SRSF1
protein-codingserine and arginine rich splicing factor 1, the group of RNA binding motif containing|Serine and arginine rich splicing factors
Gene summary
This gene encodes a member of the arginine/serine-rich splicing factor protein family. The encoded protein can either activate or repress splicing, depending on its phosphorylation state and its interaction partners. Multiple transcript variants have been found for this gene. There is a pseudogene of this gene on chromosome 13. [provided by RefSeq, Jun 2014]
- SFRS1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0957583
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0957583
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0957583
Submitter: Baylor College of Medicine Research Center
Inheritance Pattern: AD
Disease ID:MONDO:0957583
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
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 SRSF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006924.5. 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 | 3 | 3 | 24 | 30 | ||
| nonsense | 4 | 1 | 5 | |||
| start loss | 0 | |||||
| frameshift | 3 | 2 | 2 | 7 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | 4 | ||
| Total | 11 | 6 | 29 | 4 | 0 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008855.1 | 4 | MANE Select | |
| Ensembl | ENSP00000258962.4 | 4 | MANE Select | |
| RefSeq | NP_001071634.1 | 3 | Standard | |
| Ensembl | ENSP00000463223.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- IL-17 signaling pathway - Homo sapiens (human)
- Spliceosome - Homo sapiens (human)
- Herpes simplex infection - Homo sapiens (human)
- mRNA Processing
- Gene expression (Transcription)
Biological Process
- alternative mRNA splicing, via spliceosome
- regulation of alternative mRNA splicing, via spliceosome
- mRNA 5'-splice site recognition
- mRNA splicing, via spliceosome
- in utero embryonic development
Molecular Function
- RNA binding
- mRNA binding
- protein binding
- protein kinase B binding
- DNA topoisomerase binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- nuclear speck
- exon-exon junction complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000258962
- Coding exons
- 4
- Length
- 3987
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.96 | 22 | 165 | 0.133 | 0.00000878 | 1585 |
| Missense (PolyPhen) | 1 | 43.296 | 0.023097 | 478 | ||
| Synonymous | -0.254 | 59 | 56.6 | 1.04 | 0.00000260 | 527 |
| Loss of Function | 3.26 | 0 | 12.4 | 0.00 | 6.87e-7 | 124 |
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: Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. 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. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'- CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway. {ECO:0000269|PubMed:8139654}.;
Recessive Scores
- pRec
- 0.0447
Intolerance Scores
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 52.85
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.539