ZBTB33
protein-codingzinc finger and BTB domain containing 33, the group of BTB domain containing|Zinc fingers C2H2-type
Gene summary
This gene encodes a transcriptional regulator with bimodal DNA-binding specificity, which binds to methylated CGCG and also to the non-methylated consensus KAISO-binding site TCCTGCNA. The protein contains an N-terminal POZ/BTB domain and 3 C-terminal zinc finger motifs. It recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. It may contribute to the repression of target genes of the Wnt signaling pathway, and may also activate transcription of a subset of target genes by the recruitment of catenin delta-2 (CTNND2). Its interaction with catenin delta-1 (CTNND1) inhibits binding to both methylated and non-methylated DNA. It also interacts directly with the nuclear import receptor Importin-α2 (also known as karyopherin alpha2 or RAG cohort 1), which may mediate nuclear import of this protein. Alternatively spliced transcript variants encoding the same protein have been identified.[provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.6 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 ZBTB33 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001184742.2. 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 | 10 | 2 | 12 | |||
| missense | 71 | 1 | 2 | 74 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 82 | 3 | 3 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001171671.1 | 1 | MANE Select | |
| Ensembl | ENSP00000450969.1 | 1 | MANE Select | |
| RefSeq | NP_006768.1 | 1 | Standard | |
| Ensembl | ENSP00000314153.2 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Wnt Signaling Pathway and Pluripotency
- Posttranslational regulation of adherens junction stability and dissassembly
Biological Process
- regulation of transcription by RNA polymerase II
- Wnt signaling pathway
- intracellular signal transduction
- negative regulation of transcription, DNA-templated
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- protein binding
- methyl-CpG binding
- sequence-specific DNA binding
- metal ion binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326624
- Coding exons
- 1
- Length
- 7647
- Individuals with no LoFs
- 125696
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125701
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.94 | 164 | 250 | 0.655 | 0.0000184 | 4426 |
| Missense (PolyPhen) | 32 | 101.15 | 0.31635 | 1807 | ||
| Synonymous | 1.76 | 73 | 94.9 | 0.770 | 0.00000721 | 1316 |
| Loss of Function | 2.98 | 1 | 12.2 | 0.0817 | 8.43e-7 | 271 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000036 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000049 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional regulator with bimodal DNA-binding specificity. Binds to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' and also binds to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. May contribute to the repression of target genes of the Wnt signaling pathway. May also activate transcription of a subset of target genes by the recruitment of CTNND2. Represses expression of MMP7 in conjunction with transcriptional corepressors CBFA2T3, CBFA2T2 and RUNX1T1 (PubMed:23251453). {ECO:0000269|PubMed:11445535, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:15548582, ECO:0000269|PubMed:15817151, ECO:0000269|PubMed:16354688, ECO:0000269|PubMed:23251453}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.283
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 69.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |