Fetal anomalies
Gene: ZNF423

ZNF423 (zinc finger protein 423)
EnsemblGeneIds (GRCh38): ENSG00000102935
EnsemblGeneIds (GRCh37): ENSG00000102935
OMIM: 604557, Gene2Phenotype
ZNF423 is in 15 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Created: 20 Feb 2025, 9:40 p.m. | Last Modified: 20 Feb 2025, 9:40 p.m.

Panel Version: 5.16

Created: 20 Feb 2025, 9:40 p.m.
Last Modified: 20 Feb 2025, 9:40 p.m.
Panel version: 5.16

Vicki Harrison (Wessex Clinical Genetics Service)

I don't know

2 sibs with NPHP, cerebellar hypoplasia and situs inversus with homozygous variants. 2 of 96 joubert patients with heterozygous variants but no sib/parental samples tested. 1 JS patient with compound het variants but no comment about other genes tested/parental testing etc. 1 with ARPKD phenotype. Mouse data to support ciliopathy/midline anomalies.
Created: 20 Feb 2025, 9:35 p.m. | Last Modified: 20 Feb 2025, 9:35 p.m.

Panel Version: 5.15

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 19 / Nephronophthisis 14, MIM#614844

Publications

Created: 20 Feb 2025, 9:35 p.m.
Last Modified: 20 Feb 2025, 9:35 p.m.
Panel version: 5.15

Rebecca Foulger (Genomics England curator)

I don't know

Comment when marking as ready: Marked ZNF423 as Ready on April 30th 2019: Fetally-relevant phenotype but currently insufficient evidence for inclusion.
Created: 30 Apr 2019, 9:46 a.m.

Comment on list classification: Kept rating as Amber following review of literature evidence in PMID:22863007 and ZNF423 is currently Amber on the 'Rare multisystem ciliopathy disorders' panel. Fetally relevant phenotype but currently insufficient evidence for a Green gene rating.
Created: 24 Apr 2019, 7:48 p.m.

Chaki et al. (2012 PMID:22863007) identified a homozygous 2738C-T variant in the ZNF423 gene (P913L) in two Turkish siblings with with nephronophthisis-14 manifested as infantile-onset kidney disease, cerebellar vermis hypoplasia, and situs inversus. Heterozygous variants were found in two additional unrelated patients with Joubert syndrome.
Created: 24 Apr 2019, 7:40 p.m.

ZNF423 was added to the fetal panel as Amber based on a 'probable' rating in the PAGE original Additional gene list. In the PAGE paper (Lord et al., 2019, PMID:30712880) ZNF423 is listed as an Additional gene (Supplementary Table 2) based on association with a prenatal phenotype reported in the literature, with biallelic/monoallelic inheritance.
Created: 24 Apr 2019, 12:43 p.m.

Rating in original (Additional gene) PAGE list: Probable for Nephronophthisis and Joubert syndrome. Mode of pathogenicity: loss of function. Mode of inheritance: biallelic (with a note that also said to be monoallelic).
Created: 11 Dec 2018, 9:05 a.m.

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.208

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

NHS GMS
Expert Review Amber
PAGE Additional Gene List

Phenotypes

Nephronophthisis 14 614844
Joubert syndrome 19 614844

OMIM

604557

Clinvar variants

Variants in ZNF423

Penetrance

None

Publications

Panels with this gene

History Filter Activity

20 Feb 2025, Gel status: 2

Added New Source, Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to ZNF423. Publications for gene: ZNF423 were updated from 22863007 to 39071699; 33531950; 22863007; 32925911

30 Apr 2019, Gel status: 2