SRPK1
protein-codingSRSF protein kinase 1
Gene summary
This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. Alternative splicing of this gene results in multiple transcript variants. Additional alternatively spliced transcript variants have been described for this gene, but their full length nature have not been determined.[provided by RefSeq, Jul 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~88.4 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 SRPK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003137.5. 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 | 0 | |||||
| missense | 67 | 1 | 68 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 72 | 0 | 1 | 73 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003128.3 | 16 | MANE Select | |
| Ensembl | ENSP00000362931.2 | 16 | MANE Select | |
| Ensembl | ENSP00000354674.3 | 16 | Standard | |
| Ensembl | ENSP00000391069.2 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Herpes simplex infection - Homo sapiens (human)
- mRNA Processing
Biological Process
- spliceosomal complex assembly
- protein phosphorylation
- chromosome segregation
- RNA splicing
- regulation of gene expression
Molecular Function
- magnesium ion binding
- RNA binding
- protein kinase activity
- protein serine/threonine kinase activity
- protein binding
Cellular Component
- nucleus
- cytoplasm
- endoplasmic reticulum
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373825
- Coding exons
- 16
- Length
- 88377
- Individuals with no LoFs
- 125014
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 78
- Defined
- 125092
- p
- 0.000312
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.88 | 236 | 332 | 0.710 | 0.0000169 | 4296 |
| Missense (PolyPhen) | 79 | 133.28 | 0.59276 | 1758 | ||
| Synonymous | 0.657 | 110 | 119 | 0.923 | 0.00000613 | 1179 |
| Loss of Function | 3.52 | 15 | 38.6 | 0.388 | 0.00000211 | 476 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00033 | 0.00032 | rare |
| Latino/Admixed American | 0.000089 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000057 | 0.000055 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00058 | 0.00056 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K-562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation. {ECO:0000269|PubMed:10049757, ECO:0000269|PubMed:10390541, ECO:0000269|PubMed:11509566, ECO:0000269|PubMed:12134018, ECO:0000269|PubMed:14555757, ECO:0000269|PubMed:15034300, ECO:0000269|PubMed:16122776, ECO:0000269|PubMed:16209947, ECO:0000269|PubMed:18155240, ECO:0000269|PubMed:18687337, ECO:0000269|PubMed:19240134, ECO:0000269|PubMed:19477182, ECO:0000269|PubMed:19886675, ECO:0000269|PubMed:20708644, ECO:0000269|PubMed:8208298, ECO:0000269|PubMed:9237760}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.603
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |