PSPC1
protein-codingparaspeckle component 1, the group of RNA binding motif containing
Gene summary
This gene encodes a nucleolar protein that localizes to punctate subnuclear structures that occur close to splicing speckles, known as paraspeckles. These paraspeckles are composed of RNA-protein structures that include a non-coding RNA, NEAT1/Men epsilon/beta, and the Drosophila Behavior Human Splicing family of proteins, which include the product of this gene and the P54NRB/NONO and PSF/SFPQ proteins. Paraspeckles may function in the control of gene expression via an RNA nuclear retention mechanism. The protein encoded by this gene is found in paraspeckles in transcriptionally active cells, but it localizes to unique cap structures at the nucleolar periphery when RNA polymerase II transcription is inhibited, or during telophase. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene, which is also located on chromosome 13, has been identified. [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 ~108.3 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 PSPC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001354909.2. 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 | 0 | |||||
| missense | 63 | 63 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 69 | 0 | 0 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001341838.1 | 9 | MANE Select | |
| Ensembl | ENSP00000343966.4 | 9 | MANE Select | |
| RefSeq | NP_001035879.1 | 9 | Standard | |
| RefSeq | NP_001341837.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- activation of innate immune response
- regulation of transcription by RNA polymerase II
- regulation of circadian rhythm
- innate immune response
- negative regulation of transcription, DNA-templated
Molecular Function
- transcription regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA binding
- protein binding
- E-box binding
Cellular Component
- fibrillar center
- nucleus
- nucleoplasm
- cytoplasm
- nuclear matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338910
- Coding exons
- 9
- Length
- 108247
- Individuals with no LoFs
- 124549
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124551
- p
- 0.00000803
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.53 | 177 | 300 | 0.590 | 0.0000160 | 3390 |
| Missense (PolyPhen) | 21 | 56.888 | 0.36915 | 631 | ||
| Synonymous | -0.934 | 112 | 100 | 1.12 | 0.00000488 | 1008 |
| Loss of Function | 4.03 | 2 | 22.7 | 0.0881 | 0.00000133 | 263 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates, cooperatively with NONO and SFPQ, androgen receptor-mediated gene transcription activity in Sertoli cell line (By similarity). Binds to poly(A), poly(G) and poly(U) RNA homopolymers. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer (By similarity). Together with NONO, required for the formation of nuclear paraspeckles. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. {ECO:0000250|UniProtKB:Q8R326, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:28712728}.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.259
- RVIS EVS
- -0.41
- RVIS percentile EVS
- 26.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.943
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |