TFAP2A

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

Basic information

Region (hg38): 6:10393186-10419659

Previous symbols: [ "TFAP2", "AP2TF" ]

Links

ENSG00000137203 ∙ NCBI:7020 ∙ OMIM:107580 ∙ HGNC:11742 ∙ Uniprot:P05549 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• branchiooculofacial syndrome (Definitive), mode of inheritance: AD
• branchiooculofacial syndrome (Strong), mode of inheritance: AD
• branchiooculofacial syndrome (Supportive), mode of inheritance: AD
• branchiooculofacial syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Branchiooculofacial sydrome	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	1619642; 7747785; 9761567; 18423521; 19685247; 19764023; 19206157; 20358615; 20635357; 21634087; 21204207
The condition may be recognizable due to the presence of a specific pattern of congenital malformations affecting hearing as well as multiple organ systems; An individual with medulloblastoma has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TFAP2A gene.

• Branchiooculofacial syndrome (10 variants)
• not provided (4 variants)
• Inborn genetic diseases (2 variants)
• 13 conditions (1 variants)
• Chromatinopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TFAP2A 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				39	3	42
missense	10	18	67	3	2	100
nonsense	2	3	1			6
start loss						0
frameshift	3	2	1			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3	1			4
splice region			2	6		8
non coding			1	21	18	40
Total	15	26	72	63	23

Highest pathogenic variant AF is 0.00000657

Variants in TFAP2A

This is a list of pathogenic ClinVar variants found in the TFAP2A region.

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

Position	Type	Phenotype	Significance	ClinVar
6-10398278-A-G			Likely benign (Aug 24, 2019)
6-10398329-G-T			Likely benign (Aug 17, 2018)
6-10398416-CT-C		Neurodevelopmental abnormality	Uncertain significance (Jun 04, 2020)
6-10398417-T-C		Branchiooculofacial syndrome	Likely pathogenic (Nov 01, 2016)
6-10398435-C-T		TFAP2A-related disorder	Likely benign (Jun 06, 2024)
6-10398448-C-T			Uncertain significance (Aug 28, 2022)
6-10398452-T-C			Uncertain significance (Jan 20, 2023)
6-10398463-TC-T			Uncertain significance (Nov 17, 2023)
6-10398466-G-A		TFAP2A-related disorder	Uncertain significance (Apr 04, 2024)
6-10398474-G-A		not specified	Benign (Jan 29, 2024)
6-10398488-T-C			Uncertain significance (Feb 01, 2024)
6-10398511-T-G			Uncertain significance (Aug 10, 2022)
6-10398516-G-A			Likely benign (Sep 01, 2024)
6-10398522-G-A		Branchiooculofacial syndrome	Likely benign (Dec 09, 2023)
6-10398528-A-C		TFAP2A-related disorder	Uncertain significance (Dec 15, 2023)
6-10398534-C-G		Branchiooculofacial syndrome	Likely benign (Mar 29, 2024)
6-10398543-C-A			Benign (Jan 25, 2024)
6-10398544-G-A		Inborn genetic diseases	Uncertain significance (Dec 09, 2024)
6-10398549-C-T			Likely benign (Oct 09, 2022)
6-10398552-G-A			Likely benign (Jan 18, 2024)
6-10398552-G-C			Benign (Oct 11, 2023)
6-10398555-A-G			Likely benign (Dec 08, 2021)
6-10398564-G-C			Likely benign (Dec 08, 2021)
6-10398572-C-A		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
6-10398581-G-A		Inborn genetic diseases	Likely pathogenic (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TFAP2A	protein_coding	protein_coding	ENST00000379604	7	26474

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.0104	124526	0	2	124528	0.00000803

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	136	251	0.541	0.0000123	2822
Missense in Polyphen		48	120.71	0.39763		1426
Synonymous	-1.36	129	111	1.16	0.00000592	894
Loss of Function	3.73	1	18.2	0.0551	8.33e-7	204

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)	0.0000180	0.0000180
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-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region. {ECO:0000269|PubMed:11694877, ECO:0000269|PubMed:12586840}.
• Disease: DISEASE: Branchiooculofacial syndrome (BOFS) [MIM:113620]: A syndrome characterized by growth retardation, bilateral branchial sinus defects with hemangiomatous, scarred skin, cleft lip with or without cleft palate, pseudocleft of the upper lip, nasolacrimal duct obstruction, low set ears with posterior rotation, a malformed, asymmetrical nose with a broad bridge and flattened tip, conductive or sensorineural deafness, ocular and renal anomalies. {ECO:0000269|PubMed:18423521}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neural Crest Differentiation;Corticotropin-releasing hormone signaling pathway;Ectoderm Differentiation;Hypothetical Craniofacial Development Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;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;TFAP2 (AP-2) family regulates transcription of other transcription factors;TFAP2 (AP-2) family regulates transcription of cell cycle factors;TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation;Negative regulation of activity of TFAP2 (AP-2) family transcription factors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Caspase Cascade in Apoptosis (Consensus)

Recessive Scores

• pRec: 0.954

Intolerance Scores

• loftool: 0.0164
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.967
• hipred: Y
• hipred_score: 0.789
• ghis: 0.625

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• 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: Tfap2a
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; hematopoietic system phenotype; 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); 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); normal phenotype; pigmentation phenotype; digestive/alimentary phenotype; 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; growth/size/body region 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); endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: tfap2a
• Affected structure: hematopoietic multipotent progenitor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;kidney development;optic vesicle morphogenesis;optic cup structural organization;regulation of transcription by RNA polymerase II;sensory perception of sound;negative regulation of cell population proliferation;positive regulation of gene expression;retina layer formation;negative regulation of transcription by competitive promoter binding;trigeminal nerve development;oculomotor nerve formation;positive regulation of bone mineralization;embryonic forelimb morphogenesis;inner ear morphogenesis;negative regulation of apoptotic process;positive regulation of neuron apoptotic process;regulation of cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;embryonic cranial skeleton morphogenesis;roof of mouth development;bone morphogenesis;eyelid development in camera-type eye;positive regulation of tooth mineralization;cellular response to iron ion;negative regulation of reactive oxygen species metabolic process
• Cellular component: nucleus;nucleoplasm;Golgi apparatus;centrosome;cytosol;intracellular membrane-bounded organelle
• Molecular function: transcription regulatory region sequence-specific DNA binding;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;proximal promoter sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;transcription coactivator activity;protein binding;protein homodimerization activity;sequence-specific DNA binding;transcription regulatory region DNA binding;protein dimerization activity