Clarin-1 is a four-pass membrane glycoprotein that supports the organization of actin-associated membrane structures in sensory tissues. Its major studied human product contains 232 residues and an N-linked glycosylation site at Asn48. Clarin-1 promotes cortical actin remodeling and cell-surface protrusions, and vertebrate models establish roles in maintaining auditory and vestibular hair-cell function. In the inner ear, apical hair-bundle integrity and basolateral ribbon-synapse organization are separable aspects of its function. Retinal expression is enriched in MΓΌller glia, with cell-specific rescue supporting a non-cell-autonomous role in photoreceptor protection. Human loss-of-function variants cause Usher syndrome type 3A with hearing loss, retinal degeneration and variable vestibular dysfunction; some variants cause nonsyndromic retinitis pigmentosa. Glycosylation and folding influence delivery to the cell surface. The molecular operation linking clarin-1 interactions to membrane and actin organization remains unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007605 sensory perception of sound | IBA GO_REF:0000033 | ACCEPT | Summary: Clarin-1 supports auditory hair-cell function. Reason: Human serial audiometry and mouse and zebrafish loss-of-function experiments support the conserved hearing role. The current PAINT source identifies PTN002834949; its historical tree and ancestral placement were not reconstructed, so target corroboration is distinguished from complete node verification. This historical source object omits the supporting-entity fields present in the separately retained current assertion; the two representations are not independent experimental observations. This incomplete earlier review representation is now retired; active row 47 (zero-based) preserves the exact GOA supporting entities. Retirement records representation provenance and does not reject the biological annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002834949 UNRESOLVED Human audiometry and mouse/zebrafish experimental hearing premises corroborate the target function. The current target node identifier is present, but historical placement and the complete PAINT tree were not reconstructed. |
| GO:0050957 equilibrioception | IBA GO_REF:0000033 | ACCEPT | Summary: Clarin-1 contributes to vestibular function with variable penetrance. Reason: The human disease context is complemented by measured vestibular evoked-potential abnormalities in Clrn1-null mice and hearing/balance phenotypes in zebrafish. Normal balance under some ages or models does not negate the positive role. The PAINT placement is retained without claiming a reconstructed historical tree. This historical source object omits the supporting-entity fields present in the separately retained current assertion; the two representations are not independent experimental observations. This incomplete earlier review representation is now retired; active row 53 (zero-based) preserves the exact GOA supporting entities. Retirement records representation provenance and does not reject the biological annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002834949 UNRESOLVED Mouse vestibular evoked potentials and zebrafish balance experiments corroborate the target function. The current target node identifier is present, but historical placement and the complete PAINT tree were not reconstructed. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The cell surface is an established clarin-1 compartment. Reason: The UniProt cell-membrane mapping agrees with human CLRN1 surface biotinylation and colocalization in HEK293 cells, and with the separately reported wild-type versus mutant localization comparison. This historical source object omits the supporting-entity fields present in the separately retained current assertion; the two representations are not independent experimental observations. This incomplete earlier review representation is now retired; active row 46 (zero-based) preserves the exact GOA supporting entities. Retirement records representation provenance and does not reject the biological annotation. |
| GO:0007605 sensory perception of sound | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA hearing annotation agrees with experimental biology. Reason: The current rule contains a metazoan IPR026748 route that matches the target family and taxonomy, and outputs sensory perception of sound. Human audiometry and vertebrate hair-cell experiments independently support that outcome; the other alternative rule routes need not apply to CLRN1. This historical source object omits the supporting-entity fields present in the separately retained current assertion; the two representations are not independent experimental observations. This incomplete earlier review representation is now retired; active row 48 (zero-based) preserves the exact GOA supporting entities. Retirement records representation provenance and does not reject the biological annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00033578 SUPPORTS TRANSFER The current first condition set is Metazoa plus IPR026748, both present for human CLRN1; its hearing output is corroborated independently by human and vertebrate experiments. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The legacy unscoped HuRI assertion records positive binary interactions. Reason: The historical source object is an unscoped aggregate from the HuRI paper. Its positive evidence is represented in the 26 current partner-scoped assertions retained below; it is not a twenty-seventh independently detected partner. All three positive assay records for each current pair are preserved. The original source object remains unchanged as provenance, with non-core retention under the campaign supported-binding policy. This unscoped earlier review aggregate is now retired. The 26 active partner-specific rows 20β45 (zero-based) preserve the positive HuRI assertions; retirement does not negate any interaction. Supporting Evidence: PMID:32296183 pairwise verification by quadruplicate retesting |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse donor has positive microtubule-associated localization. Reason: PMID:19539019 shows endogenous clarin-1 colocalization with tubulin in mouse UB/OC-1 cells and loss of its filamentous pattern after nocodazole treatment. This supports the donor compartment at the stated cellular scope; the independently observed F-actin role is not evidence against it. Direct microtubule binding and a core microtubule function were not established. This historical source object omits the supporting-entity fields present in the separately retained current assertion; the two representations are not independent experimental observations. The microtubule experiment uses anti-clarin-1 staining of the endogenous mouse UB/OC-1 protein. The separately transfected mouse isoform-2 GFP fusion is an antibody-specificity control, not the basis of the tubulin localization claim. This incomplete earlier review representation is now retired; active row 49 (zero-based) preserves the exact GOA supporting entities. Retirement records representation provenance and does not reject the biological annotation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K445 Β· Mouse Clrn1 SUPPORTS TRANSFER The direct IDA donor record and PMID:19539019 tubulin colocalization/nocodazole experiment are positive at the assayed mouse-cell scope. |
| GO:0030140 trans-Golgi network transport vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The donor supports a post-Golgi trafficking compartment. Reason: In mouse UB/OC-1 cells, clarin-1 distribution responds to tyrphostin A8 while remaining distinct from the brefeldin-A-sensitive mannosidase compartment. The authors interpret this as post-trans-Golgi vesicular localization along microtubules. Retain the curated transfer as a trafficking context, without upgrading these imaging and perturbation observations to purified-vesicle identification or an intrinsic transport activity. This historical source object omits the supporting-entity fields present in the separately retained current assertion; the two representations are not independent experimental observations. This incomplete earlier review representation is now retired; active row 50 (zero-based) preserves the exact GOA supporting entities. Retirement records representation provenance and does not reject the biological annotation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K445 Β· Mouse Clrn1 SUPPORTS TRANSFER The direct IDA donor record is grounded in the post-Golgi distribution interpretation of the original perturbation and imaging study. |
| GO:0032420 stereocilium | IEA GO_REF:0000107 | ACCEPT | Summary: Hair-bundle localization is supported by positive ortholog and human-construct evidence. Reason: The mouse donor paper reports stereociliary immunolabeling and immunogold localization with antibody controls. Independent zebrafish experiments detect native Clrn1 using knockout controls and human CLRN1-YFP in hair bundles; fixation can remove the signal. These sources support the compartment while preserving their different species, tags and detection conditions. This historical source object omits the supporting-entity fields present in the separately retained current assertion; the two representations are not independent experimental observations. This incomplete earlier review representation is now retired; active row 51 (zero-based) preserves the exact GOA supporting entities. Retirement records representation provenance and does not reject the biological annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8K445 Β· Mouse Clrn1 SUPPORTS TRANSFER The donor IDA record and controlled stereociliary immunolabeling support the compartment. |
| GO:0045178 basal part of cell | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse donor supports a developmentally regulated basal hair-cell pool. Reason: PMID:19539019 reports basal labeling in inner and outer hair cells during early development, with the outer-hair-cell basal signal diminishing later. This is the direct donor localization premise. PMID:29985171 independently supports a basolateral synaptic function but reports unsuccessful endogenous auditory-organ CLRN1 immunodetection, so it is not substituted for direct native localization. This historical source object omits the supporting-entity fields present in the separately retained current assertion; the two representations are not independent experimental observations. This incomplete earlier review representation is now retired; active row 52 (zero-based) preserves the exact GOA supporting entities. Retirement records representation provenance and does not reject the biological annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8K445 Β· Mouse Clrn1 SUPPORTS TRANSFER The donor IDA record is supported by developmentally regulated basal hair-cell labeling in the original source. |
| GO:0005886 plasma membrane | EXP PMID:21310491 CLRN1 mutations cause nonsyndromic retinitis pigmentosa. | ACCEPT | Summary: Wild-type clarin-1 reaches the cell membrane. Reason: The complete abstract of PMID:21310491 explicitly reports wild-type protein mainly at the cell membrane and RP-associated P31L/L154W proteins retained in the ER. The full article was not recovered; independent surface biotinylation and imaging of human CLRN1 in PMID:19423712 corroborate the compartment without assuming details absent from the abstract. |
| GO:0005886 plasma membrane | IDA PMID:19423712 Clarin-1, encoded by the Usher Syndrome III causative gene, ... | ACCEPT | Summary: Human clarin-1 localizes to the plasma membrane in HEK293 cells. Reason: The expressed 232-residue human construct colocalizes with Na/K-ATPase and is labeled by membrane-impermeant surface biotinylation. These complementary assays directly support surface residence; they do not imply that all alternative products or disease variants localize identically. Supporting Evidence: |
| GO:0005902 microvillus | IDA PMID:19423712 Clarin-1, encoded by the Usher Syndrome III causative gene, ... | KEEP AS NON CORE | Summary: Microvillus enrichment is a positive cellular localization result. Reason: Human CLRN1 expressed in HEK293 cells is enriched in microvilli as well as lamellipodia. Preserve that observed compartment as non-core rather than rejecting it because the assay is heterologous; this row does not establish endogenous human sensory-cell microvillus localization. Supporting Evidence: PMID:19423712 especially enriched in microvilli and lamellipodia |
| GO:0007015 actin filament organization | IDA PMID:19423712 Clarin-1, encoded by the Usher Syndrome III causative gene, ... | ACCEPT | Summary: Clarin-1 promotes organization of cortical actin and membrane protrusions. Reason: Three independent human CLRN1-expressing HEK293 clones show expression-dependent actin-rich protrusions, and mouse loss causes disorganized stereociliary bundles. The N48K comparison also affects abundance and trafficking, so it is not an isolated catalytic-site experiment. The positive cellular organization role does not establish direct actin binding, polymerase activity or purified scaffolding. The negative actin colocalization in endogenous mouse UB/OC-1 cells in PMID:19539019 is a different localization endpoint; it does not test or overturn this human expression-dependent organization result. Supporting Evidence: PMID:19423712 Clarin-1 reorganized actin filament structures and induced lamellipodia. |
| GO:0010592 positive regulation of lamellipodium assembly | IDA PMID:19423712 Clarin-1, encoded by the Usher Syndrome III causative gene, ... | KEEP AS NON CORE | Summary: Clarin-1 expression induces lamellipodial protrusions in the tested cells. Reason: Independent human CLRN1-expressing HEK293 clones form ramifying lamellipodia with concentrated F-actin compared with control cells. This is a positive regulation phenotype within the assayed cellular context, retained without proposing it as the defining role in native hair cells. Supporting Evidence: |
| GO:0030027 lamellipodium | IDA PMID:19423712 Clarin-1, encoded by the Usher Syndrome III causative gene, ... | KEEP AS NON CORE | Summary: Clarin-1 is enriched at lamellipodia in the human cell-expression assay. Reason: The original imaging places CLRN1 in actin-rich lamellipodial protrusions. Heterologous expression limits physiological generalization but does not contradict this localization; retain the source-specific observation as non-core. Supporting Evidence: |
| GO:0048870 cell motility | IDA PMID:19423712 Clarin-1, encoded by the Usher Syndrome III causative gene, ... | MARK AS OVER ANNOTATED | Summary: The reported endpoint establishes cellular spreading and protrusions, without resolving cell translocation. Reason: GO:0048870 requires controlled self-propelled translocation of a cell from one place to another. PMID:19423712 describes low-density plating and four-day colony morphology, with loosely packed colonies and actin-rich protrusions in human CLRN1-expressing HEK293 clones. Although the authors interpret these findings as increased motility, the presented endpoint does not distinguish cell displacement from altered spreading, protrusion formation or colony organization. Mark this process scope as over-annotated while retaining the positive protrusion and localization observations in their own assertions; the heterologous model alone is not the reason for this judgment. Supporting Evidence: |
| GO:0045494 photoreceptor cell maintenance | IMP PMID:15521980 Mutation screening of USH3 gene (clarin-1) in Spanish patien... | KEEP AS NON CORE | Summary: Retinal support preserves photoreceptors through a non-cell-autonomous context. Reason: The original human mutation study associates CLRN1 with retinal degeneration but was available only as a complete abstract. Later human retinal expression and zebrafish cell-specific rescue support a MΓΌller-glial contribution to photoreceptor maintenance; low glial expression rescues light-stress susceptibility whereas rod/cone expression does not. This preserves the existing process without claiming CLRN1 is a photoreceptor-intrinsic enzyme or that a direct adhesion mechanism is resolved. |
| GO:0007605 sensory perception of sound | IMP PMID:15650299 Serial audiometry and speech recognition findings in Finnish... | ACCEPT | Summary: Human CLRN1 variants cause progressive sensorineural hearing impairment. Reason: The complete abstract reports serial audiometry in 59 Finnish patients and speech-recognition testing in 31, with genotype-dependent and age-dependent progression. The full article was not recovered, but its positive clinical observation and independent mouse and zebrafish experiments support the hearing annotation. |
| GO:0050953 sensory perception of light stimulus | IMP PMID:15521980 Mutation screening of USH3 gene (clarin-1) in Spanish patien... | KEEP AS NON CORE | Summary: CLRN1 supports vision through retinal tissue maintenance. Reason: The source clinical study links CLRN1 to retinitis pigmentosa, and independent RP families and retinal models corroborate visual dysfunction. Retain this organismal process as non-core without treating CLRN1 as a phototransduction receptor or light-sensitive molecule; the original source remains abstract-only. |
| GO:0050957 equilibrioception | IMP PMID:15521980 Mutation screening of USH3 gene (clarin-1) in Spanish patien... | ACCEPT | Summary: Vestibular involvement is compatible with variable CLRN1 disease expression. Reason: The inspected original abstract explicitly places variable vestibular dysfunction in the USH3 clinical context, although individual vestibular measurements in those families could not be checked. Independent mouse vestibular evoked potentials and zebrafish balance assays positively support the function. Preserve the original assertion without claiming the abstract supplies the unavailable family-level assay details. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βC2CD2L interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify O14523 as the partner. The partner is a ER-anchored phosphatidylinositol-transfer protein; its identity does not establish a transmembrane-transporter binding class. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βMGST3 interaction. Reason: The three positive HuRI records map the partner to MGST3/O14880. Its authenticated UniProt function and catalytic-reaction entries assign experimentally supported glutathione-transferase/peroxidase activities, establishing enzyme class beyond a domain prediction. GO:0019899 describes binding to that enzyme protein; the screen does not establish CLRN1-dependent catalysis, enzyme regulation or a native shared compartment. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βSEC22B interaction. Reason: The three positive HuRI records identify SEC22B/O75396, whose official function and SNARE-complex assignments establish the SNARE protein class. GO:0000149 describes binding to this partner. No CLRN1-mediated vesicle fusion, assembled SNARE-complex binding or particular SNARE-domain contact is inferred from the pair. Proposed replacements: SNARE binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βITGAM interaction. Reason: The three positive HuRI records identify ITGAM/P11215, the authenticated integrin alpha-M subunit. GO:0005178 records binding to this integrin protein at the assayed scope. The experiment does not establish contact with an assembled ITGAM/ITGB2 receptor, a native immune-cell interaction or an adhesion mechanism. Different tissue contexts alone do not refute the recorded pair. Proposed replacements: integrin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βTMEM50B interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify P56557 as the partner. The recorded partner identity does not resolve a narrower supported binding class. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βCTXN3 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q4LDR2 as the partner. The recorded partner identity does not resolve a narrower supported binding class. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βUNC50 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q53HI1 as the partner. UNC50 participates in trafficking regulation; that does not itself establish a transporter-binding class. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βSLC61A1 interaction. Reason: The three positive HuRI records identify SLC61A1/Q6N075. Its official FUNCTION entry attributes intracellular molybdenum uptake to experimental evidence, providing a functional transporter assignment rather than a name or membrane-domain prediction alone. GO:0044325 describes the bound transmembrane-transporter class. This assessment uses the curated partner record, not a new read of its activity paper, and assigns no transport activity to CLRN1. Proposed replacements: transmembrane transporter binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βBRICD5 isoform 2 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q6PL45-2 as the partner. The isoform-specific source is retained without extending the tested interaction to every BRICD5 product. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βTMPPE interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q6ZT21 as the partner. A metallophosphoesterase domain name alone is insufficient to assign a demonstrated catalytic partner class. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βNRM interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q8IXM6 as the partner. The nuclear-envelope protein identity does not establish a narrower binding activity. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βSLC34A3 interaction. Reason: The three positive HuRI records identify SLC34A3/Q8N130. Its official function and reaction entries establish sodium-dependent phosphate transmembrane transport. GO:0044325 describes binding to that transporter protein; neither CLRN1-mediated flux nor regulation, coupling stoichiometry or a native renal interaction follows from the binding assay. Proposed replacements: transmembrane transporter binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βFAM24B interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q8N5W8 as the partner. The recorded partner identity does not resolve a narrower supported binding class. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βTMEM86B interaction. Reason: The three positive HuRI records identify TMEM86B/Q8N661. Its official FUNCTION and CATALYTIC ACTIVITY entries attribute lysoplasmalogen hydrolysis to experimental evidence, unlike the domain-only catalytic premise for TMPPE. GO:0019899 is retained for binding to this enzyme protein, without assigning hydrolysis or lipid-metabolic regulation to CLRN1. The partner activity assignment is curated-record evidence, not a newly inspected original activity experiment. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βDRAM1 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q8N682 as the partner. An autophagy-associated partner does not by itself establish a CLRN1 autophagy or adaptor activity. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βCLDN19 isoform 2 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q8N6F1-2 as the partner. The partner is a paracellular junction component; this does not imply transmembrane transporter binding or native junction assembly by CLRN1. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βCCL4L1 interaction. Reason: The three positive HuRI records map the partner to the chemokine protein Q8NHW4/CCL4L1. The official entry establishes chemokine class and separately distinguishes its signal peptide from the mature chain. GO:0019956 describes the mapped partner class at the construct-assay scope. The unsuffixed accession and absent fragment feature do not resolve clone processing, mature-chain contact, exact natural isoform or a native extracellular interaction; those properties are not asserted. Proposed replacements: chemokine binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βCANT1 interaction. Reason: The three positive HuRI records identify CANT1/Q8WVQ1. The official function entry attributes calcium-dependent nucleotidase activity to experiments, supporting enzyme class. GO:0019899 describes this bound protein; the pair does not demonstrate activation or inhibition of CANT1 by CLRN1, secretory-pathway substrate handling or a catalytic function of CLRN1. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βTMEM239 isoform 2 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q8WW34-2 as the partner. The literal construct feature is residues 2β152 of the stated isoform, rather than evidence for every full-length product. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βZDHHC15 interaction. Reason: The three positive HuRI records identify ZDHHC15/Q96MV8. Its official record attributes protein palmitoylation to experimental evidence, beyond the presence of a DHHC domain. GO:0019899 retains that enzyme-partner specificity without asserting CLRN1 palmitoylation, an enzyme-substrate relationship or modulation of catalytic activity. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βALG8 interaction. Reason: The three positive HuRI records identify ALG8/Q9BVK2. Its official glucosyltransferase function and reaction assignments establish enzyme class. GO:0019899 describes the interaction with that protein; the screen does not show that ALG8 glycosylates CLRN1 or that CLRN1 controls oligosaccharide synthesis. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βTMEM147 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q9BVK8 as the partner. Membership of the partner in a biogenesis complex does not transfer the complex activity to CLRN1. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βTMEM222 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q9H0R3 as the partner. The literal construct feature is residues 21β208; the interaction remains scoped to that tested fragment. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βTMPRSS4 interaction. Reason: The three positive HuRI records identify TMPRSS4/Q9NRS4. Its official record establishes serine-protease activity and separately annotates proteolytic processing. GO:0002020 identifies the protease protein bound at the tested construct scope; it does not assert that the HuRI construct was activated, that contact involves the mature catalytic chain, or that CLRN1 is cleaved or inhibits the enzyme in vivo. Proposed replacements: protease binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records a positive CLRN1βTMEM140 interaction. Reason: Exact array, prey-pooling and validated two-hybrid records identify Q9NV12 as the partner. The recorded partner identity does not resolve a narrower supported binding class. Retain the experimentally recorded association as non-core without inventing a molecular mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI records a positive CLRN1βFUT9 interaction. Reason: The three positive HuRI records identify FUT9/Q9Y231. The official function and reaction entries attribute fucosyltransferase activity to experimental evidence. GO:0019899 describes binding to that enzyme protein; a CLRN1 substrate relationship, regulation of fucosylation or a native Golgi mechanism is not established. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The cell surface is an established clarin-1 compartment. Reason: The UniProt cell-membrane mapping agrees with human CLRN1 surface biotinylation and colocalization in HEK293 cells, and with the separately reported wild-type versus mutant localization comparison. This current source object preserves the explicit supporting entities missing from the historical assertion; it adds source granularity rather than another biological finding. |
| GO:0007605 sensory perception of sound | IBA GO_REF:0000033 | ACCEPT | Summary: Clarin-1 supports auditory hair-cell function. Reason: Human serial audiometry and mouse and zebrafish loss-of-function experiments support the conserved hearing role. The current PAINT source identifies PTN002834949; its historical tree and ancestral placement were not reconstructed, so target corroboration is distinguished from complete node verification. This current source object preserves the explicit supporting entities missing from the historical assertion; it adds source granularity rather than another biological finding. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002834949 UNRESOLVED Human audiometry and mouse/zebrafish experimental hearing premises corroborate the target function. The current target node identifier is present, but historical placement and the complete PAINT tree were not reconstructed. |
| GO:0007605 sensory perception of sound | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA hearing annotation agrees with experimental biology. Reason: The current rule contains a metazoan IPR026748 route that matches the target family and taxonomy, and outputs sensory perception of sound. Human audiometry and vertebrate hair-cell experiments independently support that outcome; the other alternative rule routes need not apply to CLRN1. This current source object preserves the explicit supporting entities missing from the historical assertion; it adds source granularity rather than another biological finding. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00033578 SUPPORTS TRANSFER The current first condition set is Metazoa plus IPR026748, both present for human CLRN1; its hearing output is corroborated independently by human and vertebrate experiments. |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse donor has positive microtubule-associated localization. Reason: PMID:19539019 shows endogenous clarin-1 colocalization with tubulin in mouse UB/OC-1 cells and loss of its filamentous pattern after nocodazole treatment. This supports the donor compartment at the stated cellular scope; the independently observed F-actin role is not evidence against it. Direct microtubule binding and a core microtubule function were not established. This current source object preserves the explicit supporting entities missing from the historical assertion; it adds source granularity rather than another biological finding. The microtubule experiment uses anti-clarin-1 staining of the endogenous mouse UB/OC-1 protein. The separately transfected mouse isoform-2 GFP fusion is an antibody-specificity control, not the basis of the tubulin localization claim. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K445 Β· Mouse Clrn1 SUPPORTS TRANSFER The direct IDA donor record and PMID:19539019 tubulin colocalization/nocodazole experiment are positive at the assayed mouse-cell scope. |
| GO:0030140 trans-Golgi network transport vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The donor supports a post-Golgi trafficking compartment. Reason: In mouse UB/OC-1 cells, clarin-1 distribution responds to tyrphostin A8 while remaining distinct from the brefeldin-A-sensitive mannosidase compartment. The authors interpret this as post-trans-Golgi vesicular localization along microtubules. Retain the curated transfer as a trafficking context, without upgrading these imaging and perturbation observations to purified-vesicle identification or an intrinsic transport activity. This current source object preserves the explicit supporting entities missing from the historical assertion; it adds source granularity rather than another biological finding. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K445 Β· Mouse Clrn1 SUPPORTS TRANSFER The direct IDA donor record is grounded in the post-Golgi distribution interpretation of the original perturbation and imaging study. |
| GO:0032420 stereocilium | IEA GO_REF:0000107 | ACCEPT | Summary: Hair-bundle localization is supported by positive ortholog and human-construct evidence. Reason: The mouse donor paper reports stereociliary immunolabeling and immunogold localization with antibody controls. Independent zebrafish experiments detect native Clrn1 using knockout controls and human CLRN1-YFP in hair bundles; fixation can remove the signal. These sources support the compartment while preserving their different species, tags and detection conditions. This current source object preserves the explicit supporting entities missing from the historical assertion; it adds source granularity rather than another biological finding. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8K445 Β· Mouse Clrn1 SUPPORTS TRANSFER The donor IDA record and controlled stereociliary immunolabeling support the compartment. |
| GO:0045178 basal part of cell | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse donor supports a developmentally regulated basal hair-cell pool. Reason: PMID:19539019 reports basal labeling in inner and outer hair cells during early development, with the outer-hair-cell basal signal diminishing later. This is the direct donor localization premise. PMID:29985171 independently supports a basolateral synaptic function but reports unsuccessful endogenous auditory-organ CLRN1 immunodetection, so it is not substituted for direct native localization. This current source object preserves the explicit supporting entities missing from the historical assertion; it adds source granularity rather than another biological finding. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8K445 Β· Mouse Clrn1 SUPPORTS TRANSFER The donor IDA record is supported by developmentally regulated basal hair-cell labeling in the original source. |
| GO:0050957 equilibrioception | IBA GO_REF:0000033 | ACCEPT | Summary: Clarin-1 contributes to vestibular function with variable penetrance. Reason: The human disease context is complemented by measured vestibular evoked-potential abnormalities in Clrn1-null mice and hearing/balance phenotypes in zebrafish. Normal balance under some ages or models does not negate the positive role. The PAINT placement is retained without claiming a reconstructed historical tree. This current source object preserves the explicit supporting entities missing from the historical assertion; it adds source granularity rather than another biological finding. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002834949 UNRESOLVED Mouse vestibular evoked potentials and zebrafish balance experiments corroborate the target function. The current target node identifier is present, but historical placement and the complete PAINT tree were not reconstructed. |
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Download this section (compressed HTML)Q: Does clarin-1 directly bridge defined membrane partners to the actin network, or does its organizational effect require another adaptor? The existing tripartite calcium-channel experiment identifies CaVΞ²2 as the bridge.
Q: Which current human alternative products are present and functional in hair cells and MΓΌller glia, and how do their membrane topology and trafficking differ?
Q: Which native-cell conditions explain microtubule-associated trafficking, actin-associated surface domains and the fixation sensitivity of clarin-1 localization?
Q: How does MΓΌller-glial clarin-1 protect photoreceptors, and which observed junctional changes are direct rather than consequences of tissue stress?
Experiment: Reconstitute defined clarin-1, CaVΞ²2 and harmonin combinations in membranes, with binary and simultaneous binding measurements, to distinguish partner association from clarin-1-mediated bridging.
Experiment: Compare sequence-verified human alternative products at matched expression in hair-cell and MΓΌller-glial systems, using endogenous tagging, surface delivery and actin-organization readouts.
Experiment: Test temporal and cell-specific rescue in retinal models with matched protein abundance, measuring microvillus architecture before degeneration and separating protective low expression from overexpression toxicity.
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular operation by which clarin-1 changes actin-associated membrane organization remains unresolved, including whether it directly recruits an actin linker or acts through another membrane organizer.
OPEN BIOLOGY MF_DARK
What is known: Human CLRN1 expression induces actin-rich protrusions, and mouse deletion/rescue establishes a role in sensory-cell actin and synaptic organization. Microtubule-associated localization is positive in mouse UB/OC-1 cells. The tested tripartite calcium-channel association is bridged by CaVΞ²2, not evidence that CLRN1 itself bridges the partners.
Significance: A defined molecular operation would connect the cellular organization phenotypes to a specific activity without inferring a scaffold or actin-binding function from necessity alone.
What would resolve it: Test sequence-defined clarin-1 and candidate linkers using binary and simultaneous binding measurements, matched membrane delivery and actin-organization assays.
Provenance (the field's own admissions):
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