CHD7 is an ATP-dependent chromatin remodeler that binds DNA and nucleosomes and changes histone–DNA contacts. Histone recognition and associations with other chromatin regulators help place its activity at cell-type-specific regulatory regions. CHD7 acts in nuclear chromatin and also has a nucleolar pool associated with active ribosomal DNA and rRNA expression. Human cell models establish roles in neural crest formation and neuroepithelial identity, while pathogenic variants cause CHARGE syndrome with variable craniofacial, sensory, cardiac, genital and neurodevelopmental abnormalities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: CHD7 performs chromatin remodeling on nuclear chromatin. Reason: The ancestral PAINT assertion is independently corroborated by human purified-protein remodeling and cellular chromatin occupancy. The historical PTN002473914 node placement was not reconstructed; the listed descendants are not treated as pairwise transfers. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Retain regulatory-region association without asserting intrinsic motif recognition. Reason: The exact mouse donor has an IDA annotation from PMID:23319608. Its promoter occupancy and regulatory work, together with human enhancer ChIP, support cis-regulatory-region binding. The inspected experiments do not establish intrinsic recognition of a specific DNA motif. GO:0000976 explicitly permits non-specific regulatory-region binding, making it a positive specificity correction rather than a claim that sequence discrimination is impossible. Proposed replacements: transcription cis-regulatory region binding |
| GO:0001501 skeletal system development | IMP PMID:16155193 CHARGE syndrome: the phenotypic spectrum of mutations in the... | KEEP AS NON CORE | Summary: Retain the human skeletal-development phenotype outside the molecular core. Reason: The full genotyped cohort in PMID:16155193 reports vertebral abnormalities, scoliosis and a triphalangeal thumb among CHD7 mutation carriers. These support the existing developmental assertion, while the performed molecular activity is chromatin remodeling rather than a skeletal structural constituent. Supporting Evidence: |
| GO:0001701 in utero embryonic development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the broad embryonic developmental role. Reason: Human pathogenic CHD7 variants are associated with congenital malformations in PMID:15300250 and the genotyped PMID:16155193 cohort. Human neural-crest and neuroepithelial experiments provide functional developmental context. This is a pleiotropic developmental role of chromatin regulation, not a separate embryogenesis-specific enzyme. The original source and qualifier remain unchanged. |
| GO:0001701 in utero embryonic development | IMP PMID:15300250 Mutations in a new member of the chromodomain gene family ca... | KEEP AS NON CORE | Summary: Retain the broad embryonic developmental role. Reason: Human pathogenic CHD7 variants are associated with congenital malformations in PMID:15300250 and the genotyped PMID:16155193 cohort. Human neural-crest and neuroepithelial experiments provide functional developmental context. This is a pleiotropic developmental role of chromatin regulation, not a separate embryogenesis-specific enzyme. The original source and qualifier remain unchanged. |
| GO:0003007 heart morphogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain heart morphogenesis as a developmental consequence of CHD7 function. Reason: The original human CHD7 discovery article and the larger genotyped cohort document congenital heart malformations. Human neural-crest work and Xenopus perturbation/rescue provide developmental context, with the heart outflow phenotype tested in frog. This supports the existing broad process without claiming a directly assayed human cardiac remodeling target or a cardiac-specific core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002898851 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0003007 heart morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain heart morphogenesis as a developmental consequence of CHD7 function. Reason: The original human CHD7 discovery article and the larger genotyped cohort document congenital heart malformations. Human neural-crest work and Xenopus perturbation/rescue provide developmental context, with the heart outflow phenotype tested in frog. This supports the existing broad process without claiming a directly assayed human cardiac remodeling target or a cardiac-specific core. |
| GO:0003007 heart morphogenesis | IMP PMID:15300250 Mutations in a new member of the chromodomain gene family ca... | KEEP AS NON CORE | Summary: Retain heart morphogenesis as a developmental consequence of CHD7 function. Reason: The original human CHD7 discovery article and the larger genotyped cohort document congenital heart malformations. Human neural-crest work and Xenopus perturbation/rescue provide developmental context, with the heart outflow phenotype tested in frog. This supports the existing broad process without claiming a directly assayed human cardiac remodeling target or a cardiac-specific core. |
| GO:0003677 DNA binding | IBA GO_REF:0000033 | MODIFY | Summary: Specify the directly tested DNA substrate as double-stranded DNA. Reason: Purified human CHD7 binds double-stranded DNA probes and nucleosomes by electrophoretic mobility shift assays. This supports GO:0003690 without a recognition-motif claim. The PAINT source fields remain intact; independent target assays provide the refinement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. Proposed replacements: double-stranded DNA binding Supporting Evidence: |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin binding is integral to CHD7 remodeling. Reason: Human chromatin occupancy and purified nucleosome engagement support this activity. The PAINT node history is uninspected but target evidence corroborates retention. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0003682 chromatin binding | TAS PMID:17299439 CHARGE syndrome: an update. | ACCEPT | Summary: Chromatin binding is integral to CHD7 remodeling. Reason: Human chromatin occupancy and purified nucleosome engagement support this activity. The original review is abstract-limited here; independent primary experiments establish the same function without replacing its source identity. |
| GO:0005515 protein binding | IPI PMID:20130577 CHD7 cooperates with PBAF to control multipotent neural cres... | KEEP AS NON CORE | Summary: Retain the experimentally supported PBRM1/PB1 association outside the molecular-function core. Reason: PMID:20130577 Figure 4B/D reports CHD7 immunoprecipitation and reciprocal PBRM1/PB1 immunoprecipitation in human neural-crest-like preparations. This positive complex-associated binding supports the original IPI assertion; no native direct interface is inferred. PBRM1 and SMARCC2 are PBAF subunits, whereas BRG1 is the catalytic ATPase, so the CHD8 ATPase-binding refinement is not transferable to these partners. No better evidence-backed binding class is established here. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions; lack of specificity alone does not make the association false. |
| GO:0005515 protein binding | IPI PMID:20130577 CHD7 cooperates with PBAF to control multipotent neural cres... | KEEP AS NON CORE | Summary: Retain the experimentally supported SMARCC2/BAF170 association outside the molecular-function core. Reason: PMID:20130577 Figure 4B/D reports CHD7 immunoprecipitation and reciprocal SMARCC2/BAF170 immunoprecipitation in human neural-crest-like preparations. This positive complex-associated binding supports the original IPI assertion; no native direct interface is inferred. PBRM1 and SMARCC2 are PBAF subunits, whereas BRG1 is the catalytic ATPase, so the CHD8 ATPase-binding refinement is not transferable to these partners. No better evidence-backed binding class is established here. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions; lack of specificity alone does not make the association false. |
| GO:0005515 protein binding | IPI PMID:20453063 CHD8 interacts with CHD7, a protein which is mutated in CHAR... | MODIFY | Summary: Refine the positive CHD8 interaction to ATPase binding. Reason: The original human-fragment Y2H, reciprocal HeLa co-IP and BiFC assays establish CHD7–CHD8 association; CHD8 ATPase activity is independently measured in PMID:28533432. This partner-class term does not assign ATPase regulation or a full-length binary interface. The tested CHD8 fragments derive from NP_065971.2. Proposed replacements: ATPase binding |
| GO:0005515 protein binding | IPI PMID:20453063 CHD8 interacts with CHD7, a protein which is mutated in CHAR... | MODIFY | Summary: Refine the positive CHD8 interaction to ATPase binding. Reason: The original human-fragment Y2H, reciprocal HeLa co-IP and BiFC assays establish CHD7–CHD8 association; CHD8 ATPase activity is independently measured in PMID:28533432. This partner-class term does not assign ATPase regulation or a full-length binary interface. The exact NP_065971.2 construct maps to Q9HCK8-2. Proposed replacements: ATPase binding |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is required for the CHD7 remodeling motor. Reason: Direct ATP hydrolysis and ATP-dependent nucleosome remodeling corroborate the original domain mapping. The K999R ATP-site mutant loses detectable remodeling under the tested conditions; no alternate nucleotide specificity is inferred. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: The nucleus is a principal site of CHD7 activity. Reason: Human chromatin occupancy, endogenous cellular localization and nuclear remodeling functions support this location. The original evidence source and qualifier are retained; localization does not imply identical distribution of every alternative product. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0005634 nucleus | IDA PMID:20453063 CHD8 interacts with CHD7, a protein which is mutated in CHAR... | ACCEPT | Summary: The nucleus is a principal site of CHD7 activity. Reason: Human chromatin occupancy, endogenous cellular localization and nuclear remodeling functions support this location. The original PMID:20453063 BiFC experiment uses CHD7/CHD8 fragments in HeLa nuclei; independent endogenous CHD7 localization supplies broader corroboration. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: The nucleus is a principal site of CHD7 activity. Reason: Human chromatin occupancy, endogenous cellular localization and nuclear remodeling functions support this location. The original evidence source and qualifier are retained; localization does not imply identical distribution of every alternative product. |
| GO:0005634 nucleus | TAS PMID:17299439 CHARGE syndrome: an update. | ACCEPT | Summary: The nucleus is a principal site of CHD7 activity. Reason: Human chromatin occupancy, endogenous cellular localization and nuclear remodeling functions support this location. The original evidence source and qualifier are retained; localization does not imply identical distribution of every alternative product. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Retain nucleoplasm as a core CHD7 location. Reason: Human HPA ICC/IF reports nucleoplasm in Hep-G2, MCF-7 and U2OS, and endogenous CHD7 localization corroborates the compartment. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Retain nucleoplasm as a core CHD7 location. Reason: Human HPA ICC/IF reports nucleoplasm in Hep-G2, MCF-7 and U2OS, and endogenous CHD7 localization corroborates the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944087 | ACCEPT | Summary: Retain nucleoplasm as a core CHD7 location. Reason: Human HPA ICC/IF reports nucleoplasm in Hep-G2, MCF-7 and U2OS, and endogenous CHD7 localization corroborates the compartment. The exact Reactome event models CHD6–9 ATP-dependent remodeling in nucleoplasm; direct CHD7 catalysis is independently established. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9944450 | ACCEPT | Summary: Retain nucleoplasm as a core CHD7 location. Reason: Human HPA ICC/IF reports nucleoplasm in Hep-G2, MCF-7 and U2OS, and endogenous CHD7 localization corroborates the compartment. The exact Reactome event includes CHD7 in a nucleoplasmic FAM124B-associated complex. Its physiological function is unresolved; fragment co-IP is not proof of a stable full-length ternary particle. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | ACCEPT | Summary: Retain a functionally supported nucleolar CHD7 pool. Reason: HPA records nucleolar staining in human MCF-7. Independent PMID:20591827 validates endogenous CHD7 in DLD1 nucleoli by FLAG knock-in imaging and tagged/untagged fractionation, with rDNA occupancy and rRNA-regulatory effects. The paper-defined CHD7S report adds product context, but its intron-6-stop construct is not demonstrably identical to the current Q9P2D1-3 sequence description. Nucleolar localization is not exclusive to that short product. Supporting Evidence: PMID:20591827 CHD7 is dually localized to the nucleoplasm and nucleolus file:human/CHD7/CHD7-source-evidence.json |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: Retain a functionally supported nucleolar CHD7 pool. Reason: HPA records nucleolar staining in human MCF-7. Independent PMID:20591827 validates endogenous CHD7 in DLD1 nucleoli by FLAG knock-in imaging and tagged/untagged fractionation, with rDNA occupancy and rRNA-regulatory effects. The paper-defined CHD7S report adds product context, but its intron-6-stop construct is not demonstrably identical to the current Q9P2D1-3 sequence description. Nucleolar localization is not exclusive to that short product. |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin remodeling is a defining CHD7 process. Reason: Direct human recombinant CHD7 repositions nucleosomes and changes DNA accessibility in an ATP-dependent manner. The PAINT assertion is independently corroborated; no autonomous histone-modifying activity is implied. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0006355 regulation of DNA-templated transcription | NAS PMID:17937444 Limb anomalies in patients with CHARGE syndrome: an expansio... | ACCEPT | Summary: CHD7 regulates transcription through chromatin remodeling. Reason: PMID:17937444 is a clinical limb-malformation report, not the direct transcription experiment. Independent human enhancer occupancy, expression perturbation and rescue in PMID:20130577/29440260, together with rDNA regulation in PMID:20591827, support this broad existing process. Preserve the original NAS citation while distinguishing the independent functional evidence. |
