SENP1
protein-codingSUMO specific peptidase 1, the group of SUMO specific peptidases
Gene summary
This gene encodes a cysteine protease that specifically targets members of the small ubiquitin-like modifier (SUMO) protein family. This protease regulates SUMO pathways by deconjugating sumoylated proteins. This protease also functions to process the precursor SUMO proteins into their mature form. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~66.3 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 SENP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001267594.2. 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 | 1 | 1 | ||||
| missense | 3 | 2 | 5 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 6 | 0 | 2 | 8 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001254523.1 | 17 | MANE Select | |
| Ensembl | ENSP00000447328.1 | 17 | MANE Select | |
| RefSeq | NP_001254524.1 | 17 | Standard | |
| Ensembl | ENSP00000394791.2 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- SUMO is proteolytically processed
- Post-translational protein modification
- Metabolism of proteins
- Processing and activation of SUMO
- AndrogenReceptor
Biological Process
- proteolysis
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- regulation of definitive erythrocyte differentiation
- protein sumoylation
- protein desumoylation
Molecular Function
- endopeptidase activity
- protein binding
- SUMO-specific endopeptidase activity
- SUMO-specific isopeptidase activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- focal adhesion
- nuclear membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000004980
- Coding exons
- 17
- Length
- 63411
- Individuals with no LoFs
- 124646
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 124653
- p
- 0.0000281
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.00 | 227 | 329 | 0.690 | 0.0000168 | 4218 |
| Missense (PolyPhen) | 48 | 120.79 | 0.3974 | 1528 | ||
| Synonymous | -0.0394 | 115 | 114 | 1.00 | 0.00000555 | 1172 |
| Loss of Function | 5.11 | 6 | 41.5 | 0.145 | 0.00000245 | 464 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.00011 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protease that catalyzes two essential functions in the SUMO pathway (PubMed:10652325, PubMed:15199155, PubMed:16253240, PubMed:16553580, PubMed:21829689, PubMed:21965678, PubMed:23160374, PubMed:24943844, PubMed:25406032, PubMed:29506078). The first is the hydrolysis of an alpha-linked peptide bond at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptides, SUMO1, SUMO2 and SUMO3 leading to the mature form of the proteins. The second is the deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins, by cleaving an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein. Deconjugates SUMO1 from HIPK2 (PubMed:16253240). Deconjugates SUMO1 from HDAC1 and BHLHE40/DEC1, which decreases its transcriptional repression activity (PubMed:21829689). Deconjugates SUMO1 from CLOCK, which decreases its transcriptional activation activity (PubMed:23160374). Deconjugates SUMO2 from MTA1 (PubMed:21965678). Deconjugates SUMO1 from METTL3 (PubMed:29506078). Desumoylates CCAR2 which decreases its interaction with SIRT1 (PubMed:25406032). Deconjugates SUMO1 from GPS2 (PubMed:24943844). {ECO:0000269|PubMed:10652325, ECO:0000269|PubMed:15199155, ECO:0000269|PubMed:16253240, ECO:0000269|PubMed:16553580, ECO:0000269|PubMed:21829689, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:23160374, ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:25406032, ECO:0000269|PubMed:29506078}.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.01
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.958
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |