual binding is not a channel core. Supporting Evidence: |
| GO:0010644 cell communication by electrical coupling | IEA GO_REF:0000108 | ACCEPT | Summary: Connexin-30 conducts current between adjacent cytoplasms. Reason: The source GO:1903763 names the GJB6 channel activity involved in electrical coupling, and the current process definition describes current transfer through intercellular protein channels. GJB6 supplies that conducting structure, so this process is a direct role rather than a downstream consequence of channel loss. |
| GO:0016264 gap junction assembly | IMP PMID:19285977 The role of the cytoskeleton in the formation of gap junctio... | ACCEPT | Summary: Connexin-30 provides a structural component of assembled gap junctions. Reason: Independent plaque/channel evidence supports this structural role (PMID:12767933). Limited access to PMID:19285977 does not justify rejecting an established structural contribution; no detailed trafficking or cytoskeletal binding mechanism is inferred from the perturbation context. |
| GO:0016264 gap junction assembly | NAS PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Connexin-30 contributes the channel structure assembled into gap junctions. Reason: Cx30-EYFP formed junctional plaques (PMID:12767933). GJB6 supplies the connexin building block rather than being consumed during assembly. This supports the existing annotation without claiming a separately resolved biogenesis mechanism or measured hexamer stoichiometry. Supporting Evidence: |
| GO:0030054 cell junction | IDA GO_REF:0000052 | TOO GENERAL | Summary: Connexin-30 is a component of gap-junction connections between cells. Reason: The general cell-junction location is compatible with GJB6 biology, but the established gap-junction annotation already identifies the relevant specialized junction. Current GO:0005921 is an is_a descendant of GO:0030054. Mark this location as too general without alleging that the curator’s underlying location observation is false or adding a redundant replacement. |
| GO:0035633 maintenance of blood-brain barrier | NAS PMID:30280653 Blood-Brain Barrier: From Physiology to Disease and Back. | KEEP AS NON CORE | Summary: Astroglial connexin networks contribute to blood-brain-barrier maintenance. Reason: The inspected astrocyte section of PMID:30280653 links combined Cx43/Cx30 deletion to barrier weakening and altered astrocytic endfeet. This supports a contextual role of the astroglial channel network, consistent with GJB6 supplying channel structure. Retain the existing process as non-core, without treating the combined perturbation as an isolated human GJB6 experiment or assigning endothelial specificity. The underlying experiments were not independently read. Supporting Evidence: |
| GO:0048487 beta-tubulin binding | IDA PMID:19285977 The role of the cytoskeleton in the formation of gap junctio... | UNDECIDED | Summary: Beta-tubulin specificity remains unresolved. Reason: Broad microtubule association does not identify the beta subunit; complete partner-specific results remain unavailable. Supporting Evidence: |
| GO:0051015 actin filament binding | IDA PMID:19285977 The role of the cytoskeleton in the formation of gap junctio... | KEEP AS NON CORE | Summary: Retain the reported cortical-actin interaction. Reason: Positive association and the ZO-1 control support the existing IDA claim. The abstract’s assay alternatives preclude a stronger direct-contact mechanism; retain this binding as non-core. Supporting Evidence: |
| GO:0055085 transmembrane transport | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Connexin-30 channels conduct solutes across the apposed cell membranes. Reason: Dye transfer supports conduction (PMID:12767933). Gap-junction channels traverse both apposed membranes, and the current molecular-function term is within transmembrane transporter activity. GO:0055085 does not require an unapposed hemichannel; GO:1990349 describes a related role but is not its is_a descendant. Both existing process assertions can be retained. Supporting Evidence: |
| GO:1903763 gap junction channel activity involved in cell communication by electrical coupling | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Connexin-30 channels support electrical coupling between cells. Reason: Junctional conductance supports electrical coupling (PMID:12767933). This is a channel function, not an inference that GJB6 alone generates cardiac pacemaker activity. The human transfection context is retained. Supporting Evidence: |
| GO:1990349 gap junction-mediated intercellular transport | IBA GO_REF:0000033 | ACCEPT | Summary: Connexin-30 mediates gap-junction intercellular transport. Reason: The actual AN365/PTN002633521 placement is on the GJB6 lineage and is supported by GJB6, human GJB2 and mouse Gjb2 descendant records. The incoming donor set exactly matches the retained IBD record. Direct target channel evidence and preserved membrane architecture support this inherited transport role; target self-evidence is legitimate and no functional-loss claim follows from the shorter donor list. |
| GO:1990349 gap junction-mediated intercellular transport | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Connexin-30 channels permit solute passage between neighboring cells. Reason: The measured dye transfer supports this process (PMID:12767933). The tested range does not establish a universal size cutoff or identify every physiological permeant. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which partner-specific experiments in PMID:19285977 distinguish microtubule, beta-tubulin and F-actin binding from colocalization or association through other proteins?
Suggested experts: Original study authors, GO annotation curators
Q: Which human auditory phenotypes reflect connexin-30 channel changes, and which reflect altered neighboring GJB2 regulation? Can variants with intact local regulation separate these effects?
Suggested experts: Auditory physiologists, Human geneticists, GO annotation curators
Q: How much of astroglial barrier support requires connexin-30 specifically, and how much is shared with or compensated by connexin-43?
Suggested experts: Astrocyte biologists, Blood-brain-barrier researchers
Q: Under what physiological conditions do unapposed connexin-30 hemichannels open, and how do their contributions differ from intercellular gap-junction channels?
Suggested experts: Connexin electrophysiologists
Q: Does GJB6 directly contribute to sinoatrial-node development beyond its membership in the expression program?
Suggested experts: Cardiac conduction-system biologists
Experiment: Compare sequence-verified wild-type human Cx30 and selected variants at matched surface abundance, measuring paired-cell conductance, dye transfer and junctional plaque formation separately from unpaired-cell leakage.
Hypothesis: Altered channel function can be separated from changes in abundance, localization or plaque assembly.
Experiment: Combine endogenous Cx30 perturbation and rescue with Cx43 control in an astrocyte–barrier coculture, recording intercellular coupling, barrier permeability, cell viability and endfoot organization separately.
Hypothesis: A Cx30-specific contribution can be distinguished from combined connexin-network failure and secondary cellular injury.
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