RBM5

Summary

RBM5 (RNA binding motif protein 5, HGNC:9902) is a protein-coding gene on chromosome 3p21.31, encoding RNA-binding protein 5 (P52756). Component of the spliceosome A complex. It is a selective cancer dependency (DepMap: 10.3% of cell lines).

This gene is a candidate tumor suppressor gene which encodes a nuclear RNA binding protein that is a component of the spliceosome A complex. The encoded protein plays a role in the induction of cell cycle arrest and apoptosis through pre-mRNA splicing of multiple target genes including the tumor suppressor protein p53. This gene is located within the tumor suppressor region 3p21.3, and may play a role in the inhibition of tumor transformation and progression of several malignancies including lung cancer.

Source: NCBI Gene 10181 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 100 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 10.3% of screened cell lines
• MANE Select transcript: NM_005778

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9902
Approved symbol	RBM5
Name	RNA binding motif protein 5
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	LUCA15, LUCA-15, H37
Ensembl gene	ENSG00000003756
Ensembl biotype	protein_coding
OMIM	606884
Entrez	10181

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 26 protein_coding, 16 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000347869, ENST00000395174, ENST00000404526, ENST00000417905, ENST00000433556, ENST00000437500, ENST00000438369, ENST00000441305, ENST00000441812, ENST00000461242, ENST00000462025, ENST00000464087, ENST00000464988, ENST00000469838, ENST00000471995, ENST00000474470, ENST00000474818, ENST00000475128, ENST00000475590, ENST00000479275, ENST00000489437, ENST00000492430, ENST00000492472, ENST00000493993, ENST00000494360, ENST00000496179, ENST00000852692, ENST00000852693, ENST00000852694, ENST00000852695, ENST00000852696, ENST00000852697, ENST00000852698, ENST00000852699, ENST00000852700, ENST00000852701, ENST00000852702, ENST00000936118, ENST00000936119, ENST00000936120, ENST00000936121, ENST00000936122, ENST00000952988, ENST00000952989, ENST00000952990, ENST00000952991

RefSeq mRNA: 1 — MANE Select: NM_005778 NM_005778

CCDS: CCDS2810

Canonical transcript exons

ENST00000347869 — 25 exons

Exon	Start	End
ENSE00001729771	50088919	50089029
ENSE00001902238	50118331	50119021
ENSE00003459570	50108070	50108147
ENSE00003464131	50090382	50090451
ENSE00003483200	50100532	50100605
ENSE00003483525	50109603	50109688
ENSE00003495704	50105549	50105709
ENSE00003496549	50117074	50117171
ENSE00003516173	50103083	50103166
ENSE00003517134	50115428	50115607
ENSE00003519385	50115906	50115980
ENSE00003525269	50105077	50105142
ENSE00003538631	50114180	50114251
ENSE00003539809	50113383	50113544
ENSE00003548484	50113950	50114099
ENSE00003570756	50093720	50093875
ENSE00003577405	50099982	50100051
ENSE00003579642	50092043	50092208
ENSE00003598388	50110379	50110463
ENSE00003638692	50107482	50107569
ENSE00003641467	50106767	50106864
ENSE00003644955	50110679	50110770
ENSE00003649732	50104248	50104308
ENSE00003669607	50117250	50117379
ENSE00003675462	50108232	50108304

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.9676 / max 1880.3235, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36672	65.4308	1823
36674	0.5336	268
36675	0.0033	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.43	gold quality
sural nerve	UBERON:0015488	99.24	gold quality
calcaneal tendon	UBERON:0003701	99.21	gold quality
left ovary	UBERON:0002119	99.13	gold quality
right ovary	UBERON:0002118	99.09	gold quality
right lobe of thyroid gland	UBERON:0001119	99.02	gold quality
endocervix	UBERON:0000458	98.96	gold quality
left lobe of thyroid gland	UBERON:0001120	98.95	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.92	gold quality
tibial nerve	UBERON:0001323	98.91	gold quality
adenohypophysis	UBERON:0002196	98.91	gold quality
cerebellar hemisphere	UBERON:0002245	98.88	gold quality
body of uterus	UBERON:0009853	98.88	gold quality
pituitary gland	UBERON:0000007	98.87	gold quality
granulocyte	CL:0000094	98.81	gold quality
cerebellar cortex	UBERON:0002129	98.73	gold quality
skin of leg	UBERON:0001511	98.72	gold quality
body of pancreas	UBERON:0001150	98.68	gold quality
right testis	UBERON:0004534	98.66	gold quality
skin of abdomen	UBERON:0001416	98.65	gold quality
thyroid gland	UBERON:0002046	98.64	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.63	gold quality
tibia	UBERON:0000979	98.61	gold quality
left testis	UBERON:0004533	98.60	gold quality
mucosa of stomach	UBERON:0001199	98.59	gold quality
minor salivary gland	UBERON:0001830	98.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.54	gold quality
metanephros cortex	UBERON:0010533	98.53	gold quality
ectocervix	UBERON:0012249	98.53	gold quality
left uterine tube	UBERON:0001303	98.52	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-135	no	704.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

38 targeting RBM5, 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-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6852-3P	98.54	67.60	1468

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Over-expression of the splice variant LUCA15 shortened the cell cycle and inhibited CD95-mediated apoptosis in CEM-C7 T-cells. (PMID:12581154)
• LUCA-15/RMB5 sensitises Jurkat cells to apoptosis initiated by anti-Fas antibody, TNF-alpha, or TRAIL. (PMID:15192330)
• Results provide the first evidence of an apoptotic modulatory role for LUCA-15 in MCF-7 breast carcinoma cell line, which is a non-T cell line. (PMID:15338470)
• Results suggest that LUCA-15 plays a central role in regulating cell fate consistent with its tumor suppressor activity. (PMID:16546166)
• H37 was transfected into A549 non-small cell lung cancer cells. A549/H37 cells show significant growth inhibition compared with the vector controls by in vitro and in vivo cell proliferation assays. (PMID:16585163)
• Results suggest that reversible phosphorylation of RBM5 is a mechanism capable of regulating RBM5 participation in modulating apoptosis, and perhaps tumour suppression. (PMID:16927403)
• specific allele types at C1138T and C2185T single nucleotide polymorphisms positions are correlated with different histological subtypes of non-small cell lung cancer (PMID:17606309)
• In breast tumour tissue, chimeric expression was associated with elevated levels of RBM5 mRNA, and increased tumour size. (PMID:17908320)
• suggest some of the possible, further- alternative means of the H37/RMB5 gene expression loss in tumor, including defects in transcription and post-transcriptional/translational modifications as well as mechanisms related to haploinsufficiency (PMID:18038152)
• RBM5 binds to casp-2 pre-mRNA at a U/C-rich sequence immediately upstream of the previously identified In100 splicing repressor element (PMID:18840686)
• RBM5 inhibits the transition between prespliceosomal complexes assembled around exon 6 to mature spliceosomes assembled on the flanking introns and promotes sequence-specific pairing of the distal splice sites. (PMID:18851835)
• LUST is a novel, functional, non-coding RNA that plays a role in determining the apoptotic fate of a cell by regulating the expression of RBM5 splice variants. (PMID:19559772)
• p53 transactivation is involved in the antiproliferative activity of the putative tumor suppressor RBM5. (PMID:20309933)
• alters expression of genes involved in metastasis (PMID:20338664)
• Expression of RBM5 mRNA and protein was negatively correlated with expression of EGFR and KRAS mRNA and protein in NSCLC tissues. (PMID:22537942)
• Data suggest that G-patch domain of RBM5 is indispensable for its ability to interact with DHX15; RBM5 stimulates helicase activity of DHX15 in a G-patch domain-dependent manner. (PMID:22569250)
• RBM5 may serve as a biomarker with the ability to predict a response to cisplatin (PMID:22609235)
• NMR data analysis of RBM5 RRM2 reveals several features of protein-RNA interfaces. The most striking observation is the presence of two preferred target RNA sequences, the sequences [5’-(CUCUUC)-3’] and [5’-(GAGAAG)-3’]. (PMID:22839758)
• RBM5 can inhibit the growth of lung cancer cells and induce apoptosis both in vitro and in vivo. (PMID:22866867)
• The results suggest that RBM5 expression is not directly regulated by EGFR in non-smoker related lung adenocarinomas. (PMID:22882865)
• RBM5 promotes exon 4 skipping of AID pre-mRNA by competing with the binding of U2AF65 to the polypyrimidine tract. (PMID:23017209)
• expression of RBM5 protein was significantly decreased in cancerous prostatic tissues compared to the normal tissues (PMID:23158838)
• Loss of RBM5 expression is associated with lung adenocarcinoma. (PMID:23721095)
• Antagonizes the effects of RBM5, RBM6, and RBM10 in cell colony formation. (PMID:24332178)
• RBM5 knockdown in human neuronal cells decreases caspase activation by staurosporine. (PMID:25586139)
• ICG-001 had no apparent effect on the RBM5 levels. (PMID:25738917)
• Results show that RBM5 is downregulated in smoke induced tumor; its overexpression inhibits tumor growth through cell cycle arrest and induction of apoptosis suggesting the importance of RBM5 in the pathogenesis of smoking-related cancer. (PMID:26782095)
• the mechanism of action of RBM5-AS1 in the WNT pathway via physical interactions with beta-catenin, helping organize transcriptional complexes that sustain colon cancer-initiating cells function. (PMID:27520449)
• Low RBM5 expression was significantly associated with gliomas. (PMID:28061901)
• RNA-binding motif 5 silencing reduced the messenger RNA and protein expression of the p53 target gene p21. Our results suggest that RNA-binding motif 5 downregulation is involved in gastric cancer progression and that RNA-binding motif 5 behaves as a tumor suppressor gene in gastric cancer (PMID:28347247)
• RNA binding motif protein 10 (RBM10) negatively regulates its own mRNA and protein expression and that of RNA binding motif protein 5 (RBM5) by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD). (PMID:28586478)
• results provide evidence that RBM10 expression, in RBM5-null tumors, may contribute to tumor growth and metastasis. Measurement of both RBM10 and RBM5 expression in clinical samples may therefore hold prognostic and/or potentially predictive value (PMID:28662214)
• RBM5 expression was significantly down-regulated in bladder cancer tissues. Downrergulated RBM5 inhibits bladder cancer cell apoptosis via miR-432-5p/beta-catenin signaling. (PMID:31318608)
• Circular circPSMC3 inhibits hepatocellular carcinoma migration and invasion by upregulating RBM5. (PMID:31726810)
• Conformational Dynamics from Ambiguous Zinc Coordination in the RanBP2-Type Zinc Finger of RBM5. (PMID:32450081)
• RBM5 Acts as Tumor Suppressor in Medulloblastoma through Regulating Wnt/beta-Catenin Signaling. (PMID:32610314)
• A de novo paradigm for male infertility. (PMID:35013161)
• A bacterial virulence factor interacts with the splicing factor RBM5 and stimulates formation of nuclear RBM5 granules. (PMID:36535993)
• RNA-binding protein PUM2 promotes T-cell acute lymphoblastic leukemia via competitively binding to RBM5 3’UTR with miR-28-5p. (PMID:36536516)
• Elucidating the role of RBM5 in osteoclastogenesis: a novel potential therapeutic target for osteoporosis. (PMID:38031049)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm5	ENSDARG00000098280
mus_musculus	Rbm5	ENSMUSG00000032580
rattus_norvegicus	Rbm5	ENSRNOG00000018153
drosophila_melanogaster	CG4887	FBGN0031318
drosophila_melanogaster	CG4896	FBGN0031319
caenorhabditis_elegans	rbm-5	WBGENE00020346

Paralogs (2): RBM6 (ENSG00000004534), RBM10 (ENSG00000182872)

Protein

Protein identifiers

RNA-binding protein 5 — P52756 (reviewed: P52756)

Alternative names: Protein G15, Putative tumor suppressor LUCA15, RNA-binding motif protein 5, Renal carcinoma antigen NY-REN-9

All UniProt accessions (8): P52756, C9J9P7, C9JFQ5, C9JR02, E1CJT4, F8W910, F8WE23, H7BYM9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the spliceosome A complex. Binds to ssRNA containing the consensus sequence 5’-AGGUAA-3’. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5’ and 3’ splice sites of the intron. May both positively and negatively regulate apoptosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes exclusion of exon 6 thereby producing a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes exclusion of exon 9 thereby producing a catalytically active form of CASP2/Caspase-2 that induces apoptosis.

Subunit / interactions. Component of the spliceosome A complex (also known as the prespliceosome). Appears to dissociate from the spliceosome upon formation of the spliceosome B complex (also known as the precatalytic spliceosome), in which the heterotrimeric U4/U6.U5 snRNPs are bound. Interacts with U2AF2; this interaction is direct. Also interacts with ACIN1, PRPF8, SFRS3, SNRPB, SNRPN, SNRNP70 and SNRNP200; these interactions may be indirect.

Subcellular location. Nucleus.

Tissue specificity. Isoform 5 is widely expressed in normal tissues and is expressed at increased levels in T-leukemic cell lines.

Similarity. Belongs to the RBM5/RBM10 family.

Isoforms (5)

UniProt ID	Names	Canonical?
P52756-1	1	yes
P52756-2	2
P52756-3	3
P52756-4	4
P52756-5	5, delta-6

RefSeq proteins (1): NP_005769* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000467	G_patch_dom	Domain
IPR000504	RRM_dom	Domain
IPR001876	Znf_RanBP2	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR034991	RBM5_RRM1	Domain
IPR034993	RBM5_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036443	Znf_RanBP2_sf	Homologous_superfamily
IPR041591	OCRE	Domain

Pfam: PF00076, PF00641, PF01585, PF17780

UniProt features (69 total): strand 22, modified residue 8, turn 8, splice variant 7, region of interest 5, sequence conflict 5, helix 5, domain 3, compositionally biased region 2, zinc finger region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
7PCV	X-RAY DIFFRACTION	2.42
9ZE2	ELECTRON MICROSCOPY	3.26
9ZE0	ELECTRON MICROSCOPY	3.43
7PDV	X-RAY DIFFRACTION	3.49
9ZEC	ELECTRON MICROSCOPY	3.61
9ZE3	ELECTRON MICROSCOPY	3.93
9ZED	ELECTRON MICROSCOPY	3.94
2LK0	SOLUTION NMR
2LK1	SOLUTION NMR
2LKZ	SOLUTION NMR
5MF9	SOLUTION NMR
5MFY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52756-F1	62.94	0.08

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 (8): 18, 59, 69, 72, 78, 444, 621, 624

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 180 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MORF_SNRP70, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, RODRIGUES_NTN1_TARGETS_DN, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GATA1_01, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GENTILE_UV_HIGH_DOSE_DN, REACTOME_MRNA_SPLICING

GO Biological Process (9): spliceosomal complex assembly (GO:0000245), regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splicing, via spliceosome (GO:0000398), RNA processing (GO:0006396), apoptotic process (GO:0006915), negative regulation of cell population proliferation (GO:0008285), positive regulation of apoptotic process (GO:0043065), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (7): DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA binding (GO:0003729), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), centriole (GO:0005814), cytosol (GO:0005829), perinuclear theca (GO:0033011), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
sperm flagellum	3
RNA processing	2
nucleic acid binding	2
binding	2
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
mRNA metabolic process	1
RNA binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
microtubule organizing center	1
intracellular membraneless organelle	1
cytoplasm	1
cytoskeleton	1
perinuclear region of cytoplasm	1

Protein interactions and networks

STRING

1820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM5	DHX15	O43143	839
RBM5	U2AF2	P26368	837
RBM5	RBM17	Q96I25	638
RBM5	PHF5A	Q7RTV0	634
RBM5	SRSF5	Q13243	628
RBM5	HNRNPC	P07910	609
RBM5	TIA1	P31483	608
RBM5	RBM4	Q9BWF3	587
RBM5	ELAVL1	Q15717	550
RBM5	RBM41	Q96IZ5	523
RBM5	SRSF1	Q07955	498
RBM5	RBM25	P49756	488
RBM5	RNF223	E7ERA6	476
RBM5	SF3B2	Q13435	474
RBM5	PLRG1	O43660	472
RBM5	TFIP11	Q9UBB9	472

IntAct

165 interactions, top by confidence:

A	B	Type	Score
DHX15	RBM5	psi-mi:“MI:0915”(physical association)	0.810
RBM5	DHX15	psi-mi:“MI:0914”(association)	0.810
RBM5	DHX15	psi-mi:“MI:0915”(physical association)	0.810
RBM5	DHX15	psi-mi:“MI:0407”(direct interaction)	0.810
RBM17	U2SURP	psi-mi:“MI:0914”(association)	0.740
RBM5	PRPF19	psi-mi:“MI:0915”(physical association)	0.740
PRPF19	RBM5	psi-mi:“MI:0915”(physical association)	0.740
RBM5	PRPF19	psi-mi:“MI:0407”(direct interaction)	0.740
PRPF19	RBM5	psi-mi:“MI:0407”(direct interaction)	0.740
SUZ12	EPOP	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
RBM5	U2AF2	psi-mi:“MI:0407”(direct interaction)	0.630
RBM5	MEOX1	psi-mi:“MI:0915”(physical association)	0.600
MLYCD	RBM5	psi-mi:“MI:0915”(physical association)	0.600
RBM5	MEOX2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (178): RBM5 (Affinity Capture-RNA), RBM5 (Affinity Capture-RNA), RBM5 (Two-hybrid), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS), RBM5 (Affinity Capture-MS)

ESM2 similar proteins: A0JMV4, A1A5G2, A4IGK4, A5D7H2, B2GV05, E1C1R4, O88532, O94888, P52756, P54198, P58405, P79987, Q01826, Q13033, Q13123, Q14161, Q1RMU5, Q562A2, Q5NVI3, Q5R660, Q5RCR8, Q5REX3, Q5REY7, Q5SRX1, Q5U231, Q5U252, Q60611, Q61666, Q66H91, Q66HG8, Q6GPM1, Q6NT76, Q80YA9, Q8BIE6, Q8BJA3, Q8BY87, Q8K2D3, Q8VHE0, Q8VI24, Q8WXI2

Diamond homologs: A0JMV4, A4IGK4, A4L691, A5DSB5, B2GV05, P15771, P52756, P70501, P98175, Q0IIX9, Q17784, Q1RMU5, Q5ZII9, Q66J74, Q68FU8, Q6C233, Q6DDU9, Q7TN31, Q7TQC7, Q8CH02, Q8CH09, Q8IWZ8, Q8IX01, Q8N302, Q91YE7, Q94C11, Q96BK5, Q99KG3, Q9CZX5, Q9NW75, Q9UTK6, A2A6A1, A2AKY4, Q6DF57, Q6DGZ0, Q7Z570, Q9UKJ3, P78332, P87143, Q4PC17

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 140 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
mRNA Splicing - Minor Pathway	9	19.9×	4e-08
mRNA Splicing	16	17.4×	8e-14
mRNA Polyadenylation	18	15.7×	1e-14
mRNA 3’-end processing	8	15.6×	2e-06
Processing of Capped Intron-Containing Pre-mRNA	17	13.8×	4e-13
mRNA Splicing - Major Pathway	25	13.5×	5e-19
RNA Polymerase II Transcription Termination	6	13.1×	3e-04
CHD1 and CHD2 subfamily	11	11.8×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	38.0×	2e-06
spliceosomal complex assembly	7	34.8×	3e-07
RNA splicing, via transesterification reactions	6	30.9×	5e-06
U2-type prespliceosome assembly	6	30.9×	5e-06
mRNA splicing, via spliceosome	20	15.1×	3e-15
regulation of alternative mRNA splicing, via spliceosome	7	14.1×	8e-05
negative regulation of translation	7	11.3×	3e-04
mRNA processing	14	9.1×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	68
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2690964	NM_005778.4(RBM5):c.217G>A (p.Glu73Lys)	Likely pathogenic

SpliceAI

3342 predictions. Top by Δscore:

Variant	Effect	Δscore
3:50092041:A:AG	acceptor_gain	1.0000
3:50092042:G:GG	acceptor_gain	1.0000
3:50092042:GA:G	acceptor_gain	1.0000
3:50092042:GAGT:G	acceptor_gain	1.0000
3:50092206:GAG:G	donor_gain	1.0000
3:50092207:AGGT:A	donor_loss	1.0000
3:50092209:G:A	donor_loss	1.0000
3:50092210:T:G	donor_loss	1.0000
3:50093710:T:A	acceptor_gain	1.0000
3:50093713:A:AG	acceptor_gain	1.0000
3:50093714:A:G	acceptor_gain	1.0000
3:50093718:A:AC	acceptor_loss	1.0000
3:50093718:A:AG	acceptor_gain	1.0000
3:50093719:G:GG	acceptor_gain	1.0000
3:50093719:GA:G	acceptor_gain	1.0000
3:50093719:GAGA:G	acceptor_gain	1.0000
3:50093871:GCGAT:G	donor_gain	1.0000
3:50093873:G:GT	donor_gain	1.0000
3:50093873:GAT:G	donor_gain	1.0000
3:50093876:G:GG	donor_gain	1.0000
3:50093902:GCA:G	donor_gain	1.0000
3:50093905:GTCA:G	donor_gain	1.0000
3:50093909:G:GG	donor_gain	1.0000
3:50100049:CAGG:C	donor_loss	1.0000
3:50100050:AGGTG:A	donor_loss	1.0000
3:50100051:GGTGA:G	donor_loss	1.0000
3:50100052:G:C	donor_loss	1.0000
3:50100053:T:G	donor_loss	1.0000
3:50103078:TACA:T	acceptor_loss	1.0000
3:50103079:A:AG	acceptor_gain	1.0000

AlphaMissense

5376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:50093841:T:C	L102P	1.000
3:50093850:T:C	L105P	1.000
3:50100537:A:C	S139R	1.000
3:50100539:C:A	S139R	1.000
3:50100539:C:G	S139R	1.000
3:50100546:T:C	F142L	1.000
3:50100547:T:C	F142S	1.000
3:50100548:C:A	F142L	1.000
3:50100548:C:G	F142L	1.000
3:50100549:G:C	A143P	1.000
3:50100550:C:A	A143D	1.000
3:50100552:T:C	F144L	1.000
3:50100553:T:C	F144S	1.000
3:50100554:C:A	F144L	1.000
3:50100554:C:G	F144L	1.000
3:50100561:T:C	F147L	1.000
3:50100562:T:C	F147S	1.000
3:50100563:T:A	F147L	1.000
3:50100563:T:G	F147L	1.000
3:50100579:G:C	A153P	1.000
3:50100580:C:A	A153D	1.000
3:50100588:T:A	W156R	1.000
3:50100588:T:C	W156R	1.000
3:50103152:T:A	W185R	1.000
3:50103152:T:C	W185R	1.000
3:50103154:G:C	W185C	1.000
3:50103154:G:T	W185C	1.000
3:50103158:T:A	C187S	1.000
3:50103158:T:C	C187R	1.000
3:50103159:G:A	C187Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000045975 (3:50109245 T>C), RS1000069144 (3:50102293 C>G), RS1000110849 (3:50098764 C>A,T), RS1000334926 (3:50109020 G>A), RS1000497898 (3:50093608 G>A,C), RS1000550384 (3:50093206 G>A,C), RS1000712859 (3:50100991 A>G,T), RS1000768441 (3:50108466 T>C), RS1000851865 (3:50102581 C>G,T), RS1000966575 (3:50095445 G>T), RS1001020999 (3:50088234 T>C), RS1001250180 (3:50095214 A>G), RS1001262694 (3:50107624 C>CA), RS1001315244 (3:50107338 C>T), RS1001323790 (3:50116111 G>C)

Disease associations

OMIM: gene MIM:606884 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805)

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST002223_2	HDL cholesterol	9.000000e-12
GCST003795_3	Age at first birth	5.000000e-15
GCST004232_57	HDL cholesterol levels	1.000000e-12
GCST005951_49	Body mass index	1.000000e-08
GCST006044_2	Age at first birth	2.000000e-06
GCST006045_5	Age at first birth	6.000000e-10
GCST006920_7	Regular attendance at a gym or sports club	6.000000e-10
GCST006979_65	Heel bone mineral density	3.000000e-13
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST007565_88	Morning person	7.000000e-19
GCST008070_34	HDL cholesterol levels	3.000000e-09
GCST008075_108	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-17
GCST008075_52	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-13
GCST008084_184	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-17
GCST008084_23	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-12
GCST008085_38	HDL cholesterol levels in current drinkers	5.000000e-10
GCST008295_33	Number of decayed, missing and filled tooth surfaces or use of dentures	5.000000e-12
GCST008306_37	Dentures	7.000000e-12
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST011124_15	Caffeine consumption from tea	1.000000e-08
GCST90011898_159	Alanine aminotransferase levels	7.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009101	age at first birth measurement
EFO:0004340	body mass index
EFO:0009592	social interaction measurement
EFO:0009270	heel bone mineral density
EFO:0004337	intelligence
EFO:0008328	chronotype measurement
EFO:0004329	alcohol drinking
EFO:0010078	dentures
EFO:0004346	neuroimaging measurement
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	affects expression	1
diphenylcyclopropenone	decreases expression	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
avobenzone	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
bisphenol S	affects expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Air Pollutants, Occupational	affects expression, increases abundance, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Bilirubin	decreases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	increases expression	1
Fluorouracil	affects response to substance	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Potassium Dichromate	increases expression	1

Clinical trials (associated diseases)

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