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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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IKZF4
IKAROS family zinc finger 4
Chromosome 12 · 12q13.2
NCBI Gene: 64375Ensembl: ENSG00000123411.15HGNC: HGNC:13179UniProt: F8VPL6
29PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmprotein bindingprotein homooligomerizationzinc ion bindingBlackfan-Diamond anemiaasthmatype 1 diabetes mellitusovarian neoplasm
✦AI Summary

IKZF4 (Eos) is a zinc finger transcription factor functioning as a DNA-binding protein that recognizes the GGGAATRCC sequence and acts as a transcriptional repressor 1. It plays essential roles in immune regulation and tumor suppression. In regulatory T cells, IKZF4 mediates FOXP3-dependent gene silencing and is critical for optimal Foxp3 protein expression and Treg cell function 2. IKZF4 operates within the IKZF4/NONO-RAB11FIP3 axis to facilitate PD-L1 endosomal recycling, promoting immune evasion in gastric cancer, while IKZF4 silencing enhances anti-tumor immunity 1. In non-small cell lung cancer, IKZF4 functions as a tumor suppressor by inhibiting Notch signaling 3. Genetically, IKZF4 variants associate with multiple autoimmune diseases: genome-wide association studies identified IKZF4 polymorphisms linked to alopecia areata risk 45, narcolepsy type 1 6, and type 1 diabetes 78. Notably, IKZF4 rs1701704 polymorphism shows sexual dimorphism in type 1 diabetes progression, with protective effects in females 8. These findings establish IKZF4 as a multifunctional regulator bridging adaptive immunity, autoimmunity, and cancer biology.

Sources cited
1
IKZF4 synergistically regulates RAB11FIP3 expression and facilitates PD-L1 endosomal recycling in gastric cancer immune evasion
PMID: 38211652
2
IKZF4 (Eos) is required for optimal Foxp3 protein expression and distinct aspects of regulatory T cell function
PMID: 37413709
3
IKZF4 acts as a tumor suppressor in non-small cell lung cancer by suppressing Notch signaling pathway
PMID: 37044192
4
IKZF4 variants associate with alopecia areata susceptibility in genome-wide association study
PMID: 20596022
5
IKZF4 rs1701704 polymorphism associates with alopecia areata risk in Chinese Han population
PMID: 38330583
6
IKZF4-ERBB3 locus associates with narcolepsy type 1 risk through T cell autoimmunity mechanisms
PMID: 37188663
7
IKZF4-RPS26-ERBB3 locus associates with type 1 diabetes risk in multi-ancestry genome-wide association study
PMID: 38453145
8
IKZF4 rs1701704 polymorphism shows sexual dimorphism in type 1 diabetes progression with protective effects in females
PMID: 34448034
Disease Associationsⓘ20
Blackfan-Diamond anemiaOpen Targets
0.33Weak
asthmaOpen Targets
0.30Weak
type 1 diabetes mellitusOpen Targets
0.22Weak
ovarian neoplasmOpen Targets
0.21Weak
VitiligoOpen Targets
0.18Weak
intelligenceOpen Targets
0.16Weak
hypothyroidismOpen Targets
0.15Weak
Alzheimer diseaseOpen Targets
0.13Weak
respiratory system diseaseOpen Targets
0.11Weak
thyroid diseaseOpen Targets
0.11Weak
autoimmune diseaseOpen Targets
0.11Weak
skin diseaseOpen Targets
0.11Weak
hypertensionOpen Targets
0.11Weak
childhood onset asthmaOpen Targets
0.10Weak
essential hypertensionOpen Targets
0.10Weak
allergic diseaseOpen Targets
0.10Weak
smoking initiationOpen Targets
0.10Suggestive
mathematical abilityOpen Targets
0.10Suggestive
Hashimoto's thyroiditisOpen Targets
0.09Suggestive
actinic keratosisOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KCTD3Shared pathway100%KCTD4Shared pathway100%KCTD18Shared pathway100%SAMD1Shared pathway100%KCTD15Shared pathway100%KCTD14Shared pathway100%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
96%
Heart
62%
Lung
42%
Brain
36%
Liver
36%
Gene Interaction Network
Click a node to explore
IKZF4KCTD3KCTD4KCTD18SAMD1KCTD15KCTD14
PROTEIN STRUCTURE
Preparing viewer…
PDB2MA7 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.39Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.24 [0.15–0.39]
RankingsWhere IKZF4 stands among ~20K protein-coding genes
  • #12,167of 20,598
    Most Researched29
  • #1,924of 17,882
    Most Constrained (LOEUF)0.39 · top quartile
Genes detectedIKZF4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.
PMID: 20596022
Nature · 2010
1.00
2
Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.
PMID: 37188663
Nat Commun · 2023
0.90
3
IKZF4/NONO-RAB11FIP3 axis promotes immune evasion in gastric cancer via facilitating PD-L1 endosome recycling.
PMID: 38211652
Cancer Lett · 2024
0.80
4
A multi-ancestry genome-wide association study in type 1 diabetes.
PMID: 38453145
Hum Mol Genet · 2024
0.70
5
IKZF4 acts as a novel tumor suppressor in non-small cell lung cancer by suppressing Notch signaling pathway.
PMID: 37044192
Cell Signal · 2023
0.60