IKZF2 (IKAROS family zinc finger 2)

2007-04-01 Rupa Sridharan , Stephen Smale Affiliation

Room 6730 MacDonald Research Laboratories, Howard Hughes Medical Institute, 675 Charles Young Drive South, University of California, Los Angeles, CA 90095-1662, USA.

Identity

HGNC

IKZF2

LOCATION

2q34

LOCUSID

22807

ALIAS

ANF1A2,HELIOS,ZNF1A2,ZNFN1A2

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

143kb encoding 7 exons.

Transcription

12kb transcript, alternatively spliced to give two predominant isoforms.

Proteins

Note

526 amino acids. Mouse protein migrates at 70kD.

Helios with the zinc finger domain shown as blocks and the exon junctions in black lines.

Description

Largest isoform contains four N-terminal zinc fingers used for DNA binding and two C terminal zinc fingers for homodimerization and heterodimerization with other Ikaros family members.

Expression

Largely restricted to the thymus. In mice, besides thymocytes and T cells, low levels are found in proB cells and bone marrow multipotent progenitors.

Localisation

Nuclear. Often localizes to the pericentric heterochromatin as punctate spots in cycling cells, with diffuse nuclear localization in non-cycling cells.

Function

Helios is thought to be important for T cell development and may function as a repressor of transcription. However, Helios mutant mice have not been reported. In mice, Helios can recruit the NuRD chromatin remodeling complex to the pericentric heterochromatin.

Homology

High level of identity to Ikaros over the zinc finger domains.

Implicated in

Entity name

Leukemia

Note

Shorter isoforms of Helios are expressed in certain human leukemias. They may function as dominant negative inhibitors of full-length proteins due to the lack of DNA binding domain. However, dominant negative functions have not been demonstrated experimentally.

Disease

T cell acute lymphoblastic leukemia.

Entity name

Lymphoma

Note

Overexpression of Helios in B cells of mice promotes lymphomagenesis. Overexpression of a DNA binding mutant in hematopoietic progenitors leads to aggressive and transplantable T cell lymphomas in 60% of the mice.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
16148093	2005	Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis.	Dovat S et al
9512513	1998	Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin.	Hahm K et al
10541817	1999	Human Helios, an Ikaros-related zinc finger DNA binding protein: cDNA cloning and tissue expression pattern.	Hosokawa Y et al
9560339	1998	Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors.	Kelley CM et al
11937265	2002	Overexpression of novel short isoforms of Helios in a patient with T-cell acute lymphoblastic leukemia.	Nakase K et al
17110463	2007	Expression of a non-DNA-binding isoform of Helios induces T-cell lymphoma in mice.	Zhang Z et al

Other Information

Locus ID:

NCBI: 22807
MIM: 606234
HGNC: 13177
Ensembl: ENSG00000030419

Variants:

dbSNP: 22807
ClinVar: 22807
TCGA: ENSG00000030419
COSMIC: IKZF2

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000030419	ENST00000342002	B4DWF2
ENSG00000030419	ENST00000374319	Q9UKS7
ENSG00000030419	ENST00000374326	Q9UKS7
ENSG00000030419	ENST00000412444	Q9UKS7
ENSG00000030419	ENST00000431520	Q9UKS7
ENSG00000030419	ENST00000433134	E7EUI1
ENSG00000030419	ENST00000434687	Q9UKS7
ENSG00000030419	ENST00000439848	Q9UKS7
ENSG00000030419	ENST00000442445	E7ES26
ENSG00000030419	ENST00000451136	A0A0A0MSL2
ENSG00000030419	ENST00000452786	E7EPU0
ENSG00000030419	ENST00000453575	Q9UKS7
ENSG00000030419	ENST00000457361	A0A0A0MT14

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
36510022	2023	Aging-associated HELIOS deficiency in naive CD4(+) T cells alters chromatin remodeling and promotes effector cell responses.	14
36738680	2023	Decreased frequency of regulatory T cells and level of helios gene expression in secondary progressive multiple sclerosis patients: Evidence about the development of multiple sclerosis.	1
37316189	2023	Dominant negative variants in IKZF2 cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.	2
37996909	2023	Temporal changes in regulatory T cell subsets defined by the transcription factor Helios in stroke and their potential role in stroke-associated infection: a prospective case-control study.	0
36510022	2023	Aging-associated HELIOS deficiency in naive CD4(+) T cells alters chromatin remodeling and promotes effector cell responses.	14
36738680	2023	Decreased frequency of regulatory T cells and level of helios gene expression in secondary progressive multiple sclerosis patients: Evidence about the development of multiple sclerosis.	1
37316189	2023	Dominant negative variants in IKZF2 cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.	2
37996909	2023	Temporal changes in regulatory T cell subsets defined by the transcription factor Helios in stroke and their potential role in stroke-associated infection: a prospective case-control study.	0
34561855	2022	Helios is a marker, not a driver, of human Treg stability.	25
34920454	2022	Identification of germline monoallelic mutations in IKZF2 in patients with immune dysregulation.	14
34981715	2022	Expression of Programmed Cell Death 1 and Helios Genes Correlates With rs872071A>G and rs12203592C>T Single-Nucleotide Polymorphisms of InterferonRegulatory Factor 4 in Patients with T-Cell-Mediated Rejection of Renal Allograft.	0
35651622	2022	Co-Expression of TIGIT and Helios Marks Immunosenescent CD8(+) T Cells During Aging.	5
34561855	2022	Helios is a marker, not a driver, of human Treg stability.	25
34920454	2022	Identification of germline monoallelic mutations in IKZF2 in patients with immune dysregulation.	14
34981715	2022	Expression of Programmed Cell Death 1 and Helios Genes Correlates With rs872071A>G and rs12203592C>T Single-Nucleotide Polymorphisms of InterferonRegulatory Factor 4 in Patients with T-Cell-Mediated Rejection of Renal Allograft.	0

Citation

Rupa Sridharan ; Stephen Smale

IKZF2 (IKAROS family zinc finger 2)

Atlas Genet Cytogenet Oncol Haematol. 2007-04-01

Online version: http://atlasgeneticsoncology.org/gene/42885/css/favicon/apple-touch-icon.png