TFAP2B

transcription factor AP-2 beta, the group of Transcription factor AP-2 family

Basic information

Region (hg38): 6:50818723-50847619

Links

ENSG00000008196 ∙ NCBI:7021 ∙ OMIM:601601 ∙ HGNC:11743 ∙ Uniprot:Q92481 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Char syndrome (Strong), mode of inheritance: AD
• Char syndrome (Definitive), mode of inheritance: AD
• Char syndrome (Supportive), mode of inheritance: AD
• familial patent arterial duct (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Char syndrome; Patent ductus arteriosus 2	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal	728571; 1342853; 8326495; 7645594; 9217229; 10368122; 10802654; 10955477; 11102923; 11505339; 15684060; 18752453; 21643846

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TFAP2B gene.

• not provided (2 variants)
• Char syndrome (2 variants)
• Chronic intestinal pseudoobstruction (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TFAP2B 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				19	3	22
missense	1	2	46	1	1	51
nonsense	1	2				3
start loss						0
frameshift	2		2			4
inframe indel						0
splice donor/acceptor (+/-2bp)	2		1			3
splice region			1	1		2
non coding			9	9	14	32
Total	6	4	58	29	18

Variants in TFAP2B

This is a list of pathogenic ClinVar variants found in the TFAP2B region.

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

Position	Type	Phenotype	Significance	ClinVar
6-50818858-G-A		Char syndrome	Benign (Sep 10, 2021)
6-50818894-G-A		Craniosynostosis syndrome	Likely pathogenic (Jul 23, 2019)
6-50818939-T-G			Likely benign (May 15, 2018)
6-50818957-C-G		Patent ductus arteriosus 2	Likely pathogenic (Nov 25, 2022)
6-50818966-C-G		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
6-50823397-C-G			Likely benign (May 15, 2018)
6-50823403-C-A			Likely benign (Mar 30, 2018)
6-50823415-C-T			Likely benign (Jan 03, 2022)
6-50823417-A-G			Uncertain significance (Dec 11, 2021)
6-50823422-G-A			Uncertain significance (Mar 16, 2022)
6-50823441-G-C			Uncertain significance (Oct 26, 2022)
6-50823442-G-A		TFAP2B-related disorder	Likely benign (May 06, 2019)
6-50823445-C-G			Likely benign (May 06, 2023)
6-50823451-G-C		Inborn genetic diseases	Uncertain significance (Dec 15, 2023)
6-50823486-C-G		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
6-50823492-C-A			Uncertain significance (Mar 10, 2023)
6-50823504-C-A			Uncertain significance (Feb 12, 2020)
6-50823524-C-T			Uncertain significance (Jan 26, 2021)
6-50823528-C-T		Inborn genetic diseases	Uncertain significance (Feb 01, 2023)
6-50823538-A-AC		Inborn genetic diseases	Pathogenic (Jun 18, 2024)
6-50823543-C-G		Char syndrome	Pathogenic (Oct 01, 2001)
6-50823577-C-T			Benign (Jan 18, 2024)
6-50823581-T-A			Uncertain significance (Jul 24, 2023)
6-50823597-A-AC			Pathogenic (Jul 01, 2022)
6-50823718-G-C			Uncertain significance (Mar 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TFAP2B	protein_coding	protein_coding	ENST00000393655	7	28891

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.00977	125746	0	2	125748	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.29	191	248	0.770	0.0000120	2959
Missense in Polyphen		25	58.322	0.42865		736
Synonymous	-0.812	123	112	1.10	0.00000580	966
Loss of Function	3.75	1	18.3	0.0546	8.16e-7	212

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	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-beta appears to be required for normal face and limb development and for proper terminal differentiation and function of renal tubular epithelia. {ECO:0000269|PubMed:11694877}.
• Disease: DISEASE: Char syndrome (CHAR) [MIM:169100]: An autosomal dominant disorder characterized by patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies. {ECO:0000269|PubMed:10802654, ECO:0000269|PubMed:11505339, ECO:0000269|PubMed:15684060}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Patent ductus arteriosus 2 (PDA2) [MIM:617035]: A congenital heart defect characterized by the persistent opening of fetal ductus arteriosus that fails to close after birth. Fetal ductus arteriosus connects the pulmonary artery to the descending aorta, allowing unoxygenated blood to bypass the lung and flow to the placenta. Normally, the ductus occludes shortly after birth. {ECO:0000269|PubMed:18752453, ECO:0000269|PubMed:21643846}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neural Crest Differentiation;Preimplantation Embryo;Gene expression (Transcription);Generic Transcription Pathway;SUMOylation of transcription factors;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;SUMOylation;Activation of the TFAP2 (AP-2) family of transcription factors;TFAP2 (AP-2) family regulates transcription of growth factors and their receptors;Negative regulation of activity of TFAP2 (AP-2) family transcription factors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors (Consensus)

Recessive Scores

• pRec: 0.247

Intolerance Scores

• loftool: 0.0683
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

• pHI: 0.712
• hipred: Y
• hipred_score: 0.875
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.969

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tfap2b
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;kidney development;renal water homeostasis;glucose metabolic process;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;apoptotic process;positive regulation of cell population proliferation;negative regulation of cell population proliferation;retina layer formation;magnesium ion homeostasis;regulation of BMP signaling pathway;forelimb morphogenesis;hindlimb morphogenesis;positive regulation of urine volume;aorta morphogenesis;response to drug;glucose homeostasis;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of neuron apoptotic process;positive regulation of neuron apoptotic process;skin development;fat cell differentiation;regulation of cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;sympathetic nervous system development;regulation of insulin secretion;phosphate ion homeostasis;calcium ion homeostasis;potassium ion homeostasis;sodium ion homeostasis;distal tubule development;collecting duct development;metanephric nephron development;ductus arteriosus closure;cellular ammonia homeostasis;cellular creatinine homeostasis;cellular urea homeostasis
• Cellular component: nucleus;nucleoplasm
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;enhancer sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;transcription coactivator activity;transcription corepressor activity;protein binding;RNA polymerase II general transcription initiation factor activity;protein homodimerization activity;cysteine-type endopeptidase inhibitor activity involved in apoptotic process;sequence-specific DNA binding;protein heterodimerization activity;protein dimerization activity