AEN
protein-codingapoptosis enhancing nuclease, the group of Exonucleases|MicroRNA protein coding host genes
Gene summary
Enables DNA exonuclease activity. Involved in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and response to ionizing radiation. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
- ISG20L1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.9 kbGenCC 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 AEN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022767.4. 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 | 0 | |||||
| missense | 60 | 6 | 66 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 60 | 6 | 0 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073604.3 | 3 | MANE Select | |
| Ensembl | ENSP00000331944.3 | 3 | MANE Select | |
| Ensembl | ENSP00000453631.1 | 1 | Standard | |
| Ensembl | ENSP00000607507.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- p73 transcription factor network
- Validated transcriptional targets of TAp63 isoforms
Biological Process
- response to ionizing radiation
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
- nucleic acid phosphodiester bond hydrolysis
Molecular Function
- nucleic acid binding
- exonuclease activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- nuclear membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000332810
- Coding exons
- 3
- Length
- 10987
- Individuals with no LoFs
- 125646
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 102
- Defined
- 125748
- p
- 0.000406
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.00464 | 206 | 206 | 1.00 | 0.0000130 | 2087 |
| Missense (PolyPhen) | 84 | 75.01 | 1.1198 | 747 | ||
| Synonymous | -1.53 | 100 | 82.3 | 1.21 | 0.00000496 | 667 |
| Loss of Function | -0.959 | 13 | 9.77 | 1.33 | 5.87e-7 | 104 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00055 | 0.00055 | rare |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0.0028 | 0.0028 | notable |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00056 | 0.00056 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Exonuclease with activity against single- and double- stranded DNA and RNA. Mediates p53-induced apoptosis. When induced by p53 following DNA damage, digests double-stranded DNA to form single-stranded DNA and amplifies DNA damage signals, leading to enhancement of apoptosis. {ECO:0000269|PubMed:16171785, ECO:0000269|PubMed:18264133}.;
Intolerance Scores
- LoFtool
- 0.839
- RVIS EVS
- 0.78
- RVIS percentile EVS
- 87.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.208
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |