Monogenic diabetes

Gene: ZNF808

Green List (high evidence)

PMID: 41500078 Russ-Silsby et al 2026
17 previously unreported individuals with biallelic loss-of-function ZNF808 variants.19 individuals had permanent neonatal diabetes; 12 had other diabetes phenotypes: 5 with infancy-onset diabetes, 4 with transient diabetes and 3 with diabetes diagnosed aged 10, 14 and 23 years.
Variable severity associated with the variants e.g.,:
p.(Thr630Serfs*24) was detected in a homozyogus state in Patient 14 (diabetes diagnosed at 23 yrs), as well as Patient 1 (PNDM diagnosed at 13 weeks), and in patient 11 (transient diabetes diagnosed at 1 day old).
p.(Tyr662*) detected in homozygous state in Patient 15 (diabetes diagnosed at 10yo) and heterozygous, in trans with a deletion, in Patient 13 (diabetes diagnosed at 14 years.

Created: 18 Mar 2026, 4:36 p.m. | Last Modified: 18 Mar 2026, 4:36 p.m.

Panel Version: 3.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pancreatic agenesis 3, OMIM:620991; diabetes mellitus, MONDO:0005015

Publications

• 37973953
• 41500078

Green List (high evidence)

Biallelic pathogenic protein-truncating/null variants in the ZNF808 gene cause permanent neonatal diabetes (De Franco et al 2023 PMID: 37973953) and the gene is included as a green gene on the R143 neonatal diabetes panel. More recently, the diabetes phenotype has been expanded to include transient neonatal diabetes and monogenic diabetes diagnosed in childhood and early adulthood with a MODY phenotype (Russ-Silsby et al 2026 PMID: 41500078). The paper reports three individuals with biallelic ZNF808 heterozygous loss of function variants diagnosed at ages 10, 14 and 23. All three individuals would meet current eligibility criteria for R141 testing and were in fact patients that previously had negative R141 testing and consented for further testing of ZNF808 on a research basis. Two of these patients were treated with an oral hyperglycaemic agent called a sulphonylurea and responded well to this treatment with good glycaemic control.
Sources: Expert Review

Created: 12 Mar 2026, 12:46 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Diabetes

Publications

• PMID: 41500078

Variants in this GENE are reported as part of current diagnostic practice