RBMX

Summary

RBMX (RNA binding motif protein X-linked, HGNC:9910) is a protein-coding gene on chromosome Xq26.3, encoding RNA-binding motif protein, X chromosome (P38159). RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene belongs to the RBMY gene family which includes candidate Y chromosome spermatogenesis genes. This gene, an active X chromosome homolog of the Y chromosome RBMY gene, is widely expressed whereas the RBMY gene evolved a male-specific function in spermatogenesis. Pseudogenes of this gene, found on chromosomes 1, 4, 9, 11, and 6, were likely derived by retrotransposition from the original gene. Alternatively spliced transcript variants encoding different isoforms have been identified. A snoRNA gene (SNORD61) is found in one of its introns.

Source: NCBI Gene 27316 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic X-linked intellectual disability Shashi type (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 99 total — 5 likely-pathogenic
• Phenotypes (HPO): 55
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_002139

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9910
Approved symbol	RBMX
Name	RNA binding motif protein X-linked
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	RNMX, hnRNP-G, HNRNPG
Ensembl gene	ENSG00000147274
Ensembl biotype	protein_coding
OMIM	300199
Entrez	27316

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000320676, ENST00000419968, ENST00000431446, ENST00000464781, ENST00000496459, ENST00000561733, ENST00000562646, ENST00000563370, ENST00000565438, ENST00000565907, ENST00000567262, ENST00000568578, ENST00000887809, ENST00000887810, ENST00000921279, ENST00000921280, ENST00000921281, ENST00000921282, ENST00000954875, ENST00000954876

RefSeq mRNA: 2 — MANE Select: NM_002139 NM_001164803, NM_002139

CCDS: CCDS14661, CCDS55510

Canonical transcript exons

ENST00000320676 — 9 exons

Exon	Start	End
ENSE00001765106	136880597	136880725
ENSE00001860294	136873461	136874452
ENSE00003475706	136876503	136876655
ENSE00003532874	136879319	136879453
ENSE00003579476	136875471	136875585
ENSE00003622155	136875086	136875168
ENSE00003637593	136875258	136875383
ENSE00003647217	136879017	136879123
ENSE00003649186	136877915	136878086

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 148.8336 / max 1592.1856, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200682	142.4131	1819
200684	3.6482	1415
200683	1.0975	615
200680	0.9135	540
200679	0.7613	360

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.54	gold quality
ganglionic eminence	UBERON:0004023	99.49	gold quality
cortical plate	UBERON:0005343	99.33	gold quality
left ovary	UBERON:0002119	99.05	gold quality
calcaneal tendon	UBERON:0003701	99.01	gold quality
right ovary	UBERON:0002118	98.87	gold quality
endocervix	UBERON:0000458	98.73	gold quality
ovary	UBERON:0000992	98.71	gold quality
smooth muscle tissue	UBERON:0001135	98.63	gold quality
body of uterus	UBERON:0009853	98.52	gold quality
ileal mucosa	UBERON:0000331	98.43	gold quality
rectum	UBERON:0001052	98.38	gold quality
vermiform appendix	UBERON:0001154	98.33	gold quality
oviduct epithelium	UBERON:0004804	98.32	gold quality
mucosa of stomach	UBERON:0001199	98.25	gold quality
body of pancreas	UBERON:0001150	98.19	gold quality
thymus	UBERON:0002370	98.19	gold quality
left uterine tube	UBERON:0001303	98.17	gold quality
right uterine tube	UBERON:0001302	98.10	gold quality
ectocervix	UBERON:0012249	98.06	gold quality
lymph node	UBERON:0000029	97.99	gold quality
gall bladder	UBERON:0002110	97.96	gold quality
sural nerve	UBERON:0015488	97.93	gold quality
monocyte	CL:0000576	97.89	gold quality
leukocyte	CL:0000738	97.86	gold quality
left lobe of thyroid gland	UBERON:0001120	97.85	gold quality
metanephros cortex	UBERON:0010533	97.84	gold quality
right lobe of thyroid gland	UBERON:0001119	97.81	gold quality
tibial nerve	UBERON:0001323	97.77	gold quality
pancreas	UBERON:0001264	97.75	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	39.44
E-GEOD-106540	no	1387.94
E-GEOD-93593	no	7.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
EGR1	Repression
FOS	Repression
FOSL1	Repression
JUNB	Repression
JUND	Repression
KIT	Repression
ROS1	Repression
TXNIP	Activation

Upstream regulators (CollecTRI, top): AR, TP53

miRNA regulators (miRDB)

63 targeting RBMX, 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-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-3926	98.95	69.26	1438

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 25)

• evidence provided that deletions in or around RBMX may be involved in non-obstructive azoospermia(NOA) (PMID:16491274)
• 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)
• p53 modulates DNA DSB repair by, in part, inducing hnRNP G (PMID:17387044)
• This identifies RBMX as an ARTS-1-associated protein that regulates both the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains. (PMID:18445477)
• These studies indicate that hnRNP G promotes the expression of Txnip and mediates its tumor-suppressive effect. (PMID:18541147)
• studied the genetic and expression states of hnRNP G in normal, premalignant and malignant human oral tissues to further understand the relationship between the hnRNP G alterations and the development of human oral cancer (PMID:21840245)
• Data show that RBMX accumulated at DNA lesions through multiple domains in a poly(ADP-ribose) polymerase 1-dependent manner and promoted HR by facilitating proper BRCA2 expression. (PMID:22344029)
• RBMX is a cohesion regulator that maintains the proper cohesion of sister chromatids. (PMID:22832223)
• A sequence deletion within RBMX is identified as associated with with Shashi X-linked intellectual disability syndrome. (PMID:25256757)
• Results showed that HNRNPG and HTRA2-BETA1 were specific antagonistic regulators of ERa exon7 splicing and increased HNRNPG levels were associated with improved clinical outcome of endometrial cancer through up-regulation of ERaD7 expression. (PMID:25884434)
• Host RBMX is required for the maintenance of Borna disease virus nuclear viral factories. (PMID:26333388)
• HNRNPG binds m6A-methylated RNAs through its C-terminal low-complexity region, which self-assembles into large particles in vitro. The Arg-Gly-Gly repeats within the low-complexity region are required for binding to the RNA motif exposed by m6A methylation. (PMID:28334903)
• These results suggest that satellite I RNA plays a role in stabilizing RBMX and Sororin in the ncRNP complex to maintain proper sister chromatid cohesion. (PMID:29383807)
• Study demonstrates a novel role for the splice factor hnRNPG in the pregnant myometrium. hnRNPG is required for the exclusion of exon 7 in the derivation of the dominant negative myometrial ERDelta7 isoform and is negatively regulated in an E2 dependent manner. (PMID:30502052)
• PUM binding is required for maintenance of genomic stability by NORAD whereas binding of RBMX is dispensable for this function. (PMID:31343408)
• hnRNPG associates co-transcriptionally with RNAPII and regulates alternative splicing transcriptome-wide. m(6)A near splice sites in nascent pre-mRNA modulates hnRNPG binding, which influences RNAPII occupancy patterns and promotes exon inclusion. (PMID:31445886)
• RBMX is required for activation of ATR on repetitive DNAs to maintain genome stability. (PMID:32494026)
• RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing. (PMID:33564070)
• Deletion of RBMX RGG/RG motif in Shashi-XLID syndrome leads to aberrant p53 activation and neuronal differentiation defects. (PMID:34260915)
• Transcriptional control of CBX5 by the RNA binding proteins RBMX and RBMXL1 maintains chromatin state in myeloid leukemia. (PMID:34458856)
• The Role of Alternative Splicing Factors hnRNP G and Fox-2 in the Progression and Prognosis of Esophageal Cancer. (PMID:36466711)
• Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions. (PMID:37277488)
• RBMX involves in telomere stability maintenance by regulating TERRA expression. (PMID:37756323)
• Aberrant RBMX expression is relevant for cancer prognosis and immunotherapy response. (PMID:38214653)
• [RBMX overexpression inhibits proliferation, migration, invasion and glycolysis of human bladder cancer cells by downregulating PKM2]. (PMID:38293971)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rbmx	ENSMUSG00000031134

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), A1CF (ENSG00000148584), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), 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

RNA-binding motif protein, X chromosome — P38159 (reviewed: P38159)

Alternative names: Glycoprotein p43, Heterogeneous nuclear ribonucleoprotein G

All UniProt accessions (6): P38159, H0Y6E7, H3BNC1, H3BR27, H3BT71, H3BUY5

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5’-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Also plays a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment.

Subunit / interactions. Homomultimer. Interacts with SAFB/SAFB1. Found in the supraspliceosome complex. Identified in the spliceosome C complex. Interacts with KHDRBS3. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, NCOA5 and PPP1CA. Interacts with CLK2, KHDRBS2, SAFB, TRA2B and YTHDC1. Interacts with ERAP1; the interaction is RNA-independent. Interacts with PPIA/CYPA.

Subcellular location. Nucleus.

Tissue specificity. Expressed strongly in oral keratinocytes, but only weakly detected in oral squamous cell carcinomas (at protein level).

Post-translational modifications. O-glycosylated. Arg-185 is dimethylated, probably to asymmetric dimethylarginine. Cleavage of initiator Met is partial. If Met-1 is not removed, it is acetylated. If it is removed, Val-2 is acetylated.

Disease relevance. Intellectual developmental disorder, X-linked, syndromic, Shashi type (MRXSSH) [MIM:300238] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXS11 patients manifest moderate intellectual disability and craniofacial dysmorphism. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, X-linked, syndromic, Gustavson type (MRXSG) [MIM:309555] An X-linked disorder characterized by profound intellectual disability, microcephaly, severe structural brain abnormalities, epileptic seizures, severe vision defect, hearing loss, congenital heart defects, psychomotor deficits, and death in infancy or early childhood. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The RRM domain is necessary for RNA-binding, but not for splice site selection, indicating that its splicing activity does not require direct binding to RNA.

Isoforms (3)

UniProt ID	Names	Canonical?
P38159-1	1	yes
P38159-2	2
P38159-3	3

RefSeq proteins (2): NP_001158275, NP_002130* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003954	RRM_euk-type	Domain
IPR012604	RBM1CTR	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050441	RBM	Family

Pfam: PF00076, PF08081

UniProt features (51 total): modified residue 17, compositionally biased region 9, strand 5, cross-link 3, splice variant 3, region of interest 3, chain 2, helix 2, turn 2, initiator methionine 1, domain 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2MB0	SOLUTION NMR
2MKS	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P38159-F1	54.73	0.10

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 (20): 1, 2, 30, 88, 91, 125, 144, 164, 165, 172, 174, 261, 328, 329, 330, 332, 352, 22, 80, 86

Mutagenesis-validated functional residues (1):

Position	Phenotype
22	promotes cell proliferation. inhibits transcriptional up-regulation of the txnip promoter.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 409 (showing top): MORF_SMC1L1, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, MORF_HDAC1, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, MORF_RAD21, GOBP_OSTEOBLAST_DIFFERENTIATION, TGACCTY_ERR1_Q2, MORF_HDAC2

GO Biological Process (13): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splicing, via spliceosome (GO:0000398), osteoblast differentiation (GO:0001649), transcription by RNA polymerase II (GO:0006366), membrane protein ectodomain proteolysis (GO:0006509), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of mRNA splicing, via spliceosome (GO:0048025), positive regulation of mRNA splicing, via spliceosome (GO:0048026), protein homooligomerization (GO:0051260), cellular response to interleukin-1 (GO:0071347), RNA processing (GO:0006396), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), chromatin binding (GO:0003682), RNA binding (GO:0003723), mRNA binding (GO:0003729), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (13): euchromatin (GO:0000791), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), membrane (GO:0016020), protein-containing complex (GO:0032991), supraspliceosomal complex (GO:0044530), extracellular exosome (GO:0070062), catalytic step 2 spliceosome (GO:0071013), ribonucleoprotein complex (GO:1990904), nucleolus (GO:0005730), organelle (GO:0043226)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
RHO GTPase cycle	3
RHOBTB GTPase Cycle	2
mRNA Splicing	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of mRNA splicing, via spliceosome	3
binding	3
cellular anatomical structure	3
mRNA splicing, via spliceosome	2
RNA processing	2
protein binding	2
nuclear lumen	2
spliceosomal complex	2
alternative mRNA splicing, via spliceosome	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
ossification	1
cell differentiation	1
DNA-templated transcription	1
membrane protein proteolysis	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
negative regulation of RNA splicing	1
negative regulation of mRNA processing	1
positive regulation of RNA splicing	1
positive regulation of mRNA processing	1
protein complex oligomerization	1
response to interleukin-1	1
cellular response to cytokine stimulus	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
nucleic acid binding	1
RNA binding	1
chromatin	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
cellular_component	1
extracellular vesicle	1
Prp19 complex	1

Protein interactions and networks

STRING

3354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBMX	YTHDC1	Q96MU7	899
RBMX	TOP1	P11387	888
RBMX	YTHDF1	Q9BYJ9	878
RBMX	YTHDC2	Q9H6S0	865
RBMX	YTHDF3	Q7Z739	854
RBMX	YTHDF2	Q9Y5A9	847
RBMX	HTRA2	O43464	840
RBMX	ALKBH5	Q6P6C2	834
RBMX	HNRNPC	P07910	822
RBMX	METTL3	Q86U44	819
RBMX	IGF2BP1	Q9NZI8	788
RBMX	KHDRBS1	Q07666	782
RBMX	ALYREF	Q86V81	781
RBMX	HNRNPU	Q00839	779
RBMX	ZC3H13	Q5T200	772

IntAct

410 interactions, top by confidence:

A	B	Type	Score
RBMX	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.850
KHDRBS2	RBMX	psi-mi:“MI:0915”(physical association)	0.850
RBMX	RBMX	psi-mi:“MI:0915”(physical association)	0.820
RBMX	HNRNPK	psi-mi:“MI:0915”(physical association)	0.800
HNRNPK	RBMX	psi-mi:“MI:0915”(physical association)	0.800
RBMX	RBM3	psi-mi:“MI:0915”(physical association)	0.780
RBM3	RBMX	psi-mi:“MI:0915”(physical association)	0.780
RBMY1F	RBMX	psi-mi:“MI:0915”(physical association)	0.720
PRR3	RBMX	psi-mi:“MI:0915”(physical association)	0.720
NABP1	RBMX	psi-mi:“MI:0915”(physical association)	0.720
RBMX	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.720
RBMX	RBMY1F	psi-mi:“MI:0915”(physical association)	0.720
RBMX	PRR3	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (696): RBMX (Two-hybrid), RBMX (Two-hybrid), RBMX (Two-hybrid), RBMX (Two-hybrid), RBMX (Two-hybrid), RBMX (Two-hybrid), RBMX (Two-hybrid), APOBEC3C (Two-hybrid), MAGOHB (Two-hybrid), ROBO3 (Two-hybrid), NABP1 (Two-hybrid), PRR3 (Two-hybrid), RBMY1F (Two-hybrid), KHDRBS2 (Two-hybrid), RBMX (Affinity Capture-MS)

ESM2 similar proteins: A5A6M3, D4AE41, O22703, O75526, P30352, P35637, P38159, P56959, P60824, P60825, P60826, P62995, P62996, P62997, P78814, P84586, P92965, P92966, Q01560, Q01844, Q14011, Q24491, Q27294, Q28009, Q29RT0, Q3ZBT6, Q4P2Q5, Q4R7F0, Q4R813, Q4V898, Q54Y98, Q55FQ0, Q5RF83, Q61545, Q6IRQ4, Q7ZWA3, Q8L3X8, Q8RWN5, Q8VYA5, Q91VM5

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A5A6M3, C0HFE5, D3Z4I3, D4AE41, M0R7T6, O22703, O35698, O75526, O89086, O93235, P04147, P0C8Z4, P10979, P19682, P19683, P19684, P28644, P38159, P39697, P48809, P49310, P49311, P49313, P49314, P60824, P60825, P60826, P84586, P98179, Q03250, Q03251, Q03878, Q04836, Q05966, Q08473, Q08935, Q08937, Q14011

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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
Processing of Capped Intron-Containing Pre-mRNA	12	14.9×	7e-09
mRNA 3’-end processing	5	14.9×	1e-03
mRNA Polyadenylation	9	12.0×	6e-06
mRNA Splicing	7	11.7×	2e-04
Transport of Mature mRNA derived from an Intron-Containing Transcript	5	11.5×	3e-03
mRNA Splicing - Major Pathway	13	10.8×	3e-08
Metabolism of RNA	9	5.7×	1e-03
Dengue Virus-Host Interactions	8	5.5×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of mRNA splicing, via spliceosome	6	34.0×	5e-06
regulation of alternative mRNA splicing, via spliceosome	11	28.0×	1e-10
mRNA stabilization	5	19.1×	6e-04
regulation of RNA splicing	7	16.0×	3e-05
positive regulation of translation	5	11.9×	4e-03
RNA processing	5	11.4×	5e-03
mRNA processing	12	9.8×	1e-06
mRNA splicing, via spliceosome	10	9.5×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	5
Uncertain significance	19
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2691753	NM_002139.4(RBMX):c.478CCT[2] (p.Pro162del)	Likely pathogenic
3064397	NM_002139.4(RBMX):c.388G>T (p.Asp130Tyr)	Likely pathogenic
4813203	NM_002139.4(RBMX):c.37G>C (p.Gly13Arg)	Likely pathogenic
4813204	NM_002139.4(RBMX):c.166T>C (p.Phe56Leu)	Likely pathogenic
4813205	NM_002139.4(RBMX):c.247_249del (p.Gln83del)	Likely pathogenic

SpliceAI

1209 predictions. Top by Δscore:

Variant	Effect	Δscore
X:136874453:CT:C	acceptor_loss	1.0000
X:136875081:CTTAC:C	donor_loss	1.0000
X:136875082:TTACC:T	donor_loss	1.0000
X:136875084:A:AC	donor_gain	1.0000
X:136875084:A:C	donor_loss	1.0000
X:136875085:C:CC	donor_gain	1.0000
X:136875085:C:CT	donor_loss	1.0000
X:136875090:A:C	donor_gain	1.0000
X:136875164:TATCG:T	acceptor_gain	1.0000
X:136875165:ATCG:A	acceptor_gain	1.0000
X:136875166:TCG:T	acceptor_gain	1.0000
X:136875167:C:CT	acceptor_gain	1.0000
X:136875167:CG:C	acceptor_gain	1.0000
X:136875168:GC:G	acceptor_loss	1.0000
X:136875169:C:CC	acceptor_gain	1.0000
X:136875254:TTAC:T	donor_loss	1.0000
X:136875256:A:AC	donor_gain	1.0000
X:136875256:AC:A	donor_gain	1.0000
X:136875257:C:CT	donor_gain	1.0000
X:136875257:CC:C	donor_gain	1.0000
X:136875257:CCT:C	donor_gain	1.0000
X:136875257:CCTA:C	donor_gain	1.0000
X:136875257:CCTAT:C	donor_gain	1.0000
X:136875260:ATAT:A	donor_gain	1.0000
X:136875379:AATAG:A	acceptor_gain	1.0000
X:136875380:ATAG:A	acceptor_gain	1.0000
X:136875381:TAG:T	acceptor_gain	1.0000
X:136875382:AG:A	acceptor_gain	1.0000
X:136875384:C:CC	acceptor_gain	1.0000
X:136875387:C:CT	acceptor_gain	1.0000

AlphaMissense

2481 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:136878067:A:T	I79N	1.000
X:136879065:A:C	F56L	1.000
X:136879065:A:T	F56L	1.000
X:136879066:A:G	F56S	1.000
X:136879067:A:G	F56L	1.000
X:136879072:A:T	V54D	1.000
X:136879074:A:C	F53L	1.000
X:136879074:A:T	F53L	1.000
X:136879075:A:C	F53C	1.000
X:136879075:A:G	F53S	1.000
X:136879076:A:G	F53L	1.000
X:136879080:A:C	F51L	1.000
X:136879080:A:T	F51L	1.000
X:136879081:A:C	F51C	1.000
X:136879081:A:G	F51S	1.000
X:136879082:A:C	F51V	1.000
X:136879082:A:G	F51L	1.000
X:136879082:A:T	F51I	1.000
X:136879084:C:A	G50V	1.000
X:136879084:C:T	G50E	1.000
X:136879086:T:A	R49S	1.000
X:136879086:T:G	R49S	1.000
X:136879087:C:A	R49I	1.000
X:136879087:C:G	R49T	1.000
X:136879108:T:A	D42V	1.000
X:136879108:T:G	D42A	1.000
X:136879114:A:G	M40T	1.000
X:136879333:C:A	G32V	1.000
X:136879333:C:T	G32E	1.000
X:136879334:C:G	G32R	1.000

dbSNP variants (sampled 300 via entrez): RS1000152083 (X:136873433 A>G), RS1000300812 (X:136875904 T>C,G), RS1000366885 (X:136882267 A>G), RS1000384750 (X:136875599 A>G), RS1000487139 (X:136871668 T>G), RS1000497216 (X:136872070 C>T), RS1000856560 (X:136877160 T>G), RS1001125619 (X:136880687 G>A,T), RS1001165217 (X:136881738 C>G), RS1001545949 (X:136881697 A>G), RS1001589324 (X:136872474 T>A), RS1001739231 (X:136881188 T>C), RS1001871454 (X:136880227 T>C), RS1002277799 (X:136880406 C>T), RS1002409589 (X:136876904 G>A)

Disease associations

OMIM: gene MIM:300199 | disease phenotypes: MIM:300238, MIM:309555

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic X-linked intellectual disability Shashi type	Moderate	X-linked
severe X-linked intellectual disability, Gustavson type	Moderate	X-linked

Mondo (3): syndromic X-linked intellectual disability Shashi type (MONDO:0010277), severe X-linked intellectual disability, Gustavson type (MONDO:0010661), CIC-rearranged sarcoma (MONDO:0956989)

Orphanet (2): X-linked intellectual disability, Shashi type (Orphanet:85286), Severe X-linked intellectual disability, Gustavson type (Orphanet:3078)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000053	Macroorchidism
HP:0000076	Vesicoureteral reflux
HP:0000179	Thick lower lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000336	Prominent supraorbital ridges
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000581	Blepharophimosis
HP:0000618	Blindness
HP:0000629	Periorbital fullness
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0001141	Severely reduced visual acuity
HP:0001199	Triphalangeal thumb
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001276	Hypertonia
HP:0001305	Dandy-Walker malformation
HP:0001321	Cerebellar hypoplasia
HP:0001336	Myoclonus
HP:0001374	Congenital hip dislocation
HP:0001417	X-linked inheritance
HP:0001419	X-linked recessive inheritance

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003097_46	Pediatric autoimmune diseases	6.000000e-08

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C537135	Orofaciodigital syndrome, Shashi type (supp.)
C536759	X-linked mental retardation Gustavson type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725147 (SINGLE PROTEIN)

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	4
Arsenic Trioxide	decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
arsenite	affects binding, increases reaction, increases methylation	2
sodium arsenite	decreases expression	2
Caffeine	affects phosphorylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
epigallocatechin gallate	decreases expression	1
pentanal	decreases expression	1
arsenic disulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CD 437	decreases expression	1
nickel acetate	decreases reaction, increases expression, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
dorsomorphin	affects cotreatment, decreases expression	1
PP242	increases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697734	Binding	Inhibition of RBMX (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT06414434	PHASE1	ACTIVE_NOT_RECRUITING	BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma
NCT06820957	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body