RBM15

RNA binding motif protein 15, the group of WTAP complex|RNA binding motif containing

Basic information

Region (hg38): 1:110338505-110346681

Links

ENSG00000162775 ∙ NCBI:64783 ∙ OMIM:606077 ∙ HGNC:14959 ∙ Uniprot:Q96T37 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RBM15 gene.

• Inborn genetic diseases (25 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RBM15 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3	3
missense			25	1		26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	25	1	3

Variants in RBM15

This is a list of pathogenic ClinVar variants found in the RBM15 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-110339434-C-T		not specified	Uncertain significance (Feb 02, 2024)
1-110339437-G-A		not specified	Uncertain significance (Sep 06, 2022)
1-110339454-C-T		not specified	Uncertain significance (Jun 27, 2022)
1-110339466-C-T		not specified	Uncertain significance (Sep 01, 2021)
1-110339470-T-A		not specified	Uncertain significance (Jun 23, 2021)
1-110339478-A-G		not specified	Uncertain significance (Oct 05, 2023)
1-110339479-C-G		not specified	Uncertain significance (Oct 29, 2021)
1-110339494-G-A		not specified	Uncertain significance (Oct 04, 2022)
1-110339509-G-A		not specified	Uncertain significance (Mar 05, 2024)
1-110339562-G-C		not specified	Uncertain significance (Jun 16, 2023)
1-110339831-C-G		not specified	Uncertain significance (Dec 23, 2022)
1-110339863-C-T		not specified	Uncertain significance (Feb 06, 2023)
1-110339877-T-G		not specified	Uncertain significance (Feb 15, 2023)
1-110339891-C-T			Benign (Dec 24, 2018)
1-110340114-C-T		not specified	Uncertain significance (Dec 28, 2022)
1-110340168-C-T		not specified	Uncertain significance (Jan 21, 2022)
1-110340204-C-T		not specified	Uncertain significance (Sep 17, 2021)
1-110340208-C-T		not specified	Uncertain significance (Dec 21, 2023)
1-110340249-C-T		not specified	Uncertain significance (Nov 13, 2023)
1-110340395-A-C		not specified	Uncertain significance (Oct 03, 2023)
1-110340474-C-T		not specified	Uncertain significance (Aug 10, 2021)
1-110340717-A-G		not specified	Uncertain significance (Aug 16, 2022)
1-110340760-C-T		not specified	Uncertain significance (Nov 08, 2022)
1-110341022-G-A			Benign (Jul 17, 2018)
1-110341075-C-T			Likely benign (Jul 17, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RBM15	protein_coding	protein_coding	ENST00000369784	2	8172

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00526	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.77	464	584	0.794	0.0000345	6251
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000455	0.000448
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000551	0.0000544
Finnish	0.0000503	0.0000462
European (Non-Finnish)	0.000252	0.000246
Middle Eastern	0.0000551	0.0000544
South Asian	0.000168	0.000163
Other	0.000835	0.000815

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.412
• hipred: Y
• hipred_score: 0.662
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rbm15
• Phenotype: cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; neoplasm; immune system phenotype

Gene ontology

• 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;viral process;thrombopoietin-mediated signaling pathway;negative regulation of myeloid cell differentiation;regulation of megakaryocyte differentiation;negative regulation of transcription, DNA-templated;spleen development;ventricular septum morphogenesis;placenta blood vessel development
• Cellular component: nucleus;nucleoplasm;nuclear speck;nuclear membrane;RNA N6-methyladenosine methyltransferase complex
• Molecular function: RNA binding;mRNA binding;protein binding