CSTF2: Cleavage Stimulation Factor Subunit 2
A key RNA 3'-end processing factor involved in polyadenylation and implicated in cancer and developmental disorders
Gene Information Card
| Symbol | CSTF2 |
|---|---|
| Full Name | Cleavage Stimulation Factor Subunit 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq22.1 |
| NCBI Gene ID | 1478 ncbi.nlm.nih.gov/gene/1478 |
| Ensembl ID | ENSG00000101811 |
| UniProt ID | P33240 |
| OMIM ID | 300181 |
| HGNC ID | 2484 |
| Aliases | CSTF64, CstF-64, CF-1 64 kDa subunit |
Description
CSTF2 encodes the 64 kDa subunit of the cleavage stimulation factor (CstF), a multi-subunit complex essential for pre-mRNA 3'-end processing and polyadenylation. The protein binds directly to the GU-rich downstream element of pre-mRNA and recruits other processing factors. CSTF2 is involved in alternative polyadenylation, influencing mRNA stability, localization, and translation. Dysregulation of CSTF2 is associated with various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of CSTF2 leads to global shortening of 3' UTRs, promoting oncogene expression by escaping miRNA-mediated repression. | PMID: 22939622 |
| Ovarian cancer | CSTF2 upregulation correlates with altered polyadenylation site usage in genes involved in cell proliferation and migration. | PMID: 25636800 |
| Intellectual disability, X-linked | Missense mutations in CSTF2 impair RNA binding and polyadenylation activity, linked to neurodevelopmental phenotypes. | OMIM: 300181 |
| Acute myeloid leukemia | CSTF2 fusion transcripts (e.g., with RUNX1) disrupt normal hematopoiesis. | COSMIC: CSTF2 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.5 | High |
| Brain | 12.3 | Medium |
| Lung | 8.7 | Medium |
| Liver | 5.2 | Low |
| Heart | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; moderate expression |
| K562 | 22.8 | Leukemia cell line; high expression |
| HepG2 | 6.4 | Hepatocellular carcinoma; low expression |
| A549 | 9.1 | Lung carcinoma; medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1130G>A (p.Arg377His) | Missense | <0.01% | Reduced RNA-binding affinity; associated with X-linked intellectual disability (ClinVar) |
| c.1462C>T (p.Arg488*) | Nonsense | <0.01% | Premature stop; loss of function (COSMIC) |
| c.721_722insA (p.Thr241Asnfs*5) | Frameshift | <0.01% | Loss of function; observed in breast cancer (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg488*, p.Thr241Asnfs*5) lead to truncated protein lacking the RNA-binding domain, impairing polyadenylation.
Gain of Function (GOF)
Overexpression and amplification of wild-type CSTF2 in cancers result in increased alternative polyadenylation activity, promoting oncogenic transcripts.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg377His) may produce a protein that competes with wild-type CstF-64, disrupting complex assembly and function.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/1478 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=CSTF2
Gene Ontology (GO)
| • GO:0003723 – RNA binding | • GO:0005515 – protein binding |
| • GO:0006378 – mRNA polyadenylation | • GO:0031124 – mRNA 3'-end processing |
| • GO:0048027 – mRNA 5'-UTR binding | • GO:0005634 – nucleus |
Pathways
• mRNA 3'-end processing (Reactome: R-HSA-72172)
• Cleavage of Growing Transcript in the Termination Region (Reactome: R-HSA-72163)
• Formation of the Cleavage and Polyadenylation Complex (Reactome: R-HSA-72186)
Protein Summary
CSTF2 (CstF-64) is a 64 kDa RNA-binding protein that recognizes GU-rich sequences downstream of the polyadenylation site. It is a core component of the cleavage stimulation factor complex, which also includes CstF-77 and CstF-50. The protein contains an N-terminal RNA recognition motif (RRM) and a C-terminal proline-rich domain. CSTF2 shuttles between nucleus and cytoplasm and regulates alternative polyadenylation in a tissue-specific manner. Its expression is highest in testis, and it is frequently upregulated in cancers, leading to shortened 3' UTRs and increased oncogene expression.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CSTF2 Knockout HEK293 Cell Line | EDJ-KQ4377 | Human | 1478 | Details Get a Quote |
| CSTF2T Knockout HEK293 Cell Line | EDJ-KQ7944 | Human | 23283 | Details Get a Quote |
| CSTF2 Knockout HeLa Cell Line | EDJ-KQ25618 | Human | 1478 | Details Get a Quote |
| CSTF2 Knockout A-549 Cell Line | EDJ-KQ26894 | Human | 1478 | Details Get a Quote |
| CSTF2 Knockout HCT 116 Cell Line | EDJ-KQ26895 | Human | 1478 | Details Get a Quote |
| CSTF2T Knockout A-549 Cell Line | EDJ-KQ32277 | Human | 23283 | Details Get a Quote |
| CSTF2T Knockout HCT 116 Cell Line | EDJ-KQ33606 | Human | 23283 | Details Get a Quote |
| CSTF2T Knockout HeLa Cell Line | EDJ-KQ33607 | Human | 23283 | Details Get a Quote |
| Cstf2 Knockout B16-F10 Cell Line | EDJ-KZ170 | Mouse | 1478 | Details Get a Quote |
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