HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SRSF6
serine and arginine rich splicing factor 6
Chromosome 20 · 20q13.11
NCBI Gene: 6431Ensembl: ENSG00000124193.17HGNC: HGNC:10788UniProt: Q13247
242PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of keratinocyte differentiationnegative regulation of mRNA splicing, via spliceosomeregulation of wound healingprotein bindingdengue diseasemathematical abilityMyoclonustype 1 diabetes nephropathy
✦AI Summary

SRSF6 (serine and arginine rich splicing factor 6) is a critical regulator of alternative mRNA splicing that controls constitutive and alternative splice site selection. The protein functions by binding to specific RNA motifs and recruiting other splicing factors to modulate exon inclusion or exclusion 12. SRSF6 operates through its RNA recognition motif domains, particularly the RRM2 domain, to directly bind target transcripts and regulate their splicing patterns 1. The protein cooperates with other splicing regulators including SRSF1, HNRNPC, and USP39 to orchestrate complex splicing programs 23. SRSF6 is subject to posttranslational regulation, including phosphorylation by SRPK1 and stabilization through USP7-mediated deubiquitination 45. In disease contexts, SRSF6 is frequently upregulated in cancers including colorectal cancer, prostate cancer, and thyroid carcinoma, where it promotes oncogenic splicing programs that enhance tumor progression, metastasis, and drug resistance 167. SRSF6 also plays roles in metabolic diseases like NAFLD/NASH through regulation of mitochondrial function-related gene splicing 4. The protein's critical role in cellular survival and disease progression makes it an attractive therapeutic target, with several inhibitors showing promise in preclinical studies 15.

Sources cited
1
SRSF6 binds to specific RNA motifs and its RRM2 domain is critical for regulating alternative splicing and biological function
PMID: 29114070
2
SRSF6 cooperates with SRSF1 to enhance exon inclusion through multiple functional motifs
PMID: 40161265
3
SRSF6 cooperates with HNRNPC and USP39 to modulate splice site selection
PMID: 37821439
4
SRSF6 phosphorylation is regulated by SRPK1 and affects alternative splicing of mitochondrial function-related genes
PMID: 34614409
5
SRSF6 protein levels are regulated by USP7-mediated deubiquitination and SRSF6 is critical for leukemia cell survival
PMID: 32444465
6
SRSF6 is upregulated in prostate cancer and regulates histone-chaperone HIRA splicing to affect AR and E2F activity
PMID: 39356765
7
SRSF6 is involved in drug resistance mechanisms in anaplastic thyroid carcinoma through alternative splicing reprogramming
PMID: 40083919
Disease Associationsⓘ20
dengue diseaseOpen Targets
0.37Weak
mathematical abilityOpen Targets
0.23Weak
MyoclonusOpen Targets
0.21Weak
type 1 diabetes nephropathyOpen Targets
0.20Weak
insomniaOpen Targets
0.20Weak
substance-related disorderOpen Targets
0.18Weak
obesityOpen Targets
0.18Weak
overnutritionOpen Targets
0.14Weak
premature birthOpen Targets
0.13Weak
cancerOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
melanomaOpen Targets
0.04Suggestive
acquired thrombocytopeniaOpen Targets
0.04Suggestive
systemic sclerodermaOpen Targets
0.04Suggestive
thrombophiliaOpen Targets
0.04Suggestive
smoking initiationOpen Targets
0.04Suggestive
type 2 diabetes mellitusOpen Targets
0.03Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CDC5LProtein interaction100%PABPN1Protein interaction99%SRPK1Protein interaction98%U2AF2Protein interaction97%HNRNPUProtein interaction97%HNRNPMProtein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
43%
Ovary
42%
Lung
21%
Heart
19%
Brain
11%
Gene Interaction Network
Click a node to explore
SRSF6CDC5LPABPN1SRPK1U2AF2HNRNPUHNRNPM
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q13247
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.64LoF Tolerant
pLIⓘ
0.16Tolerant
Observed/Expected LoF0.43 [0.29–0.64]
RankingsWhere SRSF6 stands among ~20K protein-coding genes
  • #1,620of 20,598
    Most Researched242 · top 10%
  • #4,560of 17,882
    Most Constrained (LOEUF)0.64
Genes detectedSRSF6
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
SRSF6-regulated alternative splicing that promotes tumour progression offers a therapy target for colorectal cancer.
PMID: 29114070
Gut · 2019
1.00
2
DRAK2 aggravates nonalcoholic fatty liver disease progression through SRSF6-associated RNA alternative splicing.
PMID: 34614409
Cell Metab · 2021
0.90
3
Multi-Omics Analysis Reveals Translational Landscapes and Regulations in Mouse and Human Oocyte Aging.
PMID: 37401155
Adv Sci (Weinh) · 2023
0.80
4
SRSF6 modulates histone-chaperone HIRA splicing to orchestrate AR and E2F activity in prostate cancer.
PMID: 39356765
Sci Adv · 2024
0.70
5
Genetic associations of protein-coding variants in venous thromboembolism.
PMID: 38561338
Nat Commun · 2024
0.68