RBM10

Summary

RBM10 (RNA binding motif protein 10, HGNC:9896) is a protein-coding gene on chromosome Xp11.3, encoding Ribosome biogenesis inhibitor MINAS-60 (P0DW28). Acts as a late-stage inhibitor of pre-60S ribosome assembly by preventing pre-60S ribosome export from nucleus. It is a selective cancer dependency (DepMap: 43.3% of cell lines).

This gene encodes a nuclear protein that belongs to a family proteins that contain an RNA-binding motif. The encoded protein associates with hnRNP proteins and may be involved in regulating alternative splicing. Defects in this gene are the cause of the X-linked recessive disorder, TARP syndrome. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 8241 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TARP syndrome (Definitive, ClinGen)
• Clinical variants (ClinVar): 433 total — 21 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 73
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 6 cancer types
• Cancer dependency (DepMap): dependent in 43.3% of screened cell lines
• MANE Select transcript: NM_005676

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9896
Approved symbol	RBM10
Name	RNA binding motif protein 10
Location	Xp11.3
Locus type	gene with protein product
Status	Approved
Aliases	DXS8237E, KIAA0122, GPATC9, ZRANB5, GPATCH9, S1-1
Ensembl gene	ENSG00000182872
Ensembl biotype	protein_coding
OMIM	300080
Entrez	8241

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 43 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000329236, ENST00000345781, ENST00000377604, ENST00000478410, ENST00000496012, ENST00000628161, ENST00000864483, ENST00000864484, ENST00000864485, ENST00000864486, ENST00000864487, ENST00000864488, ENST00000864489, ENST00000864490, ENST00000864491, ENST00000864492, ENST00000864493, ENST00000864494, ENST00000864495, ENST00000864496, ENST00000864497, ENST00000864498, ENST00000864499, ENST00000864500, ENST00000864501, ENST00000864502, ENST00000916920, ENST00000916921, ENST00000916922, ENST00000916923, ENST00000916924, ENST00000916925, ENST00000916926, ENST00000916927, ENST00000916928, ENST00000916929, ENST00000916930, ENST00000916931, ENST00000967019, ENST00000967020, ENST00000967021, ENST00000967022, ENST00000967023, ENST00000967024, ENST00000967025

RefSeq mRNA: 5 — MANE Select: NM_005676 NM_001204466, NM_001204467, NM_001204468, NM_005676, NM_152856

CCDS: CCDS14274, CCDS56600, CCDS75969, CCDS78478

Canonical transcript exons

ENST00000377604 — 24 exons

Exon	Start	End
ENSE00001289745	47185055	47185204
ENSE00001291058	47186065	47186171
ENSE00001292712	47179319	47179495
ENSE00001297542	47182162	47182326
ENSE00001305192	47181749	47181866
ENSE00001308970	47185442	47185630
ENSE00001319471	47185302	47185367
ENSE00001320068	47181951	47182042
ENSE00001323831	47175019	47175092
ENSE00001325340	47179103	47179163
ENSE00001326562	47179880	47180040
ENSE00001328478	47185716	47185790
ENSE00001878835	47186474	47186813
ENSE00001946985	47145221	47145485
ENSE00003476584	47181215	47181401
ENSE00003491469	47180212	47180309
ENSE00003535945	47186258	47186387
ENSE00003569135	47171028	47171258
ENSE00003589189	47181507	47181646
ENSE00003601157	47176500	47176586
ENSE00003637181	47180419	47180506
ENSE00003674974	47169315	47169498
ENSE00003687049	47173128	47173197
ENSE00003738384	47147357	47147498

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 94.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.1378 / max 485.8530, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196159	29.6560	1824
196158	8.0017	1785
196160	0.4801	210

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.72	gold quality
cerebellar hemisphere	UBERON:0002245	94.40	gold quality
lower esophagus mucosa	UBERON:0035834	94.40	gold quality
cerebellar cortex	UBERON:0002129	94.25	gold quality
ventricular zone	UBERON:0003053	93.91	gold quality
ganglionic eminence	UBERON:0004023	93.90	gold quality
cerebellum	UBERON:0002037	93.40	gold quality
granulocyte	CL:0000094	93.23	gold quality
left ovary	UBERON:0002119	93.02	gold quality
tendon of biceps brachii	UBERON:0008188	92.97	gold quality
right ovary	UBERON:0002118	92.91	gold quality
pituitary gland	UBERON:0000007	92.73	gold quality
adenohypophysis	UBERON:0002196	92.66	gold quality
mucosa of transverse colon	UBERON:0004991	92.65	gold quality
right uterine tube	UBERON:0001302	92.44	gold quality
right lobe of thyroid gland	UBERON:0001119	92.18	gold quality
body of uterus	UBERON:0009853	91.81	gold quality
left lobe of thyroid gland	UBERON:0001120	91.73	gold quality
cortical plate	UBERON:0005343	91.73	gold quality
apex of heart	UBERON:0002098	91.72	gold quality
ectocervix	UBERON:0012249	91.67	gold quality
endocervix	UBERON:0000458	91.50	gold quality
embryo	UBERON:0000922	91.26	gold quality
left uterine tube	UBERON:0001303	91.17	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.14	gold quality
thyroid gland	UBERON:0002046	91.06	gold quality
esophagus mucosa	UBERON:0002469	91.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.97	gold quality
right frontal lobe	UBERON:0002810	90.93	gold quality
lower esophagus	UBERON:0013473	90.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.03

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BCL2	Repression
CASP3	Repression
TNF	Activation

miRNA regulators (miRDB)

9 targeting RBM10, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4771	97.43	67.69	596

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 43.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• S1-1 constitutes hundreds of nuclear domains, which dynamically change their structures in a reversible manner; upon globally reducing RNA polymerase II transcription, S1-1 nuclear bodies enlarge and decrease in number. (PMID:18315527)
• results indicate that very few genes are involved in the last steps of the apoptotic cascade in breast cancer, among them one of the X-chromosome RBM family (PMID:18820371)
• Massively parallel sequencing of exons on the X chromosome identifies RBM10 as the gene that causes a syndromic form of cleft palate. (PMID:20451169)
• S1-1 contains multiple nuclear localisation sequence that act cooperatively. (PMID:23294349)
• This study established RBM10 as an important regulator of alternative splicing, presented a mechanistic model for RBM10-mediated splicing regulation and provided a molecular link to understanding a human congenital disorder. (PMID:24000153)
• Antagonizes the effects of RBM5, RBM6, and RBM10 in cell colony formation. (PMID:24332178)
• RBM10 regulates alternative splicing of Fas and Bcl-x genes. (PMID:24530524)
• The ability of RBM10v1 to regulate alternative splicing depends, at least in part, on a structural alteration within the second RNA recognition motif domain, and correlates with preferential expression of the NUMB exon 11 inclusion variant. (PMID:25889998)
• Src family tyrosine kinase signaling may regulate FilGAP through association with RBM10 (PMID:26751795)
• RBM10 is a tumor suppressor that represses Notch signaling and cell proliferation through the regulation of NUMB alternative splicing (PMID:26853560)
• RBM10-TFE3 fusion variant (from chromosome X paracentric inversion), therefore, appears to be a recurrent molecular event in Xp11.2 RCCs. RBM10-TFE3 fusion should be added in the list of screened fusion transcripts in targeted molecular diagnostic multiplex RT-PCR (PMID:26998913)
• RBM10 mutations contribute to lung adenocarcinoma pathogenesis. (PMID:28091594)
• Xp11 translocation renal cell carcinomas with RBM10-TFE3 gene fusion demonstrating melanotic features and overlapping morphology with t(6;11) RCC. (PMID:28288037)
• RBM10-TFE3 is a recurrent gene fusion in Xp11 translocation renal cell carcinoma. (PMID:28296677)
• RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif 10 regulates many gene pathways involving in the tumor development or progression. (PMID:28347232)
• RBM10 functions as a splicing regulator using two RNA-binding units with different specificities to promote exon skipping. (PMID:28379442)
• RNA binding motif protein 10 (RBM10) negatively regulates its own mRNA and protein expression and that of RNA binding motif protein 5 (RBM5) by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD). (PMID:28586478)
• The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations, and chromosome 1q gain highlight their likely association with tumor virulence (PMID:28634282)
• results provide evidence that RBM10 expression, in RBM5-null tumors, may contribute to tumor growth and metastasis. Measurement of both RBM10 and RBM5 expression in clinical samples may therefore hold prognostic and/or potentially predictive value (PMID:28662214)
• Our work has not only expanded the number of pre-mRNA targets for RBM10, but identified RBM10 as a novel regulator of SMN2 alternative inclusion. (PMID:28728573)
• RBM10: Harmful or helpful-many factors to consider. (PMID:29274279)
• The well-known high-fidelity RNA splice site recognition by RBM10, and probably by RBM5 and RBM6, can thus be largely rationalized by a cooperative binding action of RRM and ZnF domains (PMID:29450990)
• RBM10 binds the pre-mRNA UTR, assembles the Star-PAP complex, and guides this complex specifically to mRNAs encoding regulators of cardiac hypertrophy. (PMID:30257214)
• RBM10 acts as a tumor suppressor in osteosarcoma. This could enable to define a new strategy for diagnosis and treatment of patients with osteosarcoma. (PMID:30403180)
• we found that RBM10 activated key proliferative signaling pathways [such as the epidermal growth factor receptor (EGFR), mitogenactivated protein kinase (MAPK) and phosphoinositide 3kinase (PI3K)AKT pathways] and inhibited apoptotic pathways. In addition, we demonstrated that a high expression of RBM10 protein in patient tissue samples was associated with a shorter overall survival time and a poor prognosis (PMID:30483773)
• The present study suggests that the carcinogenesis of RBM10-TFE3 RCC in some, but not all, patients may be associated with chronic kidney disease. (PMID:30908700)
• RBM10 reduces the phosphorylation of CREB via the AKT signalling pathway, suggesting that RBM10 exhibits its effect on lung adenocarcinoma cell proliferation via the RAP1/AKT/CREB signalling pathway. (PMID:30955253)
• RNA-binding motif protein 10 induces apoptosis and suppresses proliferation by activating p53. (PMID:31591476)
• RBM10 regulates centriole duplication in HepG2 cells by ectopically assembling PLK4-STIL complexes in the nucleus. (PMID:31820547)
• Dengue virus targets RBM10 deregulating host cell splicing and innate immune response. (PMID:32432721)
• Protective effect of the RNA-binding protein RBM10 in hepatocellular carcinoma. (PMID:32572914)
• A novel missense variant in RBM10 can cause a mild form of TARP syndrome with developmental delay and dysmorphic features. (PMID:32812661)
• RBM10, a New Regulator of p53. (PMID:32947864)
• The role of RBM10 mutations in the development, treatment, and prognosis of lung adenocarcinoma. (PMID:33064970)
• RNA binding motif protein 10 suppresses lung cancer progression by controlling alternative splicing of eukaryotic translation initiation factor 4H. (PMID:33130397)
• Phenotypic spectrum of the RBM10-mediated intellectual disability and congenital malformation syndrome beyond classic TARP syndrome features. (PMID:33340101)
• RBM10: Structure, functions, and associated diseases. (PMID:33515724)
• Star-PAP RNA Binding Landscape Reveals Novel Role of Star-PAP in mRNA Metabolism That Requires RBM10-RNA Association. (PMID:34576144)
• Sequestration of RBM10 in Nuclear Bodies: Targeting Sequences and Biological Significance. (PMID:34638866)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm10	ENSDARG00000077400
mus_musculus	Rbm10	ENSMUSG00000031060
rattus_norvegicus	Rbm10	ENSRNOG00000008472
drosophila_melanogaster	CG4887	FBGN0031318
drosophila_melanogaster	CG4896	FBGN0031319
caenorhabditis_elegans	rbm-5	WBGENE00020346

Paralogs (2): RBM5 (ENSG00000003756), RBM6 (ENSG00000004534)

Protein

Protein identifiers

Ribosome biogenesis inhibitor MINAS-60 — P0DW28 (reviewed: P0DW28, P98175)

All UniProt accessions (3): P98175, A0A0S2Z4W4, A0A0S2Z4X1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a late-stage inhibitor of pre-60S ribosome assembly by preventing pre-60S ribosome export from nucleus.

Subunit / interactions. Interacts with 60S ribosome assembly factors GTPBP4 and MRTO4.

Subcellular location. Nucleus. Nucleolus.

Miscellaneous. MINAS-60 is the product of an alternative open reading frame (alt-ORF) of transcripts coding for the RBM10 (AC P98175) protein. MINAS-60 and RBM10 ORFs are overlapping and are formed by shifting the reading frame.

Isoforms (6)

UniProt ID	Names	Canonical?
P0DW28-1	Ribosome biogenesis inhibitor MINAS-60	yes
P98175-1	1
P98175-2	2
P98175-3	3
P98175-4	4
P98175-5	5

RefSeq proteins (5): NP_001191395, NP_001191396, NP_001191397, NP_005667, NP_690595 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000467	G_patch_dom	Domain
IPR000504	RRM_dom	Domain
IPR001876	Znf_RanBP2	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR034992	RBM10_RRM2	Domain
IPR035618	RBM10_OCRE	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036443	Znf_RanBP2_sf	Homologous_superfamily
IPR041591	OCRE	Domain

Pfam: PF00076, PF00641, PF01585, PF17780

UniProt features (81 total): strand 19, compositionally biased region 14, modified residue 14, region of interest 7, helix 7, turn 6, domain 3, splice variant 3, chain 2, zinc finger region 2, sequence conflict 2, sequence variant 1, initiator methionine 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2LXI	SOLUTION NMR
2M2B	SOLUTION NMR
2MXV	SOLUTION NMR
2MXW	SOLUTION NMR
5ZSW	SOLUTION NMR
5ZSY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DW28-F1	52.29	0.00
AF-P98175-F1	60.70	0.12

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 (14): 61, 89, 383, 718, 723, 733, 736, 738, 781, 797, 845, 902, 2, 30

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses

MSigDB gene sets: 366 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, MATTIOLI_MGUS_VS_PCL, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NUCLEAR_TRANSPORT, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_NUCLEOCYTOPLASMIC_TRANSPORT, GOBP_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (13): negative regulation of ribosomal large subunit export from nucleus (GO:2000204), negative regulation of transcription by RNA polymerase II (GO:0000122), mRNA splicing, via spliceosome (GO:0000398), negative regulation of mRNA splicing, via spliceosome (GO:0048025), 3’-UTR-mediated mRNA stabilization (GO:0070935), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706), vascular associated smooth muscle cell apoptotic process (GO:1905288), positive regulation of vascular associated smooth muscle cell apoptotic process (GO:1905461), vascular associated smooth muscle cell proliferation (GO:1990874), mRNA processing (GO:0006397), negative regulation of cell population proliferation (GO:0008285), RNA splicing (GO:0008380), regulation of vascular associated smooth muscle cell apoptotic process (GO:1905459)

GO Molecular Function (7): RNA binding (GO:0003723), zinc ion binding (GO:0008270), miRNA binding (GO:0035198), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleolus (GO:0005730), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
mRNA Splicing	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Dengue Virus-Host Interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vascular associated smooth muscle cell apoptotic process	2
RNA processing	2
binding	2
nuclear lumen	2
ribosomal large subunit export from nucleus	1
negative regulation of ribosomal subunit export from nucleus	1
regulation of ribosomal large subunit export from nucleus	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA splicing, via spliceosome	1
negative regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
negative regulation of mRNA processing	1
mRNA stabilization	1
negative regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
smooth muscle cell apoptotic process	1
positive regulation of smooth muscle cell apoptotic process	1
regulation of vascular associated smooth muscle cell apoptotic process	1
smooth muscle cell proliferation	1
mRNA metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of smooth muscle cell apoptotic process	1
nucleic acid binding	1
transition metal ion binding	1
regulatory RNA binding	1
protein binding	1
cation binding	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
cellular_component	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

24 interactions, top by confidence:

A	B	Type	Score
CPSF6	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
EFTUD2	NACA	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
ILF3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
LARP7	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
NONO	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
RBM15	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
SF3B4	MED19	psi-mi:“MI:2364”(proximity)	0.270
SMNDC1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SRSF1	MED19	psi-mi:“MI:2364”(proximity)	0.270
SRSF7	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SUPV3L1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
U2AF2	NACA	psi-mi:“MI:2364”(proximity)	0.270
UTP3	NACA	psi-mi:“MI:2364”(proximity)	0.270
ZC3H11A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ZC3H8	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
ZRANB2	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
HNRNPA1	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
TAF15	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270

ESM2 similar proteins: A0A023PXQ4, A0A0U1RQI7, A6NJU9, A6NNC1, A8MRT5, A8MUU9, C9JG80, E2RYF6, E5RHQ5, F8W0I5, O13534, O59779, P08399, P0C732, P0C785, P0DTH6, P0DW28, P13208, P15941, P21787, P24856, P39564, P51861, P87269, Q00130, Q01456, Q12444, Q13117, Q1HVI8, Q27905, Q2EEQ3, Q4ZJY7, Q4ZJZ0, Q5SDL7, Q63661, Q69577, Q6B0Y1, Q6RY98, Q6ZQT0, Q6ZRX8

Diamond homologs: P0DW27, P0DW28

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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	5	42.8×	2e-06
mRNA Polyadenylation	8	30.6×	3e-09
mRNA Splicing	5	23.9×	2e-05
Processing of Capped Intron-Containing Pre-mRNA	6	21.4×	4e-06
mRNA Splicing - Major Pathway	9	21.4×	3e-09
Dengue Virus-Host Interactions	10	19.9×	1e-09
Metabolism of RNA	7	12.7×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
mRNA processing	9	23.6×	2e-08
mRNA splicing, via spliceosome	7	21.4×	2e-06
RNA splicing	7	20.6×	2e-06

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 6 cancer types — BLCA, CHOL, COADREAD, LUAD, NSCLC, PAAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	18
Uncertain significance	145
Likely benign	98
Benign	51

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
11643	NM_005676.5(RBM10):c.1893dup (p.Pro632fs)	Pathogenic
11644	NM_005676.5(RBM10):c.1235G>A (p.Trp412Ter)	Pathogenic
1219405	NM_005676.5(RBM10):c.2565dup (p.Leu856fs)	Pathogenic
1323521	NM_005676.5(RBM10):c.1722C>G (p.Tyr574Ter)	Pathogenic
137613	NM_005676.5(RBM10):c.448C>T (p.Gln150Ter)	Pathogenic
1699224	NM_005676.5(RBM10):c.373G>T (p.Glu125Ter)	Pathogenic
1700155	NM_005676.5(RBM10):c.292C>T (p.Arg98Ter)	Pathogenic
1806104	NM_005676.5(RBM10):c.1993_1996del (p.Gln665fs)	Pathogenic
2573842	NM_005676.5(RBM10):c.2038C>T (p.Arg680Ter)	Pathogenic
280214	NM_005676.5(RBM10):c.170_171del (p.Asp56_Tyr57insTer)	Pathogenic
280558	NM_005676.5(RBM10):c.1693+2dup	Pathogenic
3254884	NM_005676.5(RBM10):c.579_586dup (p.Asn196fs)	Pathogenic
428617	NM_005676.5(RBM10):c.1352_1353del (p.Glu451fs)	Pathogenic
429505	NM_005676.5(RBM10):c.2214_2217del (p.Ser738fs)	Pathogenic
433146	NM_005676.5(RBM10):c.159del (p.Lys54fs)	Pathogenic
436516	NM_005676.5(RBM10):c.1249-1G>A	Pathogenic
4690060	NM_005676.5(RBM10):c.406_430del (p.Leu136fs)	Pathogenic
522056	NM_005676.5(RBM10):c.1473_1474del (p.Ser492fs)	Pathogenic
625791	GRCh37/hg19 Xp11.23(chrX:47039376-47040521)	Pathogenic
689781	NM_005676.5(RBM10):c.724+2T>C	Pathogenic
977462	NM_005676.5(RBM10):c.1804_1805del (p.Ser602fs)	Pathogenic
1333475	NM_005676.5(RBM10):c.2514C>G (p.Tyr838Ter)	Likely pathogenic
1695295	NM_005676.5(RBM10):c.2537+1G>A	Likely pathogenic
1697973	NM_005676.5(RBM10):c.2326C>T (p.Arg776Trp)	Likely pathogenic
1806258	NM_005676.5(RBM10):c.1974G>C (p.Trp658Cys)	Likely pathogenic
2101188	NM_005676.5(RBM10):c.2537_2537+3del	Likely pathogenic
2429214	NM_005676.5(RBM10):c.331C>T (p.Gln111Ter)	Likely pathogenic
2629534	NM_005676.5(RBM10):c.2430+1G>A	Likely pathogenic
2671930	NM_005676.5(RBM10):c.2100+1G>A	Likely pathogenic
3899260	NM_005676.5:c.1594_2002delinsTGTTCTTCAAAATAGC	Likely pathogenic

SpliceAI

3314 predictions. Top by Δscore:

Variant	Effect	Δscore
X:47144468:CTCA:C	donor_loss	1.0000
X:47144471:A:AT	donor_loss	1.0000
X:47144472:C:A	donor_loss	1.0000
X:47144472:CCTT:C	donor_gain	1.0000
X:47144492:T:TA	donor_gain	1.0000
X:47145216:T:TA	donor_gain	1.0000
X:47147355:A:AG	acceptor_gain	1.0000
X:47147356:G:GG	acceptor_gain	1.0000
X:47147356:GA:G	acceptor_gain	1.0000
X:47147495:GACG:G	donor_gain	1.0000
X:47147496:ACGGT:A	donor_loss	1.0000
X:47147497:CGGTG:C	donor_loss	1.0000
X:47147498:GGTGA:G	donor_loss	1.0000
X:47147499:G:C	donor_loss	1.0000
X:47147499:G:GG	donor_gain	1.0000
X:47147500:TGA:T	donor_loss	1.0000
X:47147501:GAG:G	donor_loss	1.0000
X:47169310:A:AG	acceptor_gain	1.0000
X:47169311:C:G	acceptor_gain	1.0000
X:47169311:CTAGT:C	acceptor_loss	1.0000
X:47169312:TA:T	acceptor_loss	1.0000
X:47169313:A:AG	acceptor_gain	1.0000
X:47169313:A:C	acceptor_loss	1.0000
X:47169313:AGT:A	acceptor_gain	1.0000
X:47169313:AGTG:A	acceptor_gain	1.0000
X:47169314:G:GT	acceptor_gain	1.0000
X:47169314:GT:G	acceptor_gain	1.0000
X:47169314:GTG:G	acceptor_gain	1.0000
X:47169314:GTGG:G	acceptor_gain	1.0000
X:47169314:GTGGT:G	acceptor_gain	1.0000

AlphaMissense

6071 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:47171218:T:A	V131D	1.000
X:47171221:T:A	M132K	1.000
X:47171221:T:C	M132T	1.000
X:47171221:T:G	M132R	1.000
X:47171224:T:A	L133Q	1.000
X:47171224:T:C	L133P	1.000
X:47171224:T:G	L133R	1.000
X:47171227:G:C	R134T	1.000
X:47171227:G:T	R134M	1.000
X:47171228:G:C	R134S	1.000
X:47171228:G:T	R134S	1.000
X:47171233:T:A	L136Q	1.000
X:47171233:T:C	L136P	1.000
X:47171233:T:G	L136R	1.000
X:47173129:T:A	I145N	1.000
X:47173141:T:C	L149P	1.000
X:47173171:T:A	V159D	1.000
X:47173174:G:C	R160P	1.000
X:47173177:T:C	L161P	1.000
X:47173180:T:C	M162T	1.000
X:47175024:A:C	S170R	1.000
X:47175026:C:A	S170R	1.000
X:47175026:C:G	S170R	1.000
X:47175028:G:C	R171P	1.000
X:47175030:G:C	G172R	1.000
X:47175031:G:A	G172D	1.000
X:47175031:G:T	G172V	1.000
X:47175033:T:A	F173I	1.000
X:47175033:T:C	F173L	1.000
X:47175033:T:G	F173V	1.000

dbSNP variants (sampled 300 via entrez): RS1000057304 (X:47174047 C>G), RS1000188595 (X:47183659 C>A), RS1000240932 (X:47183888 G>A), RS1000725248 (X:47149713 G>C), RS1000726175 (X:47158726 A>G), RS1001030610 (X:47176374 G>A,C,T), RS1001077666 (X:47166978 T>C), RS1001386437 (X:47158340 G>A), RS1001500493 (X:47152233 G>A), RS1001763871 (X:47151609 G>A), RS1002066103 (X:47178275 C>T), RS1002109526 (X:47160553 G>A), RS1002490348 (X:47169014 G>A), RS1003083692 (X:47181129 G>A), RS1003227882 (X:47154089 G>C)

Disease associations

OMIM: gene MIM:300080 | disease phenotypes: MIM:311900

GenCC curated gene-disease

Disease	Classification	Inheritance
TARP syndrome	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
TARP syndrome	Definitive	XL

Mondo (3): TARP syndrome (MONDO:0010711), hearing loss disorder (MONDO:0005365), intellectual disability (MONDO:0001071)

Orphanet (2): TARP syndrome (Orphanet:2886), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

73 total (30 of 73 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000085	Horseshoe kidney
HP:0000126	Hydronephrosis
HP:0000162	Glossoptosis
HP:0000175	Cleft palate
HP:0000199	Tongue nodules
HP:0000201	Pierre-Robin sequence
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000385	Small earlobe
HP:0000395	Prominent antihelix
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000648	Optic atrophy
HP:0000767	Pectus excavatum
HP:0000879	Short sternum
HP:0000954	Single transverse palmar crease
HP:0000961	Cyanosis
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C536942	TARP syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases reaction, increases abundance, increases expression, affects binding	3
Arsenic	increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Ozone	affects cotreatment, decreases expression, affects expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
Acrolein	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Mustard Gas	increases phosphorylation	1
Phthalic Acids	increases expression	1
Quercetin	decreases phosphorylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss