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Intellectual disability

Gene: ZFX

Green List (high evidence)
ZFX (zinc finger protein, X-linked)
EnsemblGeneIds (GRCh38): ENSG00000005889
EnsemblGeneIds (GRCh37): ENSG00000005889
OMIM: 314980, Gene2Phenotype
ZFX is in 3 panels

6 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
Comment on phenotypes: This gene has now been associated with phenotype in OMIM (MIM #301118), but not yet in Gene2Phenotype.
Created: 18 Apr 2024, 7 p.m. | Last Modified: 18 Apr 2024, 7 p.m.
Panel Version: 5.532

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Created: 18 Apr 2024, 7 p.m.
Last Modified: 18 Apr 2024, 7 p.m.
Panel version: 7.41

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

There are sufficient cases reported for this gene to be included as green on the R29 panel. Several LOF and missense reported as de novo or maternally inherited. Phenotype supported Zebrafish model
Created: 27 Mar 2024, 3:51 p.m. | Last Modified: 27 Mar 2024, 3:51 p.m.
Panel Version: 5.506

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Intellectual disability; developmental delay; behavioural abnormalities; hypotonia; dysmorphic facies

Publications

Created: 27 Mar 2024, 3:51 p.m.
Last Modified: 27 Mar 2024, 3:51 p.m.
Panel version: 5.506

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence for this gene to be green on this panel.
Created: 4 Mar 2024, 5:09 p.m. | Last Modified: 4 Mar 2024, 5:09 p.m.
Panel Version: 5.486
To date, germline variants in ZFX have not been associated with a phenotype in OMIM or Gen2Phen.
A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Created: 4 Mar 2024, 5:07 p.m. | Last Modified: 4 Mar 2024, 5:14 p.m.
Panel Version: 5.487

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
X-linked neurodevelopmental disorder with recurrent facial gestalt

Publications

Created: 4 Mar 2024, 5:07 p.m.
Last Modified: 4 Mar 2024, 5:14 p.m.
Panel version: 5.485

Caroline Wright (Sanger)

Red List (low evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

PMID:26740508 (2016) studied a cohort of 19 Portuguese patients with a clinical presentation overlapping Rett syndrome (RTT). The patients were selected from a previously established database of patients with ID. Patient 19 is 14_year-old boy with dyspraxic gait and no language, who acquired purposeful grasp only around 2_years of age. This patient carries two maternally inherited X linked variants: a c.C436T, p.(R146W) variant in SHROOM4 and a c.G409A, p.(D137N) variant in ZFX. Both variants are inherited from the healthy mother, who has a random X inactivation pattern. Currently no further cases to support ID involvement.
Created: 31 Oct 2017, 9:24 a.m.

Publications

Created: 31 Oct 2017, 9:24 a.m.

Panel version: Imported from Intellectual disability update Oct 2017 panel version 0.4

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:24 a.m.

Panel version: 0.306

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Intellectual developmental disorder, X-linked syndromic 37, OMIM:301118
OMIM
314980
Clinvar variants
Variants in ZFX
Penetrance
Complete
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: ZFX. Tag Q1_24_NHS_review was removed from gene: ZFX.

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

18 Apr 2024, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Intellectual developmental disorder, X-linked syndromic 37, OMIM:301118

4 Mar 2024, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: ZFX were changed from to X-linked neurodevelopmental disorder with recurrent facial gestalt

4 Mar 2024, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: ZFX were set to 26350204; 26740508

4 Mar 2024, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

4 Mar 2024, Gel status: 1

Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

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

12 Mar 2018, Gel status: 1

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene ZFX was set to ['26350204', ' 26740508']

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

ZFX was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

ZFX was added to Intellectual disabilitypanel. Sources: Expert Review Red