ZBTB49

protein-coding

zinc finger and BTB domain containing 49, the group of Zinc fingers C2H2-type|BTB domain containing

Gene summary

Enables DNA-binding transcription factor binding activity; sequence-specific DNA binding activity; and transcription coactivator binding activity. Involved in negative regulation of cell population proliferation; positive regulation of transcription by RNA polymerase II; and regulation of cell cycle. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

ZNF509

MANE transcript

NM_145291.4

Inheritance

—

ClinVar variants

U:100B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr4:4,290,251-4,321,786

External References & Databases

Ensembl (ENSG00000168826)

Transcript & Mutation Effects

hg38 • Region Span ~31.5 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 ZBTB49 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145291.4. 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	1 clinvar	4
missense			96 clinvar	7 clinvar	2 clinvar	105
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	100	8	3	111

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145291.4	RefSeq	NP_660334.3	7	MANE Select
ENST00000337872.9	Ensembl	ENSP00000338807.4	7	MANE Select
NM_001330625.2	RefSeq	NP_001317554.1	7	Standard
ENST00000502918.1	Ensembl	ENSP00000425747.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell cycle arrest
negative regulation of cell population proliferation
positive regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
transcription coactivator binding
protein binding
transcription factor binding
sequence-specific DNA binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
microtubule cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000337872
Coding exons: 7
Length: 31590
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.663	399	438	0.911	0.0000246	5083
Missense (PolyPhen)		94	142.89	0.65784		1647
Synonymous	-0.00890	176	176	1.00	0.0000110	1438
Loss of Function	1.96	17	28.3	0.602	0.00000152	325

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor. Inhibits cell proliferation by activating either CDKN1A/p21 transcription or RB1 transcription. {ECO:0000269|PubMed:25245946}.; FUNCTION: Isoform 3: Activates RB1 transcription most probably by antagonizing ZBTB17 repression of RB1. Does not bind directly RB1 promoter. {ECO:0000269|PubMed:25245946}.;

Intolerance Scores

LoFtool: 0.605
RVIS EVS: 1.09
RVIS percentile EVS: 91.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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