IKZF3: A Key Regulator of Lymphoid Development and Immune Homeostasis
IKAROS Family Zinc Finger 3 (Aiolos) – Gene Function, Expression, and Clinical Significance
Gene Information Card
| Symbol | IKZF3 |
|---|---|
| Full Name | IKAROS family zinc finger 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.1 |
| NCBI Gene ID | 22806 ncbi.nlm.nih.gov/gene/22806 |
| Ensembl ID | ENSG00000161405 |
| UniProt ID | Q9UKT9 |
| OMIM ID | 606221 |
| HGNC ID | 13178 |
| Aliases | Aiolos, ZNFN1A3, IKAROS family zinc finger 3 (Aiolos) |
Description
IKZF3 (IKAROS family zinc finger 3), commonly known as Aiolos, encodes a transcription factor belonging to the IKAROS family of zinc finger proteins. It is essential for lymphoid development, particularly B-cell differentiation and maturation, and plays a critical role in regulating immune homeostasis. IKZF3 functions as a dimer with other IKAROS family members to repress or activate target genes involved in lymphocyte proliferation and survival. Alterations in IKZF3 are associated with hematologic malignancies, including multiple myeloma and acute lymphoblastic leukemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple myeloma | IKZF3 is a therapeutic target; lenalidomide induces degradation of IKZF3 leading to anti-myeloma effects | ClinVar, COSMIC |
| Acute lymphoblastic leukemia (ALL) | IKZF3 deletions and mutations contribute to leukemogenesis and poor prognosis | ClinVar, COSMIC |
| Autoimmune disorders | IKZF3 polymorphisms are associated with susceptibility to systemic lupus erythematosus and inflammatory bowel disease | OMIM, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 45.2 | High |
| Spleen | 38.7 | High |
| Bone marrow | 30.1 | High |
| Blood | 22.5 | Medium |
| Thymus | 18.9 | Medium |
| Lung | 4.3 | Low |
| Brain | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Raji (Burkitt lymphoma) | 62.8 | B-cell line, high expression |
| K-562 (chronic myeloid leukemia) | 45.3 | Lymphoid origin, high expression |
| HEK293 (embryonic kidney) | 2.1 | Non-hematopoietic, low expression |
| HeLa (cervical carcinoma) | 1.5 | Non-hematopoietic, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly158Arg | Missense | 0.5% in ALL | Alters DNA-binding affinity |
| p.Arg183His | Missense | 0.3% in multiple myeloma | Reduces transcriptional repression |
| c.1-?_*+?del | Deletion | 2% in B-ALL | Loss of function, poor prognosis |
| p.Lys213Asn | Missense | 0.1% in autoimmune cohorts | Alters protein stability |
Mutation functional classification
Loss of Function (LOF)
Deletions and truncating mutations in IKZF3 impair its ability to repress target genes, leading to aberrant lymphocyte proliferation and contributing to leukemogenesis.
Gain of Function (GOF)
Rare missense mutations (e.g., p.Gly158Arg) may enhance DNA binding or dimerization, potentially driving oncogenic signaling in lymphoid malignancies.
Dominant Negative (DN)
Certain IKZF3 mutations produce truncated proteins that interfere with wild-type IKAROS family function, disrupting normal lymphoid differentiation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IKAROS family signaling in lymphocyte development
• B cell receptor signaling pathway
• Notch signaling pathway (cross-regulation)
• Lenalidomide-mediated degradation of IKZF1/IKZF3 in multiple myeloma
Protein Summary
IKZF3 (Aiolos) is a 509-amino acid zinc finger transcription factor predominantly expressed in lymphoid tissues. It contains N-terminal zinc fingers for DNA binding and C-terminal zinc fingers for dimerization. IKZF3 forms homo- and heterodimers with IKZF1 (Ikaros) to regulate gene expression critical for B-cell maturation, plasma cell differentiation, and immune tolerance. The protein is a direct target of immunomodulatory drugs (IMiDs) like lenalidomide, which promote its ubiquitination and proteasomal degradation in multiple myeloma cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IKZF3 Knockout HEK293 Cell Line | EDJ-KQ7679 | Human | 22806 | Details Get a Quote |
| IKZF3 Knockout HeLa Cell Line | EDJ-KQ55640 | Human | 22806 | Details Get a Quote |
| IKZF3 Knockout A-549 Cell Line | EDJ-KQ64138 | Human | 22806 | Details Get a Quote |
| IKZF3 Knockout HCT 116 Cell Line | EDJ-KQ72585 | Human | 22806 | Details Get a Quote |
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