TFAP4

protein-coding

transcription factor AP-4, the group of Basic helix-loop-helix proteins

Gene summary

Transcription factors of the basic helix-loop-helix-zipper (bHLH-ZIP) family contain a basic domain, which is used for DNA binding, and HLH and ZIP domains, which are used for oligomerization. Transcription factor AP4 activates both viral and cellular genes by binding to the symmetrical DNA sequence CAGCTG (Mermod et al., 1988 [PubMed 2833704]; Hu et al., 1990 [PubMed 2123466]).[supplied by OMIM, Jul 2009]

MANE transcript

NM_003223.3

Inheritance

—

ClinVar variants

U:37B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr16:4,257,186-4,273,075

External References & Databases

Ensembl (ENSG00000090447)

Transcript & Mutation Effects

hg38 • Region Span ~15.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TFAP4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003223.3. 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			1 clinvar			1
missense			35 clinvar		1 clinvar	36
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	37	0	1	38

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003223.3	RefSeq	NP_003214.1	7	MANE Select
ENST00000204517.11	Ensembl	ENSP00000204517.6	7	MANE Select
ENST00000572393.1	Ensembl	ENSP00000459390.1	3	Standard
ENST00000573476.1	Ensembl	ENSP00000460067.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Proteoglycans in cancer - Homo sapiens (human)

Biological Process

regulation of transcription by RNA polymerase II
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
negative regulation of cell population proliferation
positive regulation of apoptotic process
negative regulation of DNA binding

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity
transcription coactivator activity

Cellular Component

nucleus
mitochondrion
transcriptional repressor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000204517
Coding exons: 7
Length: 15890
Individuals with no LoFs: 104262
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 104264
p: 0.00000959

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	152	218	0.696	0.0000153	2180
Missense (PolyPhen)		14	52.905	0.26463		457
Synonymous	-0.277	97	93.6	1.04	0.00000680	676
Loss of Function	3.86	0	17.4	0.00	9.06e-7	182

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000039	0.000039	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000042	0.000042	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor that activates both viral and cellular genes by binding to the symmetrical DNA sequence 5'- CAGCTG-3'.;

Intolerance Scores

RVIS EVS: 0.08
RVIS percentile EVS: 60.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.797

Gene Damage Prediction

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