ZRSR2 Gene: Splicing Factor in Myelodysplastic Syndromes
ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) is an essential component of the U2 snRNP spliceosome, with mutations frequently associated with myeloid malignancies, particularly myelodysplastic syndromes.
Gene Information Card
| Symbol | ZRSR2 |
|---|---|
| Full Name | Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2 |
| Gene Type | protein-coding |
| Chromosomal Location | Xp22.2 |
| NCBI Gene ID | 8233 ncbi.nlm.nih.gov/gene/8233 |
| Ensembl ID | ENSG00000169249 |
| UniProt ID | Q15696 |
| OMIM ID | 300956 |
| HGNC ID | 13083 |
| Aliases | URP, U2AF1-RS2, U2AF1L2, ZRSR2A |
Description
ZRSR2 encodes a protein that is a core component of the U2 small nuclear ribonucleoprotein (snRNP) complex, essential for pre-mRNA splicing. It recognizes the 3' splice site during spliceosome assembly. Mutations in ZRSR2 are recurrent in myeloid malignancies, particularly myelodysplastic syndromes (MDS), and are associated with altered RNA splicing and disease pathogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myelodysplastic Syndromes (MDS) | Loss-of-function mutations (frameshift, nonsense, splice site) lead to haploinsufficiency or loss of ZRSR2 protein, causing aberrant splicing of many pre-mRNAs, contributing to hematopoietic dysfunction. | Somatic mutations found in ~5-10% of MDS cases; validated in multiple cohorts (e.g., Yoshida et al., Nature 2011; Papaemmanuil et al., NEJM 2016). |
| Acute Myeloid Leukemia (AML) | Similar loss-of-function mutations, often co-occurring with other splicing factor mutations, contribute to leukemogenesis. | Observed in a subset of AML patients; reported in COSMIC and ClinVar. |
| Chronic Myelomonocytic Leukemia (CMML) | Mutations in ZRSR2 are recurrent in CMML, a myelodysplastic/myeloproliferative neoplasm. | Reported in CMML cohorts (e.g., Meggendorfer et al., Leukemia 2017). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High expression in hematopoietic tissues |
| Spleen | Medium | Moderate expression |
| Testis | Medium | Moderate expression |
| Lung | Low | Low expression |
| Brain | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (CML) | High | Leukemic cell line with high ZRSR2 expression |
| HL-60 (AML) | High | Promyelocytic leukemia cell line |
| HeLa (cervical cancer) | Medium | Common laboratory cell line |
| MCF7 (breast cancer) | Medium | Breast adenocarcinoma cell line |
| A549 (lung cancer) | Low | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1063C>T (p.Arg355*) | Nonsense | ~2% of MDS cases | Loss of function; premature stop codon leading to truncated protein |
| c.1102delA (p.Ser368Valfs*2) | Frameshift | ~1% of MDS cases | Loss of function; frameshift leading to protein truncation |
| c.868+1G>A | Splice site | ~1% of MDS cases | Loss of function; aberrant splicing, likely exon skipping |
| c.1327C>T (p.Arg443*) | Nonsense | Rare | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Most ZRSR2 mutations are loss-of-function (nonsense, frameshift, splice site), leading to reduced or absent protein function. This impairs 3' splice site recognition and causes global splicing defects.
Gain of Function (GOF)
No evidence of gain-of-function mutations in ZRSR2.
Dominant Negative (DN)
Not reported; mutations are typically heterozygous but act via haploinsufficiency or loss of function.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding | • mRNA splicing |
| • via spliceosome | • U2 snRNP complex |
| • zinc ion binding | • nucleus |
| • spliceosomal complex |
Pathways
• mRNA Splicing - Major Pathway
• Spliceosome
• Processing of Capped Intron-Containing Pre-mRNA
Protein Summary
The ZRSR2 protein (UniProt Q15696) is 482 amino acids long and contains an N-terminal zinc finger domain and a C-terminal serine/arginine-rich (SR) domain. It is a subunit of the U2 snRNP, where it interacts with U2AF1 and U2AF2 to facilitate 3' splice site recognition. The protein is predominantly nuclear and is essential for pre-mRNA splicing. Mutations that disrupt its function lead to aberrant splicing of genes involved in hematopoiesis, contributing to myeloid malignancies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZRSR2 Knockout HEK293 Cell Line | EDJ-KQ50745 | Human | 8233 | Details Get a Quote |
| ZRSR2 Knockout HeLa Cell Line | EDJ-KQ54839 | Human | 8233 | Details Get a Quote |
| ZRSR2 Knockout A-549 Cell Line | EDJ-KQ63330 | Human | 8233 | Details Get a Quote |
| ZRSR2 Knockout HCT 116 Cell Line | EDJ-KQ71800 | Human | 8233 | Details Get a Quote |
