SRPK1

SRSF protein kinase 1

Basic information

Region (hg38): 6:35832966-35921342

Links

ENSG00000096063 ∙ NCBI:6732 ∙ OMIM:601939 ∙ HGNC:11305 ∙ Uniprot:Q96SB4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRPK1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRPK1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			27			27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	0	0

Variants in SRPK1

This is a list of pathogenic ClinVar variants found in the SRPK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-35835308-G-A		not specified	Uncertain significance (Jun 24, 2022)
6-35835327-G-A		not specified	Uncertain significance (Dec 14, 2024)
6-35835329-A-C		not specified	Uncertain significance (Aug 01, 2024)
6-35835336-C-T		not specified	Uncertain significance (May 30, 2024)
6-35869012-C-T		not specified	Uncertain significance (Nov 10, 2024)
6-35869046-C-A		not specified	Uncertain significance (Sep 03, 2024)
6-35869084-C-T		not specified	Uncertain significance (Mar 15, 2024)
6-35869098-G-A		not specified	Uncertain significance (Oct 06, 2024)
6-35869101-G-A		not specified	Uncertain significance (Feb 28, 2025)
6-35869487-T-C		not specified	Uncertain significance (Nov 08, 2024)
6-35869493-A-G		not specified	Uncertain significance (Dec 20, 2023)
6-35869500-C-T		not specified	Uncertain significance (Mar 30, 2022)
6-35869652-C-G		not specified	Uncertain significance (Aug 21, 2023)
6-35869715-T-C		not specified	Uncertain significance (Jan 31, 2025)
6-35869752-G-A		not specified	Uncertain significance (Jan 01, 2025)
6-35869813-A-C		not specified	Uncertain significance (Dec 02, 2024)
6-35869887-T-C		not specified	Uncertain significance (Jun 21, 2023)
6-35870371-T-C		not specified	Uncertain significance (Mar 04, 2025)
6-35870418-C-T		not specified	Uncertain significance (Sep 29, 2022)
6-35870443-G-A		not specified	Uncertain significance (Dec 30, 2024)
6-35872629-G-A		not specified	Uncertain significance (Jan 01, 2025)
6-35872674-T-C		not specified	Uncertain significance (Jul 13, 2022)
6-35872692-G-T		not specified	Uncertain significance (Dec 07, 2023)
6-35874267-A-T		not specified	Uncertain significance (Jan 07, 2025)
6-35874337-T-C		not specified	Uncertain significance (Aug 20, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRPK1	protein_coding	protein_coding	ENST00000373825	16	88377

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000191	1.00	125014	0	78	125092	0.000312

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.88	236	332	0.710	0.0000169	4296
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000423	0.000411
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000572	0.0000548
Finnish	0.0000467	0.0000463
European (Non-Finnish)	0.000584	0.000564
Middle Eastern	0.0000572	0.0000548
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Herpes simplex infection - Homo sapiens (human);mRNA Processing (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.603
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.56

Haploinsufficiency Scores

• pHI: 0.365
• hipred: Y
• hipred_score: 0.648
• ghis: 0.588

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Srpk1

Gene ontology

• Biological process: spliceosomal complex assembly;protein phosphorylation;chromosome segregation;RNA splicing;regulation of gene expression;viral process;sperm chromatin condensation;intracellular signal transduction;positive regulation of viral genome replication;negative regulation of viral genome replication;innate immune response;regulation of mRNA splicing, via spliceosome;regulation of mRNA processing
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum;cytosol;plasma membrane;nuclear matrix
• Molecular function: magnesium ion binding;RNA binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding