RBM15

Summary

RBM15 (RNA binding motif protein 15, HGNC:14959) is a protein-coding gene on chromosome 1p13.3, encoding RNA-binding protein 15 (Q96T37). 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. It is a selective cancer dependency (DepMap: 18.9% of cell lines).

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]).

Source: NCBI Gene 64783 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 69 total
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 18.9% of screened cell lines
• MANE Select transcript: NM_022768

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14959
Approved symbol	RBM15
Name	RNA binding motif protein 15
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	OTT, OTT1
Ensembl gene	ENSG00000162775
Ensembl biotype	protein_coding
OMIM	606077
Entrez	64783

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000369784, ENST00000487146, ENST00000602849, ENST00000617047, ENST00000618772, ENST00000650953, ENST00000652342, ENST00000652747, ENST00000654015

RefSeq mRNA: 2 — MANE Select: NM_022768 NM_001201545, NM_022768

CCDS: CCDS59198, CCDS822

Canonical transcript exons

ENST00000369784 — 3 exons

Exon	Start	End
ENSE00001380197	110345539	110345649
ENSE00003568911	110346308	110346677
ENSE00003912149	110339377	110342268

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3754 / max 330.0133, expressed in 1812 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4535	21.1805	1810
4536	0.9811	551
4537	0.2138	83

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.11	gold quality
sperm	CL:0000019	96.73	gold quality
endothelial cell	CL:0000115	96.63	gold quality
oocyte	CL:0000023	96.14	gold quality
male germ cell	CL:0000015	95.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.53	gold quality
gingival epithelium	UBERON:0001949	94.24	gold quality
tongue squamous epithelium	UBERON:0006919	93.64	gold quality
choroid plexus epithelium	UBERON:0003911	93.18	gold quality
middle temporal gyrus	UBERON:0002771	92.77	gold quality
cervix squamous epithelium	UBERON:0006922	92.66	gold quality
squamous epithelium	UBERON:0006914	92.52	gold quality
parietal pleura	UBERON:0002400	92.32	gold quality
pleura	UBERON:0000977	91.69	gold quality
gingiva	UBERON:0001828	91.64	gold quality
esophagus squamous epithelium	UBERON:0006920	91.20	gold quality
visceral pleura	UBERON:0002401	91.12	gold quality
epithelium of nasopharynx	UBERON:0001951	90.87	gold quality
hair follicle	UBERON:0002073	90.65	gold quality
amniotic fluid	UBERON:0000173	90.63	gold quality
cranial nerve II	UBERON:0000941	90.18	gold quality
bone marrow	UBERON:0002371	89.82	gold quality
germinal epithelium of ovary	UBERON:0001304	89.74	gold quality
cartilage tissue	UBERON:0002418	89.31	gold quality
trabecular bone tissue	UBERON:0002483	89.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.22	gold quality
thymus	UBERON:0002370	88.91	gold quality
metanephric glomerulus	UBERON:0004736	88.90	gold quality
epithelium of esophagus	UBERON:0001976	88.66	gold quality
renal glomerulus	UBERON:0000074	88.60	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-10	no	177.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BARX2, RBPJ

miRNA regulators (miRDB)

56 targeting RBM15, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-4672	99.50	71.58	2893

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 23)

• Fusion with MKL1 protein in acute myeloid leukemi. (PMID:15849773)
• functional and spatial changes of OTT and BSAC caused by the fusion might perturb their functions, culminating in the development of acute megakaryoblastic leukemia. (PMID:18667423)
• The deregulated activation of MAL-dependent and -independent promoters results in tissue-specific functions of OTT-MAL.[OTT-MAL] (PMID:18710951)
• HHV-8 ORF57 interacts with RBM15 and OTT3 to promote expression of viral intronless genes. (PMID:21106733)
• A four-way variant translocation originating the RBM15-MKL1 fusion gene is associated with acute megakaryoblastic leukemia. (PMID:21370421)
• RBM15 does indeed play a critical role in the survival of chronic myelogenous leukemia (CML) cells, which may have potential application in designing molecular therapies for CML treatment. (PMID:22497198)
• both Rbm15 and the leukemogenic Rbm15-Mkl1 fusion protein interact with the Setd1b histone H3-Lys4 methyltransferase (PMID:22927943)
• OTT1 regulates the alternative splicing of Mpl-TR, a truncated isoform of c-Mpl, which modulates Thrombopoietin-mediated signaling. (PMID:25468569)
• The authors demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4). (PMID:26575292)
• Study has shown that MED12 mutations can be heterogeneous in both synchronous and recurrent phyllodes tumor unlike TERT mutations. Authors have also shown that RBM15 mutations may be important in the pathogenesis of borderline/malignant phyllodes tumors. (PMID:29315289)
• RBM15 facilitates laryngeal squamous cell carcinoma progression by regulating TMBIM6 stability through IGF2BP3 dependent. (PMID:33637103)
• RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes. (PMID:34301919)
• Knockdown RBM15 Inhibits Colorectal Cancer Cell Proliferation and Metastasis Via N6-Methyladenosine (m6A) Modification of MyD88 mRNA. (PMID:34842457)
• Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11. (PMID:35381326)
• The prognostic value of N6-methyladenosine RBM15 regulators in lung adenocarcinoma. (PMID:35809319)
• RBM15 silencing promotes ferroptosis by regulating the TGF-beta/Smad2 pathway in lung cancer. (PMID:36715115)
• RBM15 m[6] A modification-mediated OTUB2 upregulation promotes cervical cancer progression via the AKT/mTOR signaling. (PMID:37334762)
• Knockdown of RBM15 inhibits tumor progression and the JAK-STAT signaling pathway in cervical cancer. (PMID:37474926)
• RBM15-mediating MDR1 mRNA m[6]A methylation regulated by the TGF-beta signaling pathway in paclitaxel-resistant ovarian cancer. (PMID:37594126)
• The m[6]A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism. (PMID:38825643)
• RBM15-Mediated N6-Methyl Adenosine (m6A) Modification of EZH2 Drives the Epithelial-Mesenchymal Transition of Cervical Cancer. (PMID:38842201)
• Identification of RBM15 as a prognostic biomarker in prostate cancer involving the regulation of prognostic m6A-related lncRNAs. (PMID:39118157)
• RBM15 Promotes High Glucose-Induced Lens Epithelial Cell Injury by Inducing PRNP N6-Methyladenine Modification During Diabetic Cataract. (PMID:39206850)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm15	ENSDARG00000073847
mus_musculus	Rbm15	ENSMUSG00000048109
rattus_norvegicus	Rbm15	ENSRNOG00000047499
drosophila_melanogaster	nonA	FBGN0004227
drosophila_melanogaster	nonA-l	FBGN0015520
drosophila_melanogaster	nito	FBGN0027548

Paralogs (7): SPEN (ENSG00000065526), SFPQ (ENSG00000116560), PSPC1 (ENSG00000121390), NONO (ENSG00000147140), RAVER1 (ENSG00000161847), RAVER2 (ENSG00000162437), RBM15B (ENSG00000259956)

Protein

Protein identifiers

RNA-binding protein 15 — Q96T37 (reviewed: Q96T37)

Alternative names: One-twenty two protein 1, RNA-binding motif protein 15

All UniProt accessions (4): A0A087WWP4, A0A494C001, A0A499FJY3, Q96T37

UniProt curated annotations — full annotation on UniProt →

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. 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. Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex. 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. 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. Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation. Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen. Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL. 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. 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. May be implicated in HOX gene regulation.

Subunit / interactions. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of METTL3 and METTL14. The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B). Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3. Interacts with RBPJ. Interacts (via SPOC domain) with SETD1B. Interacts with NXF1, the interaction is required to promote mRNA export. Interacts with SF3B1. (Microbial infection) Interacts with Epstein-Barr virus BSFL2/BMLF1.

Subcellular location. Nucleus speckle. Nucleus. Nucleoplasm. Nucleus envelope. Nucleus membrane.

Post-translational modifications. Methylated at Arg-578 by PRMT1, leading to promote ubiquitination by CNOT4 and subsequent degradation by the proteasome. Ubiquitinated by CNOT4 following methylation at Arg-578 by PRMT1.

Disease relevance. 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.

Miscellaneous. Produced by alternative initiation of isoform 2.

Similarity. Belongs to the RRM Spen family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96T37-1	1, RBM15s+ae	yes
Q96T37-2	2, RBM15L
Q96T37-3	3, RBM15S
Q96T37-4	4

RefSeq proteins (2): NP_001188474, NP_073605* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR010912	SPOC_met	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR012921	SPOC_C	Domain
IPR016194	SPOC-like_C_dom_sf	Homologous_superfamily
IPR034470	RBM15_RRM1	Domain
IPR034472	RBM15_RRM2	Domain
IPR034473	RBM15_RRM3	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076, PF07744

UniProt features (80 total): modified residue 25, compositionally biased region 13, strand 9, helix 6, cross-link 5, mutagenesis site 5, domain 4, region of interest 4, splice variant 3, sequence conflict 3, chain 1, site 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7Z27	X-RAY DIFFRACTION	1.45
9L0T	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96T37-F1	59.16	0.21

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 954–955 (breakpoint for translocation to form rbm15-mkl1)

Post-translational modifications (30): 109, 179, 208, 210, 253, 257, 259, 266, 292, 294, 365, 450, 568, 578, 578, 622, 656, 670, 674, 700 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
574–578	decreased, but not abolished methylation by prmt1.
578	decreased methylation by prmt1, leading to decreased ubiquitination by cnot4.
795	disrupts interaction with setd1b.
898	disrupts interaction with setd1b.
923	disrupts interaction with setd1b.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 233 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_RNA_METHYLATION, GOBP_PLACENTA_BLOOD_VESSEL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_REGULATION_OF_HEMOPOIESIS

GO Biological Process (12): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), RNA methylation (GO:0001510), branching involved in blood vessel morphogenesis (GO:0001569), positive regulation of transcription of Notch receptor target (GO:0007221), dosage compensation by inactivation of X chromosome (GO:0009048), thrombopoietin-mediated signaling pathway (GO:0038163), negative regulation of myeloid cell differentiation (GO:0045638), regulation of megakaryocyte differentiation (GO:0045652), spleen development (GO:0048536), ventricular septum morphogenesis (GO:0060412), placenta blood vessel development (GO:0060674), regulation of myeloid cell differentiation (GO:0045637)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), nuclear membrane (GO:0031965), RNA N6-methyladenosine methyltransferase complex (GO:0036396), nuclear envelope (GO:0005635), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
myeloid cell differentiation	2
regulation of myeloid cell differentiation	2
binding	2
cellular anatomical structure	2
nucleus	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
RNA modification	1
macromolecule methylation	1
angiogenesis	1
blood vessel morphogenesis	1
branching morphogenesis of an epithelial tube	1
Notch signaling pathway	1
positive regulation of transcription by RNA polymerase II	1
sex-chromosome dosage compensation	1
heterochromatin formation	1
chemokine-mediated signaling pathway	1
negative regulation of cell differentiation	1
megakaryocyte differentiation	1
hematopoietic or lymphoid organ development	1
ventricular septum development	1
cardiac septum morphogenesis	1
blood vessel development	1
placenta development	1
regulation of hemopoiesis	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear ribonucleoprotein granule	1
nuclear envelope	1
organelle membrane	1
methyltransferase complex	1
endomembrane system	1
organelle envelope	1

Protein interactions and networks

STRING

1642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM15	ZC3H13	Q5T200	998
RBM15	VIRMA	Q69YN4	998
RBM15	METTL3	Q86U44	998
RBM15	WTAP	Q15007	998
RBM15	METTL14	Q9HCE5	998
RBM15	CBLL1	Q75N03	997
RBM15	METTL16	Q86W50	996
RBM15	RBM15B	Q8NDT2	983
RBM15	MRTFA	Q969V6	953
RBM15	NXF1	Q9UBU9	926
RBM15	YTHDC1	Q96MU7	891
RBM15	YTHDC2	Q9H6S0	889
RBM15	ALKBH5	Q6P6C2	888
RBM15	YTHDF1	Q9BYJ9	883
RBM15	METTL4	Q8N3J2	859

IntAct

145 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
NCKIPSD	GEMIN2	psi-mi:“MI:0914”(association)	0.640
PHLPP1	USP12	psi-mi:“MI:0914”(association)	0.570
CALCOCO2	RBM15	psi-mi:“MI:0915”(physical association)	0.560
RBM15	NAV2	psi-mi:“MI:0915”(physical association)	0.560
RBM15	DDX17	psi-mi:“MI:0915”(physical association)	0.560
RBM15	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
RBM15	CEP44	psi-mi:“MI:0915”(physical association)	0.560
NAV2	RBM15	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	RBM15	psi-mi:“MI:0915”(physical association)	0.560
DDX17	RBM15	psi-mi:“MI:0915”(physical association)	0.560
RBM15	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.560
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
TOR1AIP2	TMEM223	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
RBM15B	YWHAH	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPLP0	GTPBP10	psi-mi:“MI:0914”(association)	0.530

BioGRID (245): RBM15 (Two-hybrid), RBM15 (Two-hybrid), CEP44 (Two-hybrid), LZTS2 (Two-hybrid), NAV2 (Two-hybrid), RBM15 (Affinity Capture-MS), RBM15 (Affinity Capture-MS), RBM15 (Affinity Capture-MS), RBM15 (Affinity Capture-MS), RBM15 (Co-fractionation), RBM15 (Co-fractionation), RBM15 (Co-fractionation), RBM15 (Co-fractionation), RBM15 (Affinity Capture-MS), RBM15 (Affinity Capture-MS)

ESM2 similar proteins: A1A6K6, B9DFV2, F4HWF9, F4JCU0, F4JP52, F4KDN0, G7ID19, O22812, O80567, O80678, Q08A72, Q0D3J9, Q0P5D2, Q0VBL3, Q10M00, Q16630, Q3MHY8, Q5NVH8, Q5XI29, Q5ZL34, Q6ATR0, Q6DDW4, Q6JB11, Q6NWC6, Q6ZK57, Q7KMJ6, Q7Z5Q1, Q812E0, Q8BTV2, Q8H0P8, Q8LPQ9, Q8N684, Q8W4I9, Q940D0, Q94CJ8, Q96T37, Q9CQT2, Q9LES2, Q9LKA4, Q9LKA5

Diamond homologs: A2A5N3, A2VDN6, A4QUF0, A5A6M3, A5DNX9, A6NDE4, A6NEQ0, F1QB54, F4I3B3, F4KIA8, O15042, O35698, O60176, O64380, O75494, O75526, P0C7P1, P0CB38, P0CP46, P0CP47, P0DJD3, P0DJD4, P11940, P20965, P29341, P31209, P31483, P32588, P32831, P38159, P42731, P52912, P61286, P70318, Q01085, Q05196, Q09511, Q0J9Y2, Q0VBL3, Q0WW84

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RBM15	“form complex”	RBM15/NXF1	binding
RBM15	up-regulates	SON	binding
CNOT4	“down-regulates quantity by destabilization”	RBM15	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 173 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	5	33.4×	1e-05
Activation of BH3-only proteins	6	26.1×	5e-06
Transport of Mature Transcript to Cytoplasm	5	16.7×	4e-04
mRNA 3’-end processing	9	15.5×	5e-07
Intrinsic Pathway for Apoptosis	6	15.4×	9e-05
mRNA Splicing	15	14.4×	1e-11
Processing of Capped Intron-Containing Pre-mRNA	19	13.7×	3e-14
Transport of Mature mRNA derived from an Intron-Containing Transcript	9	12.0×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal complex assembly	7	27.7×	2e-06
negative regulation of mRNA splicing, via spliceosome	5	25.2×	2e-04
RNA splicing, via transesterification reactions	5	20.5×	5e-04
mRNA export from nucleus	9	17.5×	1e-06
regulation of alternative mRNA splicing, via spliceosome	8	12.8×	4e-05
mRNA splicing, via spliceosome	20	12.1×	3e-13
RNA splicing	13	7.5×	5e-06
mRNA processing	12	6.2×	1e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — LUAD.

Clinical variants and AI predictions

ClinVar

69 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

19 predictions. Top by Δscore:

Variant	Effect	Δscore
1:110339726:T:TA	donor_gain	0.5200
1:110339727:G:GA	donor_gain	0.5200
1:110341657:G:GT	donor_gain	0.4900
1:110341716:G:GT	donor_gain	0.3800
1:110340003:G:GG	donor_gain	0.3500
1:110339621:G:GT	donor_gain	0.3300
1:110339998:GTGAT:G	donor_gain	0.3200
1:110340001:AT:A	donor_gain	0.3100
1:110340002:T:G	donor_gain	0.3100
1:110339592:G:T	donor_gain	0.3000
1:110341694:G:GT	donor_gain	0.3000
1:110339738:G:GG	donor_gain	0.2900
1:110339735:C:T	donor_gain	0.2800
1:110339737:A:AG	donor_gain	0.2800
1:110340000:GAT:G	donor_gain	0.2600
1:110339606:C:CA	donor_gain	0.2500
1:110339742:G:GT	donor_gain	0.2500
1:110339545:G:T	donor_gain	0.2400
1:110339612:G:GT	donor_gain	0.2100

AlphaMissense

6275 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:110339920:T:A	L172Q	1.000
1:110339920:T:C	L172P	1.000
1:110339926:T:A	I174K	1.000
1:110339974:T:A	L190Q	1.000
1:110339974:T:C	L190P	1.000
1:110339985:T:A	F194I	1.000
1:110339985:T:C	F194L	1.000
1:110339986:T:C	F194S	1.000
1:110339987:C:A	F194L	1.000
1:110339987:C:G	F194L	1.000
1:110339994:T:C	F197L	1.000
1:110339995:T:C	F197S	1.000
1:110339996:C:A	F197L	1.000
1:110339996:C:G	F197L	1.000
1:110339997:G:C	G198R	1.000
1:110339997:G:T	G198C	1.000
1:110339998:G:A	G198D	1.000
1:110339998:G:T	G198V	1.000
1:110340058:C:A	A218D	1.000
1:110340064:T:A	V220E	1.000
1:110340069:T:A	F222I	1.000
1:110340069:T:C	F222L	1.000
1:110340069:T:G	F222V	1.000
1:110340070:T:C	F222S	1.000
1:110340070:T:G	F222C	1.000
1:110340071:C:A	F222L	1.000
1:110340071:C:G	F222L	1.000
1:110340097:C:A	A231D	1.000
1:110340532:T:A	L376H	1.000
1:110340532:T:C	L376P	1.000

dbSNP variants (sampled 300 via entrez): RS1000282838 (1:110338407 C>A,T), RS1000360362 (1:110345744 T>A), RS1000370437 (1:110345274 T>C), RS1000477129 (1:110338279 G>C,T), RS1001540817 (1:110343737 C>A,G,T), RS1001885264 (1:110339244 A>G,T), RS1002053836 (1:110344023 GA>G), RS1002486500 (1:110340614 A>G), RS1003298834 (1:110338510 G>T), RS1003352690 (1:110338377 G>C), RS1003600718 (1:110345406 A>G), RS1003824314 (1:110340466 G>C), RS1003899906 (1:110342546 G>A), RS1004020514 (1:110345200 A>G), RS1004231127 (1:110338483 G>A)

Disease associations

OMIM: gene MIM:606077 | disease phenotypes: MIM:119530

GenCC curated gene-disease

Mondo (1): orofacial cleft (MONDO:0000358)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067173 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
Resveratrol	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	affects sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
ferrous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
cadmium sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	increases expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1
enzalutamide	affects expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Arsenic	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652245	Binding	Binding affinity to human RBM15 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 1 hybrid cell line, 1 embryonic stem cell, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8DN	Ubigene AC16 RBM15 KO	Hybrid cell line
CVCL_JL69	H9 RM	Embryonic stem cell	Female
CVCL_JL71	PBMC2-iPS4F8 RM	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

5 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04342234	Not specified	RECRUITING	Neural Network to Calculate Morphology of the Cleft Palate to Reduce Cleft Lip and Palate Treatment Burden.
NCT05867862	Not specified	COMPLETED	Implementation of a Program to Strengthen Oral Hygiene in Patient With Cleft Deformities
NCT06880094	Not specified	RECRUITING	Study of Congenital Orofacial Clefts by Implementing Optical Genome Mapping
NCT07340008	Not specified	RECRUITING	Analgosedation With Ketamine, Nalbuphine, or Dexmedetomidine for Suture Removal in Children After Cleft Surgery
NCT07557576	Not specified	RECRUITING	Effect of Opioid-Free vs Opioid-Based Anesthesia on Postoperative Pain and Emergence Agitation in Children Undergoing Cleft Surgery