RBM4B

Summary

RBM4B (RNA binding motif protein 4B, HGNC:28842) is a protein-coding gene on chromosome 11q13.2, encoding RNA-binding protein 4B (Q9BQ04). Required for the translational activation of PER1 mRNA in response to circadian clock. It is a selective cancer dependency (DepMap: 12.8% of cell lines).

Enables RNA binding activity. Predicted to be involved in circadian regulation of gene expression; entrainment of circadian clock by photoperiod; and regulation of translation. Predicted to act upstream of or within positive regulation of gene expression. Located in cytosol and nucleoplasm. Part of protein-containing complex.

Source: NCBI Gene 83759 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 69 total
• Cancer dependency (DepMap): dependent in 12.8% of screened cell lines
• MANE Select transcript: NM_031492

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28842
Approved symbol	RBM4B
Name	RNA binding motif protein 4B
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC10871, ZCCHC15, RBM4L, ZCRB3B, ZCCHC21B
Ensembl gene	ENSG00000173914
Ensembl biotype	protein_coding
OMIM	621045
Entrez	83759

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000310046, ENST00000524637, ENST00000525754, ENST00000528106, ENST00000529195, ENST00000531036, ENST00000531969, ENST00000534198, ENST00000856419, ENST00000856420, ENST00000856421, ENST00000856422, ENST00000934782, ENST00000934783, ENST00000934784, ENST00000944535

RefSeq mRNA: 2 — MANE Select: NM_031492 NM_001286135, NM_031492

CCDS: CCDS66144, CCDS8149

Canonical transcript exons

ENST00000310046 — 4 exons

Exon	Start	End
ENSE00001188165	66664998	66665578
ENSE00001188175	66668615	66669291
ENSE00002166677	66677764	66677887
ENSE00002463386	66676668	66677091

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 96.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2606 / max 110.7990, expressed in 1774 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120823	12.2606	1774

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	96.52	gold quality
ganglionic eminence	UBERON:0004023	96.22	gold quality
cerebellar hemisphere	UBERON:0002245	95.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.68	gold quality
cerebellar cortex	UBERON:0002129	95.59	gold quality
right uterine tube	UBERON:0001302	95.15	gold quality
cerebellum	UBERON:0002037	93.63	gold quality
left ovary	UBERON:0002119	92.85	gold quality
adenohypophysis	UBERON:0002196	92.53	gold quality
right ovary	UBERON:0002118	92.48	gold quality
endocervix	UBERON:0000458	92.18	gold quality
ventricular zone	UBERON:0003053	92.06	gold quality
secondary oocyte	CL:0000655	91.61	gold quality
pituitary gland	UBERON:0000007	91.49	gold quality
body of uterus	UBERON:0009853	91.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.22	gold quality
right lobe of thyroid gland	UBERON:0001119	90.54	gold quality
left lobe of thyroid gland	UBERON:0001120	90.35	gold quality
ectocervix	UBERON:0012249	90.01	gold quality
ovary	UBERON:0000992	89.87	gold quality
right adrenal gland cortex	UBERON:0035827	89.57	gold quality
minor salivary gland	UBERON:0001830	89.52	gold quality
right adrenal gland	UBERON:0001233	89.47	gold quality
metanephros cortex	UBERON:0010533	89.44	gold quality
right frontal lobe	UBERON:0002810	89.33	gold quality
tendon of biceps brachii	UBERON:0008188	89.12	gold quality
thyroid gland	UBERON:0002046	89.11	gold quality
vagina	UBERON:0000996	89.04	gold quality
lower esophagus mucosa	UBERON:0035834	88.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting RBM4B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-10522-5P	99.26	68.50	2087

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.8% of screened cell lines.

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rbm4b	ENSMUSG00000033760

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), 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 4B — Q9BQ04 (reviewed: Q9BQ04)

Alternative names: RNA-binding motif protein 30, RNA-binding motif protein 4B, RNA-binding protein 30

All UniProt accessions (5): Q9BQ04, E9PLB0, E9PM61, H0YDG8, U3KQD5

UniProt curated annotations — full annotation on UniProt →

Function. Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3’-UTR of the PER1 mRNA.

Subunit / interactions. Interacts with TNPO3, which may mediate nuclear import of the protein.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Expressed in liver and kidney (at protein level). Ubiquitously expressed.

RefSeq proteins (2): NP_001273064, NP_113680* (*=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 (13 total): strand 5, domain 2, helix 2, chain 1, zinc finger region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DGT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ04-F1	64.65	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 184 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_PHOTOPERIODISM, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GCM_ZNF198, GCM_PPM1D, TGACCTY_ERR1_Q2, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, chr11q13, SP1_Q2_01, GOBP_TRANSLATION, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, BLALOCK_ALZHEIMERS_DISEASE_UP, CCTGTGA_MIR513, ICHIBA_GRAFT_VERSUS_HOST_DISEASE_35D_DN

GO Biological Process (8): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA processing (GO:0006397), regulation of translation (GO:0006417), circadian rhythm (GO:0007623), RNA splicing (GO:0008380), positive regulation of gene expression (GO:0010628), circadian regulation of gene expression (GO:0032922), entrainment of circadian clock by photoperiod (GO:0043153)

GO Molecular Function (6): 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 (6): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), nuclear speck (GO:0016607), protein-containing complex (GO:0032991), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
regulation of gene expression	2
binding	2
nuclear lumen	2
cellular anatomical structure	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
mRNA metabolic process	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
rhythmic process	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
circadian rhythm	1
photoperiodism	1
entrainment of circadian clock	1
nucleic acid binding	1
RNA binding	1
transition metal ion binding	1
cation binding	1
intracellular membraneless organelle	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
cellular_component	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

722 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM4B	RBM41	Q96IZ5	435
RBM4B	LRRC23	Q53EV4	405
RBM4B	TRNAU1AP	Q9NX07	393
RBM4B	RNF44	Q7L0R7	383
RBM4B	GLI4	P10075	381
RBM4B	RBM42	Q9BTD8	379
RBM4B	KCNQ5	Q9NR82	374
RBM4B	IQCN	Q9H0B3	371
RBM4B	RBM45	Q8IUH3	370
RBM4B	G5EA03	G5EA03	370
RBM4B	OVCA2	Q8WZ82	366
RBM4B	RBM24	Q9BX46	363
RBM4B	NOVA2	Q9UNW9	361
RBM4B	PHRF1	Q9P1Y6	359
RBM4B	PLP2	Q04941	356

IntAct

81 interactions, top by confidence:

A	B	Type	Score
RBM4B	DZIP3	psi-mi:“MI:0915”(physical association)	0.670
DZIP3	RBM4B	psi-mi:“MI:0915”(physical association)	0.670
RPL10A	RRP8	psi-mi:“MI:0914”(association)	0.640
RBM4	RBM4B	psi-mi:“MI:0914”(association)	0.640
POP4	POP7	psi-mi:“MI:0914”(association)	0.640
RBM4B	HNRNPUL1	psi-mi:“MI:0915”(physical association)	0.560
HNRNPUL1	RBM4B	psi-mi:“MI:0915”(physical association)	0.560
ATN1	RBM4B	psi-mi:“MI:0915”(physical association)	0.560
KLF1	RBM4B	psi-mi:“MI:0915”(physical association)	0.560
SNRPA	RBM4B	psi-mi:“MI:0915”(physical association)	0.560
TSGA10IP	RBM4B	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	RBM4B	psi-mi:“MI:0915”(physical association)	0.560
RBM4B		psi-mi:“MI:0915”(physical association)	0.560
POP4	NME2P1	psi-mi:“MI:0914”(association)	0.530
KNOP1	MAGEB2	psi-mi:“MI:0914”(association)	0.530
GLYR1	MAGEB2	psi-mi:“MI:0914”(association)	0.530
RPP30	RPP40	psi-mi:“MI:0914”(association)	0.530
RBM4B	SMYD1	psi-mi:“MI:0915”(physical association)	0.510
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
HNRNPM	RBM4B	psi-mi:“MI:0915”(physical association)	0.370
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (335): RBM4B (Two-hybrid), RBM4B (Two-hybrid), RBM4B (Affinity Capture-MS), RBM4B (Affinity Capture-MS), NIP7 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP4 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), MYEF2 (Affinity Capture-MS), RPL3 (Affinity Capture-MS), ZNF324 (Affinity Capture-MS), UTP18 (Affinity Capture-MS), STAU2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y4L2, A5A6H4, A7VJC2, O01671, O17310, O19049, O61374, O88569, O97018, P04256, P09651, P09867, P17130, P19339, P21522, P22626, P31942, P49312, P51968, P51989, P51990, P51991, P51992, P52272, P61978, P61979, P61980, Q08473, Q13148, Q24668, Q28521, Q28F51, Q2HJ60, Q32P51, Q3T0D0, Q4R4M6, Q5R5H8, Q5R5W2, Q5RBU8, Q5ZIQ3

Diamond homologs: A0A0D1C8Z4, A0A0R4IEW8, A0JM51, A4IIM2, B0BN49, B8BCZ8, D3Z4I3, M0R7T6, O04425, O09032, O17310, O22173, O57406, O93235, O95319, O97018, P16914, P23241, P26378, P28659, P33240, P60824, P60825, P60826, Q06AT9, Q08E07, Q0V9L3, Q12926, Q14011, Q14498, Q14576, Q28GD4, Q28HE9, Q28IQ9, Q3MHX3, Q3ZCE8, Q4QQT3, Q4R535, Q4R979, Q5F3T7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
Major pathway of rRNA processing in the nucleolus and cytosol	8	9.2×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
rRNA processing	6	11.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

976 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66669293:T:C	acceptor_gain	0.9900
11:66676644:C:CT	donor_gain	0.9900
11:66676645:T:TT	donor_gain	0.9900
11:66676663:TTCA:T	donor_loss	0.9900
11:66676664:TCACC:T	donor_loss	0.9900
11:66676665:CA:C	donor_loss	0.9900
11:66676667:C:T	donor_loss	0.9900
11:66676669:TTGAA:T	donor_gain	0.9900
11:66676712:T:TA	donor_gain	0.9900
11:66677610:T:TA	donor_gain	0.9900
11:66677614:T:TA	donor_gain	0.9900
11:66677634:T:TA	donor_gain	0.9900
11:66677638:C:A	donor_gain	0.9900
11:66677648:T:TA	donor_gain	0.9900
11:66677649:C:A	donor_gain	0.9900
11:66677657:T:TA	donor_gain	0.9900
11:66666286:CTTA:C	donor_gain	0.9800
11:66666287:TTAT:T	donor_gain	0.9800
11:66666288:TATT:T	donor_gain	0.9800
11:66666289:ATTA:A	donor_gain	0.9800
11:66669292:C:CC	acceptor_gain	0.9800
11:66677658:C:A	donor_gain	0.9800
11:66668610:CTCAC:C	donor_loss	0.9700
11:66668611:TCACC:T	donor_loss	0.9700
11:66668612:CA:C	donor_loss	0.9700
11:66668614:C:CA	donor_loss	0.9700
11:66668616:T:TA	donor_gain	0.9700
11:66668656:A:AC	donor_gain	0.9700
11:66668657:C:CC	donor_gain	0.9700
11:66669291:CCT:C	acceptor_gain	0.9700

AlphaMissense

2331 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66669179:G:C	C175W	1.000
11:66669180:C:A	C175F	1.000
11:66669180:C:G	C175S	1.000
11:66669180:C:T	C175Y	1.000
11:66669181:A:G	C175R	1.000
11:66669181:A:T	C175S	1.000
11:66669185:T:A	K173N	1.000
11:66669185:T:G	K173N	1.000
11:66669189:G:A	S172F	1.000
11:66669191:C:A	W171C	1.000
11:66669191:C:G	W171C	1.000
11:66669193:A:G	W171R	1.000
11:66669193:A:T	W171R	1.000
11:66669194:G:C	H170Q	1.000
11:66669194:G:T	H170Q	1.000
11:66669196:G:C	H170D	1.000
11:66669209:A:C	C165W	1.000
11:66669210:C:A	C165F	1.000
11:66669210:C:G	C165S	1.000
11:66669210:C:T	C165Y	1.000
11:66669211:A:G	C165R	1.000
11:66669211:A:T	C165S	1.000
11:66669217:A:C	Y163D	1.000
11:66669218:G:C	C162W	1.000
11:66669219:C:A	C162F	1.000
11:66669219:C:G	C162S	1.000
11:66669219:C:T	C162Y	1.000
11:66669220:A:G	C162R	1.000
11:66669220:A:T	C162S	1.000
11:66669236:C:A	M156I	1.000

dbSNP variants (sampled 300 via entrez): RS1000076214 (11:66674214 C>G,T), RS1000263036 (11:66670807 C>A), RS1000650113 (11:66675108 T>C), RS1000670481 (11:66666498 A>C), RS1001116273 (11:66673695 G>A), RS1001344170 (11:66667448 T>C), RS1001439939 (11:66673930 A>G), RS1002584756 (11:66677956 A>G,T), RS1002827750 (11:66675181 C>T), RS1002965447 (11:66678109 C>A,T), RS1003110010 (11:66675427 A>G), RS1003157633 (11:66676537 T>C), RS1003343451 (11:66670600 A>C), RS1003565539 (11:66677317 C>A,T), RS1004003160 (11:66677146 G>A)

Disease associations

OMIM: gene MIM:621045 | 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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, decreases expression	3
urushiol	decreases expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ferrous chloride	decreases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol S	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Urethane	increases expression	1
Valproic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2IP	HAP1 RBM4B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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