SP100
protein-codingSP100 nuclear antigen, the group of PHD finger proteins|Bromodomain containing
Gene summary
This gene encodes a subnuclear organelle and major component of the PML (promyelocytic leukemia)-SP100 nuclear bodies. PML and SP100 are covalently modified by the SUMO-1 modifier, which is considered crucial to nuclear body interactions. The encoded protein binds heterochromatin proteins and is thought to play a role in tumorigenesis, immunity, and gene regulation. Alternatively spliced variants have been identified for this gene; one of which encodes a high-mobility group protein. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~129.7 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 SP100 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001080391.2. 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 | 1 | 3 | ||
| missense | 104 | 18 | 122 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 16 | 16 | ||||
| Total | 0 | 0 | 122 | 19 | 1 | 142 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001073860.1 | 29 | MANE Select | |
| Ensembl | ENSP00000343023.4 | 29 | MANE Select | |
| RefSeq | NP_001193630.1 | 23 | Standard | |
| RefSeq | NP_001193631.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Viral carcinogenesis - Homo sapiens (human)
- Herpes simplex infection - Homo sapiens (human)
- Cytokine Signaling in Immune system
- SUMOylation of DNA damage response and repair proteins
- Post-translational protein modification
Biological Process
- negative regulation of transcription by RNA polymerase II
- telomere maintenance
- DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
- negative regulation of endothelial cell migration
- viral process
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- protein binding
- kinase binding
- protein domain specific binding
Cellular Component
- nuclear chromosome, telomeric region
- nucleus
- nucleoplasm
- cytoplasm
- nuclear body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340126
- Coding exons
- 29
- Length
- 128149
- Individuals with no LoFs
- 125193
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 551
- Defined
- 125746
- p
- 0.00220
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.597 | 426 | 462 | 0.922 | 0.0000231 | 5911 |
| Missense (PolyPhen) | 56 | 54.733 | 1.0231 | 587 | ||
| Synonymous | 1.42 | 141 | 164 | 0.859 | 0.00000892 | 1501 |
| Loss of Function | 3.55 | 29 | 58.3 | 0.498 | 0.00000299 | 707 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0022 | 0.0022 | notable |
| Latino/Admixed American | 0.0012 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.0021 | 0.0021 | notable |
| European (Non-Finnish) | 0.0037 | 0.0036 | notable |
| South Asian | 0.000069 | 0.000065 | rare |
| Other | 0.0025 | 0.0024 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53- mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation. {ECO:0000269|PubMed:11909962, ECO:0000269|PubMed:14647468, ECO:0000269|PubMed:15247905, ECO:0000269|PubMed:15592518, ECO:0000269|PubMed:15767676, ECO:0000269|PubMed:16177824, ECO:0000269|PubMed:17245429, ECO:0000269|PubMed:21274506, ECO:0000269|PubMed:21880768}.;
Intolerance Scores
- LoFtool
- 0.494
- RVIS EVS
- 0.23
- RVIS percentile EVS
- 68.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.978
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |