ZBTB25

protein-coding

zinc finger and BTB domain containing 25, the group of Zinc fingers C2H2-type|BTB domain containing

Gene summary

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

ZNF46
C14orf51

MANE transcript

NM_006977.5

Inheritance

—

ClinVar variants

U:62B:6

Top phenotype

ZBTB25-related disorder

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr14:64,449,106-64,505,213

External References & Databases

Ensembl (ENSG00000089775)

Transcript & Mutation Effects

hg38 • Region Span ~56.1 kb

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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 ZBTB25 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 61

ZBTB25-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006977.5. 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	1 clinvar	3
missense			60 clinvar	1 clinvar	2 clinvar	63
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	62	3	3	68

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 72 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006977.5	RefSeq	NP_008908.2	2	MANE Select
ENST00000608382.6	Ensembl	ENSP00000476746.1	2	MANE Select
NM_001304507.1	RefSeq	NP_001291436.1	2	Standard
NM_001304508.1	RefSeq	NP_001291437.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
gene expression

Molecular Function

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

Cellular Component

nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000608382
Coding exons: 2
Length: 56108
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.617	207	234	0.886	0.0000117	2885
Missense (PolyPhen)		74	86.935	0.85121		1094
Synonymous	1.03	72	84.0	0.857	0.00000399	829
Loss of Function	1.17	11	16.1	0.685	9.82e-7	181

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0010	0.0010	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00026	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation.;

Recessive Scores

pRec: 0.0918

Intolerance Scores

RVIS EVS: -0.34
RVIS percentile EVS: 30.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.893

Gene Damage Prediction

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