RBM15: RNA Binding Motif Protein 15
A key regulator of RNA splicing and hematopoiesis, implicated in megakaryoblastic leukemia and intellectual disability.
Gene Information Card
| Symbol | RBM15 |
|---|---|
| Full Name | RNA Binding Motif Protein 15 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p13.3 |
| NCBI Gene ID | 64783 ncbi.nlm.nih.gov/gene/64783 |
| Ensembl ID | ENSG00000162775 |
| UniProt ID | Q96T37 |
| OMIM ID | 606077 |
| HGNC ID | 29059 |
| Aliases | OTT, SPEN |
Description
RBM15 (RNA Binding Motif Protein 15) encodes a member of the SPEN (Split Ends) family of RNA-binding proteins. It functions as a key regulator of RNA splicing, mRNA export, and transcriptional co-repression. RBM15 is essential for normal hematopoiesis, particularly megakaryocyte and B-cell development. The gene is recurrently rearranged in acute megakaryoblastic leukemia (AMKL) and is associated with X-linked intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute megakaryoblastic leukemia (AMKL) | Recurrent t(1;22)(p13;q13) translocation fusing RBM15 with MKL1, creating an oncogenic fusion protein that disrupts transcriptional regulation and hematopoiesis. | PMID: 11526407; COSMIC |
| X-linked intellectual disability | Missense and loss-of-function mutations in RBM15 impair RNA splicing and neuronal development. | PMID: 26026792; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Brain | 8.9 | Low |
| Testis | 7.3 | Low |
| Spleen | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.1 | High expression |
| HEK293 (embryonic kidney) | 9.4 | Moderate expression |
| HeLa (cervical cancer) | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | Rare | Loss of RNA-binding activity; associated with intellectual disability |
| t(1;22)(p13;q13) RBM15-MKL1 fusion | Chromosomal rearrangement | Recurrent in AMKL | Oncogenic fusion protein; disrupts normal hematopoiesis |
| c.789delG (p.Gly264Alafs*12) | Frameshift deletion | Rare | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in RBM15 lead to haploinsufficiency, impairing RNA splicing and hematopoietic differentiation.
Gain of Function (GOF)
The RBM15-MKL1 fusion protein exhibits aberrant transcriptional activation, promoting megakaryoblastic proliferation.
Dominant Negative (DN)
Some missense mutations in the RNA-binding domain may interfere with wild-type RBM15 function, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • mRNA processing (GO:0006397) |
| • RNA splicing (GO:0008380) | • nucleoplasm (GO:0005654) |
| • intracellular ribonucleoprotein complex (GO:0030529) | • positive regulation of transcription by RNA polymerase II (GO:0045944) |
Pathways
• RNA splicing (Reactome: R-HSA-72163)
• mRNA 3'-end processing (Reactome: R-HSA-72187)
• Transcriptional regulation by RUNX1 (KEGG: hsa05221)
Protein Summary
RBM15 is a 977-amino acid RNA-binding protein containing three N-terminal RNA recognition motifs (RRMs) and a C-terminal SPEN domain. It shuttles between the nucleus and cytoplasm, regulating alternative splicing and mRNA export. The protein interacts with the spliceosome and transcription factors such as RUNX1. In leukemia, the RBM15-MKL1 fusion retains the RRMs but replaces the C-terminus with MKL1's transactivation domain, leading to aberrant gene expression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RBM15 Knockout HEK293 Cell Line | EDJ-KQ3177 | Human | 64783 | Details Get a Quote |
| RBM15B Knockout HEK293 Cell Line | EDJ-KQ9067 | Human | 29890 | Details Get a Quote |
| RBM15 Knockout HCT 116 Cell Line | EDJ-KQ23220 | Human | 64783 | Details Get a Quote |
| RBM15 Knockout A-549 Cell Line | EDJ-KQ24603 | Human | 64783 | Details Get a Quote |
| RBM15 Knockout HeLa Cell Line | EDJ-KQ24605 | Human | 64783 | Details Get a Quote |
| RBM15B Knockout HCT 116 Cell Line | EDJ-KQ34286 | Human | 29890 | Details Get a Quote |
| RBM15B Knockout A-549 Cell Line | EDJ-KQ35540 | Human | 29890 | Details Get a Quote |
| RBM15B Knockout HeLa Cell Line | EDJ-KQ35542 | Human | 29890 | Details Get a Quote |
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