SUMO4
protein-codingsmall ubiquitin like modifier 4
Gene summary
This gene is a member of the SUMO gene family. This family of genes encode small ubiquitin-related modifiers that are attached to proteins and control the target proteins' subcellular localization, stability, or activity. The protein described in this record is located in the cytoplasm and specifically modifies IKBA, leading to negative regulation of NF-kappa-B-dependent transcription of the IL12B gene. A specific polymorphism in this SUMO gene, which leads to the M55V substitution, has been associated with type I diabetes. The RefSeq contains this polymorphism. [provided by RefSeq, Jul 2008]
- SMT3H4
- IDDM5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0010863
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SUMO4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001002255.2. 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 | 14 | 2 | 16 | |||
| nonsense | 0 | |||||
| start loss | 2 | 2 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 14 | 5 | 0 | 19 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001002255.1 | 1 | MANE Select | |
| Ensembl | ENSP00000318635.4 | 1 | MANE Select |
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)
Biological Process
- protein sumoylation
Molecular Function
- protein tag
- ubiquitin-like protein ligase binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326669
- Coding exons
- 1
- Length
- 683
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.164 | 48 | 51.3 | 0.935 | 0.00000260 | 624 |
| Missense (PolyPhen) | 4 | 4.6475 | 0.86068 | 83 | ||
| Synonymous | -0.218 | 21 | 19.8 | 1.06 | 0.00000113 | 178 |
| Loss of Function |
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 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin-like protein which can be covalently attached to target lysines as a monomer. Does not seem to be involved in protein degradation and may modulate protein subcellular localization, stability or activity. Upon oxidative stress, conjugates to various anti-oxidant enzymes, chaperones, and stress defense proteins. May also conjugate to NFKBIA, TFAP2A and FOS, negatively regulating their transcriptional activity, and to NR3C1, positively regulating its transcriptional activity. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I. {ECO:0000269|PubMed:15123604, ECO:0000269|PubMed:15247916, ECO:0000269|PubMed:16236267}.;
- Disease
- DISEASE: Diabetes mellitus, insulin-dependent, 5 (IDDM5) [MIM:600320]: A form of diabetes mellitus, a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:15678134, ECO:0000269|PubMed:15678135, ECO:0000269|PubMed:15678137}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.151
Intolerance Scores
- LoFtool
- 0.722
- RVIS EVS
- 0.88
- RVIS percentile EVS
- 88.96
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |