IKZF3

Chr 17AD

IKAROS family zinc finger 3

ENSG00000161405UniProt: Q9UKT9

Transcription factor that plays an important role in the regulation of lymphocyte differentiation. Plays an essential role in regulation of B-cell differentiation, proliferation and maturation to an effector state. Involved in regulating BCL2 expression and controlling apoptosis in T-cells in an IL2-dependent manner

Primary Disease Associations & Inheritance

?Immunodeficiency 84MIM #619437
AD
0
Active trials
10
Pathogenic / LP
78
ClinVar variants
5
Pubs (1 yr)
2.1
Missense Z
0.29
LOEUF· LoF intolerant
Clinical Summary— IKZF3
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Gene-Disease Validity (ClinGen)
immunodeficiency 84 · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
10 Pathogenic / Likely Pathogenic· 60 VUS of 78 total submissions
Some data sources returned errors (1)

ncbi: TypeError: fetch failed

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.29LOEUF
pLI 0.984
Z-score 3.89
OE 0.09 (0.04–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.14Z-score
OE missense 0.66 (0.58–0.74)
203 obs / 308.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.04–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.58–0.74)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 2 / 21.4Missense obs/exp: 203 / 308.9Syn Z: 0.37
DN
0.4587th %ile
GOF
0.3193th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS60
Likely Benign4
Benign4
9
Pathogenic
1
Likely Pathogenic
60
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
8
0
9
Likely Pathogenic
1
0
0
0
1
VUS
0
58
2
0
60
Likely Benign
0
2
0
2
4
Benign
0
1
2
1
4
Total16212378

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IKZF3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Non-HLA Risk Loci ERBB3/IKZF4 and ERBB2/IKZF3/GSDMB/ORMDL3 Interact to Influence Progression of Autoimmunity in Relatives of T1D Patients.
Mertens IM et al.·Diabetes Metab Res Rev
2026Open AccessCohort
H195Y mutation of IKZF3 identified in a mouse model of precursor B cell acute lymphoblastic leukemia impairs transcriptional repression activity and increases protein stability.
Rysan H et al.·J Leukoc Biol
2026Functional
[IKZF3/Aiolos and tumors].
Jia Q et al.·Zhong Nan Da Xue Xue Bao Yi Xue Ban
2025Open Access
Resveratrol improves idiopathic pulmonary fibrosis by targeting IKZF3.
Liu S et al.·J Nutr Biochem
2026
Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma.
Kegyes D et al.·Biomark Res
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients