ZNF423 – Nephronophthisis

ZNF423 has been implicated in a nephronophthisis-related ciliopathy through whole exome sequencing in a consanguineous cohort. In one affected individual, a homozygous ZNF423 variant c.3048G>C (p.Gln1016His) was identified, consistent with autosomal recessive inheritance and no additional segregation data (PMID:26489029). This single‐case report provides limited genetic evidence for ZNF423 in nephronophthisis.

Functional studies support a role for ZNF423 in ciliopathy pathogenesis. Chromatin immunoprecipitation in cell culture models demonstrates Zfp423 occupancy at intronic enhancers, regulating gene expression in developmental pathways (PMID:23762491). In mouse models, Zfp423 loss‐of‐function and patient‐derived variants produce midline brain and ciliopathy‐related phenotypes, consistent with a haploinsufficiency mechanism (PMID:32925911).

Key Take-home: Rare ZNF423 variants can underlie nephronophthisis in an autosomal recessive manner; exome sequencing facilitates diagnosis and experimental models confirm functional impact.

References

• Kidney international • 2016 • Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity. PMID:26489029
• PloS One • 2013 • Zfp423 binds autoregulatory sites in p19 cell culture model. PMID:23762491
• PLoS Genetics • 2020 • ZNF423 patient variants, truncations, and in-frame deletions in mice define an allele-dependent range of midline brain abnormalities. PMID:32925911

Evidence Based Scoring (AI generated)