RDX

Summary

RDX (radixin, HGNC:9944) is a protein-coding gene on chromosome 11q22.3, encoding Radixin (P35241). Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane.

Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. It is highly similar in sequence to both ezrin and moesin. The radixin gene has been localized by fluorescence in situ hybridization to 11q23. A truncated version representing a pseudogene (RDXP2) was assigned to Xp21.3. Another pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by Southern and PCR analyses. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5962 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 307 total — 13 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_002906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9944
Approved symbol	RDX
Name	radixin
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137710
Ensembl biotype	protein_coding
OMIM	179410
Entrez	5962

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 protein_coding, 7 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000527537, ENST00000528498, ENST00000528556, ENST00000528900, ENST00000529774, ENST00000530085, ENST00000530131, ENST00000530301, ENST00000530749, ENST00000532118, ENST00000532461, ENST00000533678, ENST00000533961, ENST00000533991, ENST00000534683, ENST00000544551, ENST00000642511, ENST00000645312, ENST00000645495, ENST00000645527, ENST00000646663, ENST00000647231, ENST00000914232, ENST00000955458

RefSeq mRNA: 6 — MANE Select: NM_002906 NM_001260492, NM_001260493, NM_001260494, NM_001260495, NM_001260496, NM_002906

CCDS: CCDS58171, CCDS58172, CCDS58173, CCDS58174, CCDS8343

Canonical transcript exons

ENST00000645495 — 14 exons

Exon	Start	End
ENSE00003461011	110236099	110236191
ENSE00003482846	110279681	110279756
ENSE00003513489	110253946	110254109
ENSE00003517777	110229441	110232033
ENSE00003549692	110233237	110233479
ENSE00003572576	110258106	110258189
ENSE00003580259	110247703	110247833
ENSE00003588483	110264779	110264874
ENSE00003615125	110255289	110255385
ENSE00003658656	110263960	110264234
ENSE00003664757	110272536	110272619
ENSE00003676472	110237492	110237652
ENSE00003786066	110257767	110257913
ENSE00003899357	110296467	110296614

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.0551 / max 1175.3433, expressed in 1810 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122193	34.6781	1797
122194	12.1330	1764
122192	4.6756	1222
122197	0.5535	336
206439	0.3988	199
122196	0.2899	138
122195	0.2756	123
122186	0.0367	6
122188	0.0079	2
122187	0.0060	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.52	gold quality
right adrenal gland cortex	UBERON:0035827	98.97	gold quality
visceral pleura	UBERON:0002401	98.88	gold quality
right adrenal gland	UBERON:0001233	98.82	gold quality
parietal pleura	UBERON:0002400	98.82	gold quality
left adrenal gland	UBERON:0001234	98.77	gold quality
adrenal cortex	UBERON:0001235	98.75	gold quality
adrenal gland	UBERON:0002369	98.71	gold quality
left adrenal gland cortex	UBERON:0035825	98.68	gold quality
pleura	UBERON:0000977	98.67	gold quality
ventricular zone	UBERON:0003053	98.59	gold quality
corpus callosum	UBERON:0002336	98.45	gold quality
secondary oocyte	CL:0000655	98.20	gold quality
tibia	UBERON:0000979	98.18	gold quality
calcaneal tendon	UBERON:0003701	98.15	gold quality
gluteal muscle	UBERON:0002000	98.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.04	gold quality
biceps brachii	UBERON:0001507	97.96	gold quality
ganglionic eminence	UBERON:0004023	97.92	gold quality
metanephric glomerulus	UBERON:0004736	97.87	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.83	gold quality
renal glomerulus	UBERON:0000074	97.82	gold quality
lateral globus pallidus	UBERON:0002476	97.74	gold quality
choroid plexus epithelium	UBERON:0003911	97.57	gold quality
germinal epithelium of ovary	UBERON:0001304	97.49	gold quality
embryo	UBERON:0000922	97.42	gold quality
triceps brachii	UBERON:0001509	97.39	gold quality
inferior olivary complex	UBERON:0002127	97.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.13	gold quality
globus pallidus	UBERON:0001875	97.07	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	138.63
E-GEOD-134144	yes	37.61
E-HCAD-10	yes	34.07
E-MTAB-8410	yes	27.93
E-CURD-46	yes	26.00
E-HCAD-5	yes	21.73
E-MTAB-8271	yes	14.79
E-GEOD-130148	yes	7.56
E-MTAB-10137	yes	5.55
E-MTAB-7051	no	896.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ICAM1	Activation

