ZBTB24

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

Basic information

Region (hg38): 6:109460631-109483239

Previous symbols: [ "ZNF450" ]

Links

ENSG00000112365 ∙ NCBI:9841 ∙ OMIM:614064 ∙ HGNC:21143 ∙ Uniprot:O43167 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency-centromeric instability-facial anomalies syndrome 2 (Strong), mode of inheritance: AR
• immunodeficiency-centromeric instability-facial anomalies syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency-Centromeric Instability-Facial Anomalies 2	AR	Allergy/Immunology/Infectious	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	Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic	21596365; 25055871
Immunodeficiency-Centromeric Instability-Facial Anomalies may be recognizable due to features including dysmorphic facial features and developmental delay

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZBTB24 gene.

• Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (327 variants)
• Inborn genetic diseases (22 variants)
• not provided (15 variants)
• not specified (6 variants)
• Kabuki syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZBTB24 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	112	7	120
missense	1		151	5	3	160
nonsense	6	2				8
start loss						0
frameshift	10	2				12
inframe indel			4			4
splice donor/acceptor (+/-2bp)	1	4				5
splice region			3	5	3	11
non coding			2	16	4	22
Total	18	8	158	133	14

Highest pathogenic variant AF is 0.0000197

Variants in ZBTB24

This is a list of pathogenic ClinVar variants found in the ZBTB24 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-109465658-C-T			Uncertain significance (Jul 14, 2023)
6-109465661-T-C			Uncertain significance (Jul 26, 2021)
6-109465666-T-TA			Uncertain significance (Jul 19, 2022)
6-109465671-A-G			Uncertain significance (Jul 18, 2023)
6-109465851-T-C		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Dec 26, 2017)
6-109465866-G-C		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Likely benign (Mar 27, 2023)
6-109465867-C-T		Immunodeficiency-centromeric instability-facial anomalies syndrome 2 • Inborn genetic diseases	Uncertain significance (Jan 20, 2023)
6-109465875-C-T		Immunodeficiency-centromeric instability-facial anomalies syndrome 2 • ZBTB24-related disorder	Benign/Likely benign (Jan 31, 2024)
6-109465876-G-A		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Aug 28, 2021)
6-109465877-T-C		Immunodeficiency-centromeric instability-facial anomalies syndrome 2 • Inborn genetic diseases	Uncertain significance (Feb 19, 2022)
6-109465879-G-A		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Dec 22, 2023)
6-109465887-C-T		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Likely benign (Dec 28, 2023)
6-109465889-C-T		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Sep 07, 2022)
6-109465890-G-A		Immunodeficiency-centromeric instability-facial anomalies syndrome 2 • ZBTB24-related disorder	Likely benign (Dec 09, 2023)
6-109465893-G-A		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Likely benign (Jan 16, 2024)
6-109465895-G-A		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Jul 19, 2022)
6-109465904-G-A		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Conflicting classifications of pathogenicity (Nov 01, 2022)
6-109465908-C-T		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Likely benign (Jan 25, 2024)
6-109465909-G-A		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Aug 27, 2021)
6-109465920-C-G		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Aug 17, 2021)
6-109465927-A-G		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
6-109465949-C-T		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Sep 01, 2021)
6-109465959-T-C		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Likely benign (Dec 14, 2023)
6-109465960-G-A		Inborn genetic diseases	Uncertain significance (Mar 24, 2023)
6-109465961-T-C		Immunodeficiency-centromeric instability-facial anomalies syndrome 2	Uncertain significance (Aug 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZBTB24	protein_coding	protein_coding	ENST00000230122	6	20644

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000209	0.999	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.01	307	361	0.850	0.0000199	4626
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.361
• hipred: N
• hipred_score: 0.394
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.908

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zbtb24
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;hematopoietic progenitor cell differentiation;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleoplasm
• 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