| GO:0007417 central nervous system development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain central nervous system development as a contextual CHD7 role. Reason: Human CHD7-depleted neuroepithelial cells lose neural identity and neuronal differentiation capacity, with BRN2 rescue supporting a transcriptional route in PMID:29440260. The genotyped clinical cohort also records CNS malformations. The developmental role is retained separately from the molecular remodeling core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002898851 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0007417 central nervous system development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain central nervous system development as a contextual CHD7 role. Reason: Human CHD7-depleted neuroepithelial cells lose neural identity and neuronal differentiation capacity, with BRN2 rescue supporting a transcriptional route in PMID:29440260. The genotyped clinical cohort also records CNS malformations. The developmental role is retained separately from the molecular remodeling core. |
| GO:0007417 central nervous system development | IMP PMID:9556299 CHARGE syndrome: report of 47 cases and review. | KEEP AS NON CORE | Summary: Retain central nervous system development as a contextual CHD7 role. Reason: Human CHD7-depleted neuroepithelial cells lose neural identity and neuronal differentiation capacity, with BRN2 rescue supporting a transcriptional route in PMID:29440260. The genotyped clinical cohort also records CNS malformations. The original 1998 CHARGE series predates gene identification; only its abstract was accessed. Independent human target evidence supports the broad biological assertion without claiming the older patients were genotyped. |
| GO:0010468 regulation of gene expression | IBA GO_REF:0000033 | ACCEPT | Summary: CHD7 regulates gene expression through chromatin-dependent mechanisms. Reason: Human enhancer-dependent transcription and nucleolar rDNA work support broad gene-expression regulation. Histone acetylation or DNA-methylation changes after CHD7 perturbation are not assigned as intrinsic CHD7 transferase activities. The PAINT node history is not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000085580 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:28533432 The ATP-dependent chromatin remodeling enzymes CHD6, CHD7, a... | ACCEPT | Summary: ATP hydrolysis is the directly measured energy-coupling activity of CHD7. Reason: Purified human CHD7 releases phosphate from ATP and remodels nucleosomes. Retain the original EXP assertion alongside the overall remodeling activity. PMID:28533432 pairs a correct CHD7 CCDS with discordant Q3L8U1 (CHD9); independent PMID:23134727 human CHD7 assays corroborate the activity, and no unverified sequence audit or all-product equivalence is claimed. |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP hydrolysis is the directly measured energy-coupling activity of CHD7. Reason: Purified human CHD7 releases phosphate from ATP and remodels nucleosomes. Retain the original IBA assertion alongside the overall remodeling activity. PMID:28533432 pairs a correct CHD7 CCDS with discordant Q3L8U1 (CHD9); independent PMID:23134727 human CHD7 assays corroborate the activity, and no unverified sequence audit or all-product equivalence is claimed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: ATP hydrolysis is the directly measured energy-coupling activity of CHD7. Reason: Purified human CHD7 releases phosphate from ATP and remodels nucleosomes. Retain the original IEA assertion alongside the overall remodeling activity. PMID:28533432 pairs a correct CHD7 CCDS with discordant Q3L8U1 (CHD9); independent PMID:23134727 human CHD7 assays corroborate the activity, and no unverified sequence audit or all-product equivalence is claimed. |
| GO:0021545 cranial nerve development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the cranial-nerve developmental phenotype at clinical scope. Reason: The full CHD7-genotyped cohort reports facial nerve palsy and other cranial sensory abnormalities. These support the existing broad developmental role without defining a nerve-specific molecular activity. Electronic and phylogenetic provenance is retained without donor-count objections. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002898851 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0021545 cranial nerve development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the cranial-nerve developmental phenotype at clinical scope. Reason: The full CHD7-genotyped cohort reports facial nerve palsy and other cranial sensory abnormalities. These support the existing broad developmental role without defining a nerve-specific molecular activity. Electronic and phylogenetic provenance is retained without donor-count objections. |
| GO:0021545 cranial nerve development | IMP PMID:9556299 CHARGE syndrome: report of 47 cases and review. | KEEP AS NON CORE | Summary: Retain the cranial-nerve developmental phenotype at clinical scope. Reason: The full CHD7-genotyped cohort reports facial nerve palsy and other cranial sensory abnormalities. These support the existing broad developmental role without defining a nerve-specific molecular activity. The exact original 1998 series is abstract-only and predates CHD7 identification; its patients are not presented as molecularly confirmed. |
| GO:0030217 T cell differentiation | IMP PMID:17684005 Immunological abnormalities in CHARGE syndrome. | KEEP AS NON CORE | Summary: Retain the developmental T-cell phenotype without a T-cell-intrinsic mechanism claim. Reason: The full PMID:17684005 study describes two CHD7-genotyped infants with severe T-cell deficiency, impaired mitogen responses and thymic-development context. Its differentiation interpretation includes deficient thymic T-cell production; it does not isolate a CHD7-dependent molecular step inside a T-cell precursor. This existing clinical IMP assertion remains a non-core developmental role, not a newly proposed immune mechanism. Supporting Evidence: |
| GO:0042393 histone binding | IBA GO_REF:0000033 | ACCEPT | Summary: Histone recognition contributes to CHD7 chromatin engagement. Reason: The PAINT histone-binding assertion is supported by in-vitro assays in which purified GST-CHD7 tandem chromodomains physically interacted with methylated H3K4 histones and peptide competition showed methylated-H3K4 specificity. Modified-histone recognition is a binding property, not histone methyltransferase activity; substrate preferences and isolated-domain scope must be distinguished from full-length remodeling. The cached Results describing Figure 5A/B distinguish the isolated tandem-chromodomain binding and peptide-competition experiments from full-length activity. Histone engagement supports the central remodeling function; it does not require a separate duplicate core or a contributes_to relation for an independently binding domain. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0042472 inner ear morphogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inner-ear morphogenesis at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document semicircular canal agenesis and hearing/vestibular abnormalities. This supports the existing inner-ear morphogenesis assertion as a developmental role of chromatin regulation, without making it a separate molecular core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002898851 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0042472 inner ear morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain inner-ear morphogenesis at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document semicircular canal agenesis and hearing/vestibular abnormalities. This supports the existing inner-ear morphogenesis assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0042472 inner ear morphogenesis | IMP PMID:15300250 Mutations in a new member of the chromodomain gene family ca... | KEEP AS NON CORE | Summary: Retain inner-ear morphogenesis at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document semicircular canal agenesis and hearing/vestibular abnormalities. This supports the existing inner-ear morphogenesis assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0043009 chordate embryonic development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the broad embryonic developmental role. Reason: Human pathogenic CHD7 variants are associated with congenital malformations in PMID:15300250 and the genotyped PMID:16155193 cohort. Human neural-crest and neuroepithelial experiments provide functional developmental context. This is a pleiotropic developmental role of chromatin regulation, not a separate embryogenesis-specific enzyme. The PAINT ancestral assertion is retained without a new reconstruction. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002898851 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. |
| GO:0043010 camera-type eye development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain eye development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document ocular coloboma. This supports the existing eye development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0043584 nose development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain nose development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document choanal atresia. This supports the existing nose development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0043584 nose development | IMP PMID:15300250 Mutations in a new member of the chromodomain gene family ca... | KEEP AS NON CORE | Summary: Retain nose development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document choanal atresia. This supports the existing nose development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0048806 genitalia development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain genitalia development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document micropenis, cryptorchidism and genital hypoplasia. This supports the existing genitalia development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0048806 genitalia development | IMP PMID:15300250 Mutations in a new member of the chromodomain gene family ca... | KEEP AS NON CORE | Summary: Retain genitalia development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document micropenis, cryptorchidism and genital hypoplasia. This supports the existing genitalia development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0050877 nervous system process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain nervous-system process at broad functional scope. Reason: GO:0050877 covers neurological system functions, including sensory perception and cognition. The human CHD7-genotyped cohort in PMID:16155193 reports hearing impairment, vestibular dysfunction and variable learning disability; this provides functional neurological context beyond lineage-development evidence alone. PMID:29440260 independently explains a developmental transcriptional mechanism but is not treated as an acute neural-function assay. Retain the existing broad assertion as non-core, without assigning CHD7 direct synaptic or electrical activity. The historical ARBA00029146 derivation was not reconstructed. |
| GO:0050890 cognition | IMP PMID:16155193 CHARGE syndrome: the phenotypic spectrum of mutations in the... | KEEP AS NON CORE | Summary: Retain the reported cognitive phenotype without assigning a direct cognitive effector activity. Reason: PMID:16155193 reports learning disabilities in 24 of 32 assessed patients older than 12 months, with no cognitive impairment in the other eight. These are actual cognitive outcomes in a CHD7-genotyped cohort, not merely an unmeasured label inferred from congenital anatomy. Sensory impairment and variable development limit causal and mechanistic attribution. Retain this existing IMP phenotype as non-core; it does not imply a universal deficit or a direct cognitive effector activity. Supporting Evidence: PMID:16155193 Learning disabilities were reported in 24 (75%) out of 32 patients PMID:16155193 Eight patients (25%) had no cognitive impairment. |
| GO:0051049 regulation of transport | IEA GO_REF:0000117 | UNDECIDED | Summary: The current transport-regulation rule match is real, but its biological basis remains unresolved. Reason: GO:0051049 concerns modulation of directed movement of substances. Current ARBA00027251 condition set 56 matches all three corresponding FunFam classifications in the authenticated CHD7 UniProt record and outputs this term. The rule route is therefore supported, although historical execution and the experimental basis of that rule branch have not been reconstructed. The reviewed CHD7 studies establish chromatin remodeling and developmental transcriptional effects but do not resolve a transport-regulatory step. Nuclear localization does not exclude regulation of transport, and lack of an identified step is not positive evidence that this broad inherited electronic assertion is false or overpropagated. Retain UNDECIDED for this biological uncertainty, not merely for an inaccessible paper. Supporting Evidence: GO_REF:0000117 file:human/CHD7/CHD7-source-evidence.json |
| GO:0060021 roof of mouth development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain roof-of-mouth development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document cleft lip and palate. This supports the existing roof-of-mouth development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0060041 retina development in camera-type eye | IMP PMID:15300250 Mutations in a new member of the chromodomain gene family ca... | KEEP AS NON CORE | Summary: Retain retina development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document ocular coloboma. This supports the existing retina development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0060123 regulation of growth hormone secretion | IMP PMID:9556299 CHARGE syndrome: report of 47 cases and review. | UNDECIDED | Summary: Growth-hormone secretion cannot be distinguished from broader growth/endocrine phenotypes in the accessed source. Reason: PMID:9556299 is a pre-gene CHARGE clinical series; its full text was not recovered. The available abstract describes growth impairment but does not resolve regulated release of growth hormone. Independent CHD7 developmental evidence does not by itself settle this precise secretion assertion. Retain the original IMP record while leaving its biological assessment unresolved. Supporting Evidence: |
| GO:0060173 limb development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain limb development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document skeletal and limb malformations. This supports the existing limb development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0060173 limb development | IMP PMID:17937444 Limb anomalies in patients with CHARGE syndrome: an expansio... | KEEP AS NON CORE | Summary: Retain limb development at the supported developmental scope. Reason: The authentic PMID:17937444 abstract explicitly describes three patients with severe limb abnormalities and heterozygous truncating CHD7 mutations. Its full body was not recovered. This positive source and the independent genotyped cohort support the broad existing limb-development assertion without inventing an assayed limb-patterning mechanism. |
| GO:0060322 head development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain head development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document craniofacial, ocular, ear and choanal malformations. This supports the existing head development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0060324 face development | IMP PMID:15300250 Mutations in a new member of the chromodomain gene family ca... | KEEP AS NON CORE | Summary: Retain face development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document craniofacial malformations. This supports the existing face development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0062009 secondary palate development | IMP PMID:15300250 Mutations in a new member of the chromodomain gene family ca... | KEEP AS NON CORE | Summary: Retain secondary-palate development at the supported developmental scope. Reason: The human CHD7 discovery article and genotyped clinical cohort document cleft palate. This supports the existing secondary-palate development assertion as a developmental role of chromatin regulation, without making it a separate molecular core. |
| GO:0140658 ATP-dependent chromatin remodeler activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP-dependent chromatin remodeling is the primary molecular activity. Reason: Purified human CHD7 changes nucleosomal DNA accessibility and nucleosome position; ATP-site mutant controls support intrinsic motor activity. The ancestral assertion is consistent with target biochemistry and is not inferred solely from the CHD family name. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473914 UNRESOLVED The PAINT ancestral assertion is retained; node placement and ancestral sequence history were not reconstructed. Target evidence is assessed independently, without donor-count or target-self-reference objections. Supporting Evidence: PMID:23134727 CHD7 is an efficient ATP-dependent nucleosome remodeling factor |
| GO:1990841 promoter-specific chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain promoter-specific chromatin binding at the documented recruitment scope. Reason: The exact mouse donor carries PMID:26102480 IDA, with target-gene and tissue extensions in the official record. Its regulatory-region remodeling work, together with human promoter/enhancer occupancy and intrinsic remodeling, supports the existing assertion. Promoter targeting need not mean CHD7 recognizes a sequence motif by itself; the historical Ensembl transfer was not reconstructed. Supporting Evidence: file:human/CHD7/CHD7-source-evidence.json |
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Download this section (compressed HTML)Q: What exact assay and patient endocrine findings support the original growth-hormone secretion assertion, as distinct from growth retardation or hormone deficiency?
Q: How do the four current products differ in ATPase/remodeling activity and nucleolar targeting, and which sequence was present in each published construct?
Q: Does CHD7 remodel rDNA promoter nucleosomes directly, and which cofactors connect its occupancy to reduced DNA methylation and increased rRNA expression?
Q: Which CHD7–CHD8 and PBAF associations occur between native full-length proteins in defined developmental cell states?
Q: Which experimental transport-regulatory role underlies ARBA00027251 condition set 56 for CHD7-like FunFam combinations, and does that role apply to human CHD7 independently of downstream developmental phenotypes?
Experiment: Compare sequence-verified current CHD7 products with matched ATPase, DNA-binding and nucleosome-remodeling assays and endogenous localization.
Experiment: Measure rDNA nucleosome position and accessibility after acute CHD7 depletion and rescue with wild-type versus ATP-site mutant protein.
Experiment: Combine endogenous partner tagging with domain-specific perturbation to distinguish direct binding from complex co-association in neural crest and neuroepithelial cells.
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