Upstream regulators (CollecTRI, top): CREB5

miRNA regulators (miRDB)

187 targeting RDX, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• amino-terminal domains of the ezrin, radixin, and moesin (ERM) proteins bind advanced glycation end products and have a role in diabetes (PMID:12734202)
• Disrupted localization of radixin and MRP2 supports the concept that radixin contributes to the canalicular localization of MRP2. (PMID:14568249)
• ezrin/radixin/moesin proteins are recruited by NHE1 Na+/H+ exchanger and have roles in regulating Akt-dependent cell survival (PMID:15096511)
• All three ERM family members can localise to the nucleus; a specific nuclear localisation sequence, which is conserved and functional in all ERM family members, is identified, implying specific regulated nuclear import. (PMID:15149851)
• results suggest that ezrin-radixin-moesin proteins are required for microvillar positioning of L-selectin and that this is important both for leukocyte tethering and L-selectin shedding (PMID:15178693)
• Ezrin, radixin and moesin are ADP-ribosylated by Pseudomonas aeruginosa ExoS (PMID:15252013)
• Conformational regulation of radixin protein function occurs by association of the FERM and C-terminal domains, whereby the membrane- and actin-binding activities are mutually suppressed [review] (PMID:15313460)
• Expression of ExoS in HeLa cells led to a loss of phosphorylation of Ezrin/radixin/moesin proteins that was dependent upon the expression of ADP-ribosyltransferase activity. (PMID:16889625)
• 2 mutant alleles of RDX in 2 consanguineous families associated with neurosensory hearing loss; sequence analysis of RDX from original DFNB24 family revealed a c.463C>T transition substitution predicted to truncate radixin in the FERM domain (PMID:17226784)
• increased CD44, ezrin, radixin, and moesin phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients. (PMID:17237445)
• RDX was differentially expressed in sclerotic hippocampi compared to non-sclerotic ones. (PMID:17515952)
• Report disturbed colocalization of multidrug resistance protein 2 and radixin in human cholestatic liver diseases. (PMID:17725603)
• Radixin and ezrin play similar roles in the apical membrane localization of ABCC2 (MRP2) and their expression level and subcellular distribution are important factors in the regulation of ABCC2 (MRP2) at the post-transcriptional level. (PMID:17825285)
• the ezrin, radixin, and moesin proteins function as positive regulators of infection by X4-tropic HIV-1 (PMID:18295815)
• Unlike ezrin and moesin, radixin (a member of the ezrin-radixin-moesin protein family)is not expressed in Jurkat cells, nor is it involved in apoptotic signaling following Fas receptor triggering in these cells. (PMID:18941185)
• No aspects of T cell receptor signaling uniquely require transgenic ezrin or moesin; instead, T cell activation appears to depend on net ezrin, radixin, and moesin (ERM)protein expression, while ezrin and moesin function together. (PMID:19124745)
• In Vitro and in Vivo Characterization of Molecular Interactions between Calmodulin, Ezrin/Radixin/Moesin, and L-selectin (PMID:19129194)
• c14orf166 was identified asa novel metastasis-associated protein, and the roles of radixin, moesin and c14orf166 in pancreatic cancer metastasis deserve further investigations. (PMID:19152423)
• A novel splice site mutation in the RDX gene causes DFNB24 hearing loss in an Iranian family. (PMID:19215054)
• These studies identify a new ERM kinase of importance in lymphocytes and confirm the role of ezrin-radixin-moesin phosphorylation in regulating cell shape and motility. (PMID:19255442)
• Data show that stimulation of the NK cell-expressed tetraspanin CD81 induces phosphorylation of ezrin/radixin/moesin proteins and leads to NK cell polarization thereby facilitating NK cell migration toward various chemokines/cytokines. (PMID:19830727)
• Ezrin, radixin, and moesin proteins are physiological substrates of the kinase activity of leucine-rich repeat kinase 2 (LRRK2). (PMID:19890007)
• Results demonstrate a new regulatory mechanism of ezrin-radixin-moesin phosphorylation by sphingolipids with opposing actions of ceramide and sphingosine 1-phosphate. (PMID:20679347)
• Data suggest that ezrin-radixin-moesin proteins are involved in the spatial regulation of Epac1 and cooperate with cAMP- and Rap-mediated signaling to regulate adhesion to the extracellular matrix. (PMID:20855527)
• the identification of radixin as a scaffolding unit for both cAMP effectors, Epac and PKA (PMID:21047789)
• Polar distribution of radixin suggest a role in promoting formation and plasticity of membrane surface projections and also suggest that radixin is an organizer and regulator of Mrp-2 and cell polarity in hepatocytes. (PMID:21160029)
• This study provides the novel evidence that increased phosphorylation of Ezrin/radixin/moesin proteins may contribute to proliferation of rheumatoid fibroblast-like synoviocytes. (PMID:21278069)
• Dysregulation of the ezrin/radixin/moesin-RAGE complex might be an important step in rearrangement of the actin cytoskeleton during proinflammatory cytokine-induced epithelial-mesenchymal transition of human alveolar epithelial cells. (PMID:21278261)
• ezrin, radixin and moesin play similar roles in the tumor cell metastatic potential and their roles of upregulating the expression of E-cadherin may be important in tumor progression (PMID:21352885)
• Ezrin, radixin, and moesin are phosphorylated in response to 2-methoxyestradiol and modulate endothelial hyperpermeability. (PMID:21659656)
• results indicate that ezrin influences the expression of P-gp at the translational level, whereas radixin is involved in membrane localization of P-gp in HepG2 cells (PMID:21837648)
• the ezrin, radixin and moesin proteins differentially modulate sphingosine 1 phosphate-induced alterations in lung endoethlial cell cytoskeleton and permeability (PMID:21864676)
• MiR-31 targeted radixin predominantly via inhibition of protein translation instead of degradation of mRNA. (PMID:22089331)
• The ERM (ezrin, radixin, moesin) proteins are novel scaffolds at the level of SOS activity control, which is relevant for both normal Ras function and dysfunction known to occur in several human cancers. (PMID:22132106)
• Data show that silencing of radixin (RDX) phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed gastric cancer (GC) cells reversed the suppressive effects of miR-409. (PMID:22179828)
• role of CCM3 and ezrin/radixin/moesin family of proteins in cell’s response to oxidative stress (PMID:22291017)
• radixin plays an important role in promoting cell migration by regulating Rac1-mediated epithelial polarity and formation of adherens junctions through Vav GEFs. (PMID:22467863)
• Radixin selectively modulates the expression and function of MRP2 in human gastric adenocarcinoma. (PMID:22469515)
• results suggest that radixin might play a critical role in pancreatic cancer progression, possibly through involvement of down-regulation of TSP-1 and E-cadherin expression. (PMID:22631643)
• Ano1, ezrin, and moesin/radixin colocalize apically in salivary gland epithelial cells, and overexpression of moesin and Ano1 in HEK cells alters the subcellular localization of both proteins (PMID:22685202)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rdx	ENSMUSG00000032050
rattus_norvegicus	Rdx	ENSRNOG00000012237
drosophila_melanogaster	Moe	FBGN0011661

