RBM15
protein-codingRNA binding motif protein 15, the group of WTAP complex|RNA binding motif containing
Gene summary
Members of the SPEN (Split-end) family of proteins, including RBM15, have repressor function in several signaling pathways and may bind to RNA through interaction with spliceosome components (Hiriart et al., 2005 [PubMed 16129689]).[supplied by OMIM, Feb 2009]
MANE transcript
NM_022768.5
Inheritance
—
ClinVar variants
U:110B:5
Top phenotype
Orofacial cleft
gnomAD constraint
pLI —, LoF o/e 0.12
Max pathogenic AF
—
Genomic locus
chr1:110,338,506-110,346,681
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.2 kbLoading mutation effect viewer...
GenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RBM15 variants in ClinVar
not specifiedTotal: 104
not providedTotal: 5
Orofacial cleftTotal: 1
NeuroblastomaTotal: 1
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022768.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 3 | 4 | |||
| missense | 107 | 2 | 109 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 110 | 2 | 3 | 115 |
Loading ClinVar variants...
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
Showing 4 of 16 transcripts
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073605.4 | 2 | MANE Select | |
| Ensembl | ENSP00000358799.3 | 2 | MANE Select | |
| RefSeq | NP_001188474.1 | 2 | Standard | |
| Ensembl | ENSP00000473552.3 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- RNA methylation
- branching involved in blood vessel morphogenesis
- positive regulation of transcription of Notch receptor target
- dosage compensation by inactivation of X chromosome
Molecular Function
- RNA binding
- mRNA binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear speck
- nuclear membrane
- RNA N6-methyladenosine methyltransferase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369784
- Coding exons
- 2
- Length
- 8172
- Individuals with no LoFs
- 125696
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 52
- Defined
- 125748
- p
- 0.000207
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.77 | 464 | 584 | 0.794 | 0.0000345 | 6251 |
| Missense (PolyPhen) | 76 | 181.46 | 0.41882 | 1936 | ||
| Synonymous | -1.66 | 258 | 226 | 1.14 | 0.0000113 | 2171 |
| Loss of Function | 4.70 | 4 | 33.2 | 0.120 | 0.00000258 | 321 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000050 | 0.000046 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00084 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA-binding protein that acts as a key regulator of N6- methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as hematopoietic cell homeostasis, alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA (PubMed:27602518). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (By similarity). Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist (PubMed:27602518). Required for the development of multiple tissues, such as the maintenance of the homeostasis of long-term hematopoietic stem cells and for megakaryocyte (MK) and B-cell differentiation (By similarity). Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation (PubMed:26575292). Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen (By similarity). Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL (By similarity). May also function as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs which are present in many retrotransposons that require to be exported prior to splicing (PubMed:17001072, PubMed:19786495). High affinity binding of pre-mRNA to RBM15 may allow targeting of the mRNP to the export helicase DBP5 in a manner that is independent of splicing-mediated NXF1 deposition, resulting in export prior to splicing (PubMed:17001072, PubMed:19786495). May be implicated in HOX gene regulation (PubMed:11344311). {ECO:0000250|UniProtKB:Q0VBL3, ECO:0000269|PubMed:17001072, ECO:0000269|PubMed:19786495, ECO:0000269|PubMed:26575292, ECO:0000269|PubMed:27602518, ECO:0000305|PubMed:11344311}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving RBM15 may be a cause of acute megakaryoblastic leukemia. Translocation t(1;22)(p13;q13) with MKL1. Although both reciprocal fusion transcripts are detected in acute megakaryoblastic leukemia (AMKL, FAB-M7), the RBM15-MKL1 chimeric protein has all the putative functional domains encoded by each gene and is the candidate oncogene. {ECO:0000269|PubMed:11344311, ECO:0000269|PubMed:11431691}.;
Recessive Scores
- pRec
- 0.430
Intolerance Scores
- LoFtool
- 0.133
- RVIS EVS
- -0.95
- RVIS percentile EVS
- 9.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |