RBM46

Summary

RBM46 (RNA binding motif protein 46, HGNC:28401) is a protein-coding gene on chromosome 4q32.1, encoding Probable RNA-binding protein 46 (Q8TBY0). Essential for male and female fertility, playing a crucial role in regulating germ cell development by ensuring the proper progression of meiosis prophase I.

Predicted to enable mRNA binding activity. Predicted to be involved in several processes, including cell cycle switching, mitotic to meiotic cell cycle; meiotic nuclear division; and spermatid differentiation. Predicted to act upstream of or within mRNA stabilization and trophectodermal cell differentiation. Predicted to be located in cytoplasm. Predicted to be active in nucleus.

Source: NCBI Gene 166863 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_144979

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28401
Approved symbol	RBM46
Name	RNA binding motif protein 46
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC27016, CT68
Ensembl gene	ENSG00000151962
Ensembl biotype	protein_coding
OMIM	620147
Entrez	166863

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000281722, ENST00000510397, ENST00000512640, ENST00000514866

RefSeq mRNA: 3 — MANE Select: NM_144979 NM_001277171, NM_001277173, NM_144979

CCDS: CCDS3790, CCDS64085, CCDS64086

Canonical transcript exons

ENST00000281722 — 5 exons

Exon	Start	End
ENSE00001002660	154796742	154796903
ENSE00001002665	154797811	154798278
ENSE00001002667	154798782	154799564
ENSE00001210770	154827868	154828813
ENSE00003842506	154781272	154781436

Expression profiles

Bgee: expression breadth broad, 68 present calls, max score 93.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0833 / max 47.8150, expressed in 16 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50186	0.0550	14
50187	0.0150	3
50188	0.0134	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.02	gold quality
secondary oocyte	CL:0000655	90.77	gold quality
buccal mucosa cell	CL:0002336	88.99	gold quality
oocyte	CL:0000023	88.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.90	gold quality
testis	UBERON:0000473	79.74	gold quality
right testis	UBERON:0004534	78.04	gold quality
left testis	UBERON:0004533	77.17	gold quality
oviduct epithelium	UBERON:0004804	61.68	silver quality
tibialis anterior	UBERON:0001385	60.14	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
sperm	CL:0000019	54.05	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
epithelial cell of pancreas	CL:0000083	53.82	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
pancreatic ductal cell	CL:0002079	53.14	silver quality
ileal mucosa	UBERON:0000331	52.41	silver quality
deltoid	UBERON:0001476	52.38	gold quality
adult organism	UBERON:0007023	51.16	silver quality
gall bladder	UBERON:0002110	51.13	gold quality
myocardium	UBERON:0002349	50.25	gold quality
tendon of biceps brachii	UBERON:0008188	47.77	gold quality
quadriceps femoris	UBERON:0001377	47.62	gold quality
islet of Langerhans	UBERON:0000006	47.47	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
cerebellar vermis	UBERON:0004720	46.54	gold quality
vastus lateralis	UBERON:0001379	45.48	gold quality
ganglionic eminence	UBERON:0004023	44.13	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting RBM46, 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-3925-3P	100.00	69.95	1237
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
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-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 2)

• RNA binding protein RBM46 regulates mitotic-to-meiotic transition in spermatogenesis. (PMID:36001654)
• Identification of RBM46 as a novel APOBEC1 cofactor for C-to-U RNA-editing activity. (PMID:38708190)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm46	ENSDARG00000079452
mus_musculus	Rbm46	ENSMUSG00000033882
rattus_norvegicus	Rbm46	ENSRNOG00000025823

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), 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

Probable RNA-binding protein 46 — Q8TBY0 (reviewed: Q8TBY0)

Alternative names: Cancer/testis antigen 68, RNA-binding motif protein 46

All UniProt accessions (2): Q8TBY0, D6RF41

UniProt curated annotations — full annotation on UniProt →

Function. Essential for male and female fertility, playing a crucial role in regulating germ cell development by ensuring the proper progression of meiosis prophase I. Regulates mitotic-to-meiotic transition in spermatogenesis by forming a complex with MEIOC and YTHDC2 which recognizes and down-regulates mitotic transcripts for a successful meiotic entry. Required for normal synaptonemal complex formation during meiosis, binding meiotic cohesin subunit mRNAs containing GCCUAU/GUUCGA motifs in their 3’UTRs regions and positively regulating their translation. Required for spermatogonial differentiation in both developing and adult testis.

Subunit / interactions. Interacts with YTHDC2, MEIOC, MOV10, CNOT6L, DDX4, UPF1 and PABPC1.

