SRSF2
protein-codingserine and arginine rich splicing factor 2, the group of RNA binding motif containing|Serine and arginine rich splicing factors|MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11. [provided by RefSeq, Sep 2010]
- SFRS2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.2 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 SRSF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001195427.2. 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 | 4 | 4 | ||||
| missense | 2 | 1 | 8 | 11 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 1 | 8 | 4 | 0 | 15 |
Highest pathogenic variant AF is 0.00009746613
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001182356.1 | 2 | MANE Select | |
| Ensembl | ENSP00000353089.5 | 2 | MANE Select | |
| RefSeq | NP_003007.2 | 2 | Standard | |
| Ensembl | ENSP00000350877.7 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Spliceosome - Homo sapiens (human)
- Herpes simplex infection - Homo sapiens (human)
- mRNA Processing
- Gene expression (Transcription)
- spliceosomal assembly
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- mRNA splicing, via spliceosome
- mRNA processing
- RNA export from nucleus
- mRNA export from nucleus
Molecular Function
- transcription corepressor activity
- RNA binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- PML body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392485
- Coding exons
- 2
- Length
- 3260
- Individuals with no LoFs
- 120664
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 120665
- p
- 0.00000414
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.71 | 55 | 148 | 0.373 | 0.00000691 | 1378 |
| Missense (PolyPhen) | 5 | 33.834 | 0.14778 | 318 | ||
| Synonymous | -2.39 | 86 | 62.0 | 1.39 | 0.00000283 | 512 |
| Loss of Function | 1.86 | 1 | 5.84 | 0.171 | 2.66e-7 | 60 |
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) | 0.0000093 | 0.0000093 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre- mRNA. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Binds to purine-rich RNA sequences, either 5'-AGSAGAGTA-3' (S=C or G) or 5'-GTTCGAGTA-3'. Can bind to beta-globin mRNA and commit it to the splicing pathway. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment. {ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21157427}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.42
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.539