Activity
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| Childhood interstitial lung disease v1.9 | ZBTB7B | Achchuthan Shanmugasundram Phenotypes for gene: ZBTB7B were changed from inborn error of immunity, MONDO:0003778; interstitial lung disease, MONDO:0015925 to inborn error of immunity, MONDO:0003778; interstitial lung disease, MONDO:0015925; Global developmental delay, HP:0001263 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.8 | ZBTB7B | Achchuthan Shanmugasundram edited their review of gene: ZBTB7B: Changed phenotypes to: inborn error of immunity, MONDO:0003778, interstitial lung disease, MONDO:0015925, Global developmental delay, HP:0001263 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.8 | ZBTB7B |
Achchuthan Shanmugasundram changed review comment from: PMID:40392549 (2025) reported a 5-year-old male patient with a novel combined immunodeficiency/allergic/fibrotic syndrome, identified with a de novo heterozygous missense variant (c.1080A>C/p.Lys360Asn) by trio whole-genome sequencing. The patient presented with severe fibroinflammatory interstitial lung disease (pulmonary lipoproteinosis with subpleural cystic/honeycomb remodeling on lung biopsy at 3.75 years), alongside CD4+ T-cell lymphopenia, CD8+ lymphocytosis, severe early-onset allergic disease, corneal defects, sensorineural hearing loss, and global developmental delay. Extensive functional studies supported a multimorphic mechanism combining dominant-negative, loss-of-function, and neomorphic gain-of-function effects on DNA binding and downstream gene targets. Lung-specific causal evidence came from lentiviral gene-transfer of K360N into healthy-donor pulmonary fibroblasts, which reproduced a profibrotic gene signature (including increased COL2A1 expression), supporting a cell-intrinsic mechanism for fibrosis independent of the immune phenotype. Sources: Literature; to: PMID:40392549 (2025) reported a 5-year-old male patient with a novel combined immunodeficiency/allergic/fibrotic syndrome, identified with a de novo heterozygous missense variant (c.1080A>C/p.Lys360Asn) by trio whole-genome sequencing. The patient presented with severe fibroinflammatory interstitial lung disease (pulmonary lipoproteinosis with subpleural cystic/honeycomb remodeling on lung biopsy at 3.75 years), alongside CD4+ T-cell lymphopenia, CD8+ lymphocytosis, severe early-onset allergic disease, corneal defects, sensorineural hearing loss, and global developmental delay. Extensive functional studies supported a multimorphic mechanism combining dominant-negative, loss-of-function, and neomorphic gain-of-function effects on DNA binding and downstream gene targets. Lung-specific causal evidence came from lentiviral gene-transfer of K360N into healthy-donor pulmonary fibroblasts, which reproduced a profibrotic gene signature (including increased COL2A1 expression), supporting a cell-intrinsic mechanism for fibrosis independent of the immune phenotype. This gene has not yet been associated with relevant phenotypes either in OMIM or in ClinGen (last accessed 07 August 2026). Sources: Literature |
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| Childhood interstitial lung disease v1.8 | ZBTB7B | Achchuthan Shanmugasundram Classified gene: ZBTB7B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.8 | ZBTB7B | Achchuthan Shanmugasundram Added comment: Comment on list classification: There is one case with a syndromic phenotype including fibroinflammatory interstitial lung disease and functional evidence reported in support of the association of ZBTB7B gene with this panel. Hence, this gene can be rated amber with the current evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.8 | ZBTB7B | Achchuthan Shanmugasundram Gene: zbtb7b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.7 | ZBTB7B |
