Covered on Genetics Home Reference: common variable immune deficiencyFrom NCBI Gene: Immunodeficiency, common variable, 13From UniProt: Defects in IKZF1 are frequent occurrences (28.6%) in acute lymphoblasic leukemia (ALL). Such alterations or deletions lead to poor prognosis for ALL. Chromosomal aberrations involving IKZF1 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;7)(q27;p12), with BCL6.

     From NCBI Gene: This gene encodes a transcription factor that belongs to the family of zinc-finger DNA-binding proteins associated with chromatin remodeling. The expression of this protein is restricted to the fetal and adult hemo-lymphopoietic system, and it functions as a regulator of lymphocyte differentiation. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. Most isoforms share a common C-terminal domain, which contains two zinc finger motifs that are required for hetero- or homo-dimerization, and for interactions with other proteins. The isoforms, however, differ in the number of N-terminal zinc finger motifs that bind DNA and in nuclear localization signal presence, resulting in members with and without DNA-binding properties. Only a few isoforms contain the requisite three or more N-terminal zinc motifs that confer high affinity binding to a specific core DNA sequence element in the promoters of target genes. The non-DNA-binding isoforms are largely found in the cytoplasm, and are thought to function as dominant-negative factors. Overexpression of some dominant-negative isoforms have been associated with B-cell malignancies, such as acute lymphoblastic leukemia (ALL). [provided by RefSeq, May 2014] From UniProt: Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067).

The following transcription factors affect gene expression:

• Sp1
• AREB6
• Pax-6
• NF-E2
• NF-E2 p45
• Meis-1
• NCX/Ncx

Tissue specificity:

Abundantly expressed in thymus, spleen and peripheral blood Leukocytes and lymph nodes. Lower expression in bone marrow and small intestine.

Molecular Function:

• Dna Binding
• Transcription Factor Activity, Sequence-Specific Dna Binding
• Transcription Regulatory Region Dna Binding
• Metal Ion Binding

Biological Processes:

• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Transcription, Dna-Templated
• Cell Cycle
• Mesoderm Development
• Covalent Chromatin Modification
• Lymphocyte Differentiation
• Erythrocyte Differentiation
• Negative Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter