SOX9 is a SOXE-family transcription factor that plays dual core roles in development. First, SOX9 is the master regulator of chondrogenesis, cooperating with SOX5 and SOX6 to drive cartilage matrix gene expression (COL2A1, ACAN) and promoting chondrocyte differentiation while antagonizing osteoblast differentiation via beta-catenin inhibition. Second, SOX9 is critical for oligodendrocyte differentiation and glial fate specification, promoting glial over neuronal fates in the CNS. SOX9 binds AACAAT-centered DNA motifs via its HMG-box domain, bends DNA, and recruits co-activators CBP/p300 and TIP60. It functions exclusively in the nucleus with nuclear localization and export signals. Post-translational modifications including phosphorylation, acetylation, and sumoylation regulate its activity. While SOX9 has additional developmental roles in sex determination, heart valve, kidney, and other epithelial programs, its core molecular functions center on transcriptional activation in cartilage and glial lineages.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: SOX9 is a bona fide RNA Pol II transcription factor with experimentally validated DNA-binding and transactivation domains (deep research, UniProt). It binds the AACAAT motif via HMG-box and activates transcription of cartilage and other target genes. Reason: This is a core molecular function of SOX9. The IBA annotation correctly captures SOX9's role as an RNA Pol II-specific transcription factor, supported by extensive experimental evidence showing DNA binding, transactivation, and regulation of Pol II-transcribed genes. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md SOX9 is a human SOXE-family transcription factor essential for lineage specification... binds AACAAT-centered motifs via its HMG-box... recruits co-activators CBP/p300 and TIP60 file:human/SOX9/SOX9-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0002009 morphogenesis of an epithelium | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: SOX9 regulates epithelial morphogenesis in multiple organs including lung, kidney, intestine, and prostate. Deep research notes roles in lung epithelium during branching morphogenesis and kidney epithelial branching. Reason: While well-supported, epithelial morphogenesis represents peripheral developmental processes rather than the core chondrogenic and gliogenic transcription factor functions of SOX9. This is a pleiotropic effect. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md involved in the lung epithelium during branching morphogenesis... Controls epithelial branching during kidney development |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: SOX9 functions in the nucleus with validated nuclear localization signals and nuclear export signals. UniProt describes nuclear localization, and deep research confirms nuclear function. Reason: Nuclear localization is essential for SOX9's transcription factor function. Multiple lines of evidence support this including NLS/NES identification and experimental demonstration of nuclear localization. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md SOX9 harbors nuclear localization and export signals... SOX9 functions in the nucleus file:human/SOX9/SOX9-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0007507 heart development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: SOX9 is involved in heart valve development and aortic valve morphogenesis with IDA evidence (PMID:22110751). GOA file shows multiple heart-related annotations. Reason: Heart development is a legitimate but peripheral function of SOX9. The core functions are chondrogenesis and gliogenesis. Heart valve development is a pleiotropic effect. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0003180 aortic valve morphogenesis biological_process ECO:0000314 IDA PMID:22110751 |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: SOX9 can act as both activator and repressor. IMP evidence (PMID:24014021, PMID:29503843) shows SOX9 can negatively regulate transcription. Deep research notes SOX9 antagonizes beta-catenin. Reason: SOX9 has documented repressive functions including inhibition of osteoblast genes and antagonism of beta-catenin signaling. This is part of its core regulatory mechanism in maintaining chondrocyte identity. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Antagonizes Ξ²-catenin in chondrocytes... prevents osteoblastic differentiation of chondrocytes by lowering beta-catenin (CTNNB1) signaling file:human/SOX9/SOX9-goa.tsv GO:0000122 negative regulation of transcription by RNA polymerase II biological_process ECO:0000314 IDA PMID:29503843 |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: SOX9 binds to enhancer and promoter regions with sequence specificity. Deep research describes binding to AACAAT-centered motifs in enhancers and super-enhancers. Reason: This is a core molecular function. SOX9 recognizes specific DNA sequences via its HMG-box domain and binds to cis-regulatory regions to activate transcription. Well-supported by experimental evidence. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers file:human/SOX9/SOX9-goa.tsv GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding molecular_function ECO:0000314 IDA PMID:22110751 |
| GO:0002062 chondrocyte differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: SOX9 is the master regulator of chondrocyte differentiation. Deep research and UniProt extensively document this role with multiple IDA/IMP evidence codes. Reason: This is arguably THE core biological process for SOX9. It is absolutely required for chondrogenesis and is the most well-characterized function of SOX9. Extensively validated experimentally. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md SOX9 is a human SOXE-family transcription factor essential for lineage specification... orchestrate chondrogenesis file:human/SOX9/SOX9-uniprot.txt Transcription factor that plays a key role in chondrocytes differentiation and skeletal development |
| GO:0032332 positive regulation of chondrocyte differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: SOX9 promotes chondrocyte differentiation with multiple IDA/IMP evidence codes (PMID:21401405, PMID:20676705). This is a more specific term capturing SOX9's role as a positive regulator. Reason: This is core function. SOX9 positively drives chondrocyte differentiation through direct transcriptional activation of cartilage genes and is required for multiple stages of chondrogenesis. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0032332 positive regulation of chondrocyte differentiation biological_process ECO:0000314 IDA PMID:21401405 |
| GO:0048709 oligodendrocyte differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: SOX9 promotes oligodendrocyte differentiation and glial fate specification. This is a critical function in neural development where SOX9 promotes glial over neuronal fates. Reason: This is a CORE function for the NEURON_DEVELOPMENT project context. SOX9 is essential for oligodendrocyte lineage specification and is the glial counterpart to proneural factors. This is NOT a peripheral function but rather one of SOX9's two major core roles (cartilage AND glia). Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md GLIOGENESIS/OLIGODENDROCYTE DIFFERENTIATION - important for glial fate specification |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: SOX9 binds DNA via its HMG-box domain. This is a well-established molecular function but is somewhat generic compared to the sequence-specific binding terms. Reason: DNA binding is a fundamental molecular function of SOX9. While more specific terms exist (sequence-specific binding), this parent term is also accurate and appropriate. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt DNA_BIND 105..173 /note='HMG box' |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of earlier nucleus annotation. Same evidence and conclusion. Reason: Duplicate annotation with IEA evidence. Nuclear localization is well-established. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | ACCEPT | Summary: SOX9 is involved in differentiation of multiple cell types including chondrocytes, glia, Sertoli cells, and various epithelial cells. This is a very broad parent term. Reason: While generic, this term is accurate. SOX9 drives differentiation programs in multiple lineages. More specific child terms are preferred but this parent term is not incorrect. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt Also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000117 | ACCEPT | Summary: SOX9 activates transcription as documented extensively. This is a parent term less specific than the RNA Pol II terms but still accurate. Reason: This broad term accurately captures SOX9's transactivation function. More specific RNA Pol II terms are preferred but this is not incorrect. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md recruits co-activators CBP/p300 and TIP60... promotes expression of genes important for chondrogenesis |
| GO:1990837 sequence-specific double-stranded DNA binding | IEA GO_REF:0000117 | ACCEPT | Summary: SOX9 binds double-stranded DNA at specific sequences via its HMG-box domain. IDA evidence exists (PMID:28473536). Reason: This accurately describes SOX9's DNA-binding mode. The HMG-box recognizes specific sequences in double-stranded DNA and bends it. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:1990837 sequence-specific double-stranded DNA binding molecular_function ECO:0000314 IDA PMID:28473536 |
| GO:0005515 protein binding | IPI PMID:12810722 A SOX9 defect of calmodulin-dependent nuclear import in camp... | REMOVE | Summary: Generic protein binding term from IPI evidence. SOX9 interacts with many partners including SOX5/6, CBP/p300, beta-catenin, but this term lacks specificity. Reason: Per guidelines, avoid generic "protein binding" annotations as they don't convey informative molecular function. More specific binding terms (e.g., transcription co-activator binding) would be better if available. Supporting Evidence: PMID:12810722 2003 Jun 16. A SOX9 defect of calmodulin-dependent nuclear import in campomelic dysplasia/autosomal sex reversal. |
| GO:0005515 protein binding | IPI PMID:21346191 Arid5a cooperates with Sox9 to stimulate chondrocyte-specifi... | REMOVE | Summary: Duplicate generic protein binding annotation from different reference. Reason: Same rationale as previous protein binding annotation. Generic and uninformative for molecular function. Supporting Evidence: PMID:21346191 2011 Feb 23. Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription. |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 binds to enhancers and promoters. This is a parent term to the more specific RNA Pol II cis-regulatory region binding. Reason: Accurate term capturing SOX9's binding to regulatory regions. More specific child terms exist but this is appropriate. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md binds the DNA minor groove... engages enhancer architectures |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of earlier IBA annotation for same term. Same evidence supports. Reason: Duplicate but accurate annotation of core molecular function. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of first IBA annotation. Multiple evidence codes support. Reason: Core molecular function, well-supported. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md SOX9 is a human SOXE-family transcription factor |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: Another term for sequence-specific binding to regulatory regions. Slight variation in term hierarchy from GO:0000978. Reason: Accurate molecular function term. While overlapping with other DNA-binding terms, this captures the regulatory region specificity. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md binds AACAAT-centered motifs via its HMG-box |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000120 | ACCEPT | Summary: SOX9 has transcriptional activator activity with documented transactivation domains (TAM and TAC). Multiple IDA evidence codes exist. Reason: Core molecular function. SOX9 is primarily a transcriptional activator, though it can also repress. Activator function is well-documented. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) file:human/SOX9/SOX9-goa.tsv GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific molecular_function ECO:0000314 IDA PMID:21367821 |
| GO:0001503 ossification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is involved in skeletal development and endochondral ossification, where it regulates the cartilage template that is replaced by bone. Reason: While SOX9 affects ossification (primarily by regulating the cartilage template for endochondral bone formation), this is a consequence of its chondrogenic function rather than a distinct core role. The core function is chondrogenesis. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt maintains chondrocyte columnar proliferation, delays prehypertrophy and then prevents osteoblastic differentiation |
| GO:0001658 branching involved in ureteric bud morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 regulates kidney development including ureteric bud branching. Reason: Kidney development is a peripheral developmental role, not part of the core cartilage/glial functions. Pleiotropic effect. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Controls epithelial branching during kidney development |
| GO:0001894 tissue homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 plays roles in maintaining tissue homeostasis in intestinal epithelium and other tissues. Reason: Tissue homeostasis represents peripheral maintenance functions rather than core transcription factor activities in cartilage and glial development. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0060729 intestinal epithelial structure maintenance biological_process |
| GO:0002062 chondrocyte differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of earlier IBA annotation for chondrocyte differentiation. Reason: Core function, multiple evidence codes support. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md master regulator of chondrocyte differentiation |
| GO:0002683 negative regulation of immune system process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 may have immunomodulatory effects in certain contexts, but this is not well-documented as a primary function. Reason: Immune regulation is a peripheral effect, not related to core chondrogenic or gliogenic functions. Likely context-dependent pleiotropic effect. |
| GO:0003170 heart valve development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is involved in heart valve development with experimental evidence. Reason: Heart valve development is peripheral to core functions. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0003180 aortic valve morphogenesis biological_process ECO:0000314 IDA PMID:22110751 |
| GO:0003415 chondrocyte hypertrophy | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 regulates chondrocyte hypertrophy. UniProt notes SOX9 is required for chondrocyte hypertrophy both indirectly and directly. Reason: Chondrocyte hypertrophy is part of SOX9's core chondrogenic program. This is a specific stage of chondrocyte maturation that SOX9 controls. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells |
| GO:0003430 growth plate cartilage chondrocyte growth | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 maintains chondrocyte proliferation in growth plate cartilage as part of its chondrogenic program. Reason: Growth plate chondrocyte regulation is part of SOX9's core chondrogenic function. This represents a specific developmental stage in cartilage biology. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt maintains chondrocyte columnar proliferation |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: General parent term for transcription factor activity. Less specific than RNA Pol II-specific terms. Reason: Accurate but broad molecular function term. More specific child terms are preferred but this is not incorrect. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md SOX9 is a human SOXE-family transcription factor |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000120 | ACCEPT | Summary: SOX9 forms complexes with partner proteins including SOX5/6, CBP/p300. It can also homodimerize. Reason: SOX9 functions as part of transcriptional regulatory complexes, cooperating with SOX5/6 on paired SOX sites and recruiting coactivators. This is accurate. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md frequently in cooperation with SOX5/6 on paired SOX sites file:human/SOX9/SOX9-uniprot.txt Homodimer; homodimerization is required for activity |
| GO:0007165 signal transduction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Extremely broad term. SOX9 responds to and mediates signaling pathways like BMP, TGF-beta, but this term is too generic. Reason: This term is overly broad and uninformative. SOX9 participates in specific signaling contexts but "signal transduction" as a general term doesn't capture its function meaningfully. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is involved in EGFR signaling in urothelial and other epithelial contexts. Deep research mentions EGFR-ERK-SOX9 cascade. Reason: EGFR pathway involvement is context-specific (urothelium, epithelial regeneration) and peripheral to core functions. Not part of cartilage/glial programs. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer |
| GO:0007417 central nervous system development | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 promotes glial fate specification and oligodendrocyte differentiation in the CNS. This is one of its core functions. Reason: CNS development via gliogenesis is a CORE function of SOX9 in the NEURON_DEVELOPMENT project context. SOX9 promotes glial over neuronal fates. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md GLIOGENESIS/OLIGODENDROCYTE DIFFERENTIATION - important for glial fate specification |
| GO:0008013 beta-catenin binding | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 interacts with beta-catenin to antagonize Wnt signaling in chondrocytes. This is a specific and informative binding term. Reason: Beta-catenin binding is a specific molecular function relevant to SOX9's mechanism of action. Unlike generic "protein binding," this term conveys functional information about SOX9's antagonism of Wnt signaling. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Antagonizes Ξ²-catenin in chondrocytes file:human/SOX9/SOX9-uniprot.txt Interacts with beta-catenin (CTNNB1); inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1 |
| GO:0010467 gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Extremely generic term for any gene expression regulation. Reason: Too broad to be informative. More specific terms about transcriptional regulation better capture SOX9's function. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: Slightly more specific than gene expression but still quite broad. Has IDA evidence (PMID:24681825). Reason: While broad, this accurately captures SOX9's role as a transcriptional activator. More specific terms are preferred but this is acceptable. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0010628 positive regulation of gene expression biological_process ECO:0000314 IDA PMID:24681825 |
| GO:0030279 negative regulation of ossification | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 delays ossification by maintaining cartilage and preventing premature osteoblast differentiation. Has IDA evidence (PMID:29503843). Reason: This is part of SOX9's core chondrogenic program. SOX9 blocks osteoblast differentiation to maintain chondrocyte identity, which delays ossification. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt prevents osteoblastic differentiation of chondrocytes by lowering beta-catenin (CTNNB1) signaling file:human/SOX9/SOX9-goa.tsv GO:0030279 negative regulation of ossification biological_process ECO:0000314 IDA PMID:29503843 |
| GO:0030850 prostate gland development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is expressed in prostate development with IEP evidence. Reason: Prostate development is a peripheral epithelial developmental role, not core cartilage/glial function. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0030850 prostate gland development biological_process ECO:0000270 IEP PMID:20103652 |
| GO:0030879 mammary gland development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 plays roles in mammary gland epithelial development. Reason: Peripheral epithelial developmental function. |
| GO:0030903 notochord development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is involved in notochord development. Reason: Notochord development is a developmental process but peripheral to core cartilage/glial functions. |
| GO:0032332 positive regulation of chondrocyte differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of earlier IBA annotation for same term. Reason: Core function with multiple evidence codes. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md master regulator of chondrocyte differentiation |
| GO:0043425 bHLH transcription factor binding | IEA GO_REF:0000107 | UNDECIDED | Summary: SOX9 may interact with bHLH transcription factors in certain contexts, but this is not well-documented as a major interaction. Reason: Unclear if this represents a significant molecular function for SOX9. Would need to review evidence for specific bHLH factor interactions relevant to SOX9's core functions. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 binds DNA in sequence-specific manner via AACAAT motif recognition. Has IDA evidence (PMID:31194875). Reason: Core molecular function, well-supported. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md binds AACAAT-centered motifs via its HMG-box file:human/SOX9/SOX9-goa.tsv GO:0043565 sequence-specific DNA binding molecular_function ECO:0000314 IDA PMID:31194875 |
| GO:0045668 negative regulation of osteoblast differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 blocks osteoblast differentiation to maintain chondrocyte identity. Has ISS evidence. Reason: This is part of SOX9's core mechanism for maintaining chondrocyte fate. SOX9 antagonizes osteoblast genes and beta-catenin to prevent osteogenesis. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt prevents osteoblastic differentiation of chondrocytes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 activates RNA Pol II transcription with multiple IDA/IMP evidence codes. Reason: Core transcriptional activator function, well-supported. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0045944 positive regulation of transcription by RNA polymerase II biological_process ECO:0000314 IDA PMID:22110751 |
| GO:0046322 negative regulation of fatty acid oxidation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Deep research mentions low lipid levels promote SOX9 expression and chondrogenic commitment, with SOX9 suppressing fatty acid oxidation. Reason: While documented, this represents a metabolic coupling to chondrogenic commitment rather than a core transcription factor function. Peripheral metabolic effect. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt when lipids levels are low, FOXO (FOXO1 and FOXO3) transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation |
| GO:0051216 cartilage development | IEA GO_REF:0000120 | ACCEPT | Summary: Broad parent term for cartilage development. SOX9 is the master regulator of cartilage development. Reason: This is a core biological process for SOX9. While less specific than chondrocyte differentiation, it accurately captures SOX9's role in cartilage biology. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md orchestrate chondrogenesis |
| GO:0060009 Sertoli cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is critical for Sertoli cell development and sex determination. Reason: Sex determination and Sertoli cell development are important biological functions of SOX9 but peripheral to the core cartilage/glial roles. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Sex determination (testis development, Sertoli cell differentiation) |
| GO:0060174 limb bud formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is involved in limb skeletal development. Reason: Limb development involves SOX9's chondrogenic function but this specific term represents a developmental context rather than core molecular function. |
| GO:0070168 negative regulation of biomineral tissue development | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 inhibits bone mineralization, maintaining cartilage. Has IDA evidence (PMID:22110751). Reason: This is part of SOX9's mechanism for maintaining cartilage identity by preventing premature mineralization and osteoblast differentiation. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0070168 negative regulation of biomineral tissue development biological_process ECO:0000314 IDA PMID:22110751 |
| GO:0070371 ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is involved in ERK signaling cascades in epithelial contexts. Reason: ERK cascade involvement is context-specific (EGFR-ERK-SOX9 in urothelium) and peripheral to core functions. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md An EGFR-ERK-SOX9 signaling cascade |
| GO:0070542 response to fatty acid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Related to the lipid/fatty acid oxidation effects noted earlier. Reason: Peripheral metabolic response, not core transcription factor function. |
| GO:0071260 cellular response to mechanical stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 may respond to mechanical stimuli in cartilage contexts. Reason: While potentially relevant to cartilage biology, this is a contextual response rather than core molecular function. |
| GO:0071364 cellular response to epidermal growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Related to EGFR signaling pathway involvement noted earlier. Reason: Context-specific response in epithelial tissues, not core function. |
| GO:0071504 cellular response to heparin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 may respond to heparin in certain contexts. Reason: Highly specific contextual response, unclear relevance to core functions. |
| GO:0071560 cellular response to transforming growth factor beta stimulus | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 responds to TGF-beta signaling which regulates chondrogenesis. Has IDA evidence (PMID:21401405). Reason: TGF-beta signaling is central to chondrogenesis regulation. SOX9's response to TGF-beta is part of its core chondrogenic program. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0071560 cellular response to transforming growth factor beta stimulus biological_process ECO:0000314 IDA PMID:21401405 |
| GO:0071599 otic vesicle development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 is involved in inner ear development. Reason: Peripheral developmental process in sensory organ development. |
| GO:0072034 renal vesicle induction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 regulates kidney development including renal vesicle formation. Reason: Peripheral kidney development function. |
| GO:0072170 metanephric tubule development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 involved in kidney tubule development. Reason: Peripheral kidney development function. |
| GO:0072190 ureter urothelium development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 regulates urothelial development. Reason: Peripheral epithelial development. |
| GO:0090184 positive regulation of kidney development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SOX9 promotes kidney development. Reason: Peripheral developmental function. |
| GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: More specific kidney branching term. Reason: Peripheral kidney development function. |
| GO:0097157 pre-mRNA intronic binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Deep research notes SOX9 regulates alternative splicing in beta cells, which may involve intronic binding. Reason: This is an interesting molecular function related to the alternative splicing role discovered in beta cells, but unclear if this is broadly relevant to SOX9's core functions. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md SOX9 persists in mature Ξ² cells and regulates alternative splicing programs |
| GO:1904864 negative regulation of beta-catenin-TCF complex assembly | IEA GO_REF:0000107 | ACCEPT | Summary: SOX9 antagonizes beta-catenin by competing for binding sites with TCF/LEF factors. Reason: This is a specific molecular mechanism by which SOX9 antagonizes Wnt signaling to maintain chondrocyte identity. Part of core chondrogenic function. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt Interacts with beta-catenin (CTNNB1); inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1 |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: SOX9 localizes to nucleoplasm as a nuclear transcription factor. Reason: Nucleoplasm is the appropriate sub-nuclear compartment for transcription factors. More specific than just "nucleus." Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:24014021 miR-1247 functions by targeting cartilage transcription fact... | ACCEPT | Summary: Duplicate of earlier IBA annotation with additional IMP evidence. Reason: SOX9 has documented repressive functions. Multiple evidence codes support. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0000122 negative regulation of transcription by RNA polymerase II biological_process ECO:0000315 IMP PMID:24014021 PMID:24014021 2013 Sep 6. miR-1247 functions by targeting cartilage transcription factor SOX9. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:21367821 Sox9 sustains chondrocyte survival and hypertrophy in part t... | ACCEPT | Summary: Duplicate with IDA evidence from different publication. Reason: Core molecular function with strong experimental support. Supporting Evidence: PMID:21367821 Sox9 sustains chondrocyte survival and hypertrophy in part through Pik3ca-Akt pathways. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:21367821 Sox9 sustains chondrocyte survival and hypertrophy in part t... | ACCEPT | Summary: Duplicate with IMP evidence. Reason: Core function with experimental evidence. Supporting Evidence: PMID:21367821 Sox9 sustains chondrocyte survival and hypertrophy in part through Pik3ca-Akt pathways. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. | ACCEPT | Summary: Duplicate with IDA evidence from heart valve study. Reason: Core molecular function. Supporting Evidence: PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. | ACCEPT | Summary: Another duplicate with IDA evidence. Reason: Core molecular function. Supporting Evidence: PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. |
| GO:0003180 aortic valve morphogenesis | IDA PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. | KEEP AS NON CORE | Summary: Specific heart valve development term with experimental evidence. Reason: Heart valve morphogenesis is peripheral to core cartilage/glial functions. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0003180 aortic valve morphogenesis biological_process ECO:0000314 IDA PMID:22110751 PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. | ACCEPT | Summary: Another duplicate from heart valve study. Reason: Core function. Supporting Evidence: PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. |
| GO:0070168 negative regulation of biomineral tissue development | IDA PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. | ACCEPT | Summary: Duplicate of earlier annotation with IDA evidence from heart valve study. Reason: Part of core mechanism for maintaining cartilage over bone. Supporting Evidence: PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:20484372 The dimerization domain of SOX9 is required for transcriptio... | ACCEPT | Summary: Multiple IDA evidence codes from different publications. Reason: Core molecular function. Supporting Evidence: PMID:20484372 May 19. The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:21412441 Failure of SOX9 regulation in 46XY disorders of sex developm... | ACCEPT | Summary: Another IDA evidence from sex determination study. Reason: Core molecular function. Supporting Evidence: PMID:21412441 Failure of SOX9 regulation in 46XY disorders of sex development with SRY, SOX9 and SF1 mutations. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:20484372 The dimerization domain of SOX9 is required for transcriptio... | ACCEPT | Summary: Duplicate IDA evidence. Reason: Core molecular function. Supporting Evidence: PMID:20484372 May 19. The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | ACCEPT | Summary: Another IDA evidence. Reason: Core molecular function. Supporting Evidence: PMID:20530484 Epub 2010 Jun 8. SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium. |
