FOXJ1 is a nuclear forkhead transcription factor that activates ciliary genes and promotes motile-cilium formation and ciliated epithelial differentiation. In human airway basal epithelial cells, RFX3 enhances FOXJ1-dependent ciliary-gene transcription. FOXJ1 can also associate with the RFX2 transcription factor. Pathogenic human variants cause a motile ciliopathy with defective respiratory ciliogenesis, hydrocephalus and disturbed left/right body asymmetry. In mouse immune cells, Foxj1 restrains NF-kappaB-linked B-cell responses; its corresponding roles in human immune cells remain less defined.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse immune-cell evidence supports contextual negative regulation of Pol II transcription. Reason: The exact Q61660 same-term IMP donor cites PMID:16002694. Foxj1 reduced IL6 promoter-reporter activity in M12 cells, and deficient mouse B cells showed increased NF-kappaB reporter activity, IL6 RNA and secretion. This supports negative transcriptional regulation in an immune context while preserving the human orthology transfer. The experiments do not establish direct FOXJ1 occupancy of the IL6 promoter or a human DNA-bound repressor/corepressor mechanism. Supporting Evidence: |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse immune-cell evidence supports contextual negative regulation of Pol II transcription. Reason: The exact Q61660 same-term IMP donor cites PMID:16002694. Foxj1 reduced IL6 promoter-reporter activity in M12 cells, and deficient mouse B cells showed increased NF-kappaB reporter activity, IL6 RNA and secretion. This supports negative transcriptional regulation in an immune context while preserving the human orthology transfer. The experiments do not establish direct FOXJ1 occupancy of the IL6 promoter or a human DNA-bound repressor/corepressor mechanism. Supporting Evidence: |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: Chromatin is the substrate-associated location of FOXJ1’s regulatory DNA activity. Reason: The TFClass ISA assertion is consistent with FOXJ1 sequence-specific regulatory DNA recognition and human ciliary-promoter activation. It describes engagement with genomic regulatory chromatin, not a stable structural chromatin subunit, histone-binding activity or verified occupancy at every target. No source-specific ChIP experiment is inferred from the reporter assays. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:9096351 The winged helix transcription factor HFH-4 is expressed dur... | TOO GENERAL | Summary: Cis-regulatory DNA binding is represented more precisely by the retained Pol II sequence-specific binding term. Reason: GO:0000978, retained elsewhere, is an is_a descendant of GO:0000976. The broad term is therefore true but already covered. The original PMID:9096351 DNA-selection/EMSA assays used mouse HFH-4, including a GST 110–236 fragment; the human host does not establish a human protein construct. Actual PAINT ancestry and independent human transcriptional activation in PMID:23822649 support the gene-level function without changing that original assay attribution. |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000117 | TOO GENERAL | Summary: Cis-regulatory DNA binding is represented more precisely by the retained Pol II sequence-specific binding term. Reason: GO:0000978, retained elsewhere, is an is_a descendant of GO:0000976. The broad term is therefore true but already covered. The original PMID:9096351 DNA-selection/EMSA assays used mouse HFH-4, including a GST 110–236 fragment; the human host does not establish a human protein construct. Actual PAINT ancestry and independent human transcriptional activation in PMID:23822649 support the gene-level function without changing that original assay attribution. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Sequence-specific recognition of Pol II regulatory DNA supports the ciliogenic transcriptional program. Reason: The authentic PTHR46805 tree places human Q92949 at AN11/PTN002483655 beneath the asserted AN1/PTN002929598 node; the literal IBD and original donor groups match. Mouse HFH-4 purified-domain motif selection and EMSA in PMID:9096351 provide biochemical grounding, while human FOXJ1 cDNA activates ciliary-promoter reporters in PMID:23822649. These complementary data support conserved Pol II regulatory DNA recognition; they do not make the mouse binding experiment a human assay or establish occupancy at every human promoter. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sequence-specific recognition of Pol II regulatory DNA supports the ciliogenic transcriptional program. Reason: The authentic PTHR46805 tree places human Q92949 at AN11/PTN002483655 beneath the asserted AN1/PTN002929598 node; the literal IBD and original donor groups match. Mouse HFH-4 purified-domain motif selection and EMSA in PMID:9096351 provide biochemical grounding, while human FOXJ1 cDNA activates ciliary-promoter reporters in PMID:23822649. These complementary data support conserved Pol II regulatory DNA recognition; they do not make the mouse binding experiment a human assay or establish occupancy at every human promoter. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | TOO GENERAL | Summary: The retained Pol II transcriptional activator activity is more informative than the unsigned TF term. Reason: GO:0001228 is an is_a descendant of GO:0000981 and is independently supported by human FOXJ1 expression and promoter-reporter experiments in PMID:23822649. The actual IBA target-node path is valid, and TFClass classification is compatible; neither source is rejected. Contextual repression of immune-response transcription in mouse cells is retained separately and does not establish a second human DNA-bound repressor activity. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | TOO GENERAL | Summary: The retained Pol II transcriptional activator activity is more informative than the unsigned TF term. Reason: GO:0001228 is an is_a descendant of GO:0000981 and is independently supported by human FOXJ1 expression and promoter-reporter experiments in PMID:23822649. The actual IBA target-node path is valid, and TFClass classification is compatible; neither source is rejected. Contextual repression of immune-response transcription in mouse cells is retained separately and does not establish a second human DNA-bound repressor activity. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: FOXJ1 activates a motile-cilia transcriptional program. Reason: Human FOXJ1 cDNA expressed in primary human airway basal cells increased ciliary-gene RNA and the activity of corresponding promoter reporters in PMID:23822649; RFX3 enhanced these effects. Mouse DNA-binding and transactivation experiments in PMID:9096351 independently ground the conserved mechanism. The original Q61660 transfer is preserved. Reporter activation and target-gene induction do not establish that FOXJ1 expression alone produces fully mature multiciliated cells. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: FOXJ1 activates a motile-cilia transcriptional program. Reason: Human FOXJ1 cDNA expressed in primary human airway basal cells increased ciliary-gene RNA and the activity of corresponding promoter reporters in PMID:23822649; RFX3 enhanced these effects. Mouse DNA-binding and transactivation experiments in PMID:9096351 independently ground the conserved mechanism. The original Q61660 transfer is preserved. Reporter activation and target-gene induction do not establish that FOXJ1 expression alone produces fully mature multiciliated cells. |
| GO:0002508 central tolerance induction | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific central-tolerance process remains unresolved from the accessible donor evidence. Reason: The exact mouse same-term IMP donor cites PMID:16339515. Its authentic abstract reports CD2-Foxj1 transgenic lupus-prone mice, peripheral T-cell lymphopenia and accumulation of mature thymocytes with impaired exit. GO:0002508 specifically concerns tolerance induction in thymus or bone marrow; altered trafficking and reduced autoimmunity do not by themselves resolve that mechanism. Full original Methods/Results were not accessible, so the original human transfer and mouse curator assertion are preserved without a negative conclusion. Supporting Evidence: |
| GO:0002508 central tolerance induction | ISS GO_REF:0000024 | UNDECIDED | Summary: The specific central-tolerance process remains unresolved from the accessible donor evidence. Reason: The exact mouse same-term IMP donor cites PMID:16339515. Its authentic abstract reports CD2-Foxj1 transgenic lupus-prone mice, peripheral T-cell lymphopenia and accumulation of mature thymocytes with impaired exit. GO:0002508 specifically concerns tolerance induction in thymus or bone marrow; altered trafficking and reduced autoimmunity do not by themselves resolve that mechanism. Full original Methods/Results were not accessible, so the original human transfer and mouse curator assertion are preserved without a negative conclusion. Supporting Evidence: |
| GO:0002635 negative regulation of germinal center formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse B-cell intrinsic experiments support restraint of germinal-center formation. Reason: The exact Q61660 IMP donor cites PMID:16002694. B-cell-only chimeras and adoptive transfers separated the B-cell effect from abnormal T-cell help; Foxj1 deficiency increased spontaneous and antigen-induced germinal-center responses, and NF-kappaB/IL6 interventions reduced the phenotype. Retain this specific immune-regulatory process as non-core human orthology-based evidence, without claiming a direct human germinal-center assay. Supporting Evidence: |
| GO:0002635 negative regulation of germinal center formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse B-cell intrinsic experiments support restraint of germinal-center formation. Reason: The exact Q61660 IMP donor cites PMID:16002694. B-cell-only chimeras and adoptive transfers separated the B-cell effect from abnormal T-cell help; Foxj1 deficiency increased spontaneous and antigen-induced germinal-center responses, and NF-kappaB/IL6 interventions reduced the phenotype. Retain this specific immune-regulatory process as non-core human orthology-based evidence, without claiming a direct human germinal-center assay. Supporting Evidence: |
| GO:0002897 positive regulation of central B cell tolerance induction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The positive immune-regulatory evidence does not establish the specifically central B-cell tolerance mechanism. Reason: The current Q61660 same-term IMP donor cites PMID:16002694, whose selected Methods/Results concern mature splenic B cells, B-cell-only chimeras, germinal centers and antibody responses. The Discussion explicitly distinguishes amplification of existing antigen responses from loss of B-cell tolerance itself. GO:0002897 requires positive regulation of central B-cell tolerance, situated in the central lymphoid compartment. This specificity exceeds the demonstrated peripheral response restraint; retain the positive B-cell activation and humoral-response annotations separately. This is a bounded assessment of the transferred process, not denial of the measured immune phenotype. Supporting Evidence: |
| GO:0002897 positive regulation of central B cell tolerance induction | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: The positive immune-regulatory evidence does not establish the specifically central B-cell tolerance mechanism. Reason: The current Q61660 same-term IMP donor cites PMID:16002694, whose selected Methods/Results concern mature splenic B cells, B-cell-only chimeras, germinal centers and antibody responses. The Discussion explicitly distinguishes amplification of existing antigen responses from loss of B-cell tolerance itself. GO:0002897 requires positive regulation of central B-cell tolerance, situated in the central lymphoid compartment. This specificity exceeds the demonstrated peripheral response restraint; retain the positive B-cell activation and humoral-response annotations separately. This is a bounded assessment of the transferred process, not denial of the measured immune phenotype. Supporting Evidence: |
| GO:0002924 negative regulation of humoral immune response mediated by circulating immunoglobulin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse perturbations support negative regulation of circulating antibody responses. Reason: The matched mouse IMP source PMID:16002694 measured enhanced antigen-specific and autoantibody responses after Foxj1 deficiency, including B-cell-only chimeras that preserve the cellular attribution. The antibody-response effect is positive evidence for this contextual regulatory process. Human ISS/IEA provenance remains a transfer rather than a human experiment; no central-tolerance mechanism is inferred from antibody titres. Supporting Evidence: |
| GO:0002924 negative regulation of humoral immune response mediated by circulating immunoglobulin | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse perturbations support negative regulation of circulating antibody responses. Reason: The matched mouse IMP source PMID:16002694 measured enhanced antigen-specific and autoantibody responses after Foxj1 deficiency, including B-cell-only chimeras that preserve the cellular attribution. The antibody-response effect is positive evidence for this contextual regulatory process. Human ISS/IEA provenance remains a transfer rather than a human experiment; no central-tolerance mechanism is inferred from antibody titres. Supporting Evidence: |
| GO:0003677 DNA binding | NAS PMID:9073514 The human hepatocyte nuclear factor 3/fork head gene FKHL13:... | TOO GENERAL | Summary: The broad DNA-binding assertion is entailed by retained regulatory sequence-specific binding. Reason: The retained GO:0000978 is an is_a descendant of GO:0003677. PMID:9073514 was inspected only as an authentic human cloning/expression abstract, so it is not represented as a verified DNA-binding assay. Actual PAINT grounding and the separate biochemical and human activation evidence support the gene-level refinement without rewriting the original NAS citation. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: A specific Pol II transcriptional activator term already captures this broad activity. Reason: GO:0001228 is an is_a descendant of GO:0003700 and is supported independently by human FOXJ1 promoter activation in PMID:23822649. The InterPro inference and original PMID:9073514 NAS row remain intact; the latter abstract establishes cloning/expression, not a newly verified functional experiment. |
| GO:0003700 DNA-binding transcription factor activity | NAS PMID:9073514 The human hepatocyte nuclear factor 3/fork head gene FKHL13:... | TOO GENERAL | Summary: A specific Pol II transcriptional activator term already captures this broad activity. Reason: GO:0001228 is an is_a descendant of GO:0003700 and is supported independently by human FOXJ1 promoter activation in PMID:23822649. The InterPro inference and original PMID:9073514 NAS row remain intact; the latter abstract establishes cloning/expression, not a newly verified functional experiment. |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | MODIFY | Summary: The exact RFX2 partner supports a specific Pol II DNA-binding transcription-factor binding refinement. Reason: The original IPI annotation names RFX2 (P48378). The cited study uses tagged human FOX proteins in HEK293T tandem-affinity/MS experiments, but its exact FOXJ1–RFX2 supplementary pair was not recovered in this consultation and current source-specific IntAct retrieval returned no row. Independently, the exact human FOXJ1–RFX2 pair is supported by PMID:32296183 Y2H records and by cellular association records from PMID:28514442 and PMID:33961781. Apply the same gene-level partner-class refinement to GO:0061629 while retaining PMID:25609649 and explicitly marking its precise pair/assay attribution unverified. The corroborating evidence does not retroactively verify that paper's exact experiment. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: The exact RFX2 partner supports a specific Pol II DNA-binding transcription-factor binding refinement. Reason: The exact source-specific IntAct record IM-25778-7145 reports FOXJ1 as tagged bait and RFX2 as prey in HEK293T anti-tag coimmunoprecipitation/AP-MS. RFX2 is a sequence-specific RNA polymerase II DNA-binding transcription factor, so GO:0061629 is more informative than generic protein binding. Retain the co-purification limit: this record alone does not establish a direct interface; the same pair has independent Y2H support in PMID:32296183. No transcription-coregulator mechanism or direction is inferred. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: The exact RFX2 partner supports a specific Pol II DNA-binding transcription-factor binding refinement. Reason: Three exact source-specific IntAct records for human RFX2 and FOXJ1 describe prey-pooling, array and validated Y2H assays in yeast, with the configuration records identifying Gal4 fusion constructs. This supports binding to the RFX2 DNA-binding transcription-factor class and the refinement to GO:0061629. It is a binary interaction assay, not a purified affinity measurement, and does not establish native cell context, transcriptional direction or coactivator activity. Dataset-wide orthogonal validation is not attributed to this exact pair. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: The exact RFX2 partner supports a specific Pol II DNA-binding transcription-factor binding refinement. Reason: Two exact source-specific IntAct records report FOXJ1 bait and RFX2 prey in anti-tag coimmunoprecipitation associations in HEK293T and HCT116 cells, consistent with the paper's BioPlex AP-MS design. GO:0061629 names the independently established RFX2 partner class. Preserve that these source-specific observations are cellular associations rather than purified binary interaction, while independent Y2H evidence supports the same gene-level pair. No particular ciliary transcriptional mechanism or direction is inferred. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: The nucleus is the functional location of the FOXJ1 transcriptional program. Reason: The actual IBA node/path and literal donor grounding support conserved nuclear activity, with human Q92949 legitimately among the experimental descendants. Human transcriptional activation and the reviewed official nuclear localization assignment are consistent with this location. PMID:17008636 was accessed only as an authentic airway-differentiation abstract, so its exact nuclear imaging assay is not newly certified. Preserve is_active_in versus located_in and all original evidence/transfer fields. |
| GO:0005634 nucleus | IDA PMID:17008636 Trefoil factor family 3 peptide promotes human airway epithe... | ACCEPT | Summary: The nucleus is the functional location of the FOXJ1 transcriptional program. Reason: The actual IBA node/path and literal donor grounding support conserved nuclear activity, with human Q92949 legitimately among the experimental descendants. Human transcriptional activation and the reviewed official nuclear localization assignment are consistent with this location. PMID:17008636 was accessed only as an authentic airway-differentiation abstract, so its exact nuclear imaging assay is not newly certified. Preserve is_active_in versus located_in and all original evidence/transfer fields. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: The nucleus is the functional location of the FOXJ1 transcriptional program. Reason: The actual IBA node/path and literal donor grounding support conserved nuclear activity, with human Q92949 legitimately among the experimental descendants. Human transcriptional activation and the reviewed official nuclear localization assignment are consistent with this location. PMID:17008636 was accessed only as an authentic airway-differentiation abstract, so its exact nuclear imaging assay is not newly certified. Preserve is_active_in versus located_in and all original evidence/transfer fields. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: The nucleus is the functional location of the FOXJ1 transcriptional program. Reason: The actual IBA node/path and literal donor grounding support conserved nuclear activity, with human Q92949 legitimately among the experimental descendants. Human transcriptional activation and the reviewed official nuclear localization assignment are consistent with this location. PMID:17008636 was accessed only as an authentic airway-differentiation abstract, so its exact nuclear imaging assay is not newly certified. Preserve is_active_in versus located_in and all original evidence/transfer fields. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | TOO GENERAL | Summary: Pol II transcriptional regulation is represented by the retained direction-specific activities. Reason: GO:0045944 is an is_a descendant of both GO:0006355 and GO:0006357 and is supported by the human FOXJ1 activation experiments in PMID:23822649. Contextual negative Pol II regulation is also retained from mouse immune evidence. The original IBA is genuinely grounded at PTN002929598; Q92949 appearing among its descendant sources is valid experimental grounding, not circularity. The broad process adds no separate regulatory function. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | TOO GENERAL | Summary: Pol II transcriptional regulation is represented by the retained direction-specific activities. Reason: GO:0045944 is an is_a descendant of both GO:0006355 and GO:0006357 and is supported by the human FOXJ1 activation experiments in PMID:23822649. Contextual negative Pol II regulation is also retained from mouse immune evidence. The original IBA is genuinely grounded at PTN002929598; Q92949 appearing among its descendant sources is valid experimental grounding, not circularity. The broad process adds no separate regulatory function. |
| GO:0006959 humoral immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: FOXJ1 has contextual orthology-supported involvement in humoral immune regulation. Reason: The current same-term mouse donor cites PMID:16339515, whose full assays remain uninspected. Independent selected original PMID:16002694 establishes B-cell intrinsic effects on germinal centers and antibody production, supporting involvement in humoral immunity at the gene level. Retention does not certify the inaccessible original donor assay, nor establish equivalent immune mechanisms in human cells. |
| GO:0006959 humoral immune response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: FOXJ1 has contextual orthology-supported involvement in humoral immune regulation. Reason: The current same-term mouse donor cites PMID:16339515, whose full assays remain uninspected. Independent selected original PMID:16002694 establishes B-cell intrinsic effects on germinal centers and antibody production, supporting involvement in humoral immunity at the gene level. Retention does not certify the inaccessible original donor assay, nor establish equivalent immune mechanisms in human cells. |
| GO:0007283 spermatogenesis | NAS PMID:9073514 The human hepatocyte nuclear factor 3/fork head gene FKHL13:... | UNDECIDED | Summary: A role in spermatogenesis cannot be resolved from the inspected human expression source. Reason: The authentic PMID:9073514 abstract describes cloning and tissue expression, including testis. Expression is relevant context but does not establish a FOXJ1-dependent spermatogenic step. The original full paper was not inspected, and airway ciliary evidence cannot be transferred automatically to sperm differentiation; preserve the NAS assertion pending source-specific evidence. Supporting Evidence: |
| GO:0007368 determination of left/right symmetry | IMP PMID:31630787 De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy wit... | KEEP AS NON CORE | Summary: Human FOXJ1-associated motile ciliopathy includes disturbed left/right asymmetry. Reason: PMID:31630787 reports human FOXJ1 variants with randomization of left/right body asymmetry alongside a motile-ciliopathy phenotype and patient-cell defects. This supports the existing developmental participation claim as a contextual outcome of the ciliogenic transcriptional program. It does not establish that FOXJ1 itself is the asymmetry signal or a ciliary motor. Left/right body asymmetry is an embryonic patterning endpoint, whereas hydrocephalus can result from disturbed cerebrospinal-fluid flow without establishing a primary brain-development defect. The patient respiratory-cell experiments establish ciliopathy but do not directly assay embryonic nodal cells. Supporting Evidence: |
| GO:0007389 pattern specification process | ISS GO_REF:0000024 | TOO GENERAL | Summary: The retained left/right asymmetry process is the more precise supported patterning context. Reason: GO:0007368 is an is_a descendant of GO:0007389 and is retained on independent human evidence in PMID:31630787. No exact current same-term mouse record was found in the complete Q61660 response, but current absence does not refute the historical ISS transfer. The broad term is true by the supported narrower patterning role and adds no separate mechanism. Supporting Evidence: |
| GO:0007420 brain development | IEA GO_REF:0000107 | UNDECIDED | Summary: Brain-development participation remains distinct from choroid-plexus expression and hydrocephalus. Reason: The inspected PMID:9096351 experiments establish mouse HFH-4 expression during choroid-plexus epithelial development and DNA-binding/transactivation, not a brain-development perturbation. The current mouse brain-development record is IEP with occurs_in CL:0000706, and the human PMID:9073514 full text remains uninspected. Human hydrocephalus in PMID:31630787 is relevant but can reflect altered ciliary physiology and does not alone resolve developmental patterning. The full original human fields, including the CL:0000706 conjunction where present, remain unchanged; choroid-plexus cells are not silently relabeled as other ependymal cells. This differs from the clinical left/right randomization supporting the separate laterality annotation: the unresolved issue here is developmental participation in brain or the original choroid-plexus context, not whether FOXJ1 contributes to motile-cilia biology. |
| GO:0007420 brain development | ISS PMID:9073514 The human hepatocyte nuclear factor 3/fork head gene FKHL13:... | UNDECIDED | Summary: Brain-development participation remains distinct from choroid-plexus expression and hydrocephalus. Reason: The inspected PMID:9096351 experiments establish mouse HFH-4 expression during choroid-plexus epithelial development and DNA-binding/transactivation, not a brain-development perturbation. The current mouse brain-development record is IEP with occurs_in CL:0000706, and the human PMID:9073514 full text remains uninspected. Human hydrocephalus in PMID:31630787 is relevant but can reflect altered ciliary physiology and does not alone resolve developmental patterning. The full original human fields, including the CL:0000706 conjunction where present, remain unchanged; choroid-plexus cells are not silently relabeled as other ependymal cells. This differs from the clinical left/right randomization supporting the separate laterality annotation: the unresolved issue here is developmental participation in brain or the original choroid-plexus context, not whether FOXJ1 contributes to motile-cilia biology. |
| GO:0007420 brain development | NAS PMID:9096351 The winged helix transcription factor HFH-4 is expressed dur... | UNDECIDED | Summary: Brain-development participation remains distinct from choroid-plexus expression and hydrocephalus. Reason: The inspected PMID:9096351 experiments establish mouse HFH-4 expression during choroid-plexus epithelial development and DNA-binding/transactivation, not a brain-development perturbation. The current mouse brain-development record is IEP with occurs_in CL:0000706, and the human PMID:9073514 full text remains uninspected. Human hydrocephalus in PMID:31630787 is relevant but can reflect altered ciliary physiology and does not alone resolve developmental patterning. The full original human fields, including the CL:0000706 conjunction where present, remain unchanged; choroid-plexus cells are not silently relabeled as other ependymal cells. This differs from the clinical left/right randomization supporting the separate laterality annotation: the unresolved issue here is developmental participation in brain or the original choroid-plexus context, not whether FOXJ1 contributes to motile-cilia biology. |
| GO:0008104 intracellular protein localization | IMP PMID:31630787 De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy wit... | KEEP AS NON CORE | Summary: Human patient-cell evidence supports altered intracellular localization of ciliogenesis-associated proteins. Reason: PMID:31630787 assessed PTK2 localization near basal bodies and the positioning of basal-body markers in FOXJ1-variant respiratory cells. Those measured protein-localization outcomes support this contextual process without assigning FOXJ1 a transport, docking or structural molecular activity. The relative contribution of altered transcription versus other downstream mechanisms was not resolved. Supporting Evidence: |
| GO:0030036 actin cytoskeleton organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse epithelial perturbations support FOXJ1-dependent organization of the apical actin network. Reason: The exact Q61660 IMP donor cites PMID:17488776. Foxj1-null mouse tracheal epithelial cultures lack the apical actin web while retaining cortical actin, and AdFoxj1 increases RhoA/B-GTP during ciliogenesis. These are positive protein-perturbation results. The study does not demonstrate actin binding/polymerization or GEF activity by FOXJ1; the inspected Methods defer the adenoviral coding construct to an earlier paper, so its exact human/product identity is not assigned. Supporting Evidence: |
| GO:0030036 actin cytoskeleton organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse epithelial perturbations support FOXJ1-dependent organization of the apical actin network. Reason: The exact Q61660 IMP donor cites PMID:17488776. Foxj1-null mouse tracheal epithelial cultures lack the apical actin web while retaining cortical actin, and AdFoxj1 increases RhoA/B-GTP during ciliogenesis. These are positive protein-perturbation results. The study does not demonstrate actin binding/polymerization or GEF activity by FOXJ1; the inspected Methods defer the adenoviral coding construct to an earlier paper, so its exact human/product identity is not assigned. Supporting Evidence: |
| GO:0032053 ciliary basal body organization | IMP PMID:31630787 De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy wit... | KEEP AS NON CORE | Summary: Human ciliary basal-body organization depends on the FOXJ1-regulated program. Reason: PMID:31630787 reports comparable CEP164-positive basal-body numbers with abnormal positioning/docking in native or differentiated FOXJ1-variant respiratory cells. This supports the existing organization phenotype in a ciliogenic context. FOXJ1 is a nuclear transcription factor; the data do not make it a basal-body component or a direct docking enzyme. Supporting Evidence: |
| GO:0032715 negative regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse B-cell experiments support negative regulation of IL6 production. Reason: The matched Q61660 IMP source PMID:16002694 measured IL6 RNA, secreted protein and promoter-reporter activity. Deficient B cells produced excess IL6, and NF-kappaB decoys and IL6 neutralization connected the cytokine response to the humoral phenotype. Preserve the human transfer and contextual status; the assays do not establish direct FOXJ1-DNA contact at the IL6 promoter. Supporting Evidence: |
| GO:0032715 negative regulation of interleukin-6 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse B-cell experiments support negative regulation of IL6 production. Reason: The matched Q61660 IMP source PMID:16002694 measured IL6 RNA, secreted protein and promoter-reporter activity. Deficient B cells produced excess IL6, and NF-kappaB decoys and IL6 neutralization connected the cytokine response to the humoral phenotype. Preserve the human transfer and contextual status; the assays do not establish direct FOXJ1-DNA contact at the IL6 promoter. Supporting Evidence: |
| GO:0033085 negative regulation of T cell differentiation in thymus | IEA GO_REF:0000107 | UNDECIDED | Summary: The donor paper’s accessible trafficking phenotype does not resolve a negative thymic differentiation claim. Reason: The exact mouse IMP donor cites PMID:16339515. Its authentic abstract describes retention of mature single-positive thymocytes and defective thymic exit in CD2-Foxj1 transgenic mice. Differentiation and egress are distinct processes, and the full original experiments could not be inspected. Preserve the existing human ISS/IEA and mouse assertion without treating an abstract-level scope question as disproof. Supporting Evidence: |
| GO:0033085 negative regulation of T cell differentiation in thymus | ISS GO_REF:0000024 | UNDECIDED | Summary: The donor paper’s accessible trafficking phenotype does not resolve a negative thymic differentiation claim. Reason: The exact mouse IMP donor cites PMID:16339515. Its authentic abstract describes retention of mature single-positive thymocytes and defective thymic exit in CD2-Foxj1 transgenic mice. Differentiation and egress are distinct processes, and the full original experiments could not be inspected. Preserve the existing human ISS/IEA and mouse assertion without treating an abstract-level scope question as disproof. Supporting Evidence: |
| GO:0035082 axoneme assembly | IMP PMID:31630787 De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy wit... | KEEP AS NON CORE | Summary: Human FOXJ1-associated ciliopathy supports a contextual axoneme-assembly role. Reason: Patient respiratory-cell analyses in PMID:31630787 show reduced multicilia and associated basal-body/axonemal outcomes, with impaired fluid transport. This supports the existing assembly claim as an effect of the ciliogenic transcriptional program, without asserting that FOXJ1 is incorporated into axonemes or that every affected cilium has a uniform ultrastructural defect. Supporting Evidence: |
| GO:0035089 establishment of apical/basal cell polarity | ISS GO_REF:0000024 | UNDECIDED | Summary: Apical organization during ciliogenesis does not by itself resolve establishment of the whole apical/basal polarity axis. Reason: The current mouse same-term donor uses the broader acts_upstream_of_or_within relation and an anatomical extension, unlike this unrestricted human involved_in row. Those exact donor fields are retained in the private provenance. Selected PMID:17488776 establishes apical actin organization and basal-body docking, but not every step of initial axis specification. The original same-term donor paper was not inspected; retain uncertainty rather than infer equivalence from related apical phenotypes. Supporting Evidence: |
| GO:0035502 metanephric part of ureteric bud development | IEP PMID:9530170 A human forkhead/winged-helix transcription factor expressed... | UNDECIDED | Summary: Developmental RNA expression alone does not settle the specific ureteric-bud process. Reason: The authentic PMID:9530170 abstract describes human FOXJ1 cloning and developmental pulmonary/renal RNA expression. The original full Methods/Results and relevant kidney images were not accessed. IEP is preserved as expression evidence; no FOXJ1 perturbation, direct target or ureteric-bud morphogenetic mechanism is inferred. Supporting Evidence: |
| GO:0042130 negative regulation of T cell proliferation | IEA GO_REF:0000107 | UNDECIDED | Summary: The mouse T-cell proliferation phenotype is positive but its detailed original evidence remains inaccessible. Reason: The exact Q61660 same-term IMP donor cites PMID:14963332, whose authentic abstract reports increased T-cell proliferation after Foxj1 deficiency in autologous mixed-lymphocyte reactions. Full Methods/Results, cell-autonomous controls and construct identities could not be inspected. The positive report is preserved rather than refuted, while the exact transfer remains undecided at the declared access scope. Supporting Evidence: |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: Sequence-specific DNA binding is covered by the retained Pol II regulatory-region term. Reason: GO:0000978 is an is_a descendant of GO:0043565. The broader InterPro-derived assertion is correct but adds no distinct function beyond the retained regulatory DNA-recognition activity. Motif selection/EMSA used mouse protein in PMID:9096351; human activation evidence and actual PAINT placement independently support conservation. |
| GO:0044458 motile cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: FOXJ1 controls the transcriptional program needed for motile-cilium formation. Reason: Human FOXJ1 variants cause a motile ciliopathy with impaired ciliogenesis and flow in patient respiratory cultures in PMID:31630787, while human FOXJ1 cDNA activates ciliary-gene expression in PMID:23822649. Together with conserved mouse evidence these support the existing specific motile-cilium assembly assertion. FOXJ1 supplies transcriptional regulation of the program; it is not claimed to be a structural axoneme component. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | TOO GENERAL | Summary: Positive transcriptional regulation is represented more specifically at Pol II. Reason: GO:0045944 is an is_a descendant of GO:0045893 and is retained with independent human ciliary-promoter activation evidence in PMID:23822649. The original mouse/Ensembl transfer remains intact. No additional distinct process is supplied by the broader unsigned-polymerase term. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:9096351 The winged helix transcription factor HFH-4 is expressed dur... | ACCEPT | Summary: Human FOXJ1 positively regulates Pol II transcription of ciliary genes. Reason: The original PMID:9096351 reporter experiments used mouse HFH-4 constructs, including full-length and deletion proteins; those remain explicitly mouse assays. Independent PMID:23822649 used human FOXJ1 cDNA in primary human airway basal cells and demonstrated increased ciliary-promoter reporter activity and target RNA. The gene-level positive Pol II process is therefore supported without falsely validating a human construct in the original citation. |
| GO:0050869 negative regulation of B cell activation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse intrinsic B-cell experiments support restraint of activation. Reason: The current Q61660 IMP donor cites PMID:16002694. B-cell-only chimeras, purified splenic B-cell stimulation and adoptive transfers showed amplified responses after Foxj1 loss, with NF-kappaB/IL6 dependence. This supports the specific negative activation process as contextual orthology-based evidence; it does not establish a central-tolerance induction mechanism or a direct human assay. Supporting Evidence: |
| GO:0050869 negative regulation of B cell activation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse intrinsic B-cell experiments support restraint of activation. Reason: The current Q61660 IMP donor cites PMID:16002694. B-cell-only chimeras, purified splenic B-cell stimulation and adoptive transfers showed amplified responses after Foxj1 loss, with NF-kappaB/IL6 dependence. This supports the specific negative activation process as contextual orthology-based evidence; it does not establish a central-tolerance induction mechanism or a direct human assay. Supporting Evidence: |
| GO:0050900 leukocyte migration | IEA GO_REF:0000107 | UNDECIDED | Summary: The mouse thymocyte-egress result is relevant to migration but original mechanistic assays remain uninspected. Reason: The matched Q61660 IMP donor cites PMID:16339515. Its abstract reports impaired CCL19-associated thymic exit, with preserved entry into lymphoid organs, after CD2-Foxj1 expression. Full Methods/Results were unavailable, so the scope of the broad leukocyte-migration assertion and the human transfer remain unresolved. The accessible positive trafficking observation is not denied. Supporting Evidence: |
| GO:0050900 leukocyte migration | ISS GO_REF:0000024 | UNDECIDED | Summary: The mouse thymocyte-egress result is relevant to migration but original mechanistic assays remain uninspected. Reason: The matched Q61660 IMP donor cites PMID:16339515. Its abstract reports impaired CCL19-associated thymic exit, with preserved entry into lymphoid organs, after CD2-Foxj1 expression. Full Methods/Results were unavailable, so the scope of the broad leukocyte-migration assertion and the human transfer remain unresolved. The accessible positive trafficking observation is not denied. Supporting Evidence: |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | TOO GENERAL | Summary: The motile-cilium assembly term captures the established assembly role more precisely. Reason: GO:0044458 is an is_a descendant of GO:0060271 and is retained on human patient-cell and transcriptional-program evidence in PMID:31630787 and PMID:23822649. The general assembly claim is true but adds no separate function. The source archive separately preserves the two original ISS observations at raw indices 55 and 56. Current reciprocal human/mouse propagated rows are not used as sole grounding because genuine mouse perturbation and human experimental evidence exist. |
| GO:0060271 cilium assembly | IMP PMID:31630787 De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy wit... | TOO GENERAL | Summary: The motile-cilium assembly term captures the established assembly role more precisely. Reason: GO:0044458 is an is_a descendant of GO:0060271 and is retained on human patient-cell and transcriptional-program evidence in PMID:31630787 and PMID:23822649. The general assembly claim is true but adds no separate function. The source archive separately preserves the two original ISS observations at raw indices 55 and 56. Current reciprocal human/mouse propagated rows are not used as sole grounding because genuine mouse perturbation and human experimental evidence exist. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | TOO GENERAL | Summary: The motile-cilium assembly term captures the established assembly role more precisely. Reason: GO:0044458 is an is_a descendant of GO:0060271 and is retained on human patient-cell and transcriptional-program evidence in PMID:31630787 and PMID:23822649. The general assembly claim is true but adds no separate function. The source archive separately preserves the two original ISS observations at raw indices 55 and 56. Current reciprocal human/mouse propagated rows are not used as sole grounding because genuine mouse perturbation and human experimental evidence exist. |
| GO:0060428 lung epithelium development | IEP PMID:9530170 A human forkhead/winged-helix transcription factor expressed... | KEEP AS NON CORE | Summary: FOXJ1 contributes to maturation of the airway epithelial ciliated-cell program. Reason: The original PMID:9096351 evidence is mouse expression and transactivation, and PMID:9530170 provides human developmental expression at the accessible abstract scope. Independent human FOXJ1 gene transfer activates ciliary genes in basal epithelial progenitors, and patient respiratory cultures show defective ciliogenesis (PMID:23822649; PMID:31630787). This supports a bounded lung-epithelial maturation role without certifying unseen original developmental assays or every earlier lung morphogenetic step. |
| GO:0060428 lung epithelium development | NAS PMID:9096351 The winged helix transcription factor HFH-4 is expressed dur... | KEEP AS NON CORE | Summary: FOXJ1 contributes to maturation of the airway epithelial ciliated-cell program. Reason: The original PMID:9096351 evidence is mouse expression and transactivation, and PMID:9530170 provides human developmental expression at the accessible abstract scope. Independent human FOXJ1 gene transfer activates ciliary genes in basal epithelial progenitors, and patient respiratory cultures show defective ciliogenesis (PMID:23822649; PMID:31630787). This supports a bounded lung-epithelial maturation role without certifying unseen original developmental assays or every earlier lung morphogenetic step. |
| GO:0060429 epithelium development | IEA GO_REF:0000107 | TOO GENERAL | Summary: The supported lung-epithelial developmental context is more informative than unrestricted epithelium development. Reason: GO:0060428 is an is_a descendant of GO:0060429 and is retained with the independent human airway evidence in PMID:23822649 and PMID:31630787. The general human transfer remains intact. This unrestricted row is distinguished from the separate choroid-plexus extended assertion, whose particular developmental evidence remains uncertain. |
| GO:0060429 epithelium development | ISS PMID:9073514 The human hepatocyte nuclear factor 3/fork head gene FKHL13:... | UNDECIDED | Summary: The choroid-plexus epithelial developmental conjunction remains unresolved. Reason: This original ISS row specifically says occurs_in CL:0000706, choroid plexus epithelial cell. The matched current mouse record is IEP with the same extension, based on the developmental expression study PMID:9096351; PMID:9073514 full text remains uninspected. Human airway ciliogenesis does not establish the extended choroid-plexus claim. Preserve the original relation/target and distinguish choroid-plexus epithelium from motile ependymal-cell physiology. |
| GO:0072016 glomerular parietal epithelial cell development | IEP PMID:9530170 A human forkhead/winged-helix transcription factor expressed... | UNDECIDED | Summary: The specific glomerular parietal epithelial developmental role is not resolved by the accessible expression record. Reason: PMID:9530170 describes human pulmonary/renal developmental expression, but the full original Methods/Results and exact glomerular figure were not read. IEP is retained as expression evidence without inventing a FOXJ1-dependent developmental mechanism. Airway function is not substituted for renal-cell evidence. Supporting Evidence: |
| GO:1901223 negative regulation of non-canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | UNDECIDED | Summary: The non-canonical NF-kappaB branch is not resolved by the inspected donor assays. Reason: The exact Q61660 IMP donor cites PMID:16002694. The inspected experiments establish NF-kappaB reporter activity, I-kappaB-beta regulation, IL6 responses and sensitivity to RELA/p65 antisense. GO:1901223 refers specifically to non-canonical NF-kappaB signaling, whose definition specifies NIK-dependent p100 processing to p52. Those branch-defining endpoints were not established in the selected source passages. Preserve the original specific assertion and positive immune evidence while leaving this branch assignment unresolved; do not substitute an obsolete broad NF-kappaB term or infer absent biology. Supporting Evidence: |
| GO:1901223 negative regulation of non-canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | UNDECIDED | Summary: The non-canonical NF-kappaB branch is not resolved by the inspected donor assays. Reason: The exact Q61660 IMP donor cites PMID:16002694. The inspected experiments establish NF-kappaB reporter activity, I-kappaB-beta regulation, IL6 responses and sensitivity to RELA/p65 antisense. GO:1901223 refers specifically to non-canonical NF-kappaB signaling, whose definition specifies NIK-dependent p100 processing to p52. Those branch-defining endpoints were not established in the selected source passages. Preserve the original specific assertion and positive immune evidence while leaving this branch assignment unresolved; do not substitute an obsolete broad NF-kappaB term or infer absent biology. Supporting Evidence: |
| GO:1901248 positive regulation of lung ciliated cell differentiation | IDA PMID:20539013 Goblet cells are derived from a FOXJ1-expressing progenitor ... | ACCEPT | Summary: Independent human evidence supports FOXJ1 promotion of the lung ciliated-cell program. Reason: In the inspected portion of PMID:20539013, a human FOXJ1 promoter drives lineage reporters and IL13 supplies the intervention; that is not a FOXJ1 coding/protein perturbation. Independent human FOXJ1 gene transfer activates ciliary genes in primary basal progenitors (PMID:23822649), and FOXJ1-variant respiratory cells show impaired ciliated-cell differentiation/flow (PMID:31630787). Together they support the existing gene-level positive differentiation role. The original citation remains source-limited, and gene transfer alone is not claimed to yield complete mature multiciliation. |
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Download this section (compressed HTML)Q: Which endogenous human FOXJ1 targets are sufficient to connect transcriptional activation to basal-body docking and mature motile-cilium formation?
Q: Do RFX2 binding and RFX3-associated enhancement recruit distinct FOXJ1 regulatory complexes in human airway cells?
Q: Does endogenous human FOXJ1 regulate B-cell activation, and can that role be separated from central tolerance and canonical versus non-canonical NF-kappaB signaling?
Q: Does FOXJ1 make a causal contribution to choroid-plexus epithelial maturation, beyond its developmental expression and the effects of motile-cilia dysfunction elsewhere?
Experiment: Combine inducible endogenous FOXJ1 depletion and wild-type rescue in differentiating primary human airway cultures with nascent-RNA profiling, occupancy mapping and stage-resolved basal-body/cilia imaging. Separate early target-gene changes from later docking and transport phenotypes.
Experiment: Compare matched RFX2 and RFX3 perturbations in the same airway differentiation system, using endogenous reciprocal association assays and promoter/target-RNA measurements. Purified pair assays can distinguish direct interfaces from cellular complex recovery.
Experiment: First establish endogenous FOXJ1 expression in defined human B-cell stages, then use controlled perturbation to measure activation, antigen responses and branch-specific NF-kappaB endpoints. NIK/p100/p52 and RELA/I-kappaB readouts should be analyzed separately; mature-cell effects should not be labeled central tolerance.
Experiment: Use stage-specific FOXJ1 perturbation in a validated choroid-plexus epithelial model, with epithelial maturation and barrier/secretory endpoints, rather than inferring development from expression alone.
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