RBM12

Summary

RBM12 (RNA binding motif protein 12, HGNC:9898) is a protein-coding gene on chromosome 20q11.22, encoding RNA-binding protein 12 (Q9NTZ6). It is a selective cancer dependency (DepMap: 16.7% of cell lines).

This gene encodes a protein that contains several RNA-binding motifs, potential transmembrane domains, and proline-rich regions. This gene and the gene for copine I overlap at map location 20q11.21. Alternative splicing in the 5’ UTR results in four transcript variants. All variants encode the same protein.

Source: NCBI Gene 10137 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 1 total
• Phenotypes (HPO): 7
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 16.7% of screened cell lines
• MANE Select transcript: NM_006047

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9898
Approved symbol	RBM12
Name	RNA binding motif protein 12
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	HRIHFB2091, KIAA0765, SWAN
Ensembl gene	ENSG00000244462
Ensembl biotype	protein_coding
OMIM	607179
Entrez	10137

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000359646, ENST00000374104, ENST00000374114, ENST00000424458, ENST00000431148, ENST00000435161, ENST00000922106, ENST00000922107

RefSeq mRNA: 4 — MANE Select: NM_006047 NM_001198838, NM_001198840, NM_006047, NM_152838

CCDS: CCDS13261

Canonical transcript exons

ENST00000374114 — 3 exons

Exon	Start	End
ENSE00001462525	35648925	35655344
ENSE00003635657	35664760	35664900
ENSE00003692173	35658930	35659014

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 95.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.3836 / max 162.8225, expressed in 1406 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187075	71.4815	1823
187076	11.8743	1804
187073	0.9180	492
187072	0.9168	555
187071	0.8499	508
187074	0.6990	415

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.40	gold quality
colonic epithelium	UBERON:0000397	94.83	gold quality
adrenal tissue	UBERON:0018303	94.63	gold quality
secondary oocyte	CL:0000655	94.47	gold quality
bone marrow cell	CL:0002092	93.33	gold quality
embryo	UBERON:0000922	92.94	gold quality
cortical plate	UBERON:0005343	92.77	gold quality
ganglionic eminence	UBERON:0004023	92.70	gold quality
islet of Langerhans	UBERON:0000006	92.69	gold quality
oocyte	CL:0000023	92.08	gold quality
amniotic fluid	UBERON:0000173	92.03	gold quality
ventricular zone	UBERON:0003053	91.89	gold quality
cartilage tissue	UBERON:0002418	91.79	gold quality
corpus epididymis	UBERON:0004359	91.76	gold quality
leukocyte	CL:0000738	91.67	gold quality
monocyte	CL:0000576	91.64	gold quality
mononuclear cell	CL:0000842	91.63	gold quality
trabecular bone tissue	UBERON:0002483	91.42	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.30	gold quality
tonsil	UBERON:0002372	91.24	gold quality
vermiform appendix	UBERON:0001154	91.21	gold quality
bone marrow	UBERON:0002371	91.19	gold quality
epithelium of nasopharynx	UBERON:0001951	91.13	gold quality
cauda epididymis	UBERON:0004360	90.97	gold quality
endometrium	UBERON:0001295	90.84	gold quality
caput epididymis	UBERON:0004358	90.63	gold quality
colonic mucosa	UBERON:0000317	90.41	gold quality
stromal cell of endometrium	CL:0002255	90.20	gold quality
lymph node	UBERON:0000029	90.11	gold quality
ovary	UBERON:0000992	90.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	196.35
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

148 targeting RBM12, 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-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AA	99.96	70.64	3753

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• RBM12 shares a promoter and 5’UTR exons with CPNE1. This genomic structure is conserved among multiple species. (PMID:18831769)
• a nonsense mutation in RBM12 showed significant association with psychosis (PMID:28628109)
• Identification and characterization of RBM12 as a novel regulator of fetal hemoglobin expression. (PMID:35622975)
• The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction. (PMID:37543364)
• RBM12 regulates the progression of hepatocellular cancer via miR-497-5p/CPNE1 Axis. (PMID:37793588)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm12	ENSDARG00000100636
rattus_norvegicus	Rbm12	ENSRNOG00000019723
drosophila_melanogaster	fus	FBGN0023441
drosophila_melanogaster	glo	FBGN0259139
caenorhabditis_elegans		WBGENE00006367
caenorhabditis_elegans	rbm-12	WBGENE00013703
caenorhabditis_elegans		WBGENE00022253

Paralogs (8): HNRNPH3 (ENSG00000096746), ESRP2 (ENSG00000103067), ESRP1 (ENSG00000104413), HNRNPH2 (ENSG00000126945), GRSF1 (ENSG00000132463), HNRNPH1 (ENSG00000169045), HNRNPF (ENSG00000169813), RBM12B (ENSG00000183808)

Protein

Protein identifiers

RNA-binding protein 12 — Q9NTZ6 (reviewed: Q9NTZ6)

Alternative names: RNA-binding motif protein 12, SH3/WW domain anchor protein in the nucleus

All UniProt accessions (4): A6PVI0, A6PVI1, Q5JX62, Q9NTZ6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Disease relevance. Schizophrenia 19 (SCZD19) [MIM:617629] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Disease susceptibility is associated with variants affecting the gene represented in this entry.

RefSeq proteins (4): NP_001185767, NP_001185769, NP_006038, NP_690051 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034591	RBM12_RRM1	Domain
IPR034594	RBM12_RRM2	Domain
IPR034854	RBM12_RRM5	Domain
IPR034855	RBM12_RRM3	Domain
IPR034856	RBM12_RRM4	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050666	ESRP	Family

Pfam: PF00076

UniProt features (57 total): strand 16, helix 13, compositionally biased region 6, modified residue 6, turn 5, domain 3, sequence variant 3, region of interest 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2EK1	X-RAY DIFFRACTION	2
2EK6	X-RAY DIFFRACTION	2.38
1WEL	SOLUTION NMR
2CPY	SOLUTION NMR
2DNN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NTZ6-F1	65.89	0.25

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 (6): 352, 375, 420, 422, 424, 525

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 176 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_BCELL_UP, AAGCAAT_MIR137, LFA1_Q6, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GTGCCTT_MIR506, GGGCATT_MIR365, GNF2_FBL, ZIC1_01, GOBP_RNA_SPLICING

GO Biological Process (1): regulation of RNA splicing (GO:0043484)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), ribonucleoprotein complex (GO:1990904), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
nucleic acid binding	1
nuclear lumen	1
cellular anatomical structure	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM12	ASB12	Q8WXK4	518
RBM12	PWWP2B	Q6NUJ5	512
RBM12	ATP8B2	P98198	440
RBM12	SETD1A	O15047	430
RBM12	RLIM	Q9NVW2	422
RBM12	ZC3H6	P61129	417
RBM12	PPEF1	O14829	414
RBM12	QSER1	Q2KHR3	410
RBM12	FAM193A	P78311	360
RBM12	GPR101	Q96P66	357
RBM12	CSE1L	P55060	353
RBM12	FRYL	O94915	353
RBM12	YLPM1	P49750	351
RBM12	GOLGA8K	D6RF30	350
RBM12	ADAM8	P78325	350

IntAct

123 interactions, top by confidence:

A	B	Type	Score
CDKN2D	CDK4	psi-mi:“MI:0914”(association)	0.970
OPTN	RBM12	psi-mi:“MI:0915”(physical association)	0.780
RBM12	OPTN	psi-mi:“MI:0915”(physical association)	0.780
MFHAS1	PGRMC2	psi-mi:“MI:0914”(association)	0.590
PRMT2	RBM12	psi-mi:“MI:0915”(physical association)	0.560
	RBM12	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
USP47	DENR	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530
CNTF	CHM	psi-mi:“MI:0914”(association)	0.530
TMA16	TNPO2	psi-mi:“MI:0914”(association)	0.530
FBXO11	LONP1	psi-mi:“MI:0914”(association)	0.530
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
SBDS	DNM1L	psi-mi:“MI:0914”(association)	0.480
CD2BP2	RBM12	psi-mi:“MI:0407”(direct interaction)	0.440
BRAP	RBM12	psi-mi:“MI:0915”(physical association)	0.370
RBM12	TBC1D4	psi-mi:“MI:0915”(physical association)	0.370
GIGYF2	RBM12	psi-mi:“MI:0915”(physical association)	0.370
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (153): RBM12 (Affinity Capture-RNA), RBM12 (Affinity Capture-RNA), RBM12 (Affinity Capture-MS), RBM12 (Affinity Capture-MS), RBM12 (Affinity Capture-MS), RBM12 (Affinity Capture-MS), RBM12 (Affinity Capture-MS), RBM12 (Co-fractionation), RBM12 (Co-fractionation), RBM12 (Co-fractionation), RBM12 (Co-fractionation), RBM12 (Co-fractionation), RBM12 (Co-fractionation), RBM12 (Affinity Capture-MS), RBM12 (Two-hybrid)

ESM2 similar proteins: A0A0R4IEW8, A0A8M1NHK4, A0AV96, A4QNI8, A9LNK9, O01671, O09032, O17310, O22173, O42632, O61374, O97018, P19339, P20965, P26378, P42731, Q08473, Q1JPY8, Q1LZD9, Q24668, Q4KLH4, Q4KM14, Q5R5P4, Q5R9H4, Q5RBM8, Q5YD48, Q5ZK88, Q61701, Q66H68, Q6DEY7, Q6YZW2, Q7SZT7, Q8GZ26, Q8LFS6, Q8R326, Q8SQ27, Q8VIJ6, Q8WXF1, Q91903, Q91WT8

Diamond homologs: A8WPC5, B2RYJ8, O35737, P31942, P31943, P52597, P55795, P70333, Q12849, Q22708, Q3SZF3, Q5E9J1, Q5RBM8, Q5RD26, Q60HC3, Q6AY09, Q794E4, Q8C5Q4, Q8K0G8, Q8R3C6, Q8R4X3, Q8SQ27, Q8VHV7, Q9NTZ6, Q9Y4C8, Q9Z2X1, Q5RFT7, Q66JV4, Q80YR9, Q8IXT5, A1L1G1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 156 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	7	13.1×	3e-04
mRNA Polyadenylation	10	8.4×	2e-04
Processing of Capped Intron-Containing Pre-mRNA	8	6.3×	4e-03
mRNA Splicing - Major Pathway	11	5.7×	6e-04
Dengue Virus-Host Interactions	11	4.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	10	6.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

649 predictions. Top by Δscore:

Variant	Effect	Δscore
20:35664880:T:TA	donor_gain	1.0000
20:35655340:CACAC:C	acceptor_gain	0.9900
20:35655342:CAC:C	acceptor_gain	0.9900
20:35655344:CCTG:C	acceptor_loss	0.9900
20:35655345:C:CA	acceptor_loss	0.9900
20:35655346:T:C	acceptor_loss	0.9900
20:35658924:TCTTA:T	donor_loss	0.9900
20:35658925:CTTA:C	donor_loss	0.9900
20:35658926:TTA:T	donor_loss	0.9900
20:35658927:TA:T	donor_loss	0.9900
20:35658928:A:AG	donor_loss	0.9900
20:35658928:A:AT	donor_loss	0.9900
20:35658929:CCT:C	donor_loss	0.9900
20:35658929:CCTG:C	donor_loss	0.9900
20:35659010:TTAGA:T	acceptor_gain	0.9900
20:35659011:TAGA:T	acceptor_gain	0.9900
20:35659015:C:CC	acceptor_gain	0.9900
20:35664854:T:TA	donor_gain	0.9900
20:35664855:C:A	donor_gain	0.9900
20:35655138:C:CT	donor_gain	0.9700
20:35659012:AGA:A	acceptor_gain	0.9700
20:35659013:GA:G	acceptor_gain	0.9700
20:35655139:C:CT	donor_gain	0.9600
20:35664753:GTCTT:G	donor_loss	0.9600
20:35664754:TCTTA:T	donor_loss	0.9600
20:35664756:TTA:T	donor_loss	0.9600
20:35664757:T:TG	donor_loss	0.9600
20:35664758:A:AG	donor_loss	0.9600
20:35664758:A:AT	donor_loss	0.9600
20:35664759:C:CT	donor_loss	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003448 (20:35661115 A>C,G), RS1000539674 (20:35660860 T>C), RS1000805847 (20:35665805 G>A), RS1000897702 (20:35657499 A>C), RS1000929258 (20:35650133 C>T), RS1000950982 (20:35664238 G>A,C), RS1001142723 (20:35659486 A>T), RS1001231578 (20:35661863 C>A,G,T), RS1001271224 (20:35657841 A>G), RS1001910668 (20:35648578 T>C), RS1001965763 (20:35656070 C>T), RS1002165285 (20:35663792 G>T), RS1002239021 (20:35663547 C>T), RS1002511816 (20:35648942 A>G), RS1002639652 (20:35658939 CAAG>C)

Disease associations

OMIM: gene MIM:607179 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0003596	Middle age onset
HP:0003829	Typified by incomplete penetrance
HP:0007302	Bipolar affective disorder
HP:0011462	Young adult onset
HP:0100543	Cognitive impairment
HP:0100753	Schizophrenia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005958_16	Waist-to-hip ratio adjusted for BMI (age >50)	6.000000e-06
GCST005962_40	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-08
GCST010002_66	Refractive error	2.000000e-20

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067423 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.56	Kd	275.8	nM	CHEMBL5653589
6.49	ED50	326.4	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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	2149201: Binding affinity to human RBM12 incubated for 45 mins by Kinobead based pull down assay	kd	0.2758	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
Benzo(a)pyrene	decreases expression, decreases methylation	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Quercetin	decreases expression, decreases phosphorylation	2
Tunicamycin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
nickel chloride	decreases expression	1
resorcinol	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases 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, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Copper	decreases expression, affects binding	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652243	Binding	Binding affinity to human RBM12 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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