ZBTB24

protein-coding

zinc finger and BTB domain containing 24, the group of BTB domain containing|Zinc fingers C2H2-type

Gene summary

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]

Previous symbols:

ZNF450

MANE transcript

NM_014797.3

Inheritance

ClinVar variants

P:59U:207B:214

Top phenotype

Immunodeficiency-Centromeric Instability-Facial Anomalies 2

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr6:109,460,632-109,483,239

External References & Databases

Ensembl (ENSG00000112365)

Transcript & Mutation Effects

hg38 • Region Span ~22.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency-centromeric instability-facial anomalies syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013553

Submitter: PanelApp Australia

immunodeficiency-centromeric instability-facial anomalies syndrome 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013553

Submitter: ClinGen

ZBTB24 is a transcriptional regulator which was first reported in relation to autosomal recessive immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome 2 in 2011 (de Greef et al., PMID: 21596365). ICF syndrome 2 is characterized by facial dysmorphism, agammaglobulinemia, recurrent infections, intellectual disability, chromosome instability, and T-cell functional deficiency. Heterozygous carriers are clinically unaffected. Nine variants (missense, nonsense, and frameshift) that have been reported in eight probands in three publications (PMIDs: 21596365, 32061411, 23486536) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by mouse models, expression studies, and in vitro functional assays (PMIDs: 39562305, 32865561, 27626380, 21596365). In summary, there is definitive evidence supporting the relationship between ZBTB24 and autosomal recessive immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome 2. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.This classification was approved by the ClinGen SCID-CID GCEP on the meeting date July 17, 2025 (SOP Version 11)].

immunodeficiency-centromeric instability-facial anomalies syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0000133

Submitter: Orphanet

immunodeficiency-centromeric instability-facial anomalies syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013553

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Immunodeficiency-Centromeric Instability-Facial Anomalies 2AR

Manifestation: Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals may demonstrate agammaglobulinemia/hypogammaglobulinemia, resulting in recurrent/severe (including fatal) respiratory and GI infections , and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial in order to decrease morbidity and mortality

Comments: Immunodeficiency-Centromeric Instability-Facial Anomalies may be recognizable due to features including dysmorphic facial features and developmental delay

Refs: 21596365; 25055871

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZBTB24 variants in ClinVar

6 Conditions Cataloged

Immunodeficiency-centromeric instability-facial anomalies syndrome 2Total: 475

Inborn genetic diseasesTotal: 85

not providedTotal: 34

not specifiedTotal: 31

ZBTB24-related disorderTotal: 20

Kabuki syndrome 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014797.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	197 clinvar	3 clinvar	204
missense		1 clinvar	201 clinvar	13 clinvar	1 clinvar	216
nonsense	13 clinvar	4 clinvar	1 clinvar			18
start loss						0
frameshift	24 clinvar	8 clinvar	1 clinvar			33
splice donor/acceptor (+/-2bp)	1 clinvar	8 clinvar				9
Total	38	21	207	210	4	480

Highest pathogenic variant AF is 0.000024782012

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014797.3	RefSeq	NP_055612.2	6	MANE Select
ENST00000230122.4	Ensembl	ENSP00000230122.4	6	MANE Select
NM_001164313.2	RefSeq	NP_001157785.1	1	Standard
ENST00000698513.1	Ensembl	ENSP00000513763.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
hematopoietic progenitor cell differentiation
positive regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription factor activity
protein binding
transcription regulatory region DNA binding
metal ion binding

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000230122
Coding exons: 6
Length: 20644
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.01	307	361	0.850	0.0000199	4626
Missense (PolyPhen)		81	112.83	0.71787		1444
Synonymous	-0.407	146	140	1.04	0.00000831	1307
Loss of Function	2.90	11	27.4	0.401	0.00000158	337

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in BMP2-induced transcription. {ECO:0000250}.;
Disease: DISEASE: Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2) [MIM:614069]: A rare disorder characterized by a variable immunodeficiency resulting in recurrent infections, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients. {ECO:0000269|PubMed:21596365}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.532
RVIS EVS: -0.11
RVIS percentile EVS: 45.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.908

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium