ZBTB4

protein-coding

zinc finger and BTB domain containing 4, the group of BTB domain containing|Zinc fingers C2H2-type

Gene summary

Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; nucleotide binding activity; and protein homodimerization activity. Involved in DNA damage response and negative regulation of transcription by RNA polymerase II. Located in nuclear body. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001128833.2

Inheritance

—

ClinVar variants

U:150B:23

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr17:7,459,366-7,484,263

External References & Databases

Ensembl (ENSG00000174282)

Transcript & Mutation Effects

hg38 • Region Span ~24.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZBTB4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 158

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001128833.2. 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			2 clinvar	3 clinvar	5 clinvar	10
missense			146 clinvar	12 clinvar	3 clinvar	161
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	150	15	8	173

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001128833.2	RefSeq	NP_001122305.1	2	MANE Select
ENST00000380599.9	Ensembl	ENSP00000369973.4	2	MANE Select
NM_020899.4	RefSeq	NP_065950.2	2	Standard
ENST00000311403.4	Ensembl	ENSP00000307858.4	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
zbtb4	Danio rerio	Structure: post-vent region Quality: curved dorsal abnormal

Gene / Model

Organism

Observed Phenotype

zbtb4

Danio rerio

Structure: post-vent region

Quality: curved dorsal

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription, DNA-templated
cellular response to DNA damage stimulus
negative regulation of transcription, DNA-templated

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity

Cellular Component

nucleus
nucleoplasm
chromosome
cytosol
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311403
Coding exons: 2
Length: 24898
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125747
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.93	498	635	0.784	0.0000398	6299
Missense (PolyPhen)		88	131.28	0.6703		1280
Synonymous	-0.338	278	271	1.03	0.0000179	2344
Loss of Function	4.76	0	26.3	0.00	0.00000156	287

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000053	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor with bimodal DNA-binding specificity. Represses transcription in a methyl-CpG-dependent manner. Binds with a higher affinity to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' but can also bind to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Can also bind specifically to a single methyl-CpG pair and can bind hemimethylated DNA but with a lower affinity compared to methylated DNA (PubMed:16354688). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (By similarity). {ECO:0000250|UniProtKB:Q5F293, ECO:0000269|PubMed:16354688}.;

Recessive Scores

pRec: 0.0822

Intolerance Scores

LoFtool: 0.220
RVIS EVS: -0.1
RVIS percentile EVS: 45.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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