Subcellular location. Cytoplasm.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TBY0-1	1	yes
Q8TBY0-2	2
Q8TBY0-3	3

RefSeq proteins (3): NP_001264100, NP_001264102, NP_659416* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR006535	HnRNP_R/Q_splicing_fac	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034434	RBM46_RRM1	Domain
IPR034435	RBM46_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR044462	RBM46_DSR	Domain
IPR047837	RBM46_RRM3	Domain

Pfam: PF00076, PF14709

UniProt features (6 total): domain 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBY0-F1	73.43	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 126 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, chr4q32, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_OOGENESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_BLASTOCYST_FORMATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_POSITIVE_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ORGANELLE_FISSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (11): trophectodermal cell differentiation (GO:0001829), male meiotic nuclear division (GO:0007140), female meiotic nuclear division (GO:0007143), spermatogenesis (GO:0007283), mRNA stabilization (GO:0048255), oogenesis (GO:0048477), spermatid differentiation (GO:0048515), cell cycle switching, mitotic to meiotic cell cycle (GO:0051728), cell differentiation (GO:0030154), meiotic cell cycle (GO:0051321), negative regulation of mRNA catabolic process (GO:1902373)

GO Molecular Function (5): mRNA binding (GO:0003729), enzyme-substrate adaptor activity (GO:0140767), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), apolipoprotein B mRNA editing enzyme complex (GO:0030895)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
meiotic nuclear division	3
cell differentiation	2
male gamete generation	2
meiotic cell cycle	2
female gamete generation	2
developmental process involved in reproduction	2
binding	2
blastocyst formation	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
germ cell development	1
spermatogenesis	1
cellular process involved in reproduction in multicellular organism	1
negative regulation of mitotic cell cycle	1
positive regulation of meiotic cell cycle	1
cell cycle switching	1
cellular developmental process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
mRNA catabolic process	1
positive regulation of gene expression	1
regulation of mRNA catabolic process	1
negative regulation of RNA catabolic process	1
negative regulation of mRNA metabolic process	1
RNA binding	1
protein-macromolecule adaptor activity	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
mRNA editing complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM46	ZFYVE28	Q9HCC9	690
RBM46	ZNF678	Q5SXM1	669
RBM46	EXD3	Q8N9H8	646
RBM46	DMRTB1	Q96MA1	606
RBM46	CPXCR1	Q8N123	571
RBM46	CCDC110	Q8TBZ0	507
RBM46	CATSPER4	Q7RTX7	493
RBM46	ARMC9	Q7Z3E5	475
RBM46	HSPBAP1	Q96EW2	470
RBM46	CTSO	P43234	460
RBM46	TMEM225	Q6GV28	442
RBM46	MEIOC	A2RUB1	441
RBM46	CTDSP2	O14595	440
RBM46	GXYLT1	Q4G148	437
RBM46	CT62	P0C5K7	435
RBM46	ZNF687	Q8N1G0	435

IntAct

31 interactions, top by confidence:

A	B	Type	Score
RBPMS2	RBM46	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	RBM46	psi-mi:“MI:0915”(physical association)	0.560
RBM46	GORASP2	psi-mi:“MI:0915”(physical association)	0.560
RBM46	CHAT	psi-mi:“MI:0915”(physical association)	0.560
RBM46		psi-mi:“MI:0915”(physical association)	0.560
RBM46	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
RBM46	GSN	psi-mi:“MI:0915”(physical association)	0.560
RBM46	HRAS	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	RBM46	psi-mi:“MI:0915”(physical association)	0.560
RBM46	RBM47	psi-mi:“MI:0915”(physical association)	0.500
RBPMS	RBM46	psi-mi:“MI:0915”(physical association)	0.370
RBM47	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
RBM46	RBPMS2	psi-mi:“MI:0915”(physical association)	0.000
FOXH1	RBM46	psi-mi:“MI:0915”(physical association)	0.000
RBM46	GORASP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): RBM46 (Co-fractionation), RBM46 (Two-hybrid), RBM46 (Affinity Capture-MS), RBM46 (Two-hybrid), FOXH1 (Two-hybrid), RBPMS2 (Two-hybrid), RBM47 (Affinity Capture-MS), RBM46 (Affinity Capture-MS), RBM46 (Two-hybrid), RBM46 (Affinity Capture-MS), RBM46 (Cross-Linking-MS (XL-MS)), RBM46 (Affinity Capture-MS), RBM46 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IEW8, A4QNI8, B5DF91, O01671, O09032, O17310, O61374, O64380, O95758, O97018, P16914, P19339, P26378, P26599, P42731, P70372, P86049, Q12926, Q14576, Q15717, Q1JQ73, Q24668, Q28FX0, Q28GD4, Q29099, Q5R9H4, Q5R9Z6, Q5U259, Q5YD48, Q60899, Q60900, Q61701, Q6DEY7, Q6GLB5, Q6GR16, Q6YZW2, Q7SZT7, Q8CH84, Q8GZ26, Q8LFS6

Diamond homologs: A0A8M1NHK4, A0AV96, A0JM51, A4FV72, A4QUF0, A8WLV5, O01671, O04425, O43040, O43390, O60506, P28659, P33240, P86049, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q14498, Q28HE9, Q2HJG2, Q2UK72, Q3UEB3, Q4QQT3, Q4R2Z0, Q4R535, Q5B630, Q5EA36, Q5R469, Q5R5P4, Q5R723, Q5R9H4, Q5RC41, Q5RC80, Q5RDA3, Q5SZQ8, Q5YD48, Q66H68, Q6DCB7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1080 predictions. Top by Δscore:

Variant	Effect	Δscore
4:154796735:A:AG	acceptor_gain	1.0000
4:154796740:A:AG	acceptor_gain	1.0000
4:154796740:AG:A	acceptor_gain	1.0000
4:154796741:G:A	acceptor_gain	1.0000
4:154796741:G:GA	acceptor_gain	1.0000
4:154796741:GGA:G	acceptor_gain	1.0000
4:154796741:GGAA:G	acceptor_gain	1.0000
4:154796741:GGAAC:G	acceptor_gain	1.0000
4:154796868:A:T	donor_gain	1.0000
4:154796881:G:GT	donor_gain	1.0000
4:154796882:A:T	donor_gain	1.0000
4:154796900:CCAG:C	donor_loss	1.0000
4:154796901:CAG:C	donor_loss	1.0000
4:154796903:GG:G	donor_loss	1.0000
4:154796904:G:T	donor_loss	1.0000
4:154797806:TTCA:T	acceptor_loss	1.0000
4:154797807:TCAG:T	acceptor_loss	1.0000
4:154797808:CAG:C	acceptor_loss	1.0000
4:154798776:TTACA:T	acceptor_loss	1.0000
4:154798777:TACA:T	acceptor_loss	1.0000
4:154798779:CAGG:C	acceptor_loss	1.0000
4:154798780:A:AC	acceptor_loss	1.0000
4:154798780:A:AG	acceptor_gain	1.0000
4:154798781:G:GG	acceptor_gain	1.0000
4:154798781:G:GT	acceptor_loss	1.0000
4:154798781:GGAAC:G	acceptor_gain	1.0000
4:154820354:T:A	acceptor_gain	1.0000
4:154781434:GGG:G	donor_gain	0.9900
4:154781435:GGG:G	donor_gain	0.9900
4:154796736:T:G	acceptor_gain	0.9900

AlphaMissense

3524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:154796873:G:A	G41R	1.000
4:154796873:G:C	G41R	1.000
4:154796874:G:A	G41E	1.000
4:154796874:G:T	G41V	1.000
4:154796877:A:C	Q42P	1.000
4:154796878:A:C	Q42H	1.000
4:154796878:A:T	Q42H	1.000
4:154796880:G:C	R43T	1.000
4:154796880:G:T	R43M	1.000
4:154796881:G:C	R43S	1.000
4:154796881:G:T	R43S	1.000
4:154797845:A:C	E62D	1.000
4:154797845:A:T	E62D	1.000
4:154797847:T:A	V63D	1.000
4:154797849:T:A	F64I	1.000
4:154797849:T:C	F64L	1.000
4:154797849:T:G	F64V	1.000
4:154797850:T:C	F64S	1.000
4:154797850:T:G	F64C	1.000
4:154797851:T:A	F64L	1.000
4:154797851:T:G	F64L	1.000
4:154797853:T:A	V65E	1.000
4:154797855:G:A	G66R	1.000
4:154797855:G:C	G66R	1.000
4:154797856:G:A	G66E	1.000
4:154797862:T:A	I68K	1.000
4:154797862:T:G	I68R	1.000
4:154797889:T:C	L77S	1.000
4:154797912:G:T	G85W	1.000
4:154797913:G:A	G85E	1.000

dbSNP variants (sampled 300 via entrez): RS1000059366 (4:154808517 G>A), RS1000195355 (4:154826305 A>G), RS1000207281 (4:154802767 T>G), RS1000284168 (4:154782584 A>G), RS1000349626 (4:154794256 CT>C), RS1000358783 (4:154795883 T>C), RS1000416226 (4:154788160 T>G), RS1000480784 (4:154801944 A>C), RS1000488727 (4:154802368 A>G), RS1000521680 (4:154820029 G>C), RS1000540584 (4:154804019 G>A,T), RS1000592775 (4:154804195 G>A), RS1000647799 (4:154797231 A>C), RS1000716397 (4:154808270 TTA>T), RS1000765038 (4:154790943 A>C,G)

Disease associations

OMIM: gene MIM:620147 | 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
GCST004735_14	Epstein-Barr virus copy number in lymphoblastoid cell lines	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
aristolochic acid I	decreases expression	1
2,6-dichloro-(1,4)benzoquinone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Copper	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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