ZBTB24

Summary

ZBTB24 (zinc finger and BTB domain containing 24, HGNC:21143) is a protein-coding gene on chromosome 6q21, encoding Zinc finger and BTB domain-containing protein 24 (O43167). May be involved in BMP2-induced transcription.

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.

Source: NCBI Gene 9841 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency-centromeric instability-facial anomalies syndrome 2 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 520 total — 41 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_014797

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21143
Approved symbol	ZBTB24
Name	zinc finger and BTB domain containing 24
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0441, BIF1, PATZ2
Ensembl gene	ENSG00000112365
Ensembl biotype	protein_coding
OMIM	614064
Entrez	9841

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000230122, ENST00000698513, ENST00000698514, ENST00000698515, ENST00000698516, ENST00000698517, ENST00000698518, ENST00000698519, ENST00000698520, ENST00000698521, ENST00000898596, ENST00000919347, ENST00000919348

RefSeq mRNA: 1 — MANE Select: NM_014797 NM_014797

CCDS: CCDS34509

Canonical transcript exons

ENST00000230122 — 7 exons

Exon	Start	End
ENSE00000458640	109475399	109475482
ENSE00000761860	109467653	109467734
ENSE00000761864	109476175	109476258
ENSE00000800396	109462594	109466574
ENSE00000800397	109476763	109476930
ENSE00000975494	109481075	109482054
ENSE00001421862	109483098	109483219

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9779 / max 105.4209, expressed in 1752 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75010	8.9779	1752
75009	2.1716	1140

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	95.72	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.20	gold quality
tendon of biceps brachii	UBERON:0008188	84.36	gold quality
middle temporal gyrus	UBERON:0002771	83.34	gold quality
hair follicle	UBERON:0002073	82.13	silver quality
epithelium of nasopharynx	UBERON:0001951	81.52	gold quality
secondary oocyte	CL:0000655	81.35	gold quality
visceral pleura	UBERON:0002401	80.53	gold quality
skin of hip	UBERON:0001554	80.38	gold quality
tendon	UBERON:0000043	80.26	gold quality
cervix squamous epithelium	UBERON:0006922	80.23	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.96	gold quality
epithelial cell of pancreas	CL:0000083	79.81	silver quality
pleura	UBERON:0000977	79.62	gold quality
gingival epithelium	UBERON:0001949	79.33	silver quality
calcaneal tendon	UBERON:0003701	79.29	gold quality
parietal pleura	UBERON:0002400	79.05	gold quality
leukocyte	CL:0000738	78.60	gold quality
monocyte	CL:0000576	78.56	gold quality
mononuclear cell	CL:0000842	78.42	gold quality
upper leg skin	UBERON:0004262	78.12	gold quality
pancreatic ductal cell	CL:0002079	78.05	silver quality
endometrium epithelium	UBERON:0004811	77.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.76	gold quality
lymph node	UBERON:0000029	77.59	gold quality
mucosa of urinary bladder	UBERON:0001259	77.32	silver quality
sperm	CL:0000019	77.08	silver quality
nephron tubule	UBERON:0001231	76.86	gold quality
germinal epithelium of ovary	UBERON:0001304	76.85	gold quality
choroid plexus epithelium	UBERON:0003911	76.78	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6524	no	97.85
E-ANND-3	no	4.42
E-HCAD-5	no	2.38

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2330.1	ZBTB24	More than 3 adjacent zinc fingers
MA2330.2	ZBTB24	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:31226215

miRNA regulators (miRDB)

121 targeting ZBTB24, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-1321	99.84	65.30	1811

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 19)

• These data indicate that ZBTB24 is involved in DNA methylation of juxtacentromeric DNA and in B cell development and/or B and T cell interactions. (PMID:21596365)
• A novel deletion in the ZBTB24 gene was responsible for causing immunodeficiency, centromeric instability and facial anomalies syndrome type 2 in this family. (PMID:21906047)
• Clinical and genetic data of mutations in DNMT3B and ZBTB24 in patients with ICF syndrome, were compared. (PMID:23486536)
• We report three novel ZBTB24 mutations in Japanese and Cape Verdean type 2 ICF syndrome patients. (PMID:23739126)
• This suggests that Bif-1 protein expression may be a useful prognostic marker in early-stage CRC (PMID:24175288)
• ICF2, caused by biallelic ZBTB24 gene mutations, is acknowledged primarily as an isolated B-cell defect. (PMID:25330735)
• Downregulation of ZBTB24 increases the expression of IRF-4 and reduces b-cell proliferation. (PMID:27098601)
• Transcriptome analysis identified Cdca7 as the top down-regulated gene in Zbtb24 homozygous mutant mESCs, which can be restored by ectopic ZBTB24 expression. Finally, we show that this regulation is conserved between species and that CDCA7 levels are reduced in patients carrying ZBTB24 nonsense mutations (PMID:27466202)
• Our results demonstrate a novel role of Bif-1 in hepatocellular carcinoma (HCC), in which Bif-1 promotes cell metastasis by regulating Cdc42 expression and activity. (PMID:27730394)
• The biallelic deletion of ZBTB24 provides strong support for the hypothesis that most ICF2 patients suffer from a ZBTB24 loss of function mechanism and confirms that complete absence of ZBTB24 is compatible with human life. This is in contrast to the observed early embryonic lethality in mice lacking functional Zbtb24 (PMID:28128455)
• Here, we performed a comparative analysis of perturbed DNA methylation landscapes in a cohort of ICF patients using an array-based assay to (i) evaluate the similarities and differences in methylation landscapes depending on patient genotypes as an index of a functional link between the four ICF factors, (ii) identify genomic regions that rely on DNMT3B, ZBTB24, CDCA7 or HELLS for their methylation status (PMID:29659838)
• data indicate that SRRM4 regulates alternative RNA splicing of the Bif-1 gene that enables PCa cells resistant to apoptotic stimuli under anti-cancer therapies, and may contribute to AdPC progression into t-NEPC. (PMID:29759485)
• in contrast to Immunodeficiency, Centromeric instability and Facial anomalies syndrome type 1 (ICF1), the subtelomeric methylation patterns in cells of ICF2-4 patients do not differ significantly from those in normal cells, and ICF2-4 cells exhibit a normal telomeric phenotype. Also knocking down the expression of ZBTB24, CDCA7 and HELLS in normal human fibroblasts does not affect subtelomeric methylation. (PMID:30010917)
• Chromatin immunoprecipitation coupled with loss-of-function approaches in model systems revealed common loci bound by ZBTB24 and DNMT3B, where they function to regulate gene body methylation. Genes coordinately regulated by ZBTB24 and DNMT3B are enriched for molecular mechanisms essential for cellular homeostasis, highlighting the importance of the ZBTB24-DNMT3B interplay in maintaining epigenetic patterns (PMID:30085123)
• this study expands the clinical and mutation spectrum of Immunodeficiency, Centromeric Instability, and Facial Anomalies Syndrome by analyzing Saudi hypogammaglobulinemia patients and a novel deletion in the ZBTB24 gene (PMID:30511102)
• ZBTB24 activates the expression of CDCA7 in T cells.ZBTB24 regulates the apoptosis of T cells via CDCA7/TRAIL-R axis. (PMID:31030944)
• Identification of ZBTB24 protein domains and motifs for heterochromatin localization and transcriptional activation. Domains and motifs important for the biological function of ZBTB24, which provides a basis for understanding the molecular mechanisms underlying the pathogenesis of ICF syndrome. (PMID:31561277)
• Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome. (PMID:32865561)
• ZBTB24 (Zinc Finger and BTB Domain Containing 24) prevents recurrent spontaneous abortion by promoting trophoblast proliferation, differentiation and migration. (PMID:35038951)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb24	ENSDARG00000075533
mus_musculus	Zbtb24	ENSMUSG00000019826
rattus_norvegicus	Zbtb24	ENSRNOG00000000308

