SF3B1 Gene: Splicing Factor 3b Subunit 1
A key component of the U2 snRNP in pre-mRNA splicing, frequently mutated in myelodysplastic syndromes and various cancers.
Gene Information Card
| Symbol | SF3B1 |
|---|---|
| Full Name | Splicing factor 3b subunit 1 |
| Gene Type | protein coding |
| Chromosomal Location | 2q33.1 |
| NCBI Gene ID | 23451 ncbi.nlm.nih.gov/gene/23451 |
| Ensembl ID | ENSG00000115524 |
| UniProt ID | O75533 |
| OMIM ID | 605590 |
| HGNC ID | 10768 |
| Aliases | PRP10, SAP155, SF3b155, MDS, Hsh155 |
Description
The SF3B1 gene encodes the largest subunit of the splicing factor 3b complex, which is a core component of the U2 small nuclear ribonucleoprotein (snRNP). This complex is essential for the recognition of the branch point during pre-mRNA splicing. SF3B1 is critical for the assembly of the spliceosome and the catalytic activation of the splicing reaction. Mutations in SF3B1 are common in hematological malignancies, particularly myelodysplastic syndromes (MDS), and are also found in various solid tumors, including breast, pancreatic, and uveal melanoma. These mutations are typically missense mutations in the HEAT repeat domains and lead to altered RNA splicing, often causing aberrant 3' splice site selection.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myelodysplastic syndromes | SF3B1 mutations cause aberrant RNA splicing, particularly affecting genes involved in mitochondrial iron metabolism and erythroid differentiation, leading to ring sideroblasts and ineffective erythropoiesis. | ClinVar, COSMIC, PMID: 21873988 |
| Chronic lymphocytic leukemia | SF3B1 mutations are recurrent and associated with poor prognosis, contributing to disease progression through altered splicing of genes involved in DNA damage response and apoptosis. | ClinVar, COSMIC, PMID: 21873988 |
| Uveal melanoma | SF3B1 mutations are frequent and lead to aberrant splicing of genes involved in cell cycle regulation and chromatin remodeling, promoting tumorigenesis. | COSMIC, PMID: 23396050 |
| Breast cancer | SF3B1 mutations are found in a subset of breast cancers, particularly in the lobular subtype, and may contribute to tumor heterogeneity and progression. | COSMIC, PMID: 25631445 |
| Pancreatic cancer | SF3B1 mutations are present in a small fraction of pancreatic ductal adenocarcinomas, potentially affecting splicing of genes involved in cell survival and proliferation. | COSMIC, PMID: 25631445 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Lymph Node | 10.2 | Medium |
| Spleen | 9.8 | Medium |
| Testis | 8.1 | Low |
| Brain | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.3 | High expression |
| HeLa (cervical cancer) | 12.1 | Moderate expression |
| MCF7 (breast cancer) | 10.5 | Moderate expression |
| A549 (lung cancer) | 9.2 | Low expression |
| HepG2 (liver cancer) | 8.7 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| K700E | Missense | ~60% in MDS with ring sideroblasts | Alters splicing of multiple genes, including ABCB7 and SLC25A37, leading to mitochondrial iron accumulation. |
| H662Q | Missense | ~10% in CLL | Affects branch point recognition, causing aberrant splicing of genes involved in DNA repair. |
| R625C | Missense | ~15% in uveal melanoma | Leads to aberrant splicing of genes such as CRIP2 and TCHP, promoting tumor growth. |
| E622D | Missense | Rare in MDS | Impairs spliceosome assembly, resulting in global splicing changes. |
| N626D | Missense | Rare in breast cancer | Alters splicing of genes involved in cell adhesion and migration. |
Mutation functional classification
Loss of Function (LOF)
Not typically loss-of-function; mutations are missense and retain some function, but may have reduced splicing fidelity.
Gain of Function (GOF)
Gain-of-function is suggested by the dominant effect of mutant SF3B1 on splicing, leading to a specific pattern of aberrant 3' splice site usage.
Dominant Negative (DN)
Mutations likely act in a dominant-negative manner, as the mutant protein is incorporated into the spliceosome and disrupts normal splicing, while the wild-type allele is often retained.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding | • mRNA splicing |
| • via spliceosome | • spliceosomal complex assembly |
| • U2 snRNP binding | • protein binding |
Pathways
• mRNA Splicing - Major Pathway
• Spliceosome
• Processing of Capped Intron-Containing Pre-mRNA
Protein Summary
The SF3B1 protein is a 130 kDa subunit of the SF3b complex, which is part of the U2 snRNP. It contains multiple HEAT repeats that mediate protein-protein interactions. SF3B1 is essential for the recognition of the branch point adenosine during pre-mRNA splicing. It interacts with other spliceosomal components, such as SF3B2, SF3B3, and PHF5A, to form the SF3b complex. The protein is localized in the nucleus and is involved in the early steps of spliceosome assembly. Mutations in SF3B1, particularly in the HEAT repeat domains, alter its conformation and binding affinity, leading to aberrant splicing of specific target genes.
Related Services
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| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SF3B1 (p.V1219=) Point Mutation in HAP1 Cell Line | EDC03600 | Human | 23451 | Details Get a Quote |
| SF3B1 (p.G877=) Point Mutation in HAP1 Cell Line | EDC03601 | Human | 23451 | Details Get a Quote |
| SF3B1 (p.K141=) Point Mutation in HAP1 Cell Line | EDC03602 | Human | 23451 | Details Get a Quote |
