SAE1
protein-codingSUMO1 activating enzyme subunit 1, the group of Ubiquitin like modifier activating enzymes
Gene summary
Posttranslational modification of proteins by the addition of the small protein SUMO (see SUMO1; MIM 601912), or sumoylation, regulates protein structure and intracellular localization. SAE1 and UBA2 (MIM 613295) form a heterodimer that functions as a SUMO-activating enzyme for the sumoylation of proteins (Okuma et al., 1999 [PubMed 9920803]).[supplied by OMIM, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~97.4 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 SAE1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005500.3. 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 | 1 | 4 | 1 | 6 | ||
| missense | 45 | 2 | 47 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 51 | 6 | 1 | 58 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005491.1 | 9 | MANE Select | |
| Ensembl | ENSP00000270225.6 | 9 | MANE Select | |
| RefSeq | NP_001139185.1 | 7 | Standard | |
| RefSeq | NP_001139186.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sae1 | Danio rerio | Structure: hematopoietic multipotent progenitor cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- er associated degradation (erad) pathway
- SUMO is conjugated to E1 (UBA2:SAE1)
- SUMO is transferred from E1 to E2 (UBE2I, UBC9)
- Post-translational protein modification
Biological Process
- protein ubiquitination
- protein sumoylation
- protein modification by small protein conjugation
- positive regulation of catalytic activity
- positive regulation of protein targeting to mitochondrion
Molecular Function
- ubiquitin activating enzyme activity
- protein binding
- protein C-terminus binding
- enzyme activator activity
- SUMO activating enzyme activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- SUMO activating enzyme complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000270225
- Coding exons
- 9
- Length
- 97356
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125746
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.563 | 170 | 192 | 0.886 | 0.0000101 | 2267 |
| Missense (PolyPhen) | 38 | 56.538 | 0.67212 | 687 | ||
| Synonymous | -0.478 | 77 | 71.8 | 1.07 | 0.00000397 | 664 |
| Loss of Function | 3.67 | 1 | 17.7 | 0.0566 | 9.29e-7 | 215 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000033 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2. {ECO:0000269|PubMed:10187858, ECO:0000269|PubMed:10217437, ECO:0000269|PubMed:11451954, ECO:0000269|PubMed:11481243, ECO:0000269|PubMed:15660128, ECO:0000269|PubMed:20164921, ECO:0000269|PubMed:9920803}.;
Recessive Scores
- pRec
- 0.125
Intolerance Scores
- LoFtool
- 0.449
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.88
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |