Inherited bleeding disorders

Gene: IKZF5

Green List (high evidence)

IKZF5 (IKAROS family zinc finger 5)
EnsemblGeneIds (GRCh38): ENSG00000095574
EnsemblGeneIds (GRCh37): ENSG00000095574
OMIM: 606238, Gene2Phenotype
IKZF5 is in 2 panels

1 review

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: New gene added. Appropriate phenotype, sufficient cases and external expert review (pers.comm) all support gene-disease association and relevance to this panel to rate gene to Green.
Created: 9 Aug 2019, 1:55 p.m. | Last Modified: 9 Aug 2019, 1:55 p.m.
Panel Version: 1.156
From abstract Lentaigne C et al (2019) PMID: 31217188: To identify novel causes of hereditary thrombocytopenia, we performed a genetic association analysis of whole-genome sequencing (WGS) data from 13,037 individuals enrolled in the NIHR BioResource, including 233 cases with isolated thrombocytopenia. We found an association between rare variants in the transcription factor (TF)-encoding gene IKZF5 and thrombocytopenia. We report five causal missense variants in or near IKZF5 zinc fingers (Znfs), of which two occurred de novo and three co-segregated in three pedigrees. A canonical DNA-Znf binding model predicts that three of the variants alter DNA recognition. Expression studies showed that chromatin binding was disrupted in mutant compared to wild-type (WT) IKZF5 and electron microscopy (EM) revealed a reduced quantity of alpha granules in normally sized platelets. Proplatelet formation (PPF) was reduced in megakaryocytes (MKs) from seven cases relative to six controls. Comparison of RNA-seq data from platelets, monocytes, neutrophils and CD4+ T-cells from three cases and 14 healthy controls showed 1,194 differentially expressed genes (DEGs) in platelets but only four DEGs in each of the other blood cell types. In conclusion, IKZF5 is a novel transcriptional regulator of megakaryopoiesis and the eighth transcription factor associated with dominant thrombocytopenia in humans.
Sources: Literature
Created: 9 Aug 2019, 1:52 p.m.

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

Phenotypes
Thrombocytopenia

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
Phenotypes
  • Thrombocytopenia
OMIM
606238
Clinvar variants
Variants in IKZF5
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Aug 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ikzf5 has been classified as Green List (High Evidence).

9 Aug 2019, Gel status: 1

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

Louise Daugherty (Genomics England Curator)

gene: IKZF5 was added gene: IKZF5 was added to Inherited bleeding disorders. Sources: Literature Mode of inheritance for gene: IKZF5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: IKZF5 were set to 31217188 Phenotypes for gene: IKZF5 were set to Thrombocytopenia Review for gene: IKZF5 was set to GREEN