| GO:1902894 negative regulation of miRNA transcription | IDA PMID:26687115 The microRNA-29 family in cartilage homeostasis and osteoart... | KEEP AS NON CORE | Summary: SOX9 regulates miRNA expression in cartilage contexts. Reason: While experimentally validated, miRNA regulation is a secondary regulatory mechanism rather than core transcription factor function. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:1902894 negative regulation of miRNA transcription biological_process ECO:0000314 IDA PMID:26687115 PMID:26687115 2015 Dec 19. The microRNA-29 family in cartilage homeostasis and osteoarthritis. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: Duplicate of earlier IEA annotation with IDA evidence. Reason: Core molecular function with experimental support. Supporting Evidence: PMID:28473536 Impact of cytosine methylation on DNA binding specificities of human transcription factors. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:31194875 The SOXE transcription factors-SOX8, SOX9 and SOX10-share a ... | ACCEPT | Summary: More IDA evidence from transactivation domain study. Reason: Core molecular function. Supporting Evidence: PMID:31194875 The SOXE transcription factors-SOX8, SOX9 and SOX10-share a bi-partite transactivation mechanism. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:31194875 The SOXE transcription factors-SOX8, SOX9 and SOX10-share a ... | ACCEPT | Summary: Duplicate with IDA evidence. Reason: Core molecular function. Supporting Evidence: PMID:31194875 The SOXE transcription factors-SOX8, SOX9 and SOX10-share a bi-partite transactivation mechanism. |
| GO:0002062 chondrocyte differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: Multiple evidence codes for this core function. Reason: Core function with ISS evidence. |
| GO:0003430 growth plate cartilage chondrocyte growth | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate with ISS evidence. Reason: Part of core chondrogenic program. |
| GO:0045668 negative regulation of osteoblast differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate with ISS evidence. Reason: Core mechanism for maintaining chondrocyte identity. |
| GO:0046322 negative regulation of fatty acid oxidation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate with ISS evidence. Reason: Peripheral metabolic effect. |
| GO:0070542 response to fatty acid | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate with ISS evidence. Reason: Peripheral metabolic response. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: SOX9 binds chromatin as a transcription factor. Deep research notes it can act as a pioneer factor at super-enhancers. Reason: Chromatin localization is appropriate for a transcription factor that engages enhancers and promoters. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Can act as a pioneer factor at super-enhancers |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: ISA evidence from TFClass database. Reason: Core molecular function supported by database annotation. |
| GO:0010628 positive regulation of gene expression | IDA PMID:24681825 The NLR-related protein NWD1 is associated with prostate can... | ACCEPT | Summary: Duplicate with IDA evidence. Reason: Core transcriptional activator function. Supporting Evidence: PMID:24681825 The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling. |
| GO:0005515 protein binding | IPI PMID:28263186 Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepim... | REMOVE | Summary: Another generic protein binding annotation (DDRGK1 interaction). Reason: Generic protein binding term. While DDRGK1 interaction affects SOX9 ubiquitination, the generic term doesn't convey functional information. Supporting Evidence: PMID:28263186 Mar 6. Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Multiple evidence codes for nuclear localization. Reason: Well-established cellular component. |
| GO:0005634 nucleus | IDA PMID:26634652 Valve Endothelial Cell-Derived TgfΞ²1 Signaling Promotes Nucl... | ACCEPT | Summary: IDA evidence for nuclear localization. Reason: Well-established with experimental evidence. Supporting Evidence: PMID:26634652 Valve Endothelial Cell-Derived TgfΞ²1 Signaling Promotes Nuclear Localization of Sox9 in Interstitial Cells Associated With Attenuated Calcification. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | ACCEPT | Summary: Another IDA evidence. Reason: Core molecular function. Supporting Evidence: PMID:20530484 Epub 2010 Jun 8. SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium. |
| GO:0061036 positive regulation of cartilage development | IDA PMID:29503843 Sox9 augments BMP2-induced chondrogenic differentiation by d... | ACCEPT | Summary: SOX9 promotes cartilage development with IDA evidence. Reason: This is essentially a parent term encompassing SOX9's chondrogenic functions. Core function. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0061036 positive regulation of cartilage development biological_process ECO:0000314 IDA PMID:29503843 PMID:29503843 Nov 2. Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells (MSCs). |
| GO:1902732 positive regulation of chondrocyte proliferation | IDA PMID:29503843 Sox9 augments BMP2-induced chondrogenic differentiation by d... | ACCEPT | Summary: SOX9 promotes chondrocyte proliferation in growth plate. Reason: Part of core chondrogenic program maintaining columnar proliferation. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt maintains chondrocyte columnar proliferation PMID:29503843 Nov 2. Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells (MSCs). |
| GO:0030279 negative regulation of ossification | IDA PMID:29503843 Sox9 augments BMP2-induced chondrogenic differentiation by d... | ACCEPT | Summary: Duplicate with IDA evidence. Reason: Part of core mechanism. Supporting Evidence: PMID:29503843 Nov 2. Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells (MSCs). |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:29503843 Sox9 augments BMP2-induced chondrogenic differentiation by d... | ACCEPT | Summary: More IDA evidence for repressive function. Reason: Documented repressive capability. Supporting Evidence: PMID:29503843 Nov 2. Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells (MSCs). |
| GO:0001502 cartilage condensation | ISS GO_REF:0000024 | ACCEPT | Summary: SOX9 is absolutely required for precartilaginous condensation, the first step in chondrogenesis. Reason: Cartilage condensation is the initial step in chondrogenesis where SOX9 is absolutely required. This is core chondrogenic function. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt Absolutely required for precartilaginous condensation, the first step in chondrogenesis |
| GO:0014036 neural crest cell fate specification | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 is involved in neural crest development. Reason: Neural crest fate specification is peripheral to core cartilage/glial functions. While SOX9 may affect neural crest, this is not its primary role. |
| GO:0071773 cellular response to BMP stimulus | ISS GO_REF:0000024 | ACCEPT | Summary: SOX9 responds to BMP signaling which regulates chondrogenesis. Reason: BMP signaling is central to chondrogenesis and SOX9 is a key effector of BMP responses in cartilage differentiation. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt Acts in cooperation with the Hedgehog pathway-dependent GLI (GLI1 and GLI3) transcription factors |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5626938 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome. Reason: Appropriate sub-nuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8985343 | ACCEPT | Summary: Another Reactome TAS annotation for nucleoplasm. Reason: Appropriate sub-nuclear compartment. |
| GO:0032332 positive regulation of chondrocyte differentiation | IDA PMID:21401405 Electroporation-mediated transfer of SOX trio genes (SOX-5, ... | ACCEPT | Summary: More IDA evidence for core function. Reason: Core chondrogenic function. Supporting Evidence: PMID:21401405 Oct 21. Electroporation-mediated transfer of SOX trio genes (SOX-5, SOX-6, and SOX-9) to enhance the chondrogenesis of mesenchymal stem cells. |
| GO:0061036 positive regulation of cartilage development | IDA PMID:21401405 Electroporation-mediated transfer of SOX trio genes (SOX-5, ... | ACCEPT | Summary: Duplicate with IDA evidence. Reason: Core chondrogenic function. Supporting Evidence: PMID:21401405 Oct 21. Electroporation-mediated transfer of SOX trio genes (SOX-5, SOX-6, and SOX-9) to enhance the chondrogenesis of mesenchymal stem cells. |
| GO:0071560 cellular response to transforming growth factor beta stimulus | IDA PMID:21401405 Electroporation-mediated transfer of SOX trio genes (SOX-5, ... | ACCEPT | Summary: Duplicate with IDA evidence. Reason: Part of core chondrogenic signaling response. Supporting Evidence: PMID:21401405 Oct 21. Electroporation-mediated transfer of SOX trio genes (SOX-5, SOX-6, and SOX-9) to enhance the chondrogenesis of mesenchymal stem cells. |
| GO:0003415 chondrocyte hypertrophy | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate with ISS evidence. Reason: Core chondrogenic program. |
| GO:0003682 chromatin binding | IDA PMID:20484372 The dimerization domain of SOX9 is required for transcriptio... | ACCEPT | Summary: SOX9 binds chromatin with IDA evidence. Reason: Chromatin binding is a specific molecular function relevant to SOX9's role as a transcription factor engaging chromatin. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0003682 chromatin binding molecular_function ECO:0000314 IDA PMID:20484372 PMID:20484372 May 19. The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template. |
| GO:0006334 nucleosome assembly | IDA PMID:20484372 The dimerization domain of SOX9 is required for transcriptio... | KEEP AS NON CORE | Summary: PMID:20484372 shows SOX9 dimerization is required for nucleosome assembly during chondrocyte-specific transcription activation. Reason: While experimentally supported, nucleosome assembly is a chromatin remodeling mechanism rather than a core transcription factor function. It's part of the mechanistic process but peripheral to the primary role. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0006334 nucleosome assembly biological_process ECO:0000314 IDA PMID:20484372 PMID:20484372 May 19. The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template. |
| GO:0006338 chromatin remodeling | IDA PMID:20484372 The dimerization domain of SOX9 is required for transcriptio... | KEEP AS NON CORE | Summary: SOX9 is involved in chromatin remodeling at target genes. Reason: Chromatin remodeling is a mechanistic process supporting transcription activation but not a core defining function of SOX9. Supporting Evidence: PMID:20484372 May 19. The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template. |
| GO:0007173 epidermal growth factor receptor signaling pathway | ISS PMID:21512138 An EGFR-ERK-SOX9 signaling cascade links urothelial developm... | KEEP AS NON CORE | Summary: Duplicate with ISS evidence. Reason: Context-specific signaling in epithelial tissues. Supporting Evidence: PMID:21512138 Epub 2011 Apr 21. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:20651055 Upregulation of SOX9 in lung adenocarcinoma and its involvem... | KEEP AS NON CORE | Summary: SOX9 promotes proliferation in certain contexts (lung adenocarcinoma study). Reason: While SOX9 does promote chondrocyte proliferation (core function), this generic proliferation term from a cancer study represents peripheral effects rather than the specific chondrocyte proliferation that is core. Supporting Evidence: PMID:20651055 Upregulation of SOX9 in lung adenocarcinoma and its involvement in the regulation of cell growth and tumorigenicity. |
| GO:0010634 positive regulation of epithelial cell migration | IMP PMID:21512138 An EGFR-ERK-SOX9 signaling cascade links urothelial developm... | KEEP AS NON CORE | Summary: SOX9 promotes epithelial cell migration in urothelial contexts. Reason: Context-specific epithelial function, not core cartilage/glial role. Supporting Evidence: PMID:21512138 Epub 2011 Apr 21. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:20651055 Upregulation of SOX9 in lung adenocarcinoma and its involvem... | ACCEPT | Summary: General transcriptional repression term with IMP evidence. Reason: SOX9 has documented repressive functions. More specific RNA Pol II term is preferred but this is acceptable. Supporting Evidence: PMID:20651055 Upregulation of SOX9 in lung adenocarcinoma and its involvement in the regulation of cell growth and tumorigenicity. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:20651055 Upregulation of SOX9 in lung adenocarcinoma and its involvem... | ACCEPT | Summary: General transcriptional activation term with IMP evidence. Reason: SOX9 is primarily a transcriptional activator. More specific RNA Pol II term is preferred but this is acceptable. Supporting Evidence: PMID:20651055 Upregulation of SOX9 in lung adenocarcinoma and its involvement in the regulation of cell growth and tumorigenicity. |
| GO:0070371 ERK1 and ERK2 cascade | ISS PMID:21512138 An EGFR-ERK-SOX9 signaling cascade links urothelial developm... | KEEP AS NON CORE | Summary: Duplicate ISS evidence. Reason: Context-specific signaling. Supporting Evidence: PMID:21512138 Epub 2011 Apr 21. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. |
| GO:0071260 cellular response to mechanical stimulus | ISS PMID:21512138 An EGFR-ERK-SOX9 signaling cascade links urothelial developm... | KEEP AS NON CORE | Summary: Duplicate ISS evidence. Reason: Context-specific response. Supporting Evidence: PMID:21512138 Epub 2011 Apr 21. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. |
| GO:0071364 cellular response to epidermal growth factor stimulus | ISS PMID:21512138 An EGFR-ERK-SOX9 signaling cascade links urothelial developm... | KEEP AS NON CORE | Summary: Duplicate ISS evidence. Reason: Context-specific response. Supporting Evidence: PMID:21512138 Epub 2011 Apr 21. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. |
| GO:0071504 cellular response to heparin | ISS PMID:21512138 An EGFR-ERK-SOX9 signaling cascade links urothelial developm... | KEEP AS NON CORE | Summary: Duplicate ISS evidence. Reason: Context-specific response. Supporting Evidence: PMID:21512138 Epub 2011 Apr 21. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. |
| GO:2000020 positive regulation of male gonad development | IDA PMID:21412441 Failure of SOX9 regulation in 46XY disorders of sex developm... | KEEP AS NON CORE | Summary: SOX9 promotes testis development with IDA evidence. Reason: Sex determination is an important SOX9 function but peripheral to core cartilage/glial roles. Supporting Evidence: PMID:21412441 Failure of SOX9 regulation in 46XY disorders of sex development with SRY, SOX9 and SF1 mutations. |
| GO:2000741 positive regulation of mesenchymal stem cell differentiation | IDA PMID:21401405 Electroporation-mediated transfer of SOX trio genes (SOX-5, ... | ACCEPT | Summary: SOX9 promotes MSC differentiation toward chondrocytes. Reason: MSC differentiation toward chondrocytes is part of the chondrogenic program. This captures an earlier step in the lineage commitment. Supporting Evidence: PMID:21401405 Oct 21. Electroporation-mediated transfer of SOX trio genes (SOX-5, SOX-6, and SOX-9) to enhance the chondrogenesis of mesenchymal stem cells. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate with ISS evidence. Reason: Core molecular function. |
| GO:0001502 cartilage condensation | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate ISS evidence. Reason: Core first step in chondrogenesis. |
| GO:0001894 tissue homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate ISS evidence. Reason: Peripheral maintenance function. |
| GO:0002683 negative regulation of immune system process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate ISS evidence. Reason: Peripheral immunomodulatory effect. |
| GO:0003170 heart valve development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate ISS evidence. Reason: Peripheral developmental function. |
| GO:0030279 negative regulation of ossification | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate ISS evidence. Reason: Core mechanism for maintaining cartilage. |
| GO:0030850 prostate gland development | IEP PMID:20103652 SOX9 elevation in the prostate promotes proliferation and co... | KEEP AS NON CORE | Summary: IEP evidence for prostate development. Reason: Peripheral epithelial development. Supporting Evidence: PMID:20103652 2010 Jan 26. SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation. |
| GO:0050679 positive regulation of epithelial cell proliferation | IEP PMID:20103652 SOX9 elevation in the prostate promotes proliferation and co... | KEEP AS NON CORE | Summary: IEP evidence from prostate study. Reason: Context-specific epithelial proliferation, not core function. Supporting Evidence: PMID:20103652 2010 Jan 26. SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation. |
| GO:0070168 negative regulation of biomineral tissue development | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate ISS evidence. Reason: Core mechanism for maintaining cartilage. |
| GO:0071347 cellular response to interleukin-1 | IEP PMID:20079164 Interleukin-1 inhibits Sox9 and collagen type II expression ... | KEEP AS NON CORE | Summary: SOX9 responds to IL-1 in intervertebral disc cells. Reason: Context-specific response in pathological conditions, not core function. Supporting Evidence: PMID:20079164 Interleukin-1 inhibits Sox9 and collagen type II expression via nuclear factor-kappaB in the cultured human intervertebral disc cells. |
| GO:0001708 cell fate specification | ISS GO_REF:0000024 | ACCEPT | Summary: SOX9 specifies cell fates including chondrocyte, glial, and Sertoli cell fates. Reason: Cell fate specification is fundamental to SOX9's function as a lineage-determining transcription factor in chondrocytes and glia. This is core. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md essential for lineage specification... glial fate specification |
| GO:0001837 epithelial to mesenchymal transition | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 is involved in EMT in various developmental contexts. Reason: EMT is a process that occurs in multiple developmental contexts but is not a core defining function of SOX9. |
| GO:0001942 hair follicle development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 plays roles in hair follicle development. Reason: Hair follicle development is peripheral epithelial function noted in deep research as one of multiple other programs. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Hair follicle morphogenesis |
| GO:0002053 positive regulation of mesenchymal cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 promotes mesenchymal cell proliferation. Reason: While related to chondrogenesis (mesenchymal condensation), this generic proliferation term is broader than the specific chondrocyte proliferation that is core. |
| GO:0003179 heart valve morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate ISS evidence for heart valve. Reason: Peripheral developmental function. |
| GO:0003203 endocardial cushion morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 involved in heart cushion development. Reason: Peripheral cardiac development function. |
| GO:0005634 nucleus | IDA PMID:12420222 RAR agonists stimulate SOX9 gene expression in breast cancer... | ACCEPT | Summary: Multiple IDA evidence codes for nuclear localization. Reason: Well-established with experimental evidence. Supporting Evidence: PMID:12420222 RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition. |
| GO:0007283 spermatogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 involved in spermatogenesis via Sertoli cell function. Reason: Peripheral reproductive developmental function. |
| GO:0010564 regulation of cell cycle process | IMP PMID:12420222 RAR agonists stimulate SOX9 gene expression in breast cancer... | KEEP AS NON CORE | Summary: SOX9 can regulate cell cycle in certain contexts. Reason: While SOX9 affects proliferation in chondrocytes, this generic cell cycle term is overly broad and not a core defining function. Supporting Evidence: PMID:12420222 RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition. |
| GO:0019100 male germ-line sex determination | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 is critical for male sex determination. Reason: Important but peripheral to core cartilage/glial functions. |
| GO:0030858 positive regulation of epithelial cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 promotes epithelial differentiation in multiple organs. Reason: Generic epithelial differentiation is peripheral to core functions. |
| GO:0030916 otic vesicle formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 involved in inner ear development. Reason: Peripheral sensory organ development. |
| GO:0032331 negative regulation of chondrocyte differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: SOX9 can negatively regulate chondrocyte differentiation at certain stages to maintain progenitor populations. Reason: This reflects SOX9's context-dependent role in maintaining chondrocyte progenitors versus promoting differentiation. Part of the nuanced chondrogenic program. |
| GO:0035019 somatic stem cell population maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 maintains stem cell populations in various tissues. Reason: While SOX9 can maintain stem/progenitor populations, this generic term doesn't capture the core cartilage/glial functions. |
| GO:0042127 regulation of cell population proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Very generic proliferation regulation term. Reason: Too generic to be informative. More specific terms about chondrocyte proliferation are preferred. |
| GO:0042981 regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 may regulate apoptosis in certain contexts. Reason: Apoptosis regulation is a peripheral effect, not a core transcription factor function. |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 may have anti-apoptotic effects. Reason: Peripheral effect, not core function. |
| GO:0045662 negative regulation of myoblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 inhibits myoblast differentiation. Reason: While SOX9 promotes chondrocyte over other mesenchymal fates, myoblast inhibition is a peripheral effect. |
| GO:0046533 negative regulation of photoreceptor cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 involved in retinal development. Reason: Peripheral retinal development function. |
| GO:0050679 positive regulation of epithelial cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate ISS evidence. Reason: Context-specific epithelial proliferation. |
| GO:0050680 negative regulation of epithelial cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 can also negatively regulate epithelial proliferation contextually. Reason: Context-dependent epithelial regulation, peripheral function. |
| GO:0051216 cartilage development | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate ISS evidence. Reason: Core chondrogenic function. |
| GO:0060008 Sertoli cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 promotes Sertoli cell differentiation. Reason: Peripheral sex determination function. |
| GO:0060041 retina development in camera-type eye | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 involved in retinal development. Reason: Peripheral sensory organ development. |
| GO:0060221 retinal rod cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: More specific retinal development term. Reason: Peripheral sensory cell differentiation. |
| GO:0060517 epithelial cell proliferation involved in prostatic bud elongation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Highly specific prostate development term. Reason: Very specific peripheral developmental process. |
| GO:0060729 intestinal epithelial structure maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 maintains intestinal epithelium. Reason: Peripheral tissue maintenance function. |
| GO:0060784 regulation of cell proliferation involved in tissue homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Generic tissue homeostasis proliferation regulation. Reason: Peripheral maintenance function. |
| GO:0061138 morphogenesis of a branching epithelium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate of earlier epithelial morphogenesis annotation. Reason: Peripheral epithelial morphogenesis. |
| GO:0071300 cellular response to retinoic acid | IEP PMID:12420222 RAR agonists stimulate SOX9 gene expression in breast cancer... | KEEP AS NON CORE | Summary: SOX9 responds to retinoic acid. Reason: Contextual signaling response, not core function. Supporting Evidence: PMID:12420222 RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition. |
| GO:0072289 metanephric nephron tubule formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: More specific kidney development term. Reason: Peripheral kidney development. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: SOX9 antagonizes Wnt/beta-catenin signaling. Reason: Wnt/beta-catenin antagonism is a core mechanism by which SOX9 maintains chondrocyte identity and blocks osteoblast differentiation. Supporting Evidence: file:human/SOX9/SOX9-deep-research-falcon.md Antagonizes Ξ²-catenin in chondrocytes |
| GO:0090103 cochlea morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SOX9 involved in inner ear cochlea development. Reason: Peripheral sensory organ development. |
| GO:0001501 skeletal system development | IMP PMID:8640233 Sex reversal by loss of the C-terminal transactivation domai... | ACCEPT | Summary: Broad term for skeletal development with IMP evidence from foundational SOX9 study. Reason: Skeletal system development encompasses SOX9's chondrogenic functions. While broad, this is a core developmental process for SOX9. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0001501 skeletal system development biological_process ECO:0000315 IMP PMID:8640233 PMID:8640233 Sex reversal by loss of the C-terminal transactivation domain of human SOX9. |
| GO:0003413 chondrocyte differentiation involved in endochondral bone morphogenesis | IMP PMID:20676705 Generation of transgenic mice for conditional overexpression... | ACCEPT | Summary: More specific term for chondrocyte differentiation in context of endochondral ossification. Reason: This captures the specific developmental context where SOX9-driven chondrogenesis creates the cartilage template for bone formation. Core function. Supporting Evidence: file:human/SOX9/SOX9-goa.tsv GO:0003413 chondrocyte differentiation involved in endochondral bone morphogenesis biological_process ECO:0000315 IMP PMID:20676705 PMID:20676705 2010 Jul 30. Generation of transgenic mice for conditional overexpression of Sox9. |
| GO:0003700 DNA-binding transcription factor activity | IMP PMID:8640233 Sex reversal by loss of the C-terminal transactivation domai... | ACCEPT | Summary: IMP evidence from foundational study. Reason: Core molecular function with experimental evidence. Supporting Evidence: PMID:8640233 Sex reversal by loss of the C-terminal transactivation domain of human SOX9. |
| GO:0005634 nucleus | IDA PMID:8640233 Sex reversal by loss of the C-terminal transactivation domai... | ACCEPT | Summary: More IDA evidence for nuclear localization. Reason: Well-established cellular component. Supporting Evidence: PMID:8640233 Sex reversal by loss of the C-terminal transactivation domain of human SOX9. |
| GO:0008584 male gonad development | IMP PMID:8640233 Sex reversal by loss of the C-terminal transactivation domai... | KEEP AS NON CORE | Summary: IMP evidence for testis development. Reason: Peripheral sex determination function. Supporting Evidence: PMID:8640233 Sex reversal by loss of the C-terminal transactivation domain of human SOX9. |
| GO:0032332 positive regulation of chondrocyte differentiation | IMP PMID:20676705 Generation of transgenic mice for conditional overexpression... | ACCEPT | Summary: More IMP evidence for core function. Reason: Core chondrogenic function. Supporting Evidence: PMID:20676705 2010 Jul 30. Generation of transgenic mice for conditional overexpression of Sox9. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:8640233 Sex reversal by loss of the C-terminal transactivation domai... | ACCEPT | Summary: IDA evidence from foundational study. Reason: Core transcriptional activator function. Supporting Evidence: PMID:8640233 Sex reversal by loss of the C-terminal transactivation domain of human SOX9. |
| GO:0005634 nucleus | IDA PMID:18512230 Quantitative assessment of glial cells in the human and guin... | ACCEPT | Summary: More IDA evidence for nucleus. Reason: Well-established. Supporting Evidence: PMID:18512230 Quantitative assessment of glial cells in the human and guinea pig enteric nervous system with an anti-Sox8/9/10 antibody. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IDA PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kina... | ACCEPT | Summary: IDA evidence for sequence-specific binding. Reason: Core molecular function. Supporting Evidence: PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kina... | ACCEPT | Summary: More IDA evidence. Reason: Core molecular function. Supporting Evidence: PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. |
| GO:0005515 protein binding | IPI PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | REMOVE | Summary: Another generic protein binding (MITF/OTX2 interactions). Reason: Generic protein binding term, uninformative. Supporting Evidence: PMID:20530484 Epub 2010 Jun 8. SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium. |
| GO:0005634 nucleus | IDA PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kina... | ACCEPT | Summary: More IDA evidence. Reason: Well-established. Supporting Evidence: PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. |
| GO:0032991 protein-containing complex | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | MARK AS OVER ANNOTATED | Summary: SOX9 forms complexes with partners. This is a very generic cellular component term. Reason: Too generic. More specific terms like "transcription regulator complex" better capture SOX9's complex formation. Supporting Evidence: PMID:20530484 Epub 2010 Jun 8. SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium. |
| GO:0034236 protein kinase A catalytic subunit binding | IPI PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kina... | ACCEPT | Summary: SOX9 interacts with PKA which phosphorylates it to enhance activity. This is a specific binding term. Reason: PKA binding and phosphorylation is a specific regulatory mechanism for SOX9 activity. Unlike generic protein binding, this conveys functional information. Supporting Evidence: file:human/SOX9/SOX9-uniprot.txt Phosphorylation at Ser-64 and Ser-211 by PKA increases transcriptional activity PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kina... | ACCEPT | Summary: IDA evidence for transcriptional activation. Reason: Core activator function. Supporting Evidence: PMID:10805756 Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | ACCEPT | Summary: More IDA evidence. Reason: Core function. Supporting Evidence: PMID:20530484 Epub 2010 Jun 8. SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium. |
| GO:0065003 protein-containing complex assembly | IDA PMID:20530484 SOX9, through interaction with microphthalmia-associated tra... | KEEP AS NON CORE | Summary: SOX9 assembles into protein complexes. Reason: While SOX9 does form complexes, this generic assembly term doesn't capture the core transcription factor function. Supporting Evidence: PMID:20530484 Epub 2010 Jun 8. SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium. |
| GO:0007165 signal transduction | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Duplicate of earlier very generic signal transduction term. Reason: Too generic to be informative. |
| GO:0072034 renal vesicle induction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate kidney development term. Reason: Peripheral kidney development. |
| GO:0090184 positive regulation of kidney development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate kidney development term. Reason: Peripheral kidney development. |
| GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate kidney branching term. Reason: Peripheral kidney development. |
| GO:0008584 male gonad development | IEP PMID:17848411 Developmental changes in human fetal testicular cell numbers... | KEEP AS NON CORE | Summary: IEP evidence for testis development. Reason: Peripheral sex determination function. Supporting Evidence: PMID:17848411 Epub 2007 Sep 11. Developmental changes in human fetal testicular cell numbers and messenger ribonucleic acid levels during the second trimester. |
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