Monogenic diabetes

Gene: KBTBD2

I don't know

Comment on list classification: Adding to this panel as Amber as despite there being 3 unrelated cases, a specific description of the phenotype is not provided in one case (GDX6) making it challenging to make genotype-phenotype correlations.

There is only one reported case with diabetes, although it is possible that the other individuals may develop diabetes later in life. It is worth noting that this association is supported by the mouse model where insulin resistance and severe diabetes is observed. However, based on the current evidence additional support is needed before this gene can be added to a diagnostic panel.

Created: 27 Nov 2025, 4:02 p.m. | Last Modified: 27 Nov 2025, 4:02 p.m.

Panel Version: 3.7

PMID: 39313616 (2024) - 3 unrelated cases with biallelic variants in this gene. Variants were LOF/missense compound het in 2 cases and homozygous LOF in the other case. Phenotypes include growth retardation (3/3), hyperglycemia and diabetes in an adolescent individual (1/3 - others thought to be too young to have developed diabetes), microcephaly (2/2), motor developmental delay. One individual had cardiomyopathy but also harboured an additional variant in MYH7 which could be contributing this phenotype.

Knock down in mice resulted in elevated expression of p85α and a phenotype involving lipodystrophy, hepatic steatosis, insulin resistance, severe diabetes and growth retardation, which recapitulates some of the features observed in human cases.
Sources: Literature

Created: 27 Nov 2025, 3:56 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder, MONDO:0700092

Publications

• 39313616