RBM39

Summary

RBM39 (RNA binding motif protein 39, HGNC:15923) is a protein-coding gene on chromosome 20q11.22, encoding RNA-binding protein 39 (Q14498). RNA-binding protein that acts as a pre-mRNA splicing factor. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

This gene encodes a member of the U2AF65 family of proteins. The encoded protein is found in the nucleus, where it co-localizes with core spliceosomal proteins. It has been shown to play a role in both steroid hormone receptor-mediated transcription and alternative splicing, and it is also a transcriptional coregulator of the viral oncoprotein v-Rel. Multiple transcript variants have been observed for this gene. A related pseudogene has been identified on chromosome X.

Source: NCBI Gene 9584 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 48 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_184234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15923
Approved symbol	RBM39
Name	RNA binding motif protein 39
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	CC1.3, HCC1, CAPER, fSAP59, CAPERalpha
Ensembl gene	ENSG00000131051
Ensembl biotype	protein_coding
OMIM	604739
Entrez	9584

Gene structure

Transcript identifiers

Ensembl transcripts: 79 — 40 protein_coding, 16 nonsense_mediated_decay, 16 retained_intron, 7 protein_coding_CDS_not_defined

ENST00000253363, ENST00000338163, ENST00000361162, ENST00000374038, ENST00000397370, ENST00000403542, ENST00000412738, ENST00000416108, ENST00000416529, ENST00000425184, ENST00000426951, ENST00000429968, ENST00000433027, ENST00000434927, ENST00000442447, ENST00000444878, ENST00000448303, ENST00000449489, ENST00000453310, ENST00000455343, ENST00000461283, ENST00000461849, ENST00000463004, ENST00000463098, ENST00000465158, ENST00000468086, ENST00000470563, ENST00000471635, ENST00000475651, ENST00000476806, ENST00000477334, ENST00000481037, ENST00000482563, ENST00000487604, ENST00000490354, ENST00000490484, ENST00000492779, ENST00000493853, ENST00000494274, ENST00000495293, ENST00000496183, ENST00000498280, ENST00000528062, ENST00000615771, ENST00000639702, ENST00000656873, ENST00000665058, ENST00000862897, ENST00000862898, ENST00000862899, ENST00000862900, ENST00000862901, ENST00000862902, ENST00000862903, ENST00000862904, ENST00000862905, ENST00000862906, ENST00000862907, ENST00000862908, ENST00000862909, ENST00000862910, ENST00000913155, ENST00000913156, ENST00000913157, ENST00000913158, ENST00000913159, ENST00000913160, ENST00000913161, ENST00000913162, ENST00000913163, ENST00000913164, ENST00000913165, ENST00000954300, ENST00000954301, ENST00000954302, ENST00000954303, ENST00000954304, ENST00000954305, ENST00000954306

RefSeq mRNA: 7 — MANE Select: NM_184234 NM_001242599, NM_001242600, NM_001323422, NM_001323423, NM_001323424, NM_004902, NM_184234

CCDS: CCDS13265, CCDS13266, CCDS56186

Canonical transcript exons

ENST00000253363 — 17 exons

Exon	Start	End
ENSE00001938005	35741941	35742260
ENSE00003467211	35724570	35724722
ENSE00003486148	35729462	35729527
ENSE00003522698	35709224	35709274
ENSE00003527284	35714185	35714389
ENSE00003531899	35704668	35704746
ENSE00003536853	35729312	35729365
ENSE00003572099	35705225	35705330
ENSE00003575057	35716740	35716805
ENSE00003592970	35725038	35725155
ENSE00003594038	35707120	35707201
ENSE00003620056	35713019	35713096
ENSE00003652108	35721740	35721877
ENSE00003673015	35731941	35732135
ENSE00003696124	35740824	35740887
ENSE00003700303	35738968	35739017
ENSE00003894015	35701347	35704581

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 214.7579 / max 1860.9602, expressed in 1825 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187093	210.2208	1825
187094	1.8386	1113
187087	1.3822	617
187091	0.8911	370
187088	0.2755	120
187089	0.1495	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.57	gold quality
calcaneal tendon	UBERON:0003701	99.53	gold quality
right lobe of thyroid gland	UBERON:0001119	99.50	gold quality
left ovary	UBERON:0002119	99.49	gold quality
right ovary	UBERON:0002118	99.48	gold quality
left lobe of thyroid gland	UBERON:0001120	99.47	gold quality
sural nerve	UBERON:0015488	99.46	gold quality
body of uterus	UBERON:0009853	99.43	gold quality
adrenal tissue	UBERON:0018303	99.42	gold quality
endocervix	UBERON:0000458	99.40	gold quality
tibial nerve	UBERON:0001323	99.40	gold quality
ventricular zone	UBERON:0003053	99.40	gold quality
adenohypophysis	UBERON:0002196	99.38	gold quality
bone marrow cell	CL:0002092	99.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.37	gold quality
right lung	UBERON:0002167	99.34	gold quality
granulocyte	CL:0000094	99.33	gold quality
body of pancreas	UBERON:0001150	99.32	gold quality
metanephros cortex	UBERON:0010533	99.32	gold quality
colonic epithelium	UBERON:0000397	99.30	gold quality
left uterine tube	UBERON:0001303	99.28	gold quality
mucosa of stomach	UBERON:0001199	99.27	gold quality
skin of abdomen	UBERON:0001416	99.27	gold quality
minor salivary gland	UBERON:0001830	99.27	gold quality
cerebellar hemisphere	UBERON:0002245	99.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.26	gold quality
upper lobe of left lung	UBERON:0008952	99.25	gold quality
body of stomach	UBERON:0001161	99.24	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.23	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	1870.17
E-HCAD-31	yes	1535.77
E-HCAD-4	yes	41.93
E-CURD-122	yes	28.19
E-CURD-88	yes	21.20
E-MTAB-6678	yes	9.49
E-MTAB-11011	no	2302.37
E-MTAB-8911	no	1082.78
E-MTAB-7316	no	1044.75
E-MTAB-7606	no	1026.07
E-CURD-46	no	12.65
E-HCAD-1	no	5.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, MYC

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 27)

• This paper describes the mouse gene. (PMID:11704680)
• 10 genes were down-regulated following treatment of the T-ALL cells with 0.15 and 1.5 microg/mL of metal ores at 72 h (PMID:15747776)
• this study identifies CAPERalpha (RNA binding motif protein 39) as a new transcriptional coregulator for v-Rel and reveals an important role in modulating Rel’s oncogenic activity. (PMID:18753212)
• Analysis of human breast cancer samples revealed that CAPER is overexpressed and undergoes a cytoplasmic-to-nuclear shift during the transition from pre-malignancy to ductal carcinoma in situ (PMID:19342371)
• Increased VEGF(165) expression is secondary to the down-regulation of CAPER-alpha by EWS/FLI-1. CAPER-alpha mediates alternative splicing and controls the shift from VEGF(189) to VEGF(165) . (PMID:22009261)
• Data show that CSE1L, DIDO1 and RBM39 mRNA expression levels correlated with chromosome 20q DNA copy number status. (PMID:22711543)
• Knockdown of CAPER expression markedly reduced human breast cancer cell proliferation in both in vitro and in vivo settings. Mechanistically, knockdown of CAPER abrogated the activity of proliferative and protein synthesis pathways. (PMID:24621503)
• Our data suggest that overexpression of HCC1/CAPERalpha may increase the proliferation and migration of NSCLC cells, and HCC1/CAPERalpha could be a promising biomarker for lung cancer (PMID:24643682)
• identify SF3b155 as the relevant ULM-containing partner of full-length CAPERalpha in human cell extracts. (PMID:24795046)
• Decreased expression of CAPERalpha appears to be correlated with appearance of microvessels in hepatocellular carcinoma (PMID:26934653)
• mammalian c-Abl plays an important role in steroid hormone receptor-mediated transcription by regulating RBM39 (PMID:27018250)
• This study therefore establishes a structural basis for specific UHM-ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells. (PMID:27050129)
• RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65. (PMID:27354116)
• The results provide a mechanism for exon 16 3’ splice site activation in which a coordinated effort among TIA1, Pcbp1, and RBM39 stabilizes or increases U2 snRNP recruitment, enhances spliceosome A complex formation, and facilitates exon definition through RBM39-mediated splicing regulation. (PMID:28193846)
• The splicing factors U2AF65 and CAPERalpha engage multivalent interactions through their low complexity RS domains. The resulting assemblies can bridge the U2snRNP component SF3b155 with repeated polypyrimidine tracts in introns, to promote alternative splicing. (PMID:31271494)
• aryl-sulfonamides neo-functionalize a shallow, non-conserved pocket on DCAF15 to selectively bind and degrade RBM39 and the closely related splicing factor RBM23 without the requirement for a high-affinity ligand (PMID:31686031)
• structural and mutational analysis of how indisulam mediates the DCAF15-RBM39 interaction (PMID:31819272)
• Inhibiting an RBM39/MLL1 epigenomic regulatory complex with dominant-negative peptides disrupts cancer cell transcription and proliferation. (PMID:34077726)
• Identification of a small molecule splicing inhibitor targeting UHM domains. (PMID:34520118)
• The transcription factor c-Jun inhibits RBM39 to reprogram pre-mRNA splicing during genotoxic stress. (PMID:36477312)
• Insights on the biological functions and diverse regulation of RNA-binding protein 39 and their implication in human diseases. (PMID:36535628)
• Molecular basis of RNA-binding and autoregulation by the cancer-associated splicing factor RBM39. (PMID:37666821)
• Arginine reprograms metabolism in liver cancer via RBM39. (PMID:37804830)
• Regulatory role of RBM39 in acute myeloid leukemia: Mediation through the PI3K/AKT pathway. (PMID:37852323)
• RBM39: A druggable metabolic sensor linking RNA splicing, transcriptional regulation, and metabolic reprogramming in cancer. (PMID:38065060)
• MORC2 regulates RBM39-mediated CDK5RAP2 alternative splicing to promote EMT and metastasis in colon cancer. (PMID:39048555)
• Deubiquitinating enzyme USP39 promotes the growth and metastasis of gastric cancer cells by modulating the degradation of RNA-binding protein RBM39. (PMID:39260689)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm39a	ENSDARG00000011613
danio_rerio	rbm39b	ENSDARG00000041853
mus_musculus	Rbm39	ENSMUSG00000027620
rattus_norvegicus	Rbm39	ENSRNOG00000019848

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), A1CF (ENSG00000148584), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), HNRNPDL (ENSG00000152795), MSI2 (ENSG00000153944), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBMXL2 (ENSG00000170748), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395), DND1 (ENSG00000256453)

Protein

Protein identifiers

RNA-binding protein 39 — Q14498 (reviewed: Q14498)

Alternative names: CAPER alpha, Hepatocellular carcinoma protein 1, RNA-binding motif protein 39, RNA-binding region-containing protein 2, Splicing factor HCC1

All UniProt accessions (16): Q14498, A0A087X122, A0A0U1RQH7, A0A0U1RQW2, A0A384NQ03, A8MYG5, F2Z2Z5, F2Z3E6, F8WF24, F8WF73, G3XAC6, H0Y4X3, H0Y6I9, H7BZG3, Q5QP22, Q5QP23

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that acts as a pre-mRNA splicing factor. Acts by promoting exon inclusion via regulation of exon cassette splicing. Also acts as a transcriptional coactivator for steroid nuclear receptors ESR1/ER-alpha and ESR2/ER-beta, and JUN/AP-1, independently of the pre-mRNA splicing factor activity.

Subunit / interactions. Interacts with NCOA6 and JUN. Interacts with ESR1 and ESR2, in the presence of estradiol (E2). Interacts with RSRC1 (via Arg/Ser-rich domain). Interacts with SF3B1. Interacts with ZNF106 (via N-terminus).

Subcellular location. Nucleus speckle.

Tissue specificity. Widely expressed. Highly expressed in pancreas, skeletal muscle, lung and brain. Expressed at intermediate level in kidney, liver and heart.

Post-translational modifications. Aryl sulfonamide anticancer drugs, such as indisulam (E7070) or E7820, promote ubiquitination and subsequent degradation by the DCX(DCAF15) complex. RBM39 degradation results in splicing defects and death in cancer cell lines. Aryl sulfonamide anticancer drugs change the substrate specificity of DCAF15 by acting as a molecular glue that promotes binding between DCAF15 and weak affinity interactor RBM39.

Miscellaneous. Antibodies against RBM39 are present in sera from a patient with hepatocellular carcinoma who developed several autoantibodies.

Similarity. Belongs to the splicing factor SR family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14498-1	1, HCC1.4	yes
Q14498-2	2, HCC1.3
Q14498-3	3

RefSeq proteins (7): NP_001229528, NP_001229529, NP_001310351, NP_001310352, NP_001310353, NP_004893, NP_909122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003954	RRM_euk-type	Domain
IPR006509	RBM39_SF	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR029123	RBM39_linker	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076, PF15519

UniProt features (71 total): strand 15, modified residue 11, helix 11, sequence variant 9, compositionally biased region 5, turn 5, region of interest 5, domain 3, cross-link 3, splice variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
4YUD	X-RAY DIFFRACTION	1.28
4OZ1	X-RAY DIFFRACTION	1.74
4OZ0	X-RAY DIFFRACTION	2.2
6UD7	X-RAY DIFFRACTION	2.3
6UE5	X-RAY DIFFRACTION	2.61
4OO6	X-RAY DIFFRACTION	2.7
6PAI	X-RAY DIFFRACTION	2.9
6Q0R	X-RAY DIFFRACTION	2.9
6Q0V	X-RAY DIFFRACTION	2.9
6Q0W	X-RAY DIFFRACTION	2.9
6SJ7	ELECTRON MICROSCOPY	3.54
2JRS	SOLUTION NMR
2MHN	SOLUTION NMR
7Q33	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14498-F1	66.47	0.14

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 (14): 2, 95, 97, 100, 117, 121, 136, 146, 334, 337, 341, 111, 119, 244

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: 298 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, DITTMER_PTHLH_TARGETS_UP, ATGCAGT_MIR217, GGCNKCCATNK_UNKNOWN, CEBPB_01, ATGTTAA_MIR302C, EVI1_05, PAX8_B, TCF4_Q5, AP1_Q4_01, SOX9_B1

GO Biological Process (4): RNA processing (GO:0006396), mRNA processing (GO:0006397), RNA splicing (GO:0008380), regulation of mRNA splicing, via spliceosome (GO:0048024)

GO Molecular Function (5): RNA binding (GO:0003723), RS domain binding (GO:0050733), U1 snRNP binding (GO:1990446), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), microtubule cytoskeleton (GO:0015630), nuclear speck (GO:0016607), protein-containing complex (GO:0032991), centriolar satellite (GO:0034451), 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
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
mRNA splicing, via spliceosome	1
regulation of RNA splicing	1
regulation of mRNA processing	1
nucleic acid binding	1
protein domain specific binding	1
snRNP binding	1
nuclear lumen	1
cytoskeleton	1
nuclear ribonucleoprotein granule	1
cellular_component	1
centrosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3207 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM39	DCAF15	Q66K64	984
RBM39	RSRC1	Q96IZ7	911
RBM39	U2AF1	Q01081	896
RBM39	LUC7L	Q9NQ29	890
RBM39	DDB1	Q16531	838
RBM39	SNRPA	P09012	817
RBM39	U2AF2	P26368	797
RBM39	DDA1	Q9BW61	771
RBM39	TBX3	O15119	745
RBM39	SF3B1	O75533	727
RBM39	SRSF1	Q07955	714
RBM39	RBM17	Q96I25	667
RBM39	PCBP1	Q15365	623
RBM39	NCOA6	Q14686	618
RBM39	LUC7L3	O95232	593

IntAct

303 interactions, top by confidence:

A	B	Type	Score
SRPK2	RBM39	psi-mi:“MI:0915”(physical association)	0.910
RBM39	SRPK2	psi-mi:“MI:0915”(physical association)	0.910
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
SAP18	RBM39	psi-mi:“MI:0915”(physical association)	0.870
RBM39	SAP18	psi-mi:“MI:0915”(physical association)	0.870
RBM39	CLK2	psi-mi:“MI:0915”(physical association)	0.780
CLK2	RBM39	psi-mi:“MI:0915”(physical association)	0.780
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
RBM39	PRPF40A	psi-mi:“MI:0915”(physical association)	0.720
RBM39	THAP1	psi-mi:“MI:0915”(physical association)	0.720
RBM39	NKAPD1	psi-mi:“MI:0915”(physical association)	0.720
PRPF40A	RBM39	psi-mi:“MI:0915”(physical association)	0.720
THAP1	RBM39	psi-mi:“MI:0915”(physical association)	0.720
NKAPD1	RBM39	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (1434): RBM39 (Affinity Capture-MS), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), RBM39 (Two-hybrid), SF3B4 (Two-hybrid), SAP18 (Two-hybrid), KIAA0907 (Two-hybrid)

ESM2 similar proteins: A0A0D1DZT6, A6R3L3, A7VJC2, B7FAL5, D0VWM8, O19049, O88569, P0CO44, P0CO45, P17130, P21522, P22626, P25555, P38922, P51990, P61978, P61979, P61980, P78814, P92964, P98179, Q01560, Q09911, Q13151, Q14498, Q15056, Q1JPH6, Q28521, Q2HJ60, Q2QKB3, Q32P51, Q3T0D0, Q4R4M6, Q4WXV6, Q5R5H8, Q5RBR8, Q5RBU8, Q5RC80, Q5XI72, Q7KMJ6

Diamond homologs: A0A0D1C8Z4, A0A0D1DZT6, A2RVS6, A5DM21, A5DW14, B5FXN8, F1QB54, F4HT49, F4I3B3, F4JHI7, G3V6S8, O08583, O13845, O22315, O35326, O59670, O74400, P04147, P19682, P19683, P19684, P20965, P49313, P49314, P78814, P82277, P97855, Q04836, Q08170, Q08935, Q08937, Q09167, Q13242, Q13243, Q13247, Q13283, Q14498, Q1ZXC2, Q28FB9, Q32LC7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ABL1	“up-regulates activity”	RBM39	phosphorylation
DCAF15	“down-regulates quantity by destabilization”	RBM39	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	5	17.9×	1e-03
KEAP1-NFE2L2 pathway	6	8.6×	5e-03
mRNA Splicing	6	7.8×	6e-03
mRNA Polyadenylation	7	7.3×	5e-03
mRNA Splicing - Major Pathway	11	7.2×	9e-05
Processing of Capped Intron-Containing Pre-mRNA	7	6.8×	5e-03
Infectious disease	12	3.5×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal complex assembly	5	28.9×	2e-04
autophagosome maturation	5	16.9×	2e-03
positive regulation of transcription elongation by RNA polymerase II	5	14.5×	3e-03
RNA splicing	12	10.2×	2e-06
chromatin remodeling	9	6.3×	2e-03
mRNA processing	8	6.1×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3069 predictions. Top by Δscore:

Variant	Effect	Δscore
20:35704664:TCA:T	donor_loss	1.0000
20:35704665:CA:C	donor_loss	1.0000
20:35704666:A:AC	donor_gain	1.0000
20:35704667:C:CC	donor_gain	1.0000
20:35704667:C:CT	donor_loss	1.0000
20:35704667:CCAG:C	donor_gain	1.0000
20:35704742:TTGCC:T	acceptor_gain	1.0000
20:35704743:TGCC:T	acceptor_gain	1.0000
20:35704744:GCC:G	acceptor_gain	1.0000
20:35704745:CC:C	acceptor_gain	1.0000
20:35704745:CCC:C	acceptor_gain	1.0000
20:35704746:CC:C	acceptor_gain	1.0000
20:35704746:CCT:C	acceptor_loss	1.0000
20:35704747:C:CC	acceptor_gain	1.0000
20:35704750:C:CT	acceptor_gain	1.0000
20:35704751:A:T	acceptor_gain	1.0000
20:35704758:A:AC	acceptor_gain	1.0000
20:35704758:A:C	acceptor_gain	1.0000
20:35705220:AATAC:A	donor_loss	1.0000
20:35705221:ATAC:A	donor_loss	1.0000
20:35705222:TACCT:T	donor_loss	1.0000
20:35705223:ACCTG:A	donor_loss	1.0000
20:35705224:CCTG:C	donor_loss	1.0000
20:35705326:CTTCT:C	acceptor_gain	1.0000
20:35705327:TTCT:T	acceptor_gain	1.0000
20:35705329:CT:C	acceptor_gain	1.0000
20:35705329:CTCTG:C	acceptor_loss	1.0000
20:35705330:TC:T	acceptor_loss	1.0000
20:35705331:C:CC	acceptor_gain	1.0000
20:35705332:T:G	acceptor_loss	1.0000

AlphaMissense

3477 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:35704529:A:C	F515L	1.000
20:35704529:A:T	F515L	1.000
20:35704530:A:G	F515S	1.000
20:35704531:A:G	F515L	1.000
20:35704543:A:C	Y511D	1.000
20:35704543:A:G	Y511H	1.000
20:35704566:G:T	A503E	1.000
20:35704572:A:C	I501R	1.000
20:35704572:A:T	I501K	1.000
20:35704672:A:C	F496L	1.000
20:35704672:A:T	F496L	1.000
20:35704673:A:C	F496C	1.000
20:35704673:A:G	F496S	1.000
20:35704674:A:G	F496L	1.000
20:35704678:C:A	R494S	1.000
20:35704678:C:G	R494S	1.000
20:35704679:C:A	R494M	1.000
20:35704679:C:G	R494T	1.000
20:35704697:A:T	V488D	1.000
20:35704701:C:G	A487P	1.000
20:35704709:G:T	A484D	1.000
20:35704710:C:G	A484P	1.000
20:35704726:G:C	C478W	1.000
20:35704728:A:G	C478R	1.000
20:35704733:A:T	V476E	1.000
20:35704737:A:C	Y475D	1.000
20:35704739:A:T	V474E	1.000
20:35704745:C:A	G472V	1.000
20:35704745:C:T	G472D	1.000
20:35704746:C:A	G472C	1.000

dbSNP variants (sampled 300 via entrez): RS1000068547 (20:35726630 C>A), RS1000084264 (20:35741778 T>C), RS1000104482 (20:35727316 C>CT), RS1000137611 (20:35713680 A>C), RS1000144872 (20:35707981 T>C), RS1000147554 (20:35735633 T>A,G), RS1000258050 (20:35740147 G>C,T), RS1000431636 (20:35707687 T>C), RS1000469046 (20:35718879 A>G), RS1000488480 (20:35730224 T>C), RS1000537810 (20:35741639 T>C), RS1000547047 (20:35724940 A>G), RS1000625796 (20:35735843 T>C), RS1000656560 (20:35725317 G>A), RS1000656836 (20:35735531 A>G)

Disease associations

OMIM: gene MIM:604739 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_66	Refractive error	2.000000e-20

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4680031 (SINGLE PROTEIN), CHEMBL6193833 (PROTEIN-PROTEIN INTERACTION)

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)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — RNA-binding proteins (RBPs)

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.00	Kd	10	nM	MOLIBRESIB
6.40	IC50	400	nM	CHEMBL3197745

PubChem BioAssay actives

2 with measured affinity, of 17 total; 2 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	2179231: Binding affinity against RBM39 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0100	uM
N-[(E)-(5-bromo-2-hydroxyphenyl)methylideneamino]-4-methylbenzenesulfonamide	2067062: Inhibition of RBM39 (unknown origin)	ic50	0.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
trichostatin A	affects expression, decreases expression	2
Vorinostat	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
quinomethionate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
quercitrin	increases expression	1
tetrahydropalmatine	decreases expression, increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases abundance, increases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
monomethylarsonous acid	decreases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4672406	Binding	Induction of RBM39 degradation in human VCaP cells assessed as AR splicing modulation by measuring reduction in AR-V7 splice variant mRNA transcript level incubated for 24 hrs in presence of AR antagonist MDV by RT-qPCR analysis	The splicing modulator sulfonamide indisulam reduces AR-V7 in prostate cancer cells. — Bioorg Med Chem

Clinical trials (associated diseases)

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