ZBTB48
protein-codingzinc finger and BTB domain containing 48, the group of Zinc fingers C2H2-type|BTB domain containing
Gene summary
Enables several functions, including identical protein binding activity; sequence-specific DNA binding activity; and zinc ion binding activity. Involved in positive regulation of DNA-templated transcription and telomere maintenance via telomere lengthening. Located in chromosome, telomeric region and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
- HKR3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.3 kbGenCC 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 ZBTB48 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005341.4. 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 | 1 | 1 | 2 | |||
| missense | 77 | 2 | 79 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 79 | 3 | 0 | 82 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005332.1 | 10 | MANE Select | |
| Ensembl | ENSP00000366902.4 | 10 | MANE Select | |
| RefSeq | NP_001265576.1 | 10 | Standard | |
| RefSeq | NP_001265577.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of transcription by RNA polymerase II
- telomere maintenance via telomere lengthening
- positive regulation of transcription, DNA-templated
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- double-stranded telomeric DNA binding
- DNA-binding transcription factor activity
- protein binding
- identical protein binding
Cellular Component
- chromosome, telomeric region
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377674
- Coding exons
- 10
- Length
- 9280
- Individuals with no LoFs
- 125708
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 125748
- p
- 0.000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.21 | 348 | 417 | 0.834 | 0.0000248 | 4526 |
| Missense (PolyPhen) | 123 | 169.95 | 0.72376 | 1751 | ||
| Synonymous | -1.63 | 200 | 173 | 1.16 | 0.0000106 | 1351 |
| Loss of Function | 3.07 | 12 | 30.2 | 0.397 | 0.00000170 | 336 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Telomere-binding protein that acts as a regulator of telomere length (PubMed:28500257, PubMed:28082411). Directly binds the telomeric double-stranded 5'-TTAGGG-3' repeat (PubMed:28500257, PubMed:28082411). Preferentially binds to telomeres that have a low concentration of shelterin complex and acts as a regulator of telomere length by initiating telomere trimming, a process that prevents the accumulation of aberrantly long telomeres (PubMed:28082411). Also acts as a transcription regulator that binds to promoter regions (PubMed:7969177, PubMed:24382891, PubMed:28500257). Regulates expression of a small subset of genes, including MTFP1 (PubMed:28500257). Regulates expression the J and/or S elements in MHC II promoter (PubMed:7969177). Acts as a negative regulator of cell proliferation by specifically activating expression of ARF, a tumor suppressor isoform of CDKN2A (PubMed:24382891). {ECO:0000269|PubMed:24382891, ECO:0000269|PubMed:28082411, ECO:0000269|PubMed:28500257, ECO:0000269|PubMed:7969177}.;
Recessive Scores
- pRec
- 0.155
Intolerance Scores
- LoFtool
- 0.566
- RVIS EVS
- -1
- RVIS percentile EVS
- 8.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.866
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |