RBM3

Summary

RBM3 (RNA binding motif protein 3, HGNC:9900) is a protein-coding gene on chromosome Xp11.23, encoding RNA-binding protein 3 (P98179). Cold-inducible mRNA binding protein that enhances global protein synthesis at both physiological and mild hypothermic temperatures.

This gene is a member of the glycine-rich RNA-binding protein family and encodes a protein with one RNA recognition motif (RRM) domain. Expression of this gene is induced by cold shock and low oxygen tension. A pseudogene exists on chromosome 1. Multiple alternatively spliced transcript variants that are predicted to encode different isoforms have been characterized although some of these variants fit nonsense-mediated decay (NMD) criteria.

Source: NCBI Gene 5935 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 27 total
• Druggable target: yes
• MANE Select transcript: NM_006743

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9900
Approved symbol	RBM3
Name	RNA binding motif protein 3
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	IS1-RNPL
Ensembl gene	ENSG00000102317
Ensembl biotype	protein_coding
OMIM	300027
Entrez	5935

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 8 protein_coding_CDS_not_defined

ENST00000354480, ENST00000376755, ENST00000376759, ENST00000466764, ENST00000472897, ENST00000485213, ENST00000488216, ENST00000489344, ENST00000490127, ENST00000491236, ENST00000491240, ENST00000886879, ENST00000886880, ENST00000915089, ENST00000915090, ENST00000915091, ENST00000915092, ENST00000915093, ENST00000951739, ENST00000951740

RefSeq mRNA: 1 — MANE Select: NM_006743 NM_006743

CCDS: CCDS14301

Canonical transcript exons

ENST00000376759 — 7 exons

Exon	Start	End
ENSE00001471618	48577465	48581162
ENSE00001547566	48574484	48574573
ENSE00003538077	48576508	48576604
ENSE00003591520	48577026	48577109
ENSE00003606332	48575168	48575283
ENSE00003641305	48576314	48576419
ENSE00003674591	48575561	48575667

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 259.3860 / max 1661.9847, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196260	157.0470	1826
196259	94.6299	1828
196261	4.9703	1654
196264	0.9506	578
196263	0.8532	510
196262	0.8097	509
196258	0.1253	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.89	gold quality
calcaneal tendon	UBERON:0003701	99.69	gold quality
penis	UBERON:0000989	99.64	gold quality
monocyte	CL:0000576	99.35	gold quality
synovial joint	UBERON:0002217	99.30	gold quality
nipple	UBERON:0002030	99.29	gold quality
mucosa of stomach	UBERON:0001199	99.26	gold quality
mononuclear cell	CL:0000842	99.19	gold quality
leukocyte	CL:0000738	99.16	gold quality
saphenous vein	UBERON:0007318	99.10	gold quality
skin of leg	UBERON:0001511	99.09	gold quality
body of pancreas	UBERON:0001150	99.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.03	gold quality
rectum	UBERON:0001052	99.01	gold quality
metanephros cortex	UBERON:0010533	98.94	gold quality
left uterine tube	UBERON:0001303	98.91	gold quality
skin of abdomen	UBERON:0001416	98.91	gold quality
lower lobe of lung	UBERON:0008949	98.91	gold quality
pharyngeal mucosa	UBERON:0000355	98.86	gold quality
right coronary artery	UBERON:0001625	98.85	gold quality
granulocyte	CL:0000094	98.83	gold quality
ganglionic eminence	UBERON:0004023	98.81	gold quality
superior surface of tongue	UBERON:0007371	98.80	gold quality
vermiform appendix	UBERON:0001154	98.79	gold quality
right lung	UBERON:0002167	98.79	gold quality
zone of skin	UBERON:0000014	98.75	gold quality
minor salivary gland	UBERON:0001830	98.75	gold quality
tibial artery	UBERON:0007610	98.75	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.74	gold quality
popliteal artery	UBERON:0002250	98.73	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-8	yes	52.70
E-GEOD-135922	yes	10.10
E-GEOD-130148	yes	3.73
E-ENAD-20	no	771.16
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

119 targeting RBM3, 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-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-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4728-5P	99.85	69.39	4718

Literature-anchored findings (GeneRIF, showing 40)

• RBM3 and CIRP are adaptatively expressed in response to hypoxia by a mechanism that involves neither HIF-1 nor mitochondria (PMID:15075239)
• From these results, it seems that the X-chromosome, through its RBM genes, plays a formerly unknown role in the regulation of programmed cell death (apoptosis) in breast cancer. (PMID:16552754)
• the RNA stabilizing and translation regulatory protein RBM3 is a novel proto-oncogene that induces transformation when overexpressed and is essential for cells to progress through mitosis. (PMID:18427544)
• pharmacological modulation of RBM3 and CIRBP may represent novel therapeutic approaches for prostate cancer. (PMID:19277990)
• Nuclear RBM3 is an independent favorable prognostic factor in breast cancer, and seems to have a specific role in estrogen receptor-positive tumors. (PMID:19734850)
• RBM3 is a critical factor providing cellular survival advantages in an adverse microenvironment presumably by restoring translation efficacy (PMID:19770690)
• RBM3 may be a useful prognostic and treatment predictive marker in epithelial ovarian cancer. (PMID:20727170)
• RBM3 is down-regulated in metastatic melanoma and high nuclear RBM3 expression in the primary tumour is an independent marker of a prolonged overal survival. (PMID:21777469)
• high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression (PMID:21955582)
• high tumor-specific nuclear expression of RBM3 is an independent predictor of good prognosis in colorectal cancer (PMID:21956899)
• the inverse association and prognostic impact of MCM3 and RBM3 expression indicate a possible interaction of these proteins in melanoma progression (PMID:22805320)
• Loss of RBM3 expression is associated with more aggressive tumors and poorer prognosis of urothelial bladder cancer. Findings may indicate that loss of RBM3 expression results in a phenotype more prone to metastatic spread than local aggressiveness. (PMID:23565664)
• A novel role of RBM3 in linking stress-regulated RNA splicing to tumorigenesis. (PMID:23667174)
• The data suggest that the overexpression of RBM3 may serve as an important molecular mechanism underlying astrocytic carcinogenesis. (PMID:23673116)
• High RBM3 expression is an independent prognostic marker in prostate cancer. (PMID:24380696)
• RBM3 may be a potential biomarker for treatment stratification in patients with metastatic non-seminomatous germ cell tumours. (PMID:25811459)
• Loss of RBM3 expression is an unfavourable prognostic marker in colorectal cancers (CRCs), and is linked to right-sided tumour localization. (PMID:25922889)
• Results show that RBM3 overexpression results in increased stemness in colon cancer cells, and inactivation of GSK3 through phosphorylation, thereby enhancing b-catenin signaling activity the colorectal cancer cells. (PMID:26331352)
• Low RBM3 immunoexpression is associated with urothelial carcinoma of the bladder. (PMID:26577765)
• The results indicate the existence of a negative feedback loop that regulates fever via reduced RBM3 levels and increased expression of miR-142-5p and miR-143. (PMID:26825461)
• Studies showed RBM3 as one of the important cold shock protein with critical roles in rapid cell adaption to the alterations of the environmental stress. Also, RBM3 plays an important role in neuroprotection, anti-apoptotic functions, cell proliferation as well as its function as proto-oncogene.[review] (PMID:27364162)
• Low RBM3 expression is associated with colon Cancer. (PMID:28373441)
• Cold induction of serine and arginine rich splicing factor 5 (SRSF5) is independent of cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3). (PMID:28536481)
• RBM3 is overexpressed in bipolar disorder patients responding to lithium treatment compared to non-responders. (PMID:28616776)
• High RBM3 expression is an independent predictor of prolonged survival in metastatic colorectal cancer patients. (PMID:28800641)
• Overexpression of RBM3 rescued SH-SY5Y cells from UV-induced apoptosis. (PMID:28831692)
• Results showed that high RBM3 expression in gastric cancer is mainly found in intestinal-type of Lauren grade and is associated with longer overall survival time. (PMID:29263314)
• results suggest that NF-kappaB p65 is a critical mediator of mild hypothermia, to which cells are exposed as an extracellular environment, and a central inducer of RBM3 expression, which is responsible for preventing cells from apoptosis (PMID:29388696)
• novel functions of RBM3 of potential significance to tissue repair, metastasis and development (PMID:29743635)
• the present study shows that decreased RBM3 expression is associated with unfavourable esophageal cancer phenotype, but not significantly linked to patient prognosis. (PMID:30419865)
• Data showed that the expression level of RBM3 was higher in human breast cancer tissues compared with adjacent nontumor tissues. A high level of RBM3 was associated with patient lymph node metastasis, high tumor grade and worse overall survival rates. Also, RBM3 upregulated ARPC2 by binding the 3’UTR, contributing to breast cancer progression. These results suggest that RBM3 acts as an oncogene in breast cancer. (PMID:30720048)
• Reduced RBM3 staining was significantly associated with advanced pathological tumor stage (pT) in NSCLCs (p = 0.0031). Subset analysis revealed that the association between reduced RBM3 staining and advanced pT stage was largely driven by the histological subgroup of lung adenocarcinoma (LUACs) (p = 0.0036). (PMID:30758670)
• Herein, we report that RBM3 is crucial for the stearoyl-CoA desaturase (SCD)-circRNA 2 formation in hepatocellular carcinoma (HCC) cells, which not only provides mechanistic insights into cancer-related circRNA dysregulation but also establishes RBM3 as an oncogene with both therapeutic potential and prognostic value (PMID:31235426)
• Cold-inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling. (PMID:31436914)
• Dual labeling of cell-type markers vs. RBM3/beta-klotho revealed enriched staining of targets in neurons in the developing brain. Identifying that RBM3/beta-klotho is abundant in neurons in the immature brain is fundamentally important to guide protocol design and conceptual frameworks germane to future testing of these neuroprotective pathways in humans. (PMID:31566073)
• For certain tumors, overexpression RBM3 might be a marker of improved survival in humans with Cancer, except for Breast Cancer. (PMID:32384455)
• Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non-small cell lung cancer. (PMID:32491279)
• Characterization of RNA-Binding Motif 3 (RBM3) Protein Levels and Nuclear Architecture Changes in Aggressive and Recurrent Prostate Cancer. (PMID:32587951)
• Role of RBM3 in the regulation of cell proliferation in hepatocellular carcinoma. (PMID:32976820)
• Long noncoding RNA MIR44352HG promotes the progression of head and neck squamous cell carcinoma by regulating the miR3835p/RBM3 axis. (PMID:33846802)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rbm3	ENSMUSG00000031167

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), 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), 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 3 — P98179 (reviewed: P98179)

Alternative names: RNA-binding motif protein 3, RNPL

All UniProt accessions (2): P98179, Q9H5V0

UniProt curated annotations — full annotation on UniProt →

Function. Cold-inducible mRNA binding protein that enhances global protein synthesis at both physiological and mild hypothermic temperatures. Reduces the relative abundance of microRNAs, when overexpressed. Enhances phosphorylation of translation initiation factors and active polysome formation.

Subunit / interactions. Interacts with RPL4. Associates with the 60S ribosomal subunits in an RNA-independent manner. Associates with ribosomes.

Subcellular location. Nucleus. Cytoplasm. Cell projection. Dendrite.

Post-translational modifications. Arg-105 is dimethylated, probably to asymmetric dimethylarginine. Phosphorylated.

Induction. Up-regulated by hypoxia.

RefSeq proteins (1): NP_006734* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034278	RBM3/CIRBP_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050441	RBM	Family

Pfam: PF00076

UniProt features (20 total): modified residue 8, strand 5, helix 2, chain 1, domain 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7EB1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98179-F1	63.28	0.00

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): 147, 155, 47, 105, 105, 105, 121, 131

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GNF2_BNIP2, PAL_PRMT5_TARGETS_UP, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, MORF_UBE2I, GGGTGGRR_PAX4_03, YY1_Q6, GOLDRATH_ANTIGEN_RESPONSE, PAX2_01, PATIL_LIVER_CANCER, GOBP_TRANSLATION, CTCTAGA_MIR526C_MIR518F_MIR526A, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, BORLAK_LIVER_CANCER_EGF_UP

GO Biological Process (4): RNA processing (GO:0006396), regulation of translation (GO:0006417), positive regulation of translation (GO:0045727), positive regulation of mRNA splicing, via spliceosome (GO:0048026)

GO Molecular Function (4): RNA binding (GO:0003723), ribosomal large subunit binding (GO:0043023), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), dendrite (GO:0030425), large ribosomal subunit (GO:0015934), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
translation	2
binding	2
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
mRNA splicing, via spliceosome	1
positive regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
positive regulation of mRNA processing	1
nucleic acid binding	1
ribosome binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
neuron projection	1
dendritic tree	1
ribosomal subunit	1

Protein interactions and networks

STRING

2794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM3	TBC1D25	Q3MII6	645
RBM3	DICER1	Q9UPY3	593
RBM3	GIT1	Q9Y2X7	583
RBM3	KHDRBS1	Q07666	538
RBM3	PRPF40A	O75400	531
RBM3	SFPQ	P23246	518
RBM3	MAGOHB	Q96A72	512
RBM3	MAGOH	P50606	507
RBM3	HNRNPH1	P31943	484
RBM3	PABPN1	Q86U42	479
RBM3	GAPDH	P00354	472
RBM3	PCBP2	Q15366	470
RBM3	PPP1R10	Q96QC0	468
RBM3	PRPF40B	Q6NWY9	466
RBM3	DDX5	P17844	463
RBM3	CELF2	O95319	463

IntAct

153 interactions, top by confidence:

A	B	Type	Score
SNRPA	RBM3	psi-mi:“MI:0915”(physical association)	0.830
KHDRBS2	RBM3	psi-mi:“MI:0915”(physical association)	0.830
RBM3	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.830
RBM3	SNRPA	psi-mi:“MI:0915”(physical association)	0.830
RBMX	RBM3	psi-mi:“MI:0915”(physical association)	0.780
RBM3	RBMX	psi-mi:“MI:0915”(physical association)	0.780
RBM3	RBMY1F	psi-mi:“MI:0915”(physical association)	0.720
RBMY1F	RBM3	psi-mi:“MI:0915”(physical association)	0.720
RBM3	RBMY1A1	psi-mi:“MI:0915”(physical association)	0.670
RBM3	HNRNPK	psi-mi:“MI:0915”(physical association)	0.670
HNRNPK	RBM3	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (225): RBM3 (Affinity Capture-MS), RBM3 (Two-hybrid), RBMY1A1 (Two-hybrid), SNRPA (Two-hybrid), RBMX (Two-hybrid), RBMY1F (Two-hybrid), KHDRBS2 (Two-hybrid), RBM3 (Affinity Capture-RNA), RBM3 (Affinity Capture-MS), RBM3 (Affinity Capture-MS), RBM3 (Affinity Capture-MS), RBM3 (Affinity Capture-MS), RBM3 (Affinity Capture-MS), RBM3 (Affinity Capture-MS), RBM3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A0LLY1, A0A2R8Y4L2, A5A6H4, O89086, O93235, P04256, P09651, P09867, P10979, P17130, P21522, P27484, P49310, P49311, P49312, P51968, P51989, P51991, P51992, P60824, P60825, P60826, P98179, Q03250, Q03251, Q03878, Q05966, Q13151, Q14011, Q28521, Q28IQ9, Q2HJ60, Q32P51, Q38896, Q41188, Q43472, Q5RF83, Q61B10, Q6URK4, Q8BG05

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A5A6M3, C0HFE5, D3Z4I3, D4AE41, M0R7T6, O22703, O35698, O75526, O89086, O93235, P04147, P0C8Z4, P10979, P19682, P19683, P19684, P28644, P38159, P39697, P48809, P49310, P49311, P49313, P49314, P60824, P60825, P60826, P84586, P98179, Q03250, Q03251, Q03878, Q04836, Q05966, Q08473, Q08935, Q08937, Q14011

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 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
Processing of Capped Intron-Containing Pre-mRNA	10	13.0×	2e-06
mRNA Polyadenylation	9	12.6×	9e-06
mRNA Splicing - Major Pathway	10	8.7×	3e-05
Dengue Virus-Host Interactions	10	7.2×	1e-04
Neddylation	9	6.8×	6e-04
Metabolism of RNA	9	6.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	8	23.5×	1e-06
intrinsic apoptotic signaling pathway	5	21.6×	9e-04
G1/S transition of mitotic cell cycle	6	14.5×	9e-04
mRNA splicing, via spliceosome	7	7.7×	4e-03
mRNA processing	8	7.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

861 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48574572:AGG:A	donor_loss	1.0000
X:48574574:GTA:G	donor_loss	1.0000
X:48575163:CACA:C	acceptor_loss	1.0000
X:48575164:ACAG:A	acceptor_gain	1.0000
X:48575166:A:AG	acceptor_gain	1.0000
X:48575166:A:AT	acceptor_loss	1.0000
X:48575166:AG:A	acceptor_gain	1.0000
X:48575167:G:GT	acceptor_gain	1.0000
X:48575167:GG:G	acceptor_gain	1.0000
X:48575167:GGA:G	acceptor_gain	1.0000
X:48575167:GGAC:G	acceptor_gain	1.0000
X:48575167:GGACT:G	acceptor_gain	1.0000
X:48575247:G:GT	donor_gain	1.0000
X:48575279:TGAGG:T	donor_gain	1.0000
X:48575280:GAGG:G	donor_gain	1.0000
X:48575280:GAGGG:G	donor_gain	1.0000
X:48575281:AGG:A	donor_gain	1.0000
X:48575281:AGGG:A	donor_loss	1.0000
X:48575282:GG:G	donor_gain	1.0000
X:48575282:GGG:G	donor_gain	1.0000
X:48575283:G:GT	donor_gain	1.0000
X:48575283:GG:G	donor_loss	1.0000
X:48575284:G:A	donor_loss	1.0000
X:48575284:G:GG	donor_gain	1.0000
X:48575285:T:A	donor_loss	1.0000
X:48575559:A:AG	acceptor_gain	1.0000
X:48575559:AGT:A	acceptor_gain	1.0000
X:48575560:G:GG	acceptor_gain	1.0000
X:48575560:GTG:G	acceptor_gain	1.0000
X:48576306:A:AG	acceptor_gain	1.0000

AlphaMissense

1014 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48575205:T:C	F9L	1.000
X:48575206:T:C	F9S	1.000
X:48575206:T:G	F9C	1.000
X:48575207:C:A	F9L	1.000
X:48575207:C:G	F9L	1.000
X:48575212:G:A	G11E	1.000
X:48575218:T:A	L13H	1.000
X:48575218:T:C	L13P	1.000
X:48575567:T:A	V37D	1.000
X:48575597:G:C	R47T	1.000
X:48575597:G:T	R47M	1.000
X:48575598:G:C	R47S	1.000
X:48575598:G:T	R47S	1.000
X:48575599:G:C	G48R	1.000
X:48575600:G:A	G48D	1.000
X:48575600:G:T	G48V	1.000
X:48575602:T:C	F49L	1.000
X:48575603:T:C	F49S	1.000
X:48575604:T:A	F49L	1.000
X:48575604:T:G	F49L	1.000
X:48575606:G:A	G50D	1.000
X:48575608:T:C	F51L	1.000
X:48575609:T:C	F51S	1.000
X:48575609:T:G	F51C	1.000
X:48575610:C:A	F51L	1.000
X:48575610:C:G	F51L	1.000
X:48575612:T:A	I52N	1.000
X:48575203:T:A	L8H	0.999
X:48575203:T:C	L8P	0.999
X:48575205:T:G	F9V	0.999

dbSNP variants (sampled 300 via entrez): RS1000865394 (X:48580059 C>G), RS1000953993 (X:48574670 C>A,T), RS1001751193 (X:48581384 C>A), RS1001850158 (X:48575975 T>G), RS1002962968 (X:48577895 A>G,T), RS1003259064 (X:48577499 C>T), RS1004377349 (X:48579601 A>G), RS1004996416 (X:48573940 G>A), RS1005107993 (X:48574292 G>A), RS1005266473 (X:48580925 C>T), RS1005996319 (X:48575433 G>A), RS1006048696 (X:48575076 C>G,T), RS1006112553 (X:48575735 C>G,T), RS1007036406 (X:48576939 C>T), RS1008037679 (X:48578418 C>G,T)

Disease associations

OMIM: gene MIM:300027 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295793 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.03	Kd	9447	nM	CHEMBL5653589
5.03	ED50	9447	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149208: Binding affinity to human RBM3 incubated for 45 mins by Kinobead based pull down assay	kd	9.4466	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
bisphenol A	affects expression, affects splicing, increases expression, affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cisplatin	decreases expression, increases response to substance	2
Lead	affects expression, increases expression	2
Quercetin	decreases expression	2
1-Methyl-4-phenylpyridinium	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
uranyl acetate	increases expression	1
deoxynivalenol	decreases expression	1
beta-lapachone	increases expression	1
sodium bichromate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases 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
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118697	Binding	Binding affinity to RBM3 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3FS	Abcam HEK293T RBM3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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