SF3A1
Splicing Factor 3a Subunit 1
Gene Information Card
| Symbol | SF3A1 |
|---|---|
| Full Name | Splicing Factor 3a Subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 10291 ncbi.nlm.nih.gov/gene/10291 |
| Ensembl ID | ENSG00000100077 |
| UniProt ID | Q15459 |
| OMIM ID | 605592 |
| HGNC ID | 10765 |
| Aliases | PRP21, PRPF21, SAP114, SF3A120 |
Description
SF3A1 encodes the largest subunit of the splicing factor 3a complex, a component of the U2 small nuclear ribonucleoprotein (snRNP). This protein is essential for pre-mRNA splicing, specifically in the recognition of the 3' splice site and the assembly of the spliceosome. SF3A1 interacts with SF3A2, SF3A3, and other spliceosomal proteins to form the active U2 snRNP. Mutations in SF3A1 are recurrent in myelodysplastic syndromes (MDS) and other hematologic malignancies, often affecting the HEAT repeat domain and altering RNA splicing patterns.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myelodysplastic syndrome | Recurrent somatic mutations (e.g., p.Thr387Ile) in the HEAT domain alter 3' splice site selection, leading to aberrant RNA splicing and dysregulated hematopoiesis. | COSMIC, ClinVar |
| Acute myeloid leukemia | SF3A1 mutations co-occur with other splicing factor mutations, contributing to leukemogenesis through spliceosomal dysfunction. | COSMIC, NCBI |
| Chronic lymphocytic leukemia | Rare SF3A1 mutations reported, potentially affecting splicing of genes involved in B-cell development. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 56.2 | High |
| Bone marrow | 38.1 | Medium |
| Lymph node | 32.5 | Medium |
| Brain | 25.8 | Medium |
| Liver | 18.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 | 42.3 | Leukemia cell line |
| HeLa | 35.7 | Cervical carcinoma |
| HEK293 | 30.1 | Embryonic kidney |
| MCF7 | 28.9 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1160C>T (p.Thr387Ile) | Missense | Recurrent in MDS (~2-5%) | Alters HEAT repeat, disrupts U2 snRNP assembly and splicing fidelity |
| c.1160C>G (p.Thr387Ser) | Missense | Rare | Similar effect on splicing as p.Thr387Ile |
| c.1160C>A (p.Thr387Asn) | Missense | Rare | Predicted damaging, affects spliceosome function |
Mutation functional classification
Loss of Function (LOF)
Not established; mutations are typically missense and may confer altered function rather than complete loss.
Gain of Function (GOF)
Not established; mutations likely alter splicing specificity rather than enhance normal function.
Dominant Negative (DN)
Proposed mechanism: mutant SF3A1 competes with wild-type in U2 snRNP, causing global splicing changes.
View complete mutation data：
Gene Ontology (GO)
| • RNA splicing | • mRNA splicing via spliceosome |
| • U2 snRNP binding | • protein binding |
| • nucleus |
Pathways
• Spliceosome (KEGG hsa03040)
• mRNA Splicing - Major Pathway (Reactome R-HSA-72163)
Protein Summary
SF3A1 is a 793-amino acid protein (UniProt Q15459) containing a HEAT repeat domain and a C-terminal SAP domain. It forms the SF3a complex with SF3A2 and SF3A3, which is essential for U2 snRNP assembly and 3' splice site recognition. The protein is ubiquitously expressed with highest levels in testis and bone marrow. Mutations in the HEAT domain are recurrent in MDS and AML, leading to altered splicing of genes involved in hematopoiesis.
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