SRPK1

Chr 6

SRSF protein kinase 1

Also known as: SFRSK1

NCBI Gene: 6732ENSG00000096063UniProt: Q96SB4

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]

71
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SRPK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 63 VUS of 71 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.60LOEUF
pLI 0.000
Z-score 3.52
OE 0.39 (0.26–0.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.88Z-score
OE missense 0.71 (0.64–0.79)
236 obs / 332.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.26–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.64–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 15 / 38.6Missense obs/exp: 236 / 332.3Syn Z: 0.66

ClinVar Variant Classifications

71 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS63
7
Pathogenic
1
Likely Pathogenic
63
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
61
2
0
63
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total06110071

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SRPK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integration of multi-omics transcriptome-wide analysis for the identification of novel therapeutic drug targets in diabetic retinopathy.
Yi G et al.·J Transl Med
2024
Serine-Arginine Protein Kinase 1 (SRPK1): a systematic review of its multimodal role in oncogenesis.
Duggan WP et al.·Mol Cell Biochem
2022Review
Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives.
Nikas IP et al.·Cells
2019Review
Spliceosomal profiling identifies EIF4A3 as a novel oncogene in hepatocellular carcinoma acting through the modulation of FGFR4 splicing.
López-Cánovas JL et al.·Clin Transl Med
2022
The many faces of SRPK1.
Bullock N et al.·J Pathol
2017
The splicing factor kinase SRPK1 is a therapeutic target for peripheral vascular disease.
Bhalla SR et al.·Am J Physiol Heart Circ Physiol
2025
Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy.
Malhi NK et al.·Am J Physiol Heart Circ Physiol
2022
CircSRPK1 mediated by the exon junction complex promotes gastric cancer progression by interacting with hnRNP A2B1 to regulate RON mRNA alternative splicing.
Yu S et al.·Cancer Lett
2025
A HIF1A/miR-485-5p/SRPK1 axis modulates the aggressiveness of glioma cells upon hypoxia.
Cheng L et al.·Exp Cell Res
2021
CDK12-inactivation-induced MYC signaling causes dependency on the splicing kinase SRPK1.
Liang J et al.·Mol Oncol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools