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

ENSG00000178951 ∙ NCBI:51341 ∙ OMIM:605878 ∙ HGNC:18078 ∙ Uniprot:O95365 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Strong), mode of inheritance: AD
• macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the ZBTB7A gene.

• Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (2 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)
• Neurodevelopmental delay (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense	1		53	4		58
nonsense		1	2			3
start loss						0
frameshift	3	2	5			10
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	4	3	61	7	0

Variants in ZBTB7A

This is a list of pathogenic ClinVar variants found in the ZBTB7A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-4047801-C-A		Inborn genetic diseases	Uncertain significance (Aug 10, 2024)
19-4047821-A-C		ZBTB7A-related disorder	Likely benign (Jun 27, 2024)
19-4047822-C-T		Inborn genetic diseases	Uncertain significance (May 29, 2024)
19-4047844-G-A		Inborn genetic diseases	Uncertain significance (Apr 22, 2022)
19-4047859-G-A			Uncertain significance (Jul 11, 2022)
19-4047861-C-A		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
19-4047862-T-A		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
19-4047896-G-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2023)
19-4047910-C-T		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
19-4047918-CG-C		Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin	Pathogenic (Feb 28, 2022)
19-4047922-CGTCGGGGGAGCTGGGCTGGGCGGGGGCGCCGGGG-C			Uncertain significance (May 18, 2021)
19-4047930-G-T		Inborn genetic diseases	Uncertain significance (Dec 04, 2024)
19-4047936-G-C		Inborn genetic diseases	Uncertain significance (May 24, 2024)
19-4047952-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
19-4047962-G-T		not specified	Likely benign (Apr 29, 2024)
19-4047971-C-T			Benign/Likely benign (Feb 05, 2021)
19-4047976-T-G		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
19-4047979-G-C		Inborn genetic diseases	Uncertain significance (Oct 24, 2024)
19-4047981-T-G		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
19-4047982-C-T		Inborn genetic diseases	Uncertain significance (Mar 31, 2022)
19-4047999-A-C		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
19-4048010-GCGGCCGCGGCGCGAGGGGACGCCGTTGCAGC-G		Neurodevelopmental delay	Pathogenic (-)
19-4048030-C-A			Uncertain significance (Jun 01, 2024)
19-4048092-C-G		Inborn genetic diseases	Uncertain significance (Mar 18, 2024)
19-4048121-GC-G			Uncertain significance (Mar 14, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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
• 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