Achchuthan Shanmugasundram changed review comment from: PMID:40392549 (2025) reported a 5-year-old male patient with a novel combined immunodeficiency/allergic/fibrotic syndrome, identified with a de novo heterozygous missense variant (c.1080A>C/p.Lys360Asn) by trio whole-genome sequencing. The patient presented with severe fibroinflammatory interstitial lung disease (pulmonary lipoproteinosis with subpleural cystic/honeycomb remodeling on lung biopsy at 3.75 years), alongside CD4+ T-cell lymphopenia, CD8+ lymphocytosis, severe early-onset allergic disease, corneal defects, sensorineural hearing loss, and global developmental delay. Extensive functional studies supported a multimorphic mechanism combining dominant-negative, loss-of-function, and neomorphic gain-of-function effects on DNA binding and downstream gene targets. Lung-specific causal evidence came from lentiviral gene-transfer of K360N into healthy-donor pulmonary fibroblasts, which reproduced a profibrotic gene signature (including increased COL2A1 expression), supporting a cell-intrinsic mechanism for fibrosis independent of the immune phenotype. This is currently a single reported case, and ILD occurs as one component of a broader multisystem syndrome rather than an isolated pulmonary phenotype, which should be considered when applying this gene to an ILD-specific panel. Sources: Literature; to: PMID:40392549 (2025) reported a 5-year-old male patient with a novel combined immunodeficiency/allergic/fibrotic syndrome, identified with a de novo heterozygous missense variant (c.1080A>C/p.Lys360Asn) by trio whole-genome sequencing. The patient presented with severe fibroinflammatory interstitial lung disease (pulmonary lipoproteinosis with subpleural cystic/honeycomb remodeling on lung biopsy at 3.75 years), alongside CD4+ T-cell lymphopenia, CD8+ lymphocytosis, severe early-onset allergic disease, corneal defects, sensorineural hearing loss, and global developmental delay. Extensive functional studies supported a multimorphic mechanism combining dominant-negative, loss-of-function, and neomorphic gain-of-function effects on DNA binding and downstream gene targets. Lung-specific causal evidence came from lentiviral gene-transfer of K360N into healthy-donor pulmonary fibroblasts, which reproduced a profibrotic gene signature (including increased COL2A1 expression), supporting a cell-intrinsic mechanism for fibrosis independent of the immune phenotype. Sources: Literature |
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| Childhood interstitial lung disease v1.7 | ZBTB7B | Achchuthan Shanmugasundram edited their review of gene: ZBTB7B: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.7 | ZBTB7B |
Achchuthan Shanmugasundram gene: ZBTB7B was added gene: ZBTB7B was added to Childhood interstitial lung disease. Sources: Literature Mode of inheritance for gene: ZBTB7B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZBTB7B were set to 40392549 Phenotypes for gene: ZBTB7B were set to inborn error of immunity, MONDO:0003778; interstitial lung disease, MONDO:0015925 Review for gene: ZBTB7B was set to RED Added comment: PMID:40392549 (2025) reported a 5-year-old male patient with a novel combined immunodeficiency/allergic/fibrotic syndrome, identified with a de novo heterozygous missense variant (c.1080A>C/p.Lys360Asn) by trio whole-genome sequencing. The patient presented with severe fibroinflammatory interstitial lung disease (pulmonary lipoproteinosis with subpleural cystic/honeycomb remodeling on lung biopsy at 3.75 years), alongside CD4+ T-cell lymphopenia, CD8+ lymphocytosis, severe early-onset allergic disease, corneal defects, sensorineural hearing loss, and global developmental delay. Extensive functional studies supported a multimorphic mechanism combining dominant-negative, loss-of-function, and neomorphic gain-of-function effects on DNA binding and downstream gene targets. Lung-specific causal evidence came from lentiviral gene-transfer of K360N into healthy-donor pulmonary fibroblasts, which reproduced a profibrotic gene signature (including increased COL2A1 expression), supporting a cell-intrinsic mechanism for fibrosis independent of the immune phenotype. This is currently a single reported case, and ILD occurs as one component of a broader multisystem syndrome rather than an isolated pulmonary phenotype, which should be considered when applying this gene to an ILD-specific panel. Sources: Literature |
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