Paralogs (6): EZR (ENSG00000092820), FRMD4B (ENSG00000114541), ERMN (ENSG00000136541), MSN (ENSG00000147065), FRMD4A (ENSG00000151474), NF2 (ENSG00000186575)

Protein

Protein identifiers

Radixin — P35241 (reviewed: P35241)

All UniProt accessions (12): P35241, A0A2R8Y4H6, A0A2R8Y5P0, A0A2R8Y5S7, A0A2R8Y7M3, B0YJ88, E9PKN5, E9PN07, E9PNP4, E9PNV3, E9PQ82, E9PRS5

UniProt curated annotations — full annotation on UniProt →

Function. Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane.

Subunit / interactions. Binds NHERF1. Interacts with NHERF1, NHERF2, LAYN, MME/NEP and ICAM2. Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain). Interacts (via FERM domain) with SPN/CD43 cytoplasmic tail. Interacts with CD44. Interacts with CLIC5; may work together in a complex which also includes EZR and MYO6 to stabilize linkages between the plasma membrane and subjacent actin cytoskeleton at the base of stereocilia.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Cleavage furrow. Cell projection. Microvillus. Stereocilium.

Post-translational modifications. Phosphorylated by tyrosine-protein kinases. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding.

Disease relevance. Deafness, autosomal recessive, 24 (DFNB24) [MIM:611022] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding.

Domain organisation. The N-terminal domain interacts with the C-terminal domain of LAYN. An interdomain interaction between its N-terminal and C-terminal domains inhibits its ability to bind LAYN. In the presence of acidic phospholipids, the interdomain interaction is inhibited and this enhances binding to LAYN.

Isoforms (5)

UniProt ID	Names	Canonical?
P35241-1	1	yes
P35241-2	2
P35241-3	3
P35241-4	4
P35241-5	5

RefSeq proteins (6): NP_001247421, NP_001247422, NP_001247423, NP_001247424, NP_001247425, NP_002897* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000798	Ez/rad/moesin-like	Family
IPR008954	Moesin_tail_sf	Homologous_superfamily
IPR011174	ERM	Family
IPR011259	ERM_C_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR018979	FERM_N	Domain
IPR018980	FERM_PH-like_C	Domain
IPR019747	FERM_CS	Conserved_site
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily
IPR041789	ERM_FERM_C	Domain
IPR046810	ERM_helical	Domain

Pfam: PF00373, PF00769, PF09379, PF09380, PF20492

UniProt features (22 total): splice variant 5, compositionally biased region 4, sequence variant 3, region of interest 3, binding site 2, modified residue 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8XZ6	X-RAY DIFFRACTION	2.12
8XZ4	X-RAY DIFFRACTION	2.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35241-F1	86.98	0.71

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 278; 60–63

Post-translational modifications (2): 83, 564

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-437239	Recycling pathway of L1
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea

MSigDB gene sets: 427 (showing top): GOBP_APICAL_PROTEIN_LOCALIZATION, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GCM_MAP4K4, GOBP_EPITHELIUM_DEVELOPMENT, ACTACCT_MIR196A_MIR196B, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_EPITHELIAL_CELL_DEVELOPMENT, TTTGTAG_MIR520D, chr11q22, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (21): regulation of cell shape (GO:0008360), positive regulation of gene expression (GO:0010628), obsolete protein kinase A signaling (GO:0010737), microvillus assembly (GO:0030033), regulation of Rap protein signal transduction (GO:0032487), cellular response to platelet-derived growth factor stimulus (GO:0036120), apical protein localization (GO:0045176), positive regulation of protein catabolic process (GO:0045732), barbed-end actin filament capping (GO:0051016), establishment of endothelial barrier (GO:0061028), establishment of protein localization to plasma membrane (GO:0061951), protein localization to plasma membrane (GO:0072659), cellular response to thyroid hormone stimulus (GO:0097067), regulation of postsynaptic neurotransmitter receptor diffusion trapping (GO:0150054), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), regulation of organelle assembly (GO:1902115), positive regulation of protein localization to early endosome (GO:1902966), regulation of adherens junction organization (GO:1903391), positive regulation of early endosome to late endosome transport (GO:2000643), establishment of protein localization (GO:0045184), actin filament capping (GO:0051693)

GO Molecular Function (9): RNA binding (GO:0003723), actin binding (GO:0003779), protein domain specific binding (GO:0019904), cadherin binding (GO:0045296), cell adhesion molecule binding (GO:0050839), protein kinase A binding (GO:0051018), ATPase binding (GO:0051117), protein binding (GO:0005515), cytoskeletal protein binding (GO:0008092)

GO Cellular Component (23): ruffle (GO:0001726), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), microvillus (GO:0005902), adherens junction (GO:0005912), focal adhesion (GO:0005925), apical plasma membrane (GO:0016324), lamellipodium (GO:0030027), filopodium (GO:0030175), T-tubule (GO:0030315), midbody (GO:0030496), cortical actin cytoskeleton (GO:0030864), cleavage furrow (GO:0032154), apical part of cell (GO:0045177), cell tip (GO:0051286), extracellular exosome (GO:0070062), cell periphery (GO:0071944), stereocilium base (GO:0120044), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), stereocilium (GO:0032420), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Sensory processing of sound	2
L1CAM interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	4
regulation of biological quality	2
cell leading edge	2
plasma membrane bounded cell projection	2
actin-based cell projection	2
plasma membrane region	2
regulation of cell morphogenesis	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
microvillus organization	1
plasma membrane bounded cell projection assembly	1
Rap protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
response to platelet-derived growth factor	1
cellular response to growth factor stimulus	1
intracellular protein localization	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
actin filament capping	1
endothelial cell development	1
establishment of protein localization to membrane	1
protein localization to membrane	1
protein localization to cell periphery	1
cellular response to hormone stimulus	1
response to thyroid hormone	1
regulation of cellular localization	1
postsynaptic neurotransmitter receptor diffusion trapping	1
regulation of receptor localization to synapse	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
regulation of organelle organization	1
regulation of cellular component biogenesis	1
organelle assembly	1
protein localization to early endosome	1

Protein interactions and networks

STRING

2678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RDX	NHERF1	O14745	998
RDX	CD44	P16070	992
RDX	ICAM2	P13598	985
RDX	EZR	P15311	984
RDX	MSN	P26038	983
RDX	SPN	P16150	952
RDX	SLC9A1	P19634	939
RDX	EPB41	P11171	894
RDX	SELL	P14151	858
RDX	NHERF2	Q15599	856
RDX	PDPN	Q86YL7	806
RDX	CLIC5	Q9NZA1	773
RDX	LAYN	Q6UX15	758
RDX	CLIC6	Q96NY7	742
RDX	ABCC2	Q92887	733

IntAct

111 interactions, top by confidence:

A	B	Type	Score
RINT1	NBAS	psi-mi:“MI:0914”(association)	0.830
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
PHLPP2	NHERF1	psi-mi:“MI:0914”(association)	0.760
EZR	MSN	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RDX	rep	psi-mi:“MI:0915”(physical association)	0.660
PLEK	CAVIN2	psi-mi:“MI:0914”(association)	0.560
MAPK10	HAX1	psi-mi:“MI:0914”(association)	0.550
RDX	KIRREL3	psi-mi:“MI:0407”(direct interaction)	0.540
KIRREL3	RDX	psi-mi:“MI:0915”(physical association)	0.540
ITGB2	RDX	psi-mi:“MI:0407”(direct interaction)	0.540
RDX	ITGB2	psi-mi:“MI:0915”(physical association)	0.540
ARHGDIA	RDX	psi-mi:“MI:0915”(physical association)	0.540
MCF2	RDX	psi-mi:“MI:0915”(physical association)	0.540
RDX	MCF2	psi-mi:“MI:0407”(direct interaction)	0.540
RDX	ARHGDIA	psi-mi:“MI:0407”(direct interaction)	0.540
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
DDX20	GAPDHS	psi-mi:“MI:0914”(association)	0.530
MISP	OBSL1	psi-mi:“MI:0914”(association)	0.530
S	EZR	psi-mi:“MI:0914”(association)	0.480

BioGRID (378): RDX (Affinity Capture-MS), VPS11 (Reconstituted Complex), ACAA2 (Co-fractionation), AKR1B1 (Co-fractionation), ARHGDIA (Co-fractionation), ARHGDIG (Co-fractionation), BCAP31 (Co-fractionation), BRWD1 (Co-fractionation), CALR (Co-fractionation), CALU (Co-fractionation), CLIC1 (Co-fractionation), ENO1 (Co-fractionation), FABP5 (Co-fractionation), HSD17B10 (Co-fractionation), HSPA4 (Co-fractionation)

ESM2 similar proteins: B0DOB5, B0WYY2, H2KZZ6, O35346, O35763, O35889, P0C1G6, P15311, P26038, P26040, P26041, P26042, P26043, P26044, P31976, P31977, P35240, P35241, P36583, P46150, P46662, P52962, P55196, P59750, Q05397, Q12929, Q15057, Q170J7, Q18685, Q24564, Q29GR8, Q2HJ49, Q32LP2, Q3UU96, Q5R4H4, Q63648, Q66I42, Q6A028, Q6IVG4, Q7PGE8

Diamond homologs: B0WYY2, B2RYE5, O35763, O43491, O70318, P12264, P15311, P26038, P26040, P26041, P26042, P26043, P26044, P26045, P29074, P31976, P31977, P35240, P35241, P46150, P46662, P52962, P59750, P86232, Q12923, Q170J7, Q24564, Q29GR8, Q2HJ49, Q32LP2, Q58CU2, Q5FVG2, Q63648, Q66I42, Q7PS12, Q8BGS1, Q8HZQ5, Q8WY64, Q9H329, Q9HCM4

