ZBTB7A
zinc finger and BTB domain containing 7A, the group of Zinc fingers C2H2-type|BTB domain containing
Basic information
Region (hg38): 19:4043303-4066899
Previous symbols: [ "ZBTB7" ]
Links
Phenotypes
GenCC
Source:
- complex neurodevelopmental disorder (Strong), mode of inheritance: AD
- macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (Strong), mode of inheritance: AD
- macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin | AD | Allergy/Immunology/Infectious; Cardiovascular | The condition may involve congenital heart anomalies, some of which may require surgical and other interventions, and awareness may allow early diagnosis and management; Individuals may have sleep apnea due to lymphoid hypertrophy or adenoid overgrowth, and awareness may allow surgical and other interventions to manage this issue | Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Hematologic; Neurologic | 31645653; 34515416 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (62 variants)
- not_provided (40 variants)
- Macrocephaly,_neurodevelopmental_delay,_lymphoid_hyperplasia,_and_persistent_fetal_hemoglobin (16 variants)
- ZBTB7A-related_disorder (4 variants)
- not_specified (4 variants)
- Hereditary_persistence_of_fetal_hemoglobin-beta-thalassemia_syndrome (3 variants)
- Neurodevelopmental_delay (1 variants)
- Intellectual_disability,_autosomal_dominant_29 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZBTB7A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015898.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 9 | |||||
| missense | 84 | 92 | ||||
| nonsense | 6 | |||||
| start loss | 0 | |||||
| frameshift | 17 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 11 | 7 | 92 | 14 | 0 |
Highest pathogenic variant AF is 0.000007729561
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ZBTB7A | protein_coding | protein_coding | ENST00000322357 | 2 | 22582 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.959 | 0.0408 | 122864 | 0 | 2 | 122866 | 0.00000814 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.04 | 175 | 404 | 0.434 | 0.0000319 | 3733 |
| Missense in Polyphen | 27 | 132.66 | 0.20352 | 1137 | ||
| Synonymous | 1.89 | 170 | 204 | 0.832 | 0.0000203 | 1187 |
| Loss of Function | 3.27 | 1 | 14.4 | 0.0694 | 7.90e-7 | 150 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000487 | 0.0000487 |
| European (Non-Finnish) | 0.00000910 | 0.00000910 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcription factor that represses the transcription of a wide range of genes involved in cell proliferation and differentiation (PubMed:14701838, PubMed:17595526, PubMed:20812024, PubMed:25514493, PubMed:26455326, PubMed:26816381). Directly and specifically binds to the consensus sequence 5'-[GA][CA]GACCCCCCCCC-3' and represses transcription both by regulating the organization of chromatin and through the direct recruitment of transcription factors to gene regulatory regions (PubMed:12004059, PubMed:17595526, PubMed:20812024, PubMed:25514493, PubMed:26816381). Negatively regulates SMAD4 transcriptional activity in the TGF-beta signaling pathway through these two mechanisms (PubMed:25514493). That is, recruits the chromatin regulator HDAC1 to the SMAD4-DNA complex and in parallel prevents the recruitment of the transcriptional activators CREBBP and EP300 (PubMed:25514493). Collaborates with transcription factors like RELA to modify the accessibility of gene transcription regulatory regions to secondary transcription factors (By similarity). Also directly interacts with transcription factors like SP1 to prevent their binding to DNA (PubMed:12004059). Functions as an androgen receptor/AR transcriptional corepressor by recruiting NCOR1 and NCOR2 to the androgen response elements/ARE on target genes (PubMed:20812024). Thereby, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Involved in the switch between fetal and adult globin expression during erythroid cells maturation (PubMed:26816381). Through its interaction with the NuRD complex regulates chromatin at the fetal globin genes to repress their transcription (PubMed:26816381). Specifically represses the transcription of the tumor suppressor ARF isoform from the CDKN2A gene (By similarity). Efficiently abrogates E2F1-dependent CDKN2A transactivation (By similarity). Regulates chondrogenesis through the transcriptional repression of specific genes via a mechanism that also requires histone deacetylation (By similarity). Regulates cell proliferation through the transcriptional regulation of genes involved in glycolysis (PubMed:26455326). Involved in adipogenesis through the regulation of genes involved in adipocyte differentiation (PubMed:14701838). Plays a key role in the differentiation of lymphoid progenitors into B and T lineages (By similarity). Promotes differentiation towards the B lineage by inhibiting the T-cell instructive Notch signaling pathway through the specific transcriptional repression of Notch downstream target genes (By similarity). Also regulates osteoclast differentiation (By similarity). May also play a role, independently of its transcriptional activity, in double-strand break repair via classical non-homologous end joining/cNHEJ (By similarity). Recruited to double-strand break sites on damage DNA, interacts with the DNA-dependent protein kinase complex and directly regulates its stability and activity in DNA repair (By similarity). May also modulate the splicing activity of KHDRBS1 toward BCL2L1 in a mechanism which is histone deacetylase- dependent and thereby negatively regulates the pro-apoptotic effect of KHDRBS1 (PubMed:24514149). {ECO:0000250|UniProtKB:O88939, ECO:0000250|UniProtKB:Q9QZ48, ECO:0000269|PubMed:12004059, ECO:0000269|PubMed:14701838, ECO:0000269|PubMed:17595526, ECO:0000269|PubMed:20812024, ECO:0000269|PubMed:24514149, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:26455326, ECO:0000269|PubMed:26816381}.;
- Pathway
- b cell survival pathway
(Consensus)
Recessive Scores
- pRec
- 0.147
Haploinsufficiency Scores
- pHI
- 0.200
- hipred
- hipred_score
- ghis
- 0.450
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Zbtb7a
- Phenotype
- immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;regulation of alternative mRNA splicing, via spliceosome;regulation of glycolytic process;chromatin organization;chromatin remodeling;transcription, DNA-templated;regulation of transcription, DNA-templated;cellular response to DNA damage stimulus;B cell differentiation;negative regulation of transforming growth factor beta receptor signaling pathway;protein localization to nucleus;regulation of apoptotic process;erythrocyte maturation;fat cell differentiation;negative regulation of Notch signaling pathway;negative regulation of transcription, DNA-templated;regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;negative regulation of androgen receptor signaling pathway;double-strand break repair via classical nonhomologous end joining;regulation of transcription regulatory region DNA binding
- Cellular component
- nucleus;cytoplasm;NuRD complex;site of double-strand break;DNA-dependent protein kinase complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;transcription corepressor binding;DNA binding;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;activating transcription factor binding;histone acetyltransferase binding;SMAD binding;metal ion binding;androgen receptor binding