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Intellectual disability

Gene: ZFHX3

Green List (high evidence)
ZFHX3 (zinc finger homeobox 3)
EnsemblGeneIds (GRCh38): ENSG00000140836
EnsemblGeneIds (GRCh37): ENSG00000140836
OMIM: 104155, Gene2Phenotype
ZFHX3 is in 4 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 26 Sep 2024, 2:57 p.m. | Last Modified: 26 Sep 2024, 2:57 p.m.
Panel Version: 7.41

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Created: 26 Sep 2024, 2:57 p.m.
Last Modified: 26 Sep 2024, 2:57 p.m.
Panel version: 7.41

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Personal communication from Nour Elkhateeb (Clinical Fellow in Genomics, Genomics England): we have data about 12 individuals with nonsense/frameshift/exon deletions in ZFHX3. Five of the variants are located in exon 9/10 or exon 9, which has been shown to harbour the highest density of pathogenic variants (PMID: 38412861). Eleven of these cases presented with developmental delay / intellectual disability and a range of other features, including dysmorphology, seizures and failure to thrive.
Created: 19 Mar 2024, 3:16 p.m. | Last Modified: 19 Mar 2024, 3:16 p.m.
Panel Version: 5.499
ZFHX3 monoallelic variants are associated with Spinocerebellar ataxia 4 (OMIM: 600223)(PMID: 38035881) and Susceptibility to Atrial fibrillation 8 (OMIM: 613055)(PMID: 37449401), neither of which include intellectual disability. PMIDs: 38412861 and PMID: 37292950 (this publication is a Preprint (18th March 2024)) report loss of function variants, including microdeletions and terminating variants, to be associated with syndromic intellectual disability. Over 20 terminating ZFHX3 variants have been reported, with an incidence of intellectual disability of 14/26 cases (22 probands and four affected family members) and global developmental delay in 18/26 cases (PMID: 38412861). Thirteen microdeletions (only affecting ZFHX3) were also reported in PMID: 38412861, intellectual disability was seen in 5/13 cases and global developmental delay in 6/13 cases.
Created: 18 Mar 2024, 4:56 p.m. | Last Modified: 18 Mar 2024, 4:56 p.m.
Panel Version: 5.499

Publications

Created: 18 Mar 2024, 4:56 p.m.
Last Modified: 18 Mar 2024, 4:56 p.m.
Panel version: 5.499

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • NHS GMS
  • Literature
Phenotypes
  • syndromic intellectual disability
OMIM
104155
Clinvar variants
Variants in ZFHX3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

26 Sep 2024, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q1_24_promote_green was removed from gene: ZFHX3. Tag Q1_24_NHS_review was removed from gene: ZFHX3.

26 Sep 2024, Gel status: 3

Added New Source, Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to ZFHX3. Source Expert Review Green was added to ZFHX3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

18 Mar 2024, Gel status: 2

Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q1_24_promote_green tag was added to gene: ZFHX3. Tag Q1_24_NHS_review tag was added to gene: ZFHX3.

18 Mar 2024, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: zfhx3 has been classified as Amber List (Moderate Evidence).

18 Mar 2024, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Sarah Leigh (Genomics England Curator)

gene: ZFHX3 was added gene: ZFHX3 was added to Intellectual disability - microarray and sequencing. Sources: Literature Mode of inheritance for gene: ZFHX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ZFHX3 were set to 38412861; 38035881; 37292950 Phenotypes for gene: ZFHX3 were set to syndromic intellectual disability