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
CREB5	“down-regulates quantity by repression”	RDX	“transcriptional regulation”
VPS11	“up-regulates activity”	RDX	binding
RHOA	“up-regulates activity”	RDX	phosphorylation
RDX	up-regulates	Platelet_aggregation
LRRK2	“up-regulates activity”	RDX	phosphorylation
ROCK1	“up-regulates activity”	RDX	phosphorylation
ROCK1	unknown	RDX	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 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
Constitutive Signaling by Aberrant PI3K in Cancer	7	13.5×	4e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	10.3×	9e-04
PIP3 activates AKT signaling	8	8.1×	9e-04
Signaling by Interleukins	7	6.8×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cell migration	9	6.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	10
Uncertain significance	176
Likely benign	65
Benign	18

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1070633	NM_002906.4(RDX):c.682_685del (p.Tyr228fs)	Pathogenic
13184	NM_002906.4(RDX):c.1732G>A (p.Asp578Asn)	Pathogenic
13185	NM_002906.4(RDX):c.1405dup (p.Ala469fs)	Pathogenic
13186	NM_002906.4(RDX):c.463C>T (p.Gln155Ter)	Pathogenic
1698704	NM_002906.4(RDX):c.1346del (p.Ala449fs)	Pathogenic
179207	NM_002906.4(RDX):c.1308del (p.Lys438fs)	Pathogenic
2418984	NM_002906.4(RDX):c.484_487del (p.His161_Lys162insTer)	Pathogenic
2498534	NM_002906.4(RDX):c.720del (p.Trp242fs)	Pathogenic
2863763	NM_002906.4(RDX):c.930_931del (p.Glu311fs)	Pathogenic
4770767	NM_002906.4(RDX):c.219_220del (p.Asn74fs)	Pathogenic
638047	NM_002906.4(RDX):c.551+2T>C	Pathogenic
982441	NM_002906.4(RDX):c.1108C>T (p.Arg370Ter)	Pathogenic
983525	NM_002906.4(RDX):c.129G>A (p.Trp43Ter)	Pathogenic
13187	NM_002906.4(RDX):c.698+1G>A	Likely pathogenic
1325000	NM_002906.4(RDX):c.1141C>T (p.Arg381Ter)	Likely pathogenic
1333282	NM_002906.4(RDX):c.1135C>T (p.Arg379Ter)	Likely pathogenic
1334117	NM_002906.4(RDX):c.513_514del (p.Arg171fs)	Likely pathogenic
3061950	NM_002906.4(RDX):c.295C>T (p.Gln99Ter)	Likely pathogenic
3075934	NM_002906.4(RDX):c.1180C>T (p.Arg394Ter)	Likely pathogenic
377252	NM_002906.4(RDX):c.467+1G>A	Likely pathogenic
4845838	NM_002906.4(RDX):c.1412dup (p.Pro472fs)	Likely pathogenic
631648	NM_002906.4(RDX):c.910C>T (p.Gln304Ter)	Likely pathogenic
983524	NM_002906.4(RDX):c.-64-1215_12+348del	Likely pathogenic

SpliceAI

3762 predictions. Top by Δscore:

Variant	Effect	Δscore
11:110131107:G:GG	donor_gain	1.0000
11:110159491:G:GG	donor_gain	1.0000
11:110232033:CCTAT:C	acceptor_loss	1.0000
11:110232034:C:A	acceptor_loss	1.0000
11:110232034:C:CC	acceptor_gain	1.0000
11:110232035:T:G	acceptor_loss	1.0000
11:110233233:ATACC:A	donor_loss	1.0000
11:110233236:C:CA	donor_loss	1.0000
11:110233289:T:TA	donor_gain	1.0000
11:110233475:AAAGC:A	acceptor_gain	1.0000
11:110233476:AAGC:A	acceptor_gain	1.0000
11:110233477:AGC:A	acceptor_gain	1.0000
11:110233478:GC:G	acceptor_gain	1.0000
11:110233479:CC:C	acceptor_gain	1.0000
11:110233480:C:CC	acceptor_gain	1.0000
11:110233480:C:T	acceptor_gain	1.0000
11:110233487:T:TC	acceptor_gain	1.0000
11:110236094:ATTAC:A	donor_loss	1.0000
11:110236095:TTACT:T	donor_loss	1.0000
11:110236096:TACT:T	donor_loss	1.0000
11:110236097:A:AC	donor_gain	1.0000
11:110236098:C:CT	donor_gain	1.0000
11:110236098:CT:C	donor_gain	1.0000
11:110236098:CTT:C	donor_gain	1.0000
11:110236121:T:TA	donor_gain	1.0000
11:110236127:T:TA	donor_gain	1.0000
11:110236188:CTGC:C	acceptor_gain	1.0000
11:110236189:TGC:T	acceptor_gain	1.0000
11:110236189:TGCCT:T	acceptor_loss	1.0000
11:110236190:GC:G	acceptor_gain	1.0000

AlphaMissense

3882 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:110231881:A:C	F580L	1.000
11:110231881:A:T	F580L	1.000
11:110231883:A:G	F580L	1.000
11:110231894:C:G	R576P	1.000
11:110231895:G:T	R576S	1.000
11:110231927:A:G	L565P	1.000
11:110253980:C:G	A309P	1.000
11:110253986:C:G	A307P	1.000
11:110253990:C:A	M305I	1.000
11:110253990:C:G	M305I	1.000
11:110253990:C:T	M305I	1.000
11:110253991:A:G	M305T	1.000
11:110253994:T:G	Q304P	1.000
11:110254023:T:A	R294S	1.000
11:110254023:T:G	R294S	1.000
11:110254024:C:G	R294T	1.000
11:110254036:A:G	L290P	1.000
11:110254042:T:G	H288P	1.000
11:110254043:G:C	H288D	1.000
11:110254048:C:A	G286V	1.000
11:110254048:C:T	G286E	1.000
11:110254049:C:G	G286R	1.000
11:110254049:C:T	G286R	1.000
11:110254053:A:C	C284W	1.000
11:110254054:C:T	C284Y	1.000
11:110254055:A:G	C284R	1.000
11:110254063:A:G	L281S	1.000
11:110254071:C:A	K278N	1.000
11:110254071:C:G	K278N	1.000
11:110254073:T:C	K278E	1.000

dbSNP variants (sampled 300 via entrez): RS1000030460 (11:110205621 A>C), RS1000054606 (11:110208443 A>C,T), RS1000082070 (11:110257263 G>A), RS1000082491 (11:110205933 T>C), RS1000109019 (11:110294132 G>A), RS1000136952 (11:110273715 T>C), RS1000225761 (11:110250705 T>G), RS1000268105 (11:110181266 A>G), RS1000313181 (11:110289249 A>C), RS1000344445 (11:110244411 C>T), RS1000346838 (11:110244502 G>T), RS1000358111 (11:110218872 G>C), RS1000377171 (11:110196354 G>C), RS1000394005 (11:110212651 T>A,C,G), RS1000420272 (11:110263029 C>T)

Disease associations

OMIM: gene MIM:179410 | disease phenotypes: MIM:611022

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 24	Strong	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	AR

Mondo (4): hearing loss disorder (MONDO:0005365), autosomal recessive nonsyndromic hearing loss 24 (MONDO:0012602), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (3): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare genetic deafness (Orphanet:96210), Rare non-syndromic genetic deafness (Orphanet:87884)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003593	Infantile onset
HP:0011476	Profound sensorineural hearing impairment

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002386_25	Cognitive function	7.000000e-06
GCST009597_64	Multiple sclerosis	2.000000e-06
GCST010479_22	Coronary artery disease	9.000000e-10
GCST011826_7	Computer vision syndrome	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003925	cognition

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
C564609	Deafness, Autosomal Recessive (supp.)
C567027	Deafness, Autosomal Recessive, 24 (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066454 (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
8.70	Kd	2.002	nM	CHEMBL3752910
8.70	ED50	2.002	nM	CHEMBL3752910

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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149213: Binding affinity to human RDX incubated for 45 mins by Kinobead based pull down assay	kd	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Benzo(a)pyrene	increases methylation, affects cotreatment, decreases expression, affects methylation	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
uranyl acetate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
tanespimycin	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	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
CHEMBL5652255	Binding	Binding affinity to human RDX 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)

301 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
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
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