Childhood interstitial lung disease

Gene: ZBTB7B

I don't know

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.

Created: 7 Aug 2026, 4:49 p.m. | Last Modified: 7 Aug 2026, 4:49 p.m.

Panel Version: 1.8

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

Created: 7 Aug 2026, 4:40 p.m. | Last Modified: 7 Aug 2026, 5:01 p.m.

Panel Version: 1.8

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
inborn error of immunity, MONDO:0003778; interstitial lung disease, MONDO:0015925; Global developmental delay, HP:0001263

Publications

• 40392549