ATF3

protein-coding

activating transcription factor 3, the group of Basic leucine zipper proteins

Gene summary

This gene encodes a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. This gene is induced by a variety of signals, including many of those encountered by cancer cells, and is involved in the complex process of cellular stress response. Multiple transcript variants encoding different isoforms have been found for this gene. It is possible that alternative splicing of this gene may be physiologically important in the regulation of target genes. [provided by RefSeq, Apr 2011]

MANE transcript

NM_001674.4

Inheritance

—

ClinVar variants

U:19B:7

Top phenotype

ATF3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr1:212,565,334-212,620,777

External References & Databases

Ensembl (ENSG00000162772)

Transcript & Mutation Effects

hg38 • Region Span ~55.4 kb

Loading mutation effect viewer...

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 ATF3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 23

not providedTotal: 2

ATF3-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001674.4. 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				6 clinvar	1 clinvar	7
missense			19 clinvar			19
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	19	6	1	26

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001674.4	RefSeq	NP_001665.1	3	MANE Select
ENST00000341491.9	Ensembl	ENSP00000344352.4	3	MANE Select
NM_001030287.4	RefSeq	NP_001025458.1	3	Standard
NM_001040619.3	RefSeq	NP_001035709.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

HTLV-I infection - Homo sapiens (human)
Tacrolimus/Cyclosporine Pathway, Pharmacodynamics
ATF4 activates genes
Myometrial Relaxation and Contraction Pathways
Photodynamic therapy-induced unfolded protein response

Biological Process

negative regulation of transcription by RNA polymerase II
gluconeogenesis
positive regulation of cell population proliferation
cellular response to amino acid starvation
skeletal muscle cell differentiation

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
DNA-binding transcription repressor activity, RNA polymerase II-specific

Cellular Component

nucleus
nucleoplasm
nucleolus
CHOP-ATF3 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341491
Coding exons: 3
Length: 55444
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.702	81	101	0.803	0.00000594	1185
Missense (PolyPhen)		24	37.297	0.64348		442
Synonymous	0.470	39	42.9	0.909	0.00000275	355
Loss of Function	1.79	3	8.68	0.346	6.42e-7	88

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Represses transcription from promoters with ATF sites. It may repress transcription by stabilizing the binding of inhibitory cofactors at the promoter. Isoform 2 activates transcription presumably by sequestering inhibitory cofactors away from the promoters.;

Recessive Scores

pRec: 0.567

Intolerance Scores

LoFtool: 0.847
RVIS EVS: 0.1
RVIS percentile EVS: 61.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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