TFAP2E

protein-coding

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

Gene summary

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II and regulation of cell population proliferation. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_178548.4

Inheritance

ClinVar variants

U:84B:1

Top phenotype

Multiple congenital anomalies/dysmorphic syndrome

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr1:35,573,314-35,595,328

External References & Databases

Ensembl (ENSG00000116819)

Transcript & Mutation Effects

hg38 • Region Span ~22.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

multiple congenital anomalies/dysmorphic syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019042

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TFAP2E variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 81

Multiple congenital anomalies/dysmorphic syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178548.4. 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			2 clinvar			2
missense			81 clinvar	1 clinvar		82
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	84	1	0	85

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178548.4	RefSeq	NP_848643.2	7	MANE Select
ENST00000373235.4	Ensembl	ENSP00000362332.3	7	MANE Select
ENST00001145830.1	Ensembl	ENSP00000810193.1	7	Standard
XM_017001139.3	RefSeq	XP_016856628.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription
Activation of the TFAP2 (AP-2) family of transcription factors
Negative regulation of activity of TFAP2 (AP-2) family transcription factors

Biological Process

regulation of transcription by RNA polymerase II
positive regulation of transcription by RNA polymerase II

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
DNA-binding transcription activator activity, RNA polymerase II-specific
protein homodimerization activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373235
Coding exons: 7
Length: 21959
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.02	184	227	0.810	0.0000150	2725
Missense (PolyPhen)		96	99.386	0.96593		964
Synonymous	0.120	103	105	0.985	0.00000740	990
Loss of Function	1.15	9	13.6	0.664	7.29e-7	179

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00013	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.000064	0.000062	rare
South Asian	0.00016	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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-epsilon may play a role in the development of the CNS and in cartilage differentiation (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.116

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.833

Gene Damage Prediction

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