RBM4

Summary

RBM4 (RNA binding motif protein 4, HGNC:9901) is a protein-coding gene on chromosome 11q13.2, encoding RNA-binding protein 4 (Q9BWF3). RNA-binding factor involved in multiple aspects of cellular processes like alternative splicing of pre-mRNA and translation regulation.

Enables RNA binding activity and cyclin binding activity. Involved in several processes, including IRES-dependent translational initiation of linear mRNA; negative regulation of translation; and regulation of alternative mRNA splicing, via spliceosome. Located in cytoplasmic stress granule; cytosol; and nuclear lumen.

Source: NCBI Gene 5936 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_002896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9901
Approved symbol	RBM4
Name	RNA binding motif protein 4
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	LARK, RBM4A, ZCRB3A, ZCCHC21
Ensembl gene	ENSG00000173933
Ensembl biotype	protein_coding
OMIM	602571
Entrez	5936

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 30 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000310092, ENST00000396053, ENST00000398692, ENST00000408993, ENST00000409406, ENST00000483858, ENST00000506523, ENST00000510173, ENST00000515838, ENST00000528039, ENST00000530235, ENST00000532968, ENST00000578778, ENST00000856077, ENST00000856078, ENST00000856079, ENST00000856080, ENST00000856081, ENST00000856082, ENST00000856083, ENST00000856084, ENST00000856085, ENST00000856086, ENST00000920193, ENST00000920194, ENST00000920195, ENST00000920196, ENST00000920197, ENST00000920198, ENST00000920199, ENST00000948566, ENST00000948567

RefSeq mRNA: 3 — MANE Select: NM_002896 NM_001198843, NM_001198844, NM_002896

CCDS: CCDS41676, CCDS55776, CCDS55777

Canonical transcript exons

ENST00000310092 — 4 exons

Exon	Start	End
ENSE00002210311	66638703	66638752
ENSE00003513724	66639700	66640123
ENSE00003639911	66643450	66644140
ENSE00003902345	66646027	66646468

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 70.6999 / max 670.1680, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115361	64.9878	1821
115360	5.3784	1738
115365	0.3337	132

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.92	gold quality
ganglionic eminence	UBERON:0004023	98.86	gold quality
ventricular zone	UBERON:0003053	98.18	gold quality
body of pancreas	UBERON:0001150	97.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.84	gold quality
cerebellar hemisphere	UBERON:0002245	97.83	gold quality
cerebellar cortex	UBERON:0002129	97.76	gold quality
right adrenal gland	UBERON:0001233	97.71	gold quality
left ovary	UBERON:0002119	97.69	gold quality
right ovary	UBERON:0002118	97.66	gold quality
right adrenal gland cortex	UBERON:0035827	97.62	gold quality
right lobe of thyroid gland	UBERON:0001119	97.59	gold quality
left adrenal gland	UBERON:0001234	97.58	gold quality
right uterine tube	UBERON:0001302	97.57	gold quality
adenohypophysis	UBERON:0002196	97.57	gold quality
mucosa of transverse colon	UBERON:0004991	97.57	gold quality
granulocyte	CL:0000094	97.56	gold quality
left adrenal gland cortex	UBERON:0035825	97.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.48	gold quality
body of stomach	UBERON:0001161	97.45	gold quality
lower esophagus	UBERON:0013473	97.43	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.43	gold quality
body of uterus	UBERON:0009853	97.38	gold quality
left lobe of thyroid gland	UBERON:0001120	97.31	gold quality
lower esophagus mucosa	UBERON:0035834	97.31	gold quality
minor salivary gland	UBERON:0001830	97.26	gold quality
endocervix	UBERON:0000458	97.25	gold quality
metanephros cortex	UBERON:0010533	97.21	gold quality
colonic epithelium	UBERON:0000397	97.05	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.47
E-MTAB-7303	no	2088.00
E-CURD-112	no	2.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting RBM4, 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-6077	99.99	68.04	2299
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-374C-3P	98.47	67.93	451
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-6511A-3P	97.60	66.61	713
HSA-MIR-6511B-3P	97.60	66.61	713
HSA-MIR-630	97.50	66.38	921
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-4776-5P	97.14	66.63	405
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-3192-5P	96.98	65.76	1926

Literature-anchored findings (GeneRIF, showing 35)

• Data show that the nuclear matrix protein matrin 3, cytoskeletal motor protein HMP, and the circadian clock protein lark were significantly decreased in fetal Down syndrome brain. (PMID:12469345)
• the regulated alternative splicing of alpha-TM by the antagonistic splicing regulators RBM4 and PTB (PMID:16260624)
• RBM4 is expressed in the human brain regions affected in tauopathy, including the hippocampus and frontal cortex. RBM4 is involved in tau exon 10 alternative splicing (PMID:16777844)
• Wilms tumor 1 protein, WT1 interacts with the novel splicing regulator RBM4, the longer isoform of WT1 is able to inhibit the effect of RBM4 on alternative splicing. (PMID:16934801)
• a previously unrecognized paradigm for the RNA-binding protein RBM4 in its phosphorylation-modulated dual action as a suppressor of cap-dependent and enhancer of IRES-mediated translation in response to stress signals (PMID:17284590)
• human brain, expression of RBM4a was strongly up-regulated in cerebellum as compared to forebrain. (PMID:18708123)
• RBM4 is an RNA-binding protein involved in diverse cellular processes that include alternative splicing of pre-mRNA, translation, and RNA silencing. (PMID:18723113)
• The alternative splicing imbalance of CoAA and RBM4, because of loss of their common enhancer in cancer, may deregulate stem/progenitor cell differentiation (PMID:19416963)
• Data show that RBM4 interacts directly with Ago2 during muscle cell differentiation and may recruit Ago2 to suppress translation of target mRNAs. (PMID:19801630)
• RBM4 may synergize its effect on muscle cell-specific alternative splicing by down-regulating PTB expression and antagonizing the activity of PTB in exon selection (PMID:21518792)
• RBM4 homologs exert different effects on 5’ splice site utilization and exon selection, and exhibit different subnuclear localization patterns. (PMID:23527094)
• role in negative feed-forward loop that disrupts inflammattory cytokine translation following Toll-like receptor 4 response (PMID:23897118)
• we propose the emerging role of RBM4 in regulating the adipocyte-specific splicing events and transcription cascade, which subsequently facilitate the development and function of brown adipocyte-like cells. (PMID:24389249)
• Up-regulation of RBM4 is associated with breast cancer. (PMID:25140042)
• RBM4 is a tumor suppressor with therapeutic potential and clinical values as a prognostic factor. (PMID:25203323)
• The results indicate that the alanine-rich C-terminal domain, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4. (PMID:25414336)
• Loss of RBM4 expression is associated with colorectal cancer. (PMID:26506517)
• alternative splicing patterns were altered by knockdown of RBM4 in several types of neoplasms (PMID:26898347)
• hese findings suggest that RBM4 is a new biomarker in gastric cancer, as the reduced expression of this protein is correlated with poor differentiation, lymph node status and distant metastasis (PMID:27324405)
• RBM4 is induced and is involved in the PKM splicing switch and neuronal gene expression during hypoxia-induced neuronal differentiation. (PMID:27821480)
• The impact of the RBM4-initiated splicing cascade on modulating the carcinogenic signature of colorectal cancer cells. (PMID:28276498)
• TPM1-AS regulates the alternative splicing of TPM1 through an interaction with RBM4 and involves in TPM1-mediated filopodium formation and migration of cancer cells (PMID:28754317)
• RBM4-SRSF3-MAP4K4 constitutes a novel mechanism for manipulating the metastasis of colorectal cancer cells through the JNK1 signaling pathway. (PMID:29138007)
• RBM4 can mediate the inflammatory response. (PMID:31489484)
• The SRSF1 and RBM4 constitute an antagonistic mechanism on regulating the splicing profiles of HIF-1alpha gene, which is relevant to the oncogenic signatures of lung cancer cells. (PMID:31491447)
• USP3 promotes proliferation of non-small cell lung cancer through regulating RBM4. (PMID:32271432)
• Rbm24 regulates inner-ear-specific alternative splicing and is essential for maintaining auditory and motor coordination. (PMID:32887533)
• Posttranscriptional regulation of human endogenous retroviruses by RNA-binding motif protein 4, RBM4. (PMID:33020268)
• G-Quadruplex Regulation of VEGFA mRNA Translation by RBM4. (PMID:35054929)
• RNA-binding motif 4 promotes angiogenesis in HCC by selectively activating VEGF-A expression. (PMID:36496136)
• RBM4 inhibits the growth of clear cell renal cell carcinoma by enhancing the stability of p53 mRNA. (PMID:36585906)
• RBM4 regulates cellular senescence via miR1244/SERPINE1 axis. (PMID:36639375)
• RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis. (PMID:37080995)
• A Comprehensive Prognostic and Immune Infiltration Analysis of RBM4 in Pan-Cancer. (PMID:38420804)
• Overexpression of RBM4 promotes acute myeloid leukemia cell differentiation by regulating alternative splicing of TFEB. (PMID:39214303)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rbm4	ENSMUSG00000094936
rattus_norvegicus	Rbm4	ENSRNOG00000050741

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), 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), 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 4 — Q9BWF3 (reviewed: Q9BWF3)

Alternative names: Lark homolog, RNA-binding motif protein 4, RNA-binding motif protein 4a

All UniProt accessions (4): Q9BWF3, D6R9K7, E9PB51, J3QRR5

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding factor involved in multiple aspects of cellular processes like alternative splicing of pre-mRNA and translation regulation. Modulates alternative 5’-splice site and exon selection. Acts as a muscle cell differentiation-promoting factor. Activates exon skipping of the PTB pre-mRNA during muscle cell differentiation. Antagonizes the activity of the splicing factor PTBP1 to modulate muscle cell-specific exon selection of alpha tropomyosin. Binds to intronic pyrimidine-rich sequence of the TPM1 and MAPT pre-mRNAs. Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3’-UTR of the PER1 mRNA. Exerts a suppressive activity on Cap-dependent translation via binding to CU-rich responsive elements within the 3’UTR of mRNAs, a process increased under stress conditions or during myocytes differentiation. Recruits EIF4A1 to stimulate IRES-dependent translation initiation in respons to cellular stress. Associates to internal ribosome entry segment (IRES) in target mRNA species under stress conditions. Plays a role for miRNA-guided RNA cleavage and translation suppression by promoting association of AGO2-containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5’-CGCGCG[GCA]-3’ motif in vitro.

Subunit / interactions. Interacts with TNPO3; the interaction mediates nuclear import of the protein and is disrupted by nuclear Ran bound to GTP. Interacts with EIF4G1 and WT1. Interacts with EIF4A1; the interaction is modulated under stress-induced conditions. Interacts with AGO1. Interacts with AGO2; the interaction occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with DDX5; the interaction occurs in an RNA-independent manner. Interacts with RBPMS; the interaction allows cooperative assembly of RNA-bound stable cell-specific alternative splicing regulatory complexes.

Subcellular location. Nucleus. Nucleolus. Nucleus speckle. Cytoplasm. Cytoplasmic granule.

Tissue specificity. Expressed in the cerebellum. Expressed in neurons and glial cells, including layers II neurons in the frontal cortex and CA1 pyramidal neurons in the hippocampus. Expressed in heart, liver, pancreas, skeletal muscle, placenta, primary fibroblasts and peripheral blood monocytes (at protein level). Ubiquitously expressed. Highly expressed in heart, placenta and skeletal muscle. Weakly expressed in pancreas, kidney, liver, lung and brain.

Post-translational modifications. Phosphorylation on Ser-309 is induced upon cell muscle differentiation. Phosphorylated. Phosphorylated in vitro on Ser-309 by SRPK1. Phosphorylation on Ser-309 is induced upon cell stress signaling, which alters its subcellular localization and may modulate its activity on IRES-mediated mRNA translation.

Miscellaneous. May be due to an intron retention. May be due to exon skipping.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BWF3-1	1	yes
Q9BWF3-2	2
Q9BWF3-3	3
Q9BWF3-4	4

RefSeq proteins (3): NP_001185772, NP_001185773, NP_002887* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR001878	Znf_CCHC	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034897	RBM4_RRM1	Domain
IPR034898	RBM4_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050502	Euk_RNA-bind_prot	Family

Pfam: PF00076, PF00098

UniProt features (26 total): splice variant 5, mutagenesis site 5, strand 4, domain 2, helix 2, modified residue 2, cross-link 2, chain 1, sequence conflict 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DNQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWF3-F1	64.81	0.32

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 (4): 86, 309, 79, 92

Mutagenesis-validated functional residues (5):

Position	Phenotype
37	abrogates regulation of alternative splice site selection; when associated with a-39; a-113 and a-115.
39	abrogates regulation of alternative splice site selection; when associated with a-37; a-113 and a-115.
113	abrogates regulation of alternative splice site selection; when associated with a-37; a-39 and a-115.
115	abrogates regulation of alternative splice site selection; when associated with a-37; a-39 and a-113.
309	inhibits ires-mediated mrna translation. does not inhibit interaction with eif4a1. inhibits localization in cytoplasm an

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9931510	Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes

MSigDB gene sets: 276 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GOBP_REGULATION_OF_TRANSLATION_IN_RESPONSE_TO_STRESS, GOBP_PHOTOPERIODISM, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (26): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), cap-independent translational initiation (GO:0002190), IRES-dependent translational initiation of linear mRNA (GO:0002192), RNA processing (GO:0006396), mRNA processing (GO:0006397), circadian rhythm (GO:0007623), RNA splicing (GO:0008380), negative regulation of translation (GO:0017148), pancreas development (GO:0031016), negative regulation of translation in response to stress (GO:0032055), circadian regulation of gene expression (GO:0032922), miRNA-mediated gene silencing by inhibition of translation (GO:0035278), insulin secretion involved in cellular response to glucose stimulus (GO:0035773), enteroendocrine cell differentiation (GO:0035883), entrainment of circadian clock by photoperiod (GO:0043153), positive regulation of translation (GO:0045727), negative regulation of translational initiation (GO:0045947), regulation of insulin receptor signaling pathway (GO:0046626), response to arsenic-containing substance (GO:0046685), regulation of nucleocytoplasmic transport (GO:0046822), positive regulation of muscle cell differentiation (GO:0051149), circadian regulation of translation (GO:0097167), regulation of gene expression (GO:0010468), cell differentiation (GO:0030154), regulatory ncRNA-mediated gene silencing (GO:0031047), glucose homeostasis (GO:0042593)

GO Molecular Function (12): RNA binding (GO:0003723), mRNA binding (GO:0003729), mRNA 3’-UTR binding (GO:0003730), zinc ion binding (GO:0008270), cyclin binding (GO:0030332), miRNA binding (GO:0035198), pre-mRNA intronic binding (GO:0097157), pre-mRNA intronic pyrimidine-rich binding (GO:0097158), nucleic acid binding (GO:0003676), protein binding (GO:0005515), pre-mRNA binding (GO:0036002), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), nuclear speck (GO:0016607), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Circadian clock	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
translation	3
negative regulation of translation	3
RNA processing	2
regulation of translation	2
RNA binding	2
binding	2
nuclear lumen	2
cytoplasm	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
cytoplasmic translational initiation	1
cap-independent translational initiation of linear mRNA	1
IRES-mediated translation initiation factor activity	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
rhythmic process	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
animal organ development	1
cellular response to stress	1
regulation of translation in response to stress	1
circadian rhythm	1
regulation of gene expression	1
miRNA-mediated post-transcriptional gene silencing	1
insulin secretion	1
establishment of localization in cell	1
cellular response to glucose stimulus	1
epithelial cell differentiation	1
photoperiodism	1
entrainment of circadian clock	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
translational initiation	1
regulation of translational initiation	1
insulin receptor signaling pathway	1
regulation of signal transduction	1
response to chemical	1

Protein interactions and networks

STRING

2220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM4	EIF4E2	O60573	993
RBM4	EPAS1	Q99814	989
RBM4	AGO2	Q9UKV8	953
RBM4	SRSF3	P23152	750
RBM4	YTHDF2	Q9Y5A9	738
RBM4	EIF4E	P06730	654
RBM4	SRSF10	O75494	652
RBM4	RBM10	P98175	650
RBM4	AGO1	Q9UL18	618
RBM4	RBM11	P57052	616
RBM4	RBM25	P49756	612
RBM4	RBM5	P52756	587
RBM4	KHDRBS1	Q07666	576
RBM4	SRPK1	Q96SB4	536
RBM4	RBM6	P78332	521
RBM4	XRN2	Q9H0D6	521

IntAct

182 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CTBP2	ZNF217	psi-mi:“MI:0914”(association)	0.690
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RBM4	RBM4B	psi-mi:“MI:0914”(association)	0.640
CRYAA	RBM4	psi-mi:“MI:0915”(physical association)	0.560
RBM4	ATN1	psi-mi:“MI:0915”(physical association)	0.560
	RBM4	psi-mi:“MI:0915”(physical association)	0.560
RBM4	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
KLK6	RBM4	psi-mi:“MI:0915”(physical association)	0.560
CDK18	UBL4A	psi-mi:“MI:0914”(association)	0.530
NSA2	TYW5	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530

BioGRID (442): RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Two-hybrid), RBM4 (Affinity Capture-MS), PPL (Affinity Capture-MS), PPM1G (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), RBM4 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M1NHK4, A0AV96, A0JMV4, A4IGK4, O01367, O17310, O75122, P51113, Q06AT9, Q07666, Q08BJ2, Q0V9L3, Q0VFL3, Q1LZD9, Q28F51, Q2KHP9, Q3MHX3, Q4KLH4, Q4R979, Q5NVC8, Q5R5P4, Q5R9H4, Q5XI81, Q5YD48, Q64LC9, Q66H68, Q6DDU9, Q6GLC9, Q6IQ97, Q6YZW2, Q7TSY6, Q80WE1, Q8BRT1, Q8C7Q4, Q8VC70, Q8VE92, Q91WT8, Q923K9, Q95168, Q9ASP6

Diamond homologs: A0A0D1DZT6, A2RVS6, A5A6M3, D4AE41, F4JHI7, G3V6S8, O22315, O22703, O35326, O75494, O81127, O93235, P19682, P26686, P28644, P30352, P33240, P38159, P60824, P60825, P60826, P78814, P84103, P84104, P84586, P92964, Q01130, Q02427, Q04836, Q06AT9, Q07955, Q08170, Q09167, Q0VCY7, Q10021, Q13242, Q13243, Q13247, Q14011, Q16629

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WT1	down-regulates	RBM4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 202 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
FGFR2 alternative splicing	6	17.6×	7e-05
Signaling by FGFR2	5	14.2×	1e-03
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	5	12.8×	2e-03
Signaling by FGFR	5	12.0×	2e-03
mRNA Polyadenylation	18	11.0×	8e-12
Processing of Capped Intron-Containing Pre-mRNA	19	10.8×	3e-12
mRNA Splicing - Major Pathway	28	10.6×	2e-18
mRNA Splicing	13	9.9×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
alternative mRNA splicing, via spliceosome	8	29.8×	7e-08
negative regulation of mRNA splicing, via spliceosome	7	29.6×	6e-07
regulation of mRNA splicing, via spliceosome	5	24.5×	1e-04
ribosomal large subunit biogenesis	7	17.1×	2e-05
spliceosomal complex assembly	5	16.6×	7e-04
mRNA splicing, via spliceosome	24	12.1×	2e-16
regulation of alternative mRNA splicing, via spliceosome	9	12.1×	1e-05
RNA processing	9	10.9×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1325 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66640078:G:GT	donor_gain	1.0000
11:66640117:TTTCA:T	donor_gain	1.0000
11:66640120:CAAG:C	donor_loss	1.0000
11:66640121:AAG:A	donor_loss	1.0000
11:66640122:AGG:A	donor_loss	1.0000
11:66640123:GGT:G	donor_loss	1.0000
11:66640124:G:T	donor_loss	1.0000
11:66640125:T:G	donor_loss	1.0000
11:66643448:A:G	acceptor_gain	1.0000
11:66645766:G:GT	donor_gain	1.0000
11:66645767:A:T	donor_gain	1.0000
11:66639695:CCCA:C	acceptor_loss	0.9900
11:66639695:CCCAG:C	acceptor_gain	0.9900
11:66639696:CCAGG:C	acceptor_gain	0.9900
11:66639697:CAG:C	acceptor_gain	0.9900
11:66639697:CAGGC:C	acceptor_gain	0.9900
11:66639698:A:AC	acceptor_loss	0.9900
11:66639698:A:AG	acceptor_gain	0.9900
11:66639698:AG:A	acceptor_gain	0.9900
11:66639698:AGG:A	acceptor_gain	0.9900
11:66639698:AGGCT:A	acceptor_loss	0.9900
11:66639699:G:GG	acceptor_gain	0.9900
11:66639699:G:GT	acceptor_gain	0.9900
11:66639699:GG:G	acceptor_gain	0.9900
11:66639699:GGC:G	acceptor_gain	0.9900
11:66639699:GGCT:G	acceptor_gain	0.9900
11:66640120:CAAGG:C	donor_loss	0.9900
11:66640121:AAGG:A	donor_loss	0.9900
11:66640122:AGGT:A	donor_loss	0.9900
11:66640124:G:C	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000086987 (11:66638683 C>G,T), RS1000177182 (11:66640753 T>A), RS1000341221 (11:66646975 C>T), RS1000426657 (11:66657867 G>A,T), RS1000670481 (11:66666498 A>C), RS1000790607 (11:66660375 CAG>C,CAGAG), RS1000847861 (11:66650769 A>G), RS1000886489 (11:66655404 C>A,T), RS1001028747 (11:66656342 G>A,T), RS1001037740 (11:66663402 T>C), RS1001110667 (11:66649570 A>G), RS1001141716 (11:66649235 C>T), RS1001175922 (11:66647257 C>G), RS1001317182 (11:66655062 T>C), RS1001327300 (11:66658869 G>A)

Disease associations

OMIM: gene MIM:602571 | 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
GCST001241_12	Bipolar disorder	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
sodium arsenite	affects cotreatment, affects localization, affects binding, increases reaction, increases phosphorylation (+4 more)	3
methylmercuric chloride	decreases expression, increases expression	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases methylation	2
Smoke	decreases expression, decreases reaction, increases abundance	2
Dronabinol	decreases expression, increases expression	2
Aflatoxin B1	increases methylation, decreases methylation	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
trichostatin A	decreases expression	1
arsenite	increases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
SB 203580	affects localization, decreases reaction	1
monomethylarsonous acid	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Decitabine	decreases expression, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects splicing, increases abundance, affects cotreatment	1
Caffeine	increases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydralazine	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3FT	Abcam HEK293T RBM4 KO	Transformed cell line	Female
CVCL_E2IM	HAP1 RBM4 (-) 1	Cancer cell line	Male
CVCL_E2IN	HAP1 RBM4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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