ETAA1

protein-coding

ETAA1 activator of ATR kinase

Gene summary

Enables protein serine/threonine kinase activator activity. Involved in several processes, including positive regulation of protein serine/threonine kinase activity; regulation of cell cycle phase transition; and replication fork processing. Located in nuclear replication fork and nuclear speck. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_019002.4

Inheritance

—

ClinVar variants

U:107B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr2:67,397,322-67,412,089

External References & Databases

Ensembl (ENSG00000143971)

Transcript & Mutation Effects

hg38 • Region Span ~14.8 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 ETAA1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019002.4. 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					3 clinvar	3
missense			107 clinvar	12 clinvar		119
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	107	12	3	122

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019002.4	RefSeq	NP_061875.2	6	MANE Select
ENST00000272342.6	Ensembl	ENSP00000272342.5	6	MANE Select
ENST00000462772.2	Ensembl	ENSP00000495585.1	2	Standard
ENST00000644028.1	Ensembl	ENSP00000495888.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA repair
cellular response to DNA damage stimulus
replication fork processing
positive regulation of protein serine/threonine kinase activity
regulation of DNA damage checkpoint

Molecular Function

protein binding
protein serine/threonine kinase activator activity

Cellular Component

nuclear replication fork

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000272342
Coding exons: 6
Length: 13227
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125710
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.244	439	454	0.968	0.0000205	6151
Missense (PolyPhen)		89	106.95	0.83214		1652
Synonymous	0.812	149	162	0.919	0.00000776	1680
Loss of Function	3.68	10	32.7	0.306	0.00000148	459

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00045	0.00044	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity (PubMed:27601467, PubMed:27723720, PubMed:27723717). Recruited to stalled replication forks via interaction with the RPA complex and directly stimulates ATR kinase activity independently of TOPBP1 (PubMed:27723720, PubMed:27723717). Probably only regulates a subset of ATR targets (PubMed:27723720, PubMed:27723717). {ECO:0000269|PubMed:27601467, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720}.;

Recessive Scores

pRec: 0.0788

Intolerance Scores

LoFtool: 0.844
RVIS EVS: 1.49
RVIS percentile EVS: 95.36

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.0338

Gene Damage Prediction

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