Childhood interstitial lung disease

Gene: RAB5B

I don't know

Comment on list classification: The rating of this gene will remain amber on this panel as agreed with the NHS Genomic Medicine Service.

Created: 26 Jan 2026, 6:41 p.m. | Last Modified: 26 Jan 2026, 6:41 p.m.

Panel Version: 0.6

Comment on list classification: As there is only one human case and functional evidence from C. elegans and proband's lung biopsy reported so far, this gene should be rated amber with current evidence.

Created: 31 Dec 2025, 5:43 p.m. | Last Modified: 31 Dec 2025, 5:43 p.m.

Panel Version: 0.4

PMID:35121658 reported a female child of Pakistani descent presenting with interstitial lung disease (ILD) suggestive of a surfactant dysfunction disorder, dysmorphic features, and global developmental delay. A de novo heterozygous variant in RAB5B gene (c.406G>C/ p.Asp136His) was identified via trio exome sequencing and confirmed by Sanger sequencing.

There is functional evidence available from Caenorhabditis elegans, where knocking the proband variant into the conserved position (Asp135) of the ortholog showed that the variant is damaging, producing a strong dominant negative gene product. Evidence is also available from immunostaining studies of the proband's lung biopsy, indicating dominant negative-acting RAB5B Asp136His and EE dysfunction cause a defect in processing/trafficking to produce mature SP-B and SP-C, resulting in interstitial lung disease.

This gene has not yet been associated with any phenotypes either in ClinGen, Gene2Phenotype or PanelApp Australia.

Created: 31 Dec 2025, 5:42 p.m. | Last Modified: 31 Dec 2025, 5:42 p.m.

Panel Version: 0.3

Comment on phenotypes: This gene has not yet been associated with any phenotypes in OMIM (as of 30 December 2025).

Created: 30 Dec 2025, 7:22 p.m. | Last Modified: 30 Dec 2025, 7:22 p.m.

Panel Version: 0.2

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
interstitial lung disease, MONDO:0015925

Publications

• 35121658