RBM25

Summary

RBM25 (RNA binding motif protein 25, HGNC:23244) is a protein-coding gene on chromosome 14q24.2, encoding RNA-binding protein 25 (P49756). RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

Enables mRNA binding activity. Involved in regulation of alternative mRNA splicing, via spliceosome and regulation of apoptotic process. Located in nuclear speck.

Source: NCBI Gene 58517 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 70 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_021239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23244
Approved symbol	RBM25
Name	RNA binding motif protein 25
Location	14q24.2
Locus type	gene with protein product
Status	Approved
Aliases	S164, fSAP94, NET52, Snu71
Ensembl gene	ENSG00000119707
Ensembl biotype	protein_coding
OMIM	612427
Entrez	58517

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261973, ENST00000525161, ENST00000525321, ENST00000526754, ENST00000527432, ENST00000527449, ENST00000528081, ENST00000530978, ENST00000531500, ENST00000532192, ENST00000532483, ENST00000532683, ENST00000895918, ENST00000927342, ENST00000927343, ENST00000927344, ENST00000945459

RefSeq mRNA: 1 — MANE Select: NM_021239 NM_021239

CCDS: CCDS32113

Canonical transcript exons

ENST00000261973 — 19 exons

Exon	Start	End
ENSE00002165155	73119713	73123899
ENSE00002171062	73058534	73058705
ENSE00003535471	73111528	73111802
ENSE00003540930	73112152	73112250
ENSE00003544212	73088001	73088161
ENSE00003554367	73099380	73099433
ENSE00003558080	73076319	73076368
ENSE00003571796	73071627	73071747
ENSE00003578826	73103192	73103478
ENSE00003583737	73110831	73111155
ENSE00003584983	73106196	73106285
ENSE00003585442	73077369	73077536
ENSE00003589521	73099667	73099750
ENSE00003606760	73114286	73114333
ENSE00003643756	73105859	73106081
ENSE00003645897	73107826	73107899
ENSE00003651881	73109342	73109492
ENSE00003786581	73096915	73097100
ENSE00003787165	73083494	73083551

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 106.7962 / max 4070.5615, expressed in 1826 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140495	76.8409	1826
140496	16.2285	1796
140494	3.2452	1473
140511	2.7728	910
140499	2.3643	989
140501	1.4918	700
140502	1.1854	505
140497	0.9393	515
140498	0.7264	355
140500	0.6401	255

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.97	gold quality
sural nerve	UBERON:0015488	99.13	gold quality
medial globus pallidus	UBERON:0002477	99.03	gold quality
visceral pleura	UBERON:0002401	98.73	gold quality
globus pallidus	UBERON:0001875	98.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.54	gold quality
pylorus	UBERON:0001166	98.47	gold quality
tendon	UBERON:0000043	98.23	gold quality
pleura	UBERON:0000977	98.23	gold quality
parietal pleura	UBERON:0002400	98.22	gold quality
cardia of stomach	UBERON:0001162	98.03	gold quality
pericardium	UBERON:0002407	97.51	gold quality
buccal mucosa cell	CL:0002336	97.47	gold quality
seminal vesicle	UBERON:0000998	97.43	gold quality
lateral globus pallidus	UBERON:0002476	97.29	gold quality
calcaneal tendon	UBERON:0003701	97.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.21	gold quality
cranial nerve II	UBERON:0000941	97.17	gold quality
right uterine tube	UBERON:0001302	97.13	gold quality
mucosa of stomach	UBERON:0001199	97.08	gold quality
superior surface of tongue	UBERON:0007371	97.07	gold quality
tibial nerve	UBERON:0001323	97.06	gold quality
body of pancreas	UBERON:0001150	96.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.97	gold quality
endometrium	UBERON:0001295	96.79	gold quality
skin of hip	UBERON:0001554	96.78	gold quality
caput epididymis	UBERON:0004358	96.74	gold quality
urethra	UBERON:0000057	96.70	gold quality
tibia	UBERON:0000979	96.65	gold quality
cerebellar hemisphere	UBERON:0002245	96.64	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	5.27
E-MTAB-9689	no	333.05
E-HCAD-31	no	2.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting RBM25, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 12)

• RED120 may function to couple splicing with mRNA 3’-end formation. (PMID:17560998)
• These data suggest a novel mode for Bcl-x(S) 5’ ss activation in which binding of RBM25 with exonic element CGGGCA may stabilize the pre-mRNA-U1 snRNP through interactions with hLuc7A. (PMID:18663000)
• RBM25/LUC7L3-mediated abnormal SCN5A mRNA splicing reduced Na+ channel current 91.1+/-9.3% to a range known to cause sudden death. (PMID:21859973)
• Structure-guided mutagenesis reveals a positively charged nucleic-acid-binding surface in the RBM25 PWI domain (PMID:23190262)
• Data suggest that RBM25 is required for the viability of multiple human cell lines, suggesting that it could play a key role in pre-mRNA splicing; a region of RBM25 spanning Lys77 binds with high affinity to SRSF2, a crucial protein in exon definition, but only when Lys77 is unmethylated. (RBM25 = RNA binding motif protein 25; SRSF2 = serine- and arginine-rich splicing factor 2) (PMID:28655759)
• RBM25 binds directly to circAMOTL1L and induces its biogenesis, whereas p53 regulates EMT via direct activation of RBM25 gene. (PMID:30531834)
• controls the splicing of key genes, including those encoding the apoptotic regulator BCL-X and the MYC inhibitor BIN1 (PMID:30635567)
• Systematic profiling of alternative splicing events and splicing factors in left- and right-sided colon cancer. (PMID:31586988)
• Prognostic alternative splicing regulatory network of RBM25 in hepatocellular carcinoma. (PMID:33830865)
• Posttranscriptional Regulation of the Human LDL Receptor by the U2-Spliceosome. (PMID:34809444)
• Alternative splicing of BCL-x is controlled by RBM25 binding to a G-quadruplex in BCL-x pre-mRNA. (PMID:37811881)
• RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2. (PMID:39110401)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm25b	ENSDARG00000006395
mus_musculus	Rbm25	ENSMUSG00000010608
rattus_norvegicus	Rbm25	ENSRNOG00000002874
rattus_norvegicus	Rbm25l1	ENSRNOG00000064553
drosophila_melanogaster	CG4119	FBGN0028474
caenorhabditis_elegans		WBGENE00019250

Protein

Protein identifiers

RNA-binding protein 25 — P49756 (reviewed: P49756)

Alternative names: Arg/Glu/Asp-rich protein of 120 kDa, Protein S164, RNA-binding motif protein 25, RNA-binding region-containing protein 7

All UniProt accessions (4): P49756, E9PQU5, E9PSE8, H0YE46

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing. Involved in apoptotic cell death through the regulation of the apoptotic factor BCL2L1 isoform expression. Modulates the ratio of proapoptotic BCL2L1 isoform S to antiapoptotic BCL2L1 isoform L mRNA expression. When overexpressed, stimulates proapoptotic BCL2L1 isoform S 5’-splice site (5’-ss) selection, whereas its depletion caused the accumulation of antiapoptotic BCL2L1 isoform L. Promotes BCL2L1 isoform S 5’-ss usage through the 5’-CGGGCA-3’ RNA sequence. Its association with LUC7L3 promotes U1 snRNP binding to a weak 5’ ss in a 5’-CGGGCA-3’-dependent manner. Binds to the exonic splicing enhancer 5’-CGGGCA-3’ RNA sequence located within exon 2 of the BCL2L1 pre-mRNA. Also involved in the generation of an abnormal and truncated splice form of SCN5A in heart failure.

Subunit / interactions. Interacts with LUC7L3 and SRRM1. Specifically associates with functional splicing complexes, including Sm proteins and U1, U2, U4, U5 and U6 snRNAs. Associates with exon junction complex (EJC) proteins, including APEX1, DDX39B, NCBP1, RBM8A and RNPS1. Interaction with NCBP1 is RNA-dependent.

Subcellular location. Nucleus speckle. Cytoplasm.

Post-translational modifications. Sumoylated.

Domain organisation. The PWI domain binds nucleic acids with significant help from its N-terminal flanking basic region. It has an equal preference for binding to single- or double-stranded species, and it contributes to RBM25 role in modulation of alternative splicing, maybe by mediating RNA-dependent association with LUC7L3.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (4)

UniProt ID	Names	Canonical?
P49756-1	1	yes
P49756-2	2
P49756-3	3
P49756-4	4

RefSeq proteins (1): NP_067062* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002483	PWI_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034268	RBM25_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036483	PWI_dom_sf	Homologous_superfamily
IPR052768	RBM25	Family

Pfam: PF00076, PF01480

UniProt features (50 total): cross-link 8, modified residue 7, helix 7, compositionally biased region 6, region of interest 6, splice variant 6, mutagenesis site 4, domain 2, sequence conflict 2, chain 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3V53	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49756-F1	68.23	0.27

Functional residue map

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

Post-translational modifications (15): 135, 226, 229, 583, 677, 683, 703, 261, 273, 430, 578, 671, 688, 697, 722

Mutagenesis-validated functional residues (4):

Position	Phenotype
734–736	reduced dna/rna binding.
777–778	reduced dna/rna binding.
825	reduced dna/rna binding; when associated with a-828.
828	reduced dna/rna binding; when associated with a-825.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation

MSigDB gene sets: 187 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GCM_ZNF198, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, ONKEN_UVEAL_MELANOMA_UP, chr14q24, WANG_LMO4_TARGETS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, REACTOME_MRNA_3_END_PROCESSING, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, BILD_E2F3_ONCOGENIC_SIGNATURE, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA

GO Biological Process (4): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA processing (GO:0006397), RNA splicing (GO:0008380), regulation of apoptotic process (GO:0042981)

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

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
cellular anatomical structure	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
mRNA metabolic process	1
apoptotic process	1
regulation of programmed cell death	1
nucleic acid binding	1
RNA binding	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2668 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM25	LUC7L	Q9NQ29	982
RBM25	SNRNP70	P08621	958
RBM25	SRRM1	Q8IYB3	956
RBM25	PRPF40A	O75400	931
RBM25	NCBP1	Q09161	925
RBM25	SNRPC	P09234	896
RBM25	SRRM2	Q9UQ35	882
RBM25	SNRPA	P09012	852
RBM25	LUC7L3	O95232	755
RBM25	RBM11	P57052	652
RBM25	YY1	P25490	624
RBM25	RBM4	Q9BWF3	612
RBM25	SF3B1	O75533	593
RBM25	NCBP2	P52298	592
RBM25	KHDRBS1	Q07666	591

IntAct

167 interactions, top by confidence:

A	B	Type	Score
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
NRBP1	TSC22D2	psi-mi:“MI:0914”(association)	0.730
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
POLQ	RBM25	psi-mi:“MI:0915”(physical association)	0.560
RBM25	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
SRRM4	RBM25	psi-mi:“MI:0915”(physical association)	0.560
RBM25	PRPF40A	psi-mi:“MI:0915”(physical association)	0.560
RBM25	PRPF40A	psi-mi:“MI:0914”(association)	0.560
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
TMEM63B	SLC19A2	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
SNRPC	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
RGS9	GNB5	psi-mi:“MI:0914”(association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
CYLD	RBM25	psi-mi:“MI:0407”(direct interaction)	0.440
RBM25	RPS16	psi-mi:“MI:0915”(physical association)	0.400
CAPRIN1	RBM25	psi-mi:“MI:0915”(physical association)	0.400
PTK2	RBM25	psi-mi:“MI:0915”(physical association)	0.400
CHTOP	SAP18	psi-mi:“MI:0915”(physical association)	0.400
RBM25	SF3A2	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	RBM25	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (405): RBM25 (Affinity Capture-RNA), RBM25 (Affinity Capture-RNA), RBM25 (Affinity Capture-RNA), RBM25 (Affinity Capture-MS), RBM25 (Affinity Capture-MS), RBM25 (Affinity Capture-MS), RBM25 (Biochemical Activity), RBM25 (Affinity Capture-MS), RBM25 (Affinity Capture-MS), RBM25 (Two-hybrid), PRPF40A (Co-fractionation), PRPF40B (Co-fractionation), PUF60 (Co-fractionation), RBM25 (Co-fractionation), RBM25 (Co-fractionation)

ESM2 similar proteins: A2RTL5, A6QLS2, B2RY56, O15042, P30189, P30640, P34433, P34594, P49756, Q10580, Q28C44, Q2TBE0, Q3LSS0, Q4V7C9, Q4X1D7, Q502P0, Q5M9I6, Q5M9Q1, Q5PQR4, Q5R7X2, Q5R814, Q5R8J6, Q5VTL8, Q5XHJ5, Q6AXY7, Q6DDA4, Q6DH74, Q6GLZ8, Q6NV83, Q6NWI1, Q6P7Y3, Q7L4I2, Q7SI59, Q7ZVW9, Q7ZYR8, Q80SY5, Q8GXN9, Q8IMP6, Q8N5F7, Q99LX5

Diamond homologs: B2RY56, O04319, P33240, P49756, Q5AI15, Q5RDA3, Q8BIQ5, Q8C7E9, Q8HXM1, Q8VY15, Q8WZK0, Q9H0L4, Q9M9G6, A2SW84, A6PVI3, A8Y1R8, B0W939, B1WC40, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5G279, B7P877, C0H859, C1BY64, O14327, O75821, P15771, P27476, P40561, P42731, P49314

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 208 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
Transport of Mature Transcript to Cytoplasm	7	17.9×	7e-06
mRNA Splicing	24	17.7×	3e-21
RNA Polymerase II Transcription Termination	10	14.7×	1e-07
mRNA 3’-end processing	11	14.5×	2e-08
Processing of Capped Intron-Containing Pre-mRNA	25	13.8×	2e-19
mRNA Polyadenylation	22	13.0×	2e-16
mRNA Splicing - Major Pathway	34	12.5×	3e-25
mRNA Splicing - Minor Pathway	7	10.5×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA cis splicing, via spliceosome	7	37.1×	1e-07
U2-type prespliceosome assembly	8	26.7×	1e-07
regulation of mRNA splicing, via spliceosome	5	23.7×	3e-04
mRNA splicing, via spliceosome	28	13.7×	8e-21
mRNA transcription by RNA polymerase II	7	12.4×	3e-04
positive regulation of transcription elongation by RNA polymerase II	7	11.3×	4e-04
mRNA export from nucleus	7	11.1×	4e-04
positive regulation of miRNA transcription	7	10.9×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3661 predictions. Top by Δscore:

Variant	Effect	Δscore
14:73071623:TTA:T	acceptor_gain	1.0000
14:73071624:TA:T	acceptor_gain	1.0000
14:73071625:A:AG	acceptor_gain	1.0000
14:73071625:A:T	acceptor_gain	1.0000
14:73071625:AGACT:A	acceptor_gain	1.0000
14:73071626:G:GG	acceptor_gain	1.0000
14:73071626:GA:G	acceptor_gain	1.0000
14:73071626:GAC:G	acceptor_gain	1.0000
14:73071626:GACT:G	acceptor_gain	1.0000
14:73071626:GACTG:G	acceptor_gain	1.0000
14:73071743:TCCAG:T	donor_gain	1.0000
14:73071744:CCAG:C	donor_gain	1.0000
14:73071745:CAG:C	donor_gain	1.0000
14:73071746:AG:A	donor_gain	1.0000
14:73071746:AGGT:A	donor_loss	1.0000
14:73071747:GG:G	donor_gain	1.0000
14:73071747:GGTA:G	donor_loss	1.0000
14:73071748:G:GG	donor_gain	1.0000
14:73071748:GTA:G	donor_loss	1.0000
14:73076313:TCTTA:T	acceptor_loss	1.0000
14:73076314:CTTA:C	acceptor_loss	1.0000
14:73076315:TTAGG:T	acceptor_loss	1.0000
14:73076316:TA:T	acceptor_loss	1.0000
14:73076317:A:AG	acceptor_gain	1.0000
14:73076317:AG:A	acceptor_gain	1.0000
14:73076318:G:GG	acceptor_gain	1.0000
14:73076318:G:GT	acceptor_loss	1.0000
14:73076318:GG:G	acceptor_gain	1.0000
14:73076369:G:GG	donor_gain	1.0000
14:73077362:A:AG	acceptor_gain	1.0000

AlphaMissense

5563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:73077478:T:A	V89D	1.000
14:73077480:T:A	F90I	1.000
14:73077480:T:C	F90L	1.000
14:73077480:T:G	F90V	1.000
14:73077481:T:C	F90S	1.000
14:73077481:T:G	F90C	1.000
14:73077482:T:A	F90L	1.000
14:73077482:T:G	F90L	1.000
14:73077484:T:A	V91D	1.000
14:73077486:G:A	G92S	1.000
14:73077486:G:C	G92R	1.000
14:73077486:G:T	G92C	1.000
14:73077487:G:A	G92D	1.000
14:73077487:G:C	G92A	1.000
14:73077487:G:T	G92V	1.000
14:73077491:C:A	N93K	1.000
14:73077491:C:G	N93K	1.000
14:73077493:T:A	I94N	1.000
14:73077493:T:C	I94T	1.000
14:73077493:T:G	I94S	1.000
14:73077505:C:A	A98D	1.000
14:73077510:G:C	D100H	1.000
14:73077510:G:T	D100Y	1.000
14:73077511:A:T	D100V	1.000
14:73077517:T:C	L102P	1.000
14:73077520:T:A	I103K	1.000
14:73077529:T:C	L106P	1.000
14:73077532:T:C	L107S	1.000
14:73083497:T:C	C110R	1.000
14:73083498:G:A	C110Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000014961 (14:73105348 G>A,C), RS1000040566 (14:73097957 G>A), RS1000072095 (14:73112517 G>A), RS1000076325 (14:73073031 T>C), RS1000080886 (14:73063302 A>G), RS1000084669 (14:73065403 C>G,T), RS1000136972 (14:73067372 A>G), RS1000271507 (14:73114384 T>C), RS1000354760 (14:73060942 A>G), RS1000367053 (14:73093753 C>T), RS1000483220 (14:73093921 C>T), RS1000498507 (14:73089547 G>A), RS1000602527 (14:73124360 C>T), RS1000608705 (14:73083959 G>A), RS1000728992 (14:73088334 A>G)

Disease associations

OMIM: gene MIM:612427 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): CIC-rearranged sarcoma (MONDO:0956989)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007269_327	Pulse pressure	5.000000e-13
GCST010002_156	Refractive error	7.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725150 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.85	Kd	14	nM	MOLIBRESIB
7.70	IC50	20	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 9 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179135: Binding affinity against RBM25 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0140	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
bisphenol A	decreases expression, affects cotreatment	3
sodium arsenite	affects cotreatment, increases expression, decreases expression, affects splicing, increases abundance	3
trichostatin A	affects cotreatment, decreases expression	2
Arsenic	affects splicing, increases abundance, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	affects reaction, decreases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Demecolcine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dinitrochlorobenzene	affects binding	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652247	Binding	Binding affinity to human RBM25 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT06414434	PHASE1	ACTIVE_NOT_RECRUITING	BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma
NCT06820957	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body