Paralogs (36): ZNF302 (ENSG00000089335), ZNF184 (ENSG00000096654), CTCF (ENSG00000102974), ZNF574 (ENSG00000105732), ZNF142 (ENSG00000115568), CTCFL (ENSG00000124092), ZNF473 (ENSG00000142528), ZNF827 (ENSG00000151612), ZNF689 (ENSG00000156853), ZNF208 (ENSG00000160321), ZNF91 (ENSG00000167232), ZNF526 (ENSG00000167625), ZNF764 (ENSG00000169951), ZNF747 (ENSG00000169955), ZNF282 (ENSG00000170265), ZNF160 (ENSG00000170949), ZNF497 (ENSG00000174586), ZBTB34 (ENSG00000177125), ZNF771 (ENSG00000179965), ZNF48 (ENSG00000180035), ZNF594 (ENSG00000180626), ZBTB37 (ENSG00000185278), ZFP92 (ENSG00000189420), ZNF107 (ENSG00000196247), ZNF729 (ENSG00000196350), ZNF569 (ENSG00000196437), ZNF420 (ENSG00000197050), ZNF785 (ENSG00000197162), ZNF665 (ENSG00000197497), ZNF181 (ENSG00000197841), ZNF347 (ENSG00000197937), ZNF84 (ENSG00000198040), ZBTB48 (ENSG00000204859), ZNF845 (ENSG00000213799), ZNF99 (ENSG00000213973), ZNF688 (ENSG00000229809)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 24 — O43167 (reviewed: O43167)

Alternative names: Zinc finger protein 450

All UniProt accessions (7): O43167, A0A8V8TLS8, A0A8V8TLT3, A0A8V8TLV5, A0A8V8TMC2, A0A8V8TNA6, A0A8V8TNL7

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in BMP2-induced transcription.

Subunit / interactions. Interacts with MN1.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed, with highest levels in naive B-cells.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43167-1	1	yes
O43167-2	2

RefSeq proteins (1): NP_055612* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050457	ZnFinger_BTB_dom_contain	Family

Pfam: PF00096, PF00651

UniProt features (22 total): zinc finger region 8, region of interest 3, compositionally biased region 3, splice variant 2, sequence variant 2, chain 1, domain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43167-F1	56.98	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 193 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, BROWNE_HCMV_INFECTION_6HR_DN, PUJANA_CHEK2_PCC_NETWORK, MODULE_379, MODULE_123, GARY_CD5_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MODULE_98, MODULE_242, MODULE_104, MODULE_7, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MODULE_181, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, MODULE_41

GO Biological Process (2): hematopoietic progenitor cell differentiation (GO:0002244), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
hemopoiesis	1
cell differentiation	1
transcription by RNA polymerase II	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB24	CDCA7	Q9BWT1	724
ZBTB24	HELLS	Q9NRZ9	711
ZBTB24	DNMT3B	Q9UBC3	609
ZBTB24	PPIL6	Q8IXY8	474
ZBTB24	MYNN	Q9NPC7	396
ZBTB24	APLF	Q8IW19	393
ZBTB24	CENPA	P49450	391
ZBTB24	TCEA2	Q15560	387
ZBTB24	TCEA3	O75764	386
ZBTB24	TCEA1	P23193	380
ZBTB24	PARP3	Q9Y6F1	380
ZBTB24	ZNF830	Q96NB3	370
ZBTB24	PKNOX1	P55347	363
ZBTB24	SPRY1	O43609	353
ZBTB24	NFIC	P08651	353
ZBTB24	SLC6A1	P30531	353
ZBTB24	KIAA0040	Q15053	353

IntAct

335 interactions, top by confidence:

A	B	Type	Score
ZBTB24	MDFI	psi-mi:“MI:0915”(physical association)	0.840
MDFI	ZBTB24	psi-mi:“MI:0915”(physical association)	0.840
KLF15	ZBTB24	psi-mi:“MI:0915”(physical association)	0.830
ZBTB24	KLF15	psi-mi:“MI:0915”(physical association)	0.830
ZBTB24	LDOC1	psi-mi:“MI:0915”(physical association)	0.780
ZBTB24	BLZF1	psi-mi:“MI:0915”(physical association)	0.780
LDOC1	ZBTB24	psi-mi:“MI:0915”(physical association)	0.780
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
CDA	ZBTB24	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	ZBTB24	psi-mi:“MI:0915”(physical association)	0.720
ZBTB24	POGZ	psi-mi:“MI:0915”(physical association)	0.720
ZBTB24	CEP70	psi-mi:“MI:0915”(physical association)	0.720
CEP76	ZBTB24	psi-mi:“MI:0915”(physical association)	0.720
ZBTB24	TRIM41	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	ZBTB24	psi-mi:“MI:0915”(physical association)	0.720
MID2	ZBTB24	psi-mi:“MI:0915”(physical association)	0.720
ZBTB24	TSC22D4	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (200): BAX (Reconstituted Complex), ZBTB24 (Reconstituted Complex), ZBTB24 (Reconstituted Complex), ZBTB24 (Two-hybrid), ZBTB24 (Two-hybrid), ZBTB24 (Two-hybrid), ZBTB24 (Two-hybrid), ZBTB24 (Two-hybrid), ZBTB24 (Two-hybrid), ZBTB24 (Two-hybrid), MID2 (Two-hybrid), ZBTB43 (Two-hybrid), POGZ (Two-hybrid), CCNDBP1 (Two-hybrid), LDOC1 (Two-hybrid)

ESM2 similar proteins: A1L1J6, A2ANX9, A7Y7X5, E9Q8T2, G5E8B9, O15060, O43167, O43829, O62836, O95625, P08048, P0C6P6, P10925, P17010, P17012, P20662, P52739, Q01611, Q08376, Q0VCB0, Q2FAY8, Q3TTC2, Q4V8R6, Q52V16, Q5DU09, Q5PPG4, Q5R5M1, Q5R5N5, Q5RAU9, Q5SVQ8, Q6B4Z5, Q6GNP2, Q6INV8, Q7TS63, Q7ZVR6, Q80V63, Q80X44, Q811F1, Q8K3J5, Q92010

Diamond homologs: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829, O88282, O88939, O93567, O95365, P24278, P41182, P41183, P52739, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2T9Z7, Q3B725, Q3B7N9, Q3SWU4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	5	12.9×	2e-03
Viral mRNA Translation	5	12.9×	2e-03
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	5	12.8×	2e-03
Selenocysteine synthesis	5	12.3×	2e-03
Eukaryotic Translation Termination	5	12.3×	2e-03
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	5	12.0×	2e-03
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	5	12.0×	2e-03
Formation of a pool of free 40S subunits	5	11.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	5	12.3×	8e-03
translation	6	8.2×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

520 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	41
Likely pathogenic	13
Uncertain significance	192
Likely benign	242
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074302	NM_014797.3(ZBTB24):c.909dup (p.Lys304Ter)	Pathogenic
1353720	NM_014797.3(ZBTB24):c.1118C>G (p.Ser373Ter)	Pathogenic
1526123	NM_014797.3(ZBTB24):c.501dup (p.Val168fs)	Pathogenic
2028359	NM_014797.3(ZBTB24):c.389del (p.Asn130fs)	Pathogenic
2071437	NM_014797.3(ZBTB24):c.1439dup (p.His480fs)	Pathogenic
2429329	NM_014797.3(ZBTB24):c.953-2A>G	Pathogenic
2703195	NM_014797.3(ZBTB24):c.377_378del (p.Thr126fs)	Pathogenic
2725726	NM_014797.3(ZBTB24):c.1161del (p.Phe387fs)	Pathogenic
2734924	NM_014797.3(ZBTB24):c.787A>T (p.Lys263Ter)	Pathogenic
2750593	NM_014797.3(ZBTB24):c.1125_1135del (p.Gln375fs)	Pathogenic
2793751	NM_014797.3(ZBTB24):c.993del (p.Phe331fs)	Pathogenic
2809786	NM_014797.3(ZBTB24):c.868_875dup (p.Arg295fs)	Pathogenic
2826131	NM_014797.3(ZBTB24):c.971_972delinsAA (p.Cys324Ter)	Pathogenic
2840471	NM_014797.3(ZBTB24):c.911_914del (p.Lys304fs)	Pathogenic
2841373	NM_014797.3(ZBTB24):c.1272_1281del (p.Leu425fs)	Pathogenic
2863511	NM_014797.3(ZBTB24):c.226_227del (p.Ile76fs)	Pathogenic
2865191	NM_014797.3(ZBTB24):c.431del (p.Gly144fs)	Pathogenic
2866507	NM_014797.3(ZBTB24):c.44_50del (p.His15fs)	Pathogenic
2870778	NM_014797.3(ZBTB24):c.825_844del (p.His276fs)	Pathogenic
2879709	NM_014797.3(ZBTB24):c.658G>T (p.Glu220Ter)	Pathogenic
2880060	NM_014797.3(ZBTB24):c.350_351del (p.Lys117fs)	Pathogenic
2915423	NM_014797.3(ZBTB24):c.795dup (p.Asp266fs)	Pathogenic
2956344	NM_014797.3(ZBTB24):c.593_594del (p.Phe198fs)	Pathogenic
3004627	NM_014797.3(ZBTB24):c.997C>T (p.Gln333Ter)	Pathogenic
31093	NM_014797.3(ZBTB24):c.958C>T (p.Arg320Ter)	Pathogenic
31095	NM_014797.3(ZBTB24):c.833C>G (p.Ser278Ter)	Pathogenic
3246027	NC_000006.11:g.(?109787054)(109803229_?)del	Pathogenic
3246028	NC_000006.11:g.(?109788836)(109788957_?)del	Pathogenic
3609158	NM_014797.3(ZBTB24):c.433_434del (p.Ala145fs)	Pathogenic
3638359	NM_014797.3(ZBTB24):c.758dup (p.Tyr253Ter)	Pathogenic

SpliceAI

1410 predictions. Top by Δscore:

Variant	Effect	Δscore
6:109466575:C:CC	acceptor_gain	1.0000
6:109475482:CCT:C	acceptor_gain	1.0000
6:109475484:T:C	acceptor_gain	1.0000
6:109475484:T:TC	acceptor_gain	1.0000
6:109475488:C:CT	acceptor_gain	1.0000
6:109476170:CGTA:C	donor_loss	1.0000
6:109476171:GTA:G	donor_loss	1.0000
6:109476172:TA:T	donor_loss	1.0000
6:109476174:CCTG:C	donor_loss	1.0000
6:109476926:CTCCC:C	acceptor_gain	1.0000
6:109476928:CCC:C	acceptor_gain	1.0000
6:109476929:CC:C	acceptor_gain	1.0000
6:109476929:CCC:C	acceptor_gain	1.0000
6:109476930:CC:C	acceptor_gain	1.0000
6:109476930:CCT:C	acceptor_loss	1.0000
6:109476931:C:CA	acceptor_loss	1.0000
6:109482054:TCT:T	acceptor_loss	1.0000
6:109482055:C:A	acceptor_loss	1.0000
6:109482055:C:CC	acceptor_gain	1.0000
6:109466570:CTCCT:C	acceptor_gain	0.9900
6:109466571:TCCT:T	acceptor_gain	0.9900
6:109466572:CCT:C	acceptor_gain	0.9900
6:109466572:CCTC:C	acceptor_gain	0.9900
6:109466573:CT:C	acceptor_gain	0.9900
6:109466573:CTC:C	acceptor_gain	0.9900
6:109466574:TC:T	acceptor_loss	0.9900
6:109466574:TCT:T	acceptor_gain	0.9900
6:109467595:A:AC	donor_gain	0.9900
6:109467596:C:CC	donor_gain	0.9900
6:109467733:ACC:A	acceptor_loss	0.9900

