Paediatric disorders - additional genes
Gene: ZNRF3EnsemblGeneIds (GRCh38): ENSG00000183579
EnsemblGeneIds (GRCh37): ENSG00000183579
OMIM: 612062, Gene2Phenotype
ZNRF3 is in 4 panels
1 review
Achchuthan Shanmugasundram (Genomics England Curator)
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 24 Feb 2025, 11:46 a.m. | Last Modified: 24 Feb 2025, 11:46 a.m.
Panel Version: 6.12
Comment on list classification: There are eight individuals reported with complex neurodevelopmental disorder and four patients reported with congenital heart defects. There are only two patients with moderate intellectual disability and hence the evidence is not sufficient for this gene to be rated green on the intellectual disability panel. This gene is therefore being added to this panel for patients with variants in this gene to be picked by the Paediatric disorders WGS clinical indication.Created: 18 Sep 2024, 11:47 a.m. | Last Modified: 18 Sep 2024, 11:47 a.m.
Panel Version: 5.8
PMID:39168120 reported 12 individuals from 11 families with heterozygous de novo variants in ZNRF3 gene (the variant was inherited only in the son of a father-son pair) and presented with various phenotypes.
Eight of these individuals harboured missense variants and displayed a complex neurodevelopmental disorder, of which missense variants clustered in the RING ligase domain are associated with macrocephalic NDD. In contrast, four individuals harbouring de novo truncating or de novo or inherited large in-frame deletion variants presented with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. Overall, 4 individuals had congenital heart defects, 2 had moderate intellectual disability and 2 had microcephaly. There is also supporting functional evidence available from in vitro assays.
This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: LiteratureCreated: 18 Sep 2024, 11:39 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
complex neurodevelopmental disorder, MONDO:0100038; congenital heart disease, MONDO:0005453
Publications
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- NHS GMS
- Expert Review Green
- Literature
- Phenotypes
-
- complex neurodevelopmental disorder, MONDO:0100038
- congenital heart disease, MONDO:0005453
- Tags
- OMIM
- 612062
- Clinvar variants
- Variants in ZNRF3
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag gene-checked tag was added to gene: ZNRF3.
Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_24_promote_green was removed from gene: ZNRF3.
Added New Source, Added New Source, Status Update
Achchuthan Shanmugasundram (Genomics England Curator)Source Expert Review Green was added to ZNRF3. Source NHS GMS was added to ZNRF3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: znrf3 has been classified as Amber List (Moderate Evidence).
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: ZNRF3 were changed from complex neurodevelopmental disorder, MONDO:0100038; congenital heart disease, MONDO:0005453 to complex neurodevelopmental disorder, MONDO:0100038; congenital heart disease, MONDO:0005453
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: ZNRF3 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038; congenital heart disease, MONDO:0005453
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_24_promote_green tag was added to gene: ZNRF3.
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)gene: ZNRF3 was added gene: ZNRF3 was added to Paediatric disorders - additional genes. Sources: Literature Mode of inheritance for gene: ZNRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZNRF3 were set to 39168120 Phenotypes for gene: ZNRF3 were set to complex neurodevelopmental disorder, MONDO:0100038 Review for gene: ZNRF3 was set to AMBER