ZBTB21

protein-coding

zinc finger and BTB domain containing 21, the group of Zinc fingers C2H2-type|BTB domain containing

Gene summary

Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; POZ domain binding activity; and methyl-CpG binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

ZNF295

MANE transcript

NM_001098402.2

Inheritance

—

ClinVar variants

U:159B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr21:41,986,831-42,010,387

External References & Databases

Ensembl (ENSG00000173276)

Transcript & Mutation Effects

hg38 • Region Span ~23.6 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 ZBTB21 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 160

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001098402.2. 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			1 clinvar	2 clinvar		3
missense			156 clinvar	6 clinvar		162
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	159	8	0	167

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001098402.2	RefSeq	NP_001091872.1	1	MANE Select
ENST00000310826.10	Ensembl	ENSP00000308759.5	1	MANE Select
NM_001098403.2	RefSeq	NP_001091873.1	2	Standard
NM_001320729.2	RefSeq	NP_001307658.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
negative regulation of transcription, DNA-templated

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310826
Coding exons: 1
Length: 23557
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.512	548	583	0.940	0.0000329	7013
Missense (PolyPhen)		152	226.7	0.6705		2759
Synonymous	-1.58	270	239	1.13	0.0000151	2100
Loss of Function	4.67	3	31.1	0.0964	0.00000164	423

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a transcription repressor. {ECO:0000269|PubMed:15629158}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

RVIS EVS: -0.1
RVIS percentile EVS: 45.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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