AlphaMissense

4633 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:109466532:G:C	F471L	1.000
6:109466532:G:T	F471L	1.000
6:109466534:A:G	F471L	1.000
6:109467694:G:C	F443L	1.000
6:109467694:G:T	F443L	1.000
6:109467696:A:G	F443L	1.000
6:109466448:A:C	F499L	0.999
6:109466448:A:T	F499L	0.999
6:109466449:A:G	F499S	0.999
6:109466450:A:G	F499L	0.999
6:109466471:A:G	C492R	0.999
6:109466505:G:C	H480Q	0.999
6:109466505:G:T	H480Q	0.999
6:109466507:G:C	H480D	0.999
6:109466533:A:G	F471S	0.999
6:109466544:A:C	C467W	0.999
6:109466545:C:T	C467Y	0.999
6:109466546:A:G	C467R	0.999
6:109466555:A:G	C464R	0.999
6:109467657:G:C	H456D	0.999
6:109467667:G:C	H452Q	0.999
6:109467667:G:T	H452Q	0.999
6:109467669:G:C	H452D	0.999
6:109467677:A:G	L449P	0.999
6:109467695:A:G	F443S	0.999
6:109467706:A:C	C439W	0.999
6:109467707:C:G	C439S	0.999
6:109467707:C:T	C439Y	0.999
6:109467708:A:G	C439R	0.999
6:109467708:A:T	C439S	0.999

dbSNP variants (sampled 300 via entrez): RS1000131103 (6:109464469 C>A,T), RS1000185032 (6:109468408 T>C), RS1000258667 (6:109467938 A>C), RS1000418728 (6:109483669 G>C), RS1000475340 (6:109474824 A>G,T), RS1000586243 (6:109469744 C>T), RS1000695429 (6:109476808 G>C), RS1000763109 (6:109475182 T>A), RS1000869267 (6:109475854 T>C,G), RS1000972741 (6:109462097 A>G), RS1001084108 (6:109462410 G>A), RS1001212527 (6:109476376 G>A,T), RS1001240860 (6:109482991 C>A), RS1001587418 (6:109483153 G>A), RS1001606718 (6:109482546 G>A)

Disease associations

OMIM: gene MIM:614064 | disease phenotypes: MIM:614069, MIM:147920

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency-centromeric instability-facial anomalies syndrome 2	Definitive	Autosomal recessive
immunodeficiency-centromeric instability-facial anomalies syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency-centromeric instability-facial anomalies syndrome 2	Definitive	AR

Mondo (3): immunodeficiency-centromeric instability-facial anomalies syndrome 2 (MONDO:0013553), Kabuki syndrome 1 (MONDO:0007843), immunodeficiency-centromeric instability-facial anomalies syndrome (MONDO:0000133)

Orphanet (2): ICF syndrome (Orphanet:2268), Kabuki syndrome (Orphanet:2322)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000331	Short chin
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001334	Communicating hydrocephalus
HP:0001510	Growth delay
HP:0001537	Umbilical hernia
HP:0001874	Abnormality of neutrophils
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0002014	Diarrhea
HP:0002024	Malabsorption
HP:0002090	Pneumonia
HP:0002205	Recurrent respiratory infections
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002788	Recurrent upper respiratory tract infections
HP:0002850	Decreased circulating total IgM

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000175_27	Height	4.000000e-06
GCST000817_135	Height	3.000000e-08
GCST006427_50	Depression in smokers	3.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537362	Immunodeficiency syndrome, variable (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5069371 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Ethyl Methanesulfonate	decreases expression	2
Methyl Methanesulfonate	decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
2-butenal	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
vanadyl sulfate	decreases expression	1
mercuric bromide	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Adenine	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	decreases expression	1
Colchicine	decreases expression	1
Demecolcine	decreases expression	1
Drugs, Chinese Herbal	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5059504	Binding	Proteomics fold change data (SUDHL4 cells, 1h)	Data for DCP probe CCT369260

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TY51	HAP1 ZBTB24 (-) 1	Cancer cell line	Male
CVCL_TY52	HAP1 ZBTB24 (-) 2	Cancer cell line	Male
CVCL_TY53	HAP1 ZBTB24 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03855631	Not specified	COMPLETED	Exploiting Epigenome Editing in Kabuki Syndrome: a New Route Towards Gene Therapy for Rare Genetic Disorders