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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SRSF4
serine and arginine rich splicing factor 4
Chromosome 1 · 1p35.3
NCBI Gene: 6429Ensembl: ENSG00000116350.19HGNC: HGNC:10786UniProt: Q08170
157PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nuclear speckprotein bindingRNA bindingnegative regulation of mRNA splicing, via spliceosomedengue diseasespinal cord injuryimmune system diseaseGriscelli disease
✦AI Summary

SRSF4 (serine and arginine rich splicing factor 4) is a nuclear RNA-binding protein that regulates alternative splicing of pre-mRNA transcripts 1. The protein contains RNA recognition motifs and a serine/arginine-rich domain typical of SR proteins, and localizes to the nucleus via multiple nuclear localization sequences in its RS domain 2. SRSF4 functions as both a splicing activator and repressor depending on the target transcript - it promotes inclusion of Fas exon 6 by binding to a novel enhancer sequence 3, activates CLK1 exon 4 inclusion 4, and regulates RPL22L1 isoform switching in glioblastoma 5. The protein requires phosphorylation for optimal function, as demonstrated in enterovirus A71 infection where phosphorylated SRSF4 facilitates IRES-dependent viral translation 6. SRSF4 has significant disease relevance, contributing to temozolomide resistance in glioma through regulation of DNA double-strand break repair 7, and mutations in SRSF4 cause mitochondrial dysfunction leading to bone marrow failure 8. These findings highlight SRSF4's dual role in normal cellular RNA processing and pathological processes, making it a potential therapeutic target in cancer and genetic disorders.

Sources cited
1
SRSF4 is involved in alternative splicing and mRNA processing as part of the SR protein family
PMID: 29789787
2
SRSF4 localizes to the nucleus via multiple nuclear localization sequences in its RS domain
PMID: 32050040
3
SRSF4 promotes Fas exon 6 inclusion by binding to a novel enhancer sequence
PMID: 30376989
4
SRSF4 acts as an activator of CLK1 exon 4 inclusion
PMID: 39251328
5
SRSF4 regulates RPL22L1 isoform switching in glioblastoma
PMID: 36192632
6
Phosphorylated SRSF4 facilitates IRES-dependent viral translation in enterovirus A71 infection
PMID: 40522993
7
SRSF4 contributes to temozolomide resistance in glioma through regulation of DNA double-strand break repair
PMID: 37014544
8
SRSF4 mutations cause mitochondrial dysfunction leading to bone marrow failure
PMID: 38396760
Disease Associationsⓘ20
dengue diseaseOpen Targets
0.37Weak
spinal cord injuryOpen Targets
0.28Weak
immune system diseaseOpen Targets
0.20Weak
Griscelli diseaseOpen Targets
0.07Suggestive
Griscelli disease type 3Open Targets
0.07Suggestive
Griscelli syndrome type 3Open Targets
0.07Suggestive
nervous system benign neoplasmOpen Targets
0.06Suggestive
uncombable hair syndromeOpen Targets
0.06Suggestive
Griscelli disease type 1Open Targets
0.05Suggestive
Griscelli syndrome type 1Open Targets
0.05Suggestive
Abruptio PlacentaeOpen Targets
0.05Suggestive
head injuryOpen Targets
0.05Suggestive
postinflammatory pulmonary fibrosisOpen Targets
0.05Suggestive
oculocutaneous albinism type 3Open Targets
0.05Suggestive
ulcerative colitisOpen Targets
0.04Suggestive
hypotrichosis 8Open Targets
0.04Suggestive
Microcephaly - albinism - digital anomaliesOpen Targets
0.04Suggestive
microcephaly-albinism-digital anomalies syndromeOpen Targets
0.04Suggestive
Clouston syndromeOpen Targets
0.04Suggestive
ankylosing spondylitisOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SART1Protein interaction100%CDC5LProtein interaction100%PABPN1Protein interaction99%HTATSF1Protein interaction99%SNRNP70Protein interaction99%PRPF38AProtein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
75%
Liver
75%
Ovary
71%
Brain
52%
Heart
41%
Gene Interaction Network
Click a node to explore
SRSF4SART1CDC5LPABPN1HTATSF1SNRNP70PRPF38A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q08170
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.31Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.15 [0.08–0.31]
RankingsWhere SRSF4 stands among ~20K protein-coding genes
  • #2,874of 20,598
    Most Researched157 · top quartile
  • #1,219of 17,882
    Most Constrained (LOEUF)0.31 · top 10%
Genes detectedSRSF4
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells.
PMID: 36192632
Nat Cell Biol · 2022
1.00
2
Impaired Mitochondrial Function and Marrow Failure in Patients Carrying a Variant of the
PMID: 38396760
Int J Mol Sci · 2024
0.90
3
Physiological and Pathological Function of Serine/Arginine-Rich Splicing Factor 4 and Related Diseases.
PMID: 29789787
Biomed Res Int · 2018
0.80
4
Regulatory interplay between SR proteins governs
PMID: 39251328
RNA · 2024
0.70
5
Poison cassette exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia.
PMID: 36620874
Nucleic Acids Res · 2023
0.68