ATE1
protein-codingarginyltransferase 1
Gene summary
This gene encodes an arginyltransferase, an enzyme that is involved in posttranslational conjugation of arginine to N-terminal aspartate or glutamate residues. Conjugation of arginine to the N-terminal aspartate or glutamate targets proteins for ubiquitin-dependent degradation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~219.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005453
Submitter: ClinGen
*ATE1* was first reported in relation to autosomal recessive congenital heart disease in 2016 (Priest et al., PMID: 27058611). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, and phenotypic variability. Therefore, atrioventricular septal defect and congenital heart disease have been lumped into one disease entity. Two unique variants, a missense and a CNV, have been reported in two probands in two publications (PMIDs: 27058611, 31552105). However, the missense variant had a high minor allele frequency (> 0.00001) in gnomAD v4 and a very low REVEL score (0.009), and was, therefore, not scored. The gene-disease relationship is supported by a knockout mouse model and functional alteration data (PMIDs: 12098698, 16222293, 16794040). Although there is sufficient experimental evidence, the genetic evidence is not convincing enough to support the relationship. In summary, the evidence supporting the relationship between *ATE1* and autosomal recessive congenital heart diseases has been disputed, and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role *ATE1* plays in this disease. This gene-disease pair was originally evaluated by the Congenital Heart Disease GCEP on August 14, 2023 (SOP version 9). It was reevaluated on April 13, 2026. As a result of this reevaluation, the classification did not change. No new evidence has been reviewed or added (SOP version 12).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ATE1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001001976.3. 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 | 2 | 2 | 4 | |||
| missense | 74 | 1 | 75 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 76 | 3 | 0 | 79 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001001976.1 | 12 | MANE Select | |
| Ensembl | ENSP00000224652.6 | 12 | MANE Select | |
| RefSeq | NP_001275663.1 | 8 | Standard | |
| RefSeq | NP_001275664.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- proteasomal protein catabolic process
- protein arginylation
Molecular Function
- arginyltransferase activity
- protein binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369043
- Coding exons
- 12
- Length
- 188378
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125748
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.634 | 244 | 274 | 0.892 | 0.0000138 | 3392 |
| Missense (PolyPhen) | 40 | 74.765 | 0.53501 | 910 | ||
| Synonymous | -0.989 | 112 | 99.5 | 1.13 | 0.00000553 | 911 |
| Loss of Function | 3.85 | 9 | 32.8 | 0.275 | 0.00000187 | 386 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.00018 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the post-translational conjugation of arginine to the N-terminal aspartate or glutamate of a protein. This arginylation is required for degradation of the protein via the ubiquitin pathway. Does not arginylate cysteine residues (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.117
Intolerance Scores
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.823
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |