SUMO1
protein-codingsmall ubiquitin like modifier 1
Gene summary
This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last four amino acids of the carboxy-terminus have been cleaved off. Several pseudogenes have been reported for this gene. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Jul 2008]
- UBL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0013378
Submitter: G2P
Inheritance Pattern: Unknown
Disease ID:MONDO:0013378
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SUMO1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003352.8. 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 | 4 | 4 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 5 | 0 | 0 | 5 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003343.1 | 5 | MANE Select | |
| Ensembl | ENSP00000376077.2 | 5 | MANE Select | |
| RefSeq | NP_001005781.1 | 5 | Standard | |
| RefSeq | NP_001005782.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA transport - Homo sapiens (human)
- Fluid shear stress and atherosclerosis - Homo sapiens (human)
- TGF-Ncore
- Androgen receptor signaling pathway
- TP53 Network
Biological Process
- negative regulation of transcription by RNA polymerase II
- DNA repair
- double-strand break repair via nonhomologous end joining
- viral process
- protein sumoylation
Molecular Function
- transcription corepressor binding
- RNA binding
- protein binding
- protein C-terminus binding
- transcription factor binding
Cellular Component
- heterochromatin
- fibrillar center
- XY body
- nucleus
- nuclear envelope
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392246
- Coding exons
- 5
- Length
- 32429
- Individuals with no LoFs
- 124729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124730
- p
- 0.00000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.51 | 18 | 47.1 | 0.382 | 0.00000199 | 666 |
| Missense (PolyPhen) | 2 | 10.599 | 0.1887 | 153 | ||
| Synonymous | -0.185 | 16 | 15.1 | 1.06 | 7.31e-7 | 164 |
| Loss of Function | 2.36 | 0 | 6.47 | 0.00 | 2.71e-7 | 91 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| 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) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1 (PubMed:19223394). Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3 (PubMed:24651376). {ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:19223394, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24651376, ECO:0000269|PubMed:9019411, ECO:0000269|PubMed:9162015}.;
- Disease
- DISEASE: Non-syndromic orofacial cleft 10 (OFC10) [MIM:613705]: A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. {ECO:0000269|PubMed:16990542}. Note=The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.;
Recessive Scores
- pRec
- 0.697
Intolerance Scores
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 60.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |