RBM33

Summary

RBM33 (RNA binding motif protein 33, HGNC:27223) is a protein-coding gene on chromosome 7q36.3, encoding RNA-binding protein 33 (Q96EV2). RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as mRNA export, mRNA stability and/or translation. It is a selective cancer dependency (DepMap: 22.7% of cell lines).

Enables N6-methyladenosine-containing RNA reader activity and lncRNA binding activity. Involved in RNA export from nucleus and regulation of mRNA stability. Located in cytoplasm. Is active in nucleus.

Source: NCBI Gene 155435 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 158 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 22.7% of screened cell lines
• MANE Select transcript: NM_053043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27223
Approved symbol	RBM33
Name	RNA binding motif protein 33
Location	7q36.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686F102, MGC20460, DKFZp434D1319
Ensembl gene	ENSG00000184863
Ensembl biotype	protein_coding
OMIM	620833
Entrez	155435

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000287912, ENST00000307403, ENST00000341148, ENST00000392755, ENST00000392759, ENST00000392761, ENST00000401878, ENST00000438356, ENST00000440108, ENST00000486747

RefSeq mRNA: 1 — MANE Select: NM_053043 NM_053043

CCDS: CCDS5941

Canonical transcript exons

ENST00000401878 — 18 exons

Exon	Start	End
ENSE00000858000	155672867	155672915
ENSE00001149669	155665175	155665253
ENSE00001390292	155774559	155774647
ENSE00001512994	155744961	155745602
ENSE00001512996	155739715	155740026
ENSE00001512999	155738060	155738403
ENSE00001562600	155644661	155644919
ENSE00001661564	155678608	155678684
ENSE00001738840	155680590	155680908
ENSE00001747351	155706860	155707068
ENSE00001803502	155700773	155700944
ENSE00001830553	155774993	155781480
ENSE00003511504	155763812	155764018
ENSE00003571940	155711203	155711455
ENSE00003587715	155737530	155737662
ENSE00003620213	155741819	155742106
ENSE00003621716	155766467	155766655
ENSE00003654935	155718385	155718443

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 97.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.7964 / max 654.4916, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82240	24.2607	1817
82237	3.2988	1434
82238	1.1811	772
82239	0.7848	474
82243	0.2709	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.75	gold quality
sural nerve	UBERON:0015488	97.32	gold quality
bone marrow cell	CL:0002092	95.77	gold quality
tendon	UBERON:0000043	94.93	gold quality
thymus	UBERON:0002370	94.24	gold quality
tendon of biceps brachii	UBERON:0008188	92.89	gold quality
buccal mucosa cell	CL:0002336	92.84	gold quality
tibialis anterior	UBERON:0001385	92.84	gold quality
colonic epithelium	UBERON:0000397	92.60	gold quality
ileal mucosa	UBERON:0000331	92.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.19	gold quality
cerebellar hemisphere	UBERON:0002245	91.08	gold quality
cerebellar cortex	UBERON:0002129	91.01	gold quality
tibial nerve	UBERON:0001323	90.80	gold quality
cerebellum	UBERON:0002037	90.38	gold quality
oocyte	CL:0000023	90.34	gold quality
right lung	UBERON:0002167	90.21	gold quality
lower esophagus mucosa	UBERON:0035834	89.58	gold quality
monocyte	CL:0000576	89.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.33	gold quality
muscle of leg	UBERON:0001383	89.22	gold quality
blood	UBERON:0000178	89.17	gold quality
leukocyte	CL:0000738	89.13	gold quality
skin of abdomen	UBERON:0001416	88.89	gold quality
gastrocnemius	UBERON:0001388	88.85	gold quality
skin of leg	UBERON:0001511	88.84	gold quality
body of pancreas	UBERON:0001150	88.79	gold quality
secondary oocyte	CL:0000655	88.67	gold quality
small intestine	UBERON:0002108	88.41	gold quality
corpus callosum	UBERON:0002336	88.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.13
E-MTAB-4850	no	381.42
E-MTAB-6142	no	106.71

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• RBM33 is a unique m[6]A RNA-binding protein that regulates ALKBH5 demethylase activity and substrate selectivity. (PMID:37257451)
• Biogenesis of circRBM33 mediated by N6-methyladenosine and its function in abdominal aortic aneurysm. (PMID:39246182)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm33a	ENSDARG00000068562
danio_rerio	rbm33b	ENSDARG00000094896
mus_musculus	Rbm33	ENSMUSG00000048271
rattus_norvegicus	Rbm33	ENSRNOG00000006718

Protein

Protein identifiers

RNA-binding protein 33 — Q96EV2 (reviewed: Q96EV2)

Alternative names: Proline-rich protein 8, RNA-binding motif protein 33

All UniProt accessions (8): A0A0C4DFS3, A8MTF7, C9J7M3, Q96EV2, H0Y3K3, H0Y3K4, H7BXM6, H7C0H2

UniProt curated annotations — full annotation on UniProt →

Function. RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as mRNA export, mRNA stability and/or translation. Binds a subset of intronless RNAs containing GC-rich elements, such as NORAD, and promotes their nuclear export by recruiting target RNAs to components of the NXF1-NXT1 RNA export machinery. Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, promoting their demethylation by ALKBH5. Acts as an molecular adapter, which (1) promotes ALKBH5 recruitment to m6A-containing transcripts and (2) activates ALKBH5 demethylase activity by recruiting SENP1, leading to ALKBH5 deSUMOylation and subsequent activation.

Subunit / interactions. Associates with the NXF1-NXT1 RNA export complex. Interacts with ALKBH5; facilitating ALKBH5 recruitment to m6A-containing transcripts. Interacts with SENP1; promoting ALKBH5 deSUMOylation and subsequent activation.

Subcellular location. Nucleus. Cytoplasm.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96EV2-1	1	yes
Q96EV2-2	2

RefSeq proteins (1): NP_444271* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR039878	RBM33	Family

UniProt features (49 total): compositionally biased region 18, modified residue 12, region of interest 6, mutagenesis site 5, splice variant 2, initiator methionine 1, chain 1, domain 1, cross-link 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EV2-F1	46.75	0.09

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 (13): 2, 41, 205, 233, 470, 741, 765, 951, 973, 991, 1028, 1028, 960

Mutagenesis-validated functional residues (5):

Position	Phenotype
1101	abolished interaction with alkbh5.
1106	does not affect interaction with alkbh5.
1110	does not affect interaction with alkbh5.
1134	abolished interaction with alkbh5.
1169	does not affect interaction with alkbh5.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 138 (showing top): WANG_CLIM2_TARGETS_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HEIDENBLAD_AMPLICON_8Q24_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_NUCLEAR_TRANSPORT, GTGCCTT_MIR506, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, HAND1E47_01, GOBP_NUCLEAR_EXPORT, TGCCTTA_MIR124A, GOBP_RNA_LOCALIZATION

GO Biological Process (4): RNA export from nucleus (GO:0006405), regulation of mRNA stability (GO:0043488), mRNA transport (GO:0051028), mRNA destabilization (GO:0061157)

GO Molecular Function (5): RNA binding (GO:0003723), protein-macromolecule adaptor activity (GO:0030674), lncRNA binding (GO:0106222), N6-methyladenosine-containing RNA reader activity (GO:1990247), nucleic acid binding (GO:0003676)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA transport	2
RNA binding	2
nuclear export	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
negative regulation of gene expression	1
regulation of mRNA stability	1
RNA destabilization	1
positive regulation of mRNA catabolic process	1
nucleic acid binding	1
protein binding	1
molecular adaptor activity	1
protein-RNA adaptor activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM33	RNF32	Q9H0A6	655
RBM33	NOM1	Q5C9Z4	643
RBM33	LMBR1	Q8WVP7	542
RBM33	CNPY1	Q3B7I2	541
RBM33	SACK1C	Q9BQN1	507
RBM33	FGGY	Q96C11	489
RBM33	PGBD5	Q8N414	488
RBM33	C1orf52	Q8N6N3	446
RBM33	AIG1	Q9NVV5	435
RBM33	TESPA1	A2RU30	424
RBM33	USP24	Q9UPU5	422
RBM33	DNAJC21	Q5F1R6	414
RBM33	DDX50	Q9BQ39	401
RBM33	ASPHD2	Q6ICH7	393
RBM33	ZC3H14	Q6PJT7	388

IntAct

51 interactions, top by confidence:

A	B	Type	Score
MAP2K1	RAF1	psi-mi:“MI:0914”(association)	0.960
CDK8	MED19	psi-mi:“MI:0914”(association)	0.850
YES1	RBM33	psi-mi:“MI:0407”(direct interaction)	0.440
GSK3B	SEC16A	psi-mi:“MI:0914”(association)	0.420
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
FOXG1	RBM33	psi-mi:“MI:0915”(physical association)	0.400
Tuba3a	PFDN1	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
THOC1	TARS3	psi-mi:“MI:0914”(association)	0.350
THOC7	ALYREF	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
EEA1	SEC16A	psi-mi:“MI:0914”(association)	0.350
LMNA	ZNF724	psi-mi:“MI:0914”(association)	0.350
RAB5A	SEC16A	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ARHGAP27	MCRIP1	psi-mi:“MI:0914”(association)	0.350
ZIC3	MYO1C	psi-mi:“MI:0914”(association)	0.350
SOX5		psi-mi:“MI:0914”(association)	0.350
SOX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
RBM33	DDX39A	psi-mi:“MI:0914”(association)	0.350
RPL35A	SMCHD1	psi-mi:“MI:0914”(association)	0.350
RBM33	BAG2	psi-mi:“MI:0914”(association)	0.350
AR	MED6	psi-mi:“MI:2364”(proximity)	0.270
RAVER1	KDM6A	psi-mi:“MI:2364”(proximity)	0.270
SP7	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
CPSF6	CNOT1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (154): MYO9B (Affinity Capture-MS), TRMT2A (Affinity Capture-MS), EME1 (Affinity Capture-MS), ATF6B (Affinity Capture-MS), KPTN (Affinity Capture-MS), RBM33 (Proximity Label-MS), RBM33 (Affinity Capture-MS), RBM33 (Affinity Capture-MS), RBM33 (Affinity Capture-MS), RBM33 (Affinity Capture-MS), RBM33 (Affinity Capture-MS), RBM33 (Affinity Capture-MS), RBM33 (Affinity Capture-MS), EME1 (Affinity Capture-MS), KPTN (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IZ84, A0JMU8, A1L1K8, A5D7H5, B2RRE7, O15234, O60293, O75420, P48634, P61129, P61406, Q04637, Q14444, Q1ECZ4, Q1LZB6, Q3TLH4, Q5CZI8, Q5JSZ5, Q5JVS0, Q5M9G3, Q5RAK6, Q5TM26, Q5U236, Q5VK71, Q5XJD3, Q60865, Q6IMN6, Q6MG48, Q6NZJ6, Q7TPM1, Q7TQG1, Q7TQH0, Q7TSC1, Q80XI3, Q86US8, Q8BWW4, Q8BXJ2, Q8BYK8, Q8K3W3, Q8K3X0

Diamond homologs: Q96EV2, Q9CXK9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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 3’-end processing	9	32.2×	3e-09
Transport of Mature mRNA derived from an Intron-Containing Transcript	8	22.1×	5e-07
RNA Polymerase II Transcription Termination	5	20.0×	3e-04
mRNA Polyadenylation	8	12.8×	2e-05
Processing of Capped Intron-Containing Pre-mRNA	8	11.9×	2e-05
mRNA Splicing	5	10.0×	7e-03
mRNA Splicing - Major Pathway	10	9.9×	5e-06
Dengue Virus-Host Interactions	11	9.1×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
mRNA transport	5	20.9×	6e-04
mRNA processing	12	15.0×	1e-08
RNA splicing	10	14.0×	6e-07
mRNA splicing, via spliceosome	8	11.6×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	121
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
560044	Single allele	Likely pathogenic

SpliceAI

5659 predictions. Top by Δscore:

Variant	Effect	Δscore
7:155644916:GGAG:G	donor_gain	1.0000
7:155644917:GAG:G	donor_gain	1.0000
7:155644917:GAGG:G	donor_gain	1.0000
7:155644920:G:GG	donor_gain	1.0000
7:155665173:A:AG	acceptor_gain	1.0000
7:155665174:G:GG	acceptor_gain	1.0000
7:155665250:ACAGG:A	donor_loss	1.0000
7:155665251:CAGG:C	donor_loss	1.0000
7:155665253:GGT:G	donor_loss	1.0000
7:155665254:GTA:G	donor_loss	1.0000
7:155665255:T:G	donor_loss	1.0000
7:155672864:A:AG	acceptor_gain	1.0000
7:155672864:AAGT:A	acceptor_gain	1.0000
7:155672865:A:G	acceptor_gain	1.0000
7:155672866:G:GG	acceptor_gain	1.0000
7:155672866:GT:G	acceptor_gain	1.0000
7:155672915:GGTA:G	donor_loss	1.0000
7:155672916:G:GA	donor_loss	1.0000
7:155678602:A:AG	acceptor_gain	1.0000
7:155678604:TTA:T	acceptor_loss	1.0000
7:155678605:TAG:T	acceptor_loss	1.0000
7:155678606:A:AG	acceptor_gain	1.0000
7:155678606:A:G	acceptor_loss	1.0000
7:155678607:G:GT	acceptor_gain	1.0000
7:155678607:GAA:G	acceptor_gain	1.0000
7:155678680:TTCAG:T	donor_loss	1.0000
7:155678681:TCAGG:T	donor_loss	1.0000
7:155678682:CAGG:C	donor_loss	1.0000
7:155678683:AG:A	donor_loss	1.0000
7:155678684:GGTAC:G	donor_loss	1.0000

AlphaMissense

7634 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:155678636:T:C	L67P	1.000
7:155700863:T:C	F220L	1.000
7:155700864:T:C	F220S	1.000
7:155700864:T:G	F220C	1.000
7:155700865:C:A	F220L	1.000
7:155700865:C:G	F220L	1.000
7:155700930:T:C	I242T	1.000
7:155700942:T:C	L246S	1.000
7:155706863:T:A	L248H	1.000
7:155706863:T:C	L248P	1.000
7:155706874:G:C	A252P	1.000
7:155706887:T:C	L256S	1.000
7:155706895:T:C	F259L	1.000
7:155706896:T:C	F259S	1.000
7:155706896:T:G	F259C	1.000
7:155706897:T:A	F259L	1.000
7:155706897:T:G	F259L	1.000
7:155711408:T:A	I385K	1.000
7:155711408:T:C	I385T	1.000
7:155711408:T:G	I385R	1.000
7:155711414:T:A	I387N	1.000
7:155711414:T:C	I387T	1.000
7:155711414:T:G	I387S	1.000
7:155711425:T:C	F391L	1.000
7:155711426:T:C	F391S	1.000
7:155711427:C:A	F391L	1.000
7:155711427:C:G	F391L	1.000
7:155741894:C:A	R709S	1.000
7:155741901:T:C	L711S	1.000
7:155745013:A:C	Q797P	1.000

dbSNP variants (sampled 300 via entrez): RS1000001590 (7:155726821 G>A), RS1000073813 (7:155672669 T>C), RS1000079528 (7:155771791 G>T), RS1000088544 (7:155666883 CTTT>C,CTTTT), RS1000142149 (7:155671231 A>G,T), RS1000156295 (7:155692079 T>C,G), RS1000166627 (7:155751009 A>T), RS1000182224 (7:155659083 A>G), RS1000189338 (7:155664094 A>C), RS1000204791 (7:155698814 T>C), RS1000209920 (7:155777474 G>C), RS1000228530 (7:155706526 T>C), RS1000246241 (7:155738803 A>G,T), RS1000260125 (7:155698487 T>C), RS1000349027 (7:155744788 C>T)

Disease associations

OMIM: gene MIM:620833 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1247	Metabolite levels	2.000000e-06
GCST009391_284	Metabolite levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010423	triacylglycerol 54:5 measurement
EFO:0010424	triacylglycerol 54:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
methylmercuric chloride	increases expression, decreases expression	2
sodium arsenite	increases abundance, increases expression	2
Arsenic	increases expression, affects methylation, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	affects methylation, affects cotreatment	1
2-butenal	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	affects phosphorylation	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	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
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Leflunomide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Amiodarone	increases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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