ZBTB46

protein-coding

zinc finger and BTB domain containing 46, the group of Zinc fingers C2H2-type|BTB domain containing

Gene summary

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and transcription coregulator activity. Involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

ZNF340
BTBD4

MANE transcript

NM_001369741.1

Inheritance

—

ClinVar variants

U:95B:2

Top phenotype

Marfanoid habitus and intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr20:63,743,668-63,832,038

External References & Databases

Ensembl (ENSG00000130584)

Transcript & Mutation Effects

hg38 • Region Span ~88.4 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 ZBTB46 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 2

Marfanoid habitus and intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001369741.1. 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	1 clinvar		2
missense			94 clinvar	1 clinvar		95
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	95	2	0	97

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001369741.1	RefSeq	NP_001356670.1	4	MANE Select
ENST00000245663.9	Ensembl	ENSP00000245663.3	4	MANE Select
NM_025224.4	RefSeq	NP_079500.2	4	Standard
ENST00000302995.2	Ensembl	ENSP00000303102.2	4	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 granulocyte differentiation
negative regulation of macrophage differentiation
negative regulation of monocyte differentiation
negative regulation of dendritic cell differentiation

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000245663
Coding exons: 4
Length: 87579
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125731
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.24	287	415	0.691	0.0000296	3815
Missense (PolyPhen)		63	123.16	0.51152		1137
Synonymous	-1.35	232	207	1.12	0.0000177	1193
Loss of Function	3.68	4	23.0	0.174	0.00000159	210

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000043	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Function as a transcriptional repressor for PRDM1. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.240
RVIS EVS: -0.86
RVIS percentile EVS: 10.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.765

Gene Damage Prediction

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