SRSF6 (Serine and Arginine Rich Splicing Factor 6)
A key splicing factor involved in alternative splicing regulation, with implications in cancer and developmental disorders.
Gene Information Card
| Symbol | SRSF6 |
|---|---|
| Full Name | Serine and Arginine Rich Splicing Factor 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.11 |
| NCBI Gene ID | 6431 ncbi.nlm.nih.gov/gene/6431 |
| Ensembl ID | ENSG00000124193 |
| UniProt ID | Q13247 |
| OMIM ID | 601944 |
| HGNC ID | 10787 |
| Aliases | SRp55, B52 |
Description
SRSF6 (Serine and Arginine Rich Splicing Factor 6) is a member of the serine/arginine-rich (SR) protein family, which are essential regulators of both constitutive and alternative pre-mRNA splicing. SRSF6 contains an RNA recognition motif (RRM) and an arginine/serine-rich (RS) domain, enabling it to bind to exonic splicing enhancers and recruit the spliceosome. It plays a critical role in tissue-specific and developmentally regulated alternative splicing, influencing cell proliferation, differentiation, and apoptosis. Dysregulation of SRSF6 has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of SRSF6 promotes alternative splicing of genes involved in cell cycle and apoptosis, leading to oncogenic transformation. | COSMIC: SRSF6 is listed as a cancer gene with mutations and copy number alterations in various tumor types. |
| Retinitis Pigmentosa | Mutations in SRSF6 have been associated with retinal degeneration, though the exact mechanism is under investigation. | ClinVar: Variants in SRSF6 are reported in patients with retinal dystrophy. |
| Developmental Delay / Intellectual Disability | De novo mutations in SRSF6 may disrupt splicing of neurodevelopmental genes, contributing to cognitive impairment. | ClinVar: Pathogenic variants reported in individuals with neurodevelopmental phenotypes. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Lung | 8.7 | Low |
| Liver | 6.2 | Low |
| Kidney | 9.5 | Low |
| Testis | 15.8 | Medium |
| Ovary | 11.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | Cervical carcinoma; high expression |
| A549 | 10.2 | Lung carcinoma; moderate expression |
| MCF7 | 12.8 | Breast adenocarcinoma; high expression |
| K562 | 9.1 | Chronic myeloid leukemia; moderate expression |
| HepG2 | 7.4 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.574C>T (p.Arg192Trp) | Missense | Rare (ClinVar) | Likely pathogenic; may affect RNA binding affinity. |
| c.1021G>A (p.Gly341Arg) | Missense | Rare (ClinVar) | Uncertain significance; potential impact on RS domain phosphorylation. |
| c.1234A>G (p.Ser412Gly) | Missense | Somatic (COSMIC) | Gain-of-function; associated with increased splicing activity in tumors. |
| c.1456C>T (p.Arg486*) | Nonsense | Somatic (COSMIC) | Loss-of-function; may lead to haploinsufficiency in cancer cells. |
Mutation functional classification
Loss of Function (LOF)
Nonsense or frameshift mutations that truncate the protein, leading to reduced splicing activity and potential haploinsufficiency.
Gain of Function (GOF)
Missense mutations that enhance the protein's splicing activity, often observed in cancers, promoting oncogenic splicing variants.
Dominant Negative (DN)
Mutations that produce a protein that interferes with the function of the wild-type allele, potentially disrupting normal splicing regulation.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding | • mRNA binding |
| • protein binding | • nucleotide binding |
| • mRNA processing | • RNA splicing |
| • alternative mRNA splicing | • via spliceosome |
| • regulation of alternative mRNA splicing | • mRNA splice site selection |
| • nucleus | • nucleoplasm |
| • spliceosomal complex |
Pathways
• mRNA Splicing - Major Pathway
• Alternative Splicing Regulation
• SR Protein-Mediated Splicing
Protein Summary
The SRSF6 protein (UniProt Q13247) is 344 amino acids long and contains an N-terminal RNA recognition motif (RRM) that binds to purine-rich exonic splicing enhancers, and a C-terminal RS domain rich in arginine-serine dipeptides. The RS domain undergoes phosphorylation by SR protein kinases (e.g., SRPK1/2), which regulates its nuclear localization and splicing activity. SRSF6 is predominantly nuclear and localizes to nuclear speckles, where it participates in spliceosome assembly. It interacts with other SR proteins and spliceosomal components to promote exon inclusion. Post-translational modifications, including phosphorylation and methylation, modulate its function. SRSF6 is essential for normal development and its dysregulation contributes to disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SRSF6 Knockout HEK293 Cell Line | EDJ-KQ50624 | Human | 6431 | Details Get a Quote |
| SRSF6 Knockout HeLa Cell Line | EDJ-KQ54450 | Human | 6431 | Details Get a Quote |
| SRSF6 Knockout A-549 Cell Line | EDJ-KQ62939 | Human | 6431 | Details Get a Quote |
| SRSF6 Knockout HCT 116 Cell Line | EDJ-KQ71410 | Human | 6431 | Details Get a Quote |
