ZBTB24

Chr 6AR

zinc finger and BTB domain containing 24

Also known as: BIF1, ICF2, PATZ2, ZNF450

NCBI Gene: 9841ENSG00000112365UniProt: O43167

Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in nucleus. Implicated in immunodeficiency-centromeric instability-facial anomalies syndrome 2. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Immunodeficiency-centromeric instability-facial anomalies syndrome 2MIM #614069
AR
575
ClinVar variants
77
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZBTB24
🧬
Gene-Disease Validity (ClinGen)
immunodeficiency-centromeric instability-facial anomalies syndrome 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
77 Pathogenic / Likely Pathogenic· 223 VUS of 575 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.66LOEUF
pLI 0.000
Z-score 2.90
OE 0.40 (0.25–0.66)
Tolerant

Typical tolerance to LoF variation

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.
1.01Z-score
OE missense 0.85 (0.77–0.93)
307 obs / 361.1 exp
Tolerant

Mild missense constraint

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.0.40 (0.25–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.77–0.93)
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.1.04
0≤1.21.6
LoF obs/exp: 11 / 27.4Missense obs/exp: 307 / 361.1Syn Z: -0.41

ClinVar Variant Classifications

575 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic15
VUS223
Likely Benign255
Benign14
Conflicting6
62
Pathogenic
15
Likely Pathogenic
223
VUS
255
Likely Benign
14
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
0
38
0
62
Likely Pathogenic
12
1
2
0
15
VUS
3
200
19
1
223
Likely Benign
0
10
49
196
255
Benign
0
1
8
5
14
Conflicting
—6
Total39212116202575

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

View in ClinVar →

Protein Context — Lollipop Plot

ZBTB24 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency-centromeric instability-facial anomalies syndrome 2

MIM #614069

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ZBTB24
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ZBTB24 regulates the apoptosis of human T cells via CDCA7/TRAIL-receptor axis.
Qin XY et al.·Biochem Biophys Res Commun
2019
Investigation of Transcription Factor and Cytokine Gene Expression Levels in Helper T Cell Subsets Among Turkish Patients Diagnosed with ICF2 (Novel ZBTB24 gene Variant) and ICF3 (CDCA7 Variant) Syndrome.
Duran T et al.·J Clin Immunol
2024Cohort
Case report: Novel multi-exon homozygous deletion of ZBTB24 causes immunodeficiency, centromeric instability, and facial anomalies syndrome 2.
Long Y et al.·Front Immunol
2025Case report
A functional assay to classify ZBTB24 missense variants of unknown significance.
Wu H et al.·Hum Mutat
2019Functional
Evaluation of Clinical and Immunological Alterations Associated with ICF Syndrome.
Bilgic Eltan S et al.·J Clin Immunol
2023
Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features.
Sharifinejad N et al.·Front Immunol
2022
Downregulation of ZBTB24 hampers the G0/1- to S-phase cell-cycle transition via upregulating the expression of IRF-4 in human B cells.
Liang J et al.·Genes Immun
2016
In-depth immune profiling of a patient with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2 caused by a novel mutation in ZBTB24.
Roark CM et al.·Clin Exp Immunol
2025Case report
Enhanced CD19 activity in B cells contributes to immunodeficiency in mice deficient in the ICF syndrome gene Zbtb24.
Ying Z et al.·Cell Mol Immunol
2023
DNA methylation in disease: Immunodeficiency, Centromeric instability, Facial anomalies syndrome.
Vukic M et al.·Essays Biochem
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools