AREL1
protein-codingapoptosis resistant E3 ubiquitin protein ligase 1, the group of HECT domain containing
Gene summary
Enables ubiquitin protein ligase activity. Involved in negative regulation of apoptotic process; protein polyubiquitination; and ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]
- KIAA0317
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.7 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 AREL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001039479.2. 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 | 1 | 4 | |||
| missense | 119 | 119 | ||||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 126 | 1 | 0 | 127 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001034568.1 | 18 | MANE Select | |
| Ensembl | ENSP00000348714.4 | 18 | MANE Select | |
| RefSeq | NP_001397975.1 | 18 | Standard | |
| RefSeq | NP_001424360.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Immune System
- Adaptive Immune System
- Antigen processing: Ubiquitination & Proteasome degradation
- Class I MHC mediated antigen processing & presentation
Biological Process
- protein polyubiquitination
- ubiquitin-dependent protein catabolic process
- apoptotic process
- protein ubiquitination
- negative regulation of apoptotic process
Molecular Function
- ubiquitin-protein transferase activity
- ubiquitin protein ligase activity
Cellular Component
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000356357
- Coding exons
- 18
- Length
- 59679
- Individuals with no LoFs
- 124789
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 43
- Defined
- 124832
- p
- 0.000172
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.50 | 382 | 474 | 0.806 | 0.0000274 | 5392 |
| Missense (PolyPhen) | 131 | 184.07 | 0.7117 | 2068 | ||
| Synonymous | -0.392 | 182 | 175 | 1.04 | 0.00000952 | 1595 |
| Loss of Function | 3.74 | 19 | 46.5 | 0.409 | 0.00000264 | 514 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00019 | 0.00019 | rare |
| European (Non-Finnish) | 0.00025 | 0.00023 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits apoptosis by ubiquitinating and targeting for degradation a number of proapoptotic proteins including DIABLO/SMAC, HTRA2 and SEPT4/ARTS which are released from the mitochondrion into the cytosol following apoptotic stimulation. {ECO:0000269|PubMed:23479728}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 13.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |