RADX

Summary

RADX (RPA1 related single stranded DNA binding protein, X-linked, HGNC:25486) is a protein-coding gene on chromosome Xq22.3, encoding RPA-related protein RADX (Q6NSI4). Single-stranded DNA-binding protein recruited to replication forks to maintain genome stability.

Enables single-stranded DNA binding activity. Involved in negative regulation of double-strand break repair via homologous recombination. Located in nuclear speck and replication fork.

Source: NCBI Gene 55086 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 113 total
• MANE Select transcript: NM_018015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25486
Approved symbol	RADX
Name	RPA1 related single stranded DNA binding protein, X-linked
Location	Xq22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14191, FLJ10178
Ensembl gene	ENSG00000147231
Ensembl biotype	protein_coding
OMIM	301146
Entrez	55086

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000372544, ENST00000372548, ENST00000421550, ENST00000461251, ENST00000478395, ENST00000497124

RefSeq mRNA: 2 — MANE Select: NM_018015 NM_001184782, NM_018015

CCDS: CCDS14519, CCDS55470

Canonical transcript exons

ENST00000372548 — 14 exons

Exon	Start	End
ENSE00000979281	106625090	106625282
ENSE00000979282	106632625	106632733
ENSE00000979283	106632932	106633023
ENSE00000979284	106633130	106633252
ENSE00000979285	106636543	106636647
ENSE00000979287	106640552	106640721
ENSE00001092559	106669163	106669330
ENSE00001275307	106622651	106622793
ENSE00001275319	106637760	106637924
ENSE00001411620	106639527	106639687
ENSE00001914217	106678128	106679439
ENSE00001939451	106611978	106612723
ENSE00003578211	106662015	106662305
ENSE00003629443	106648313	106648386

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 90.27.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7846 / max 370.6436, expressed in 870 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197156	3.1082	819
197157	0.5545	215
197158	0.0741	32
197159	0.0477	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	90.27	gold quality
adenohypophysis	UBERON:0002196	88.73	gold quality
islet of Langerhans	UBERON:0000006	86.98	gold quality
bronchial epithelial cell	CL:0002328	86.91	gold quality
hypothalamus	UBERON:0001898	85.68	gold quality
ventricular zone	UBERON:0003053	84.78	gold quality
ganglionic eminence	UBERON:0004023	82.55	gold quality
left ovary	UBERON:0002119	82.33	gold quality
nucleus accumbens	UBERON:0001882	81.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.76	gold quality
epithelium of bronchus	UBERON:0002031	81.13	gold quality
right ovary	UBERON:0002118	80.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.92	gold quality
bronchus	UBERON:0002185	79.70	gold quality
ovary	UBERON:0000992	78.58	gold quality
mucosa of stomach	UBERON:0001199	78.46	gold quality
tibial nerve	UBERON:0001323	77.74	gold quality
right uterine tube	UBERON:0001302	77.70	gold quality
endothelial cell	CL:0000115	77.37	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	77.18	gold quality
endocervix	UBERON:0000458	76.78	gold quality
corpus callosum	UBERON:0002336	76.31	gold quality
pancreas	UBERON:0001264	76.20	gold quality
calcaneal tendon	UBERON:0003701	76.16	gold quality
body of uterus	UBERON:0009853	76.05	gold quality
left lobe of thyroid gland	UBERON:0001120	75.72	gold quality
caudate nucleus	UBERON:0001873	75.62	gold quality
right lobe of thyroid gland	UBERON:0001119	75.39	gold quality
thyroid gland	UBERON:0002046	75.09	gold quality
metanephros cortex	UBERON:0010533	74.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.40
E-MTAB-7606	no	128.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting RADX, 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-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540

Literature-anchored findings (GeneRIF, showing 5)

• By antagonizing RAD51 at forks, RADX allows cells to maintain a high capacity for homology-directed repair while ensuring that replication functions of RAD51 are properly regulated. Thus, RADX is essential to achieve the proper balance of RAD51 activity to maintain genome stability. (PMID:28735897)
• RADX interacts with single-stranded DNA to promote replication fork stability. (PMID:29021206)
• RADX buffers RAD51 to ensure the right amount of reversal and protection to maintain genome stability. (PMID:30021152)
• RADX controls RAD51 filament dynamics to regulate replication fork stability. (PMID:33453169)
• Oligomerization of DNA replication regulatory protein RADX is essential to maintain replication fork stability. (PMID:35120927)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	radx	ENSDARG00000010331
mus_musculus	Radx	ENSMUSG00000042498
rattus_norvegicus	Radx	ENSRNOG00000011120

Protein

Protein identifiers

RPA-related protein RADX — Q6NSI4 (reviewed: Q6NSI4)

Alternative names: RPA-related and RAD51-antagonist, X-chromosome

All UniProt accessions (2): Q6NSI4, B1AQ74

UniProt curated annotations — full annotation on UniProt →

Function. Single-stranded DNA-binding protein recruited to replication forks to maintain genome stability. Prevents fork collapse by antagonizing the accumulation of RAD51 at forks to ensure the proper balance of fork remodeling and protection without interfering with the capacity of cells to complete homologous recombination of double-strand breaks.

Subcellular location. Chromosome.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6NSI4-1	1	yes
Q6NSI4-2	2
Q6NSI4-3	3
Q6NSI4-4	4

RefSeq proteins (2): NP_001171711, NP_060485* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR040893	RADX	Family

Pfam: PF17659

UniProt features (23 total): mutagenesis site 7, sequence conflict 5, splice variant 4, region of interest 2, compositionally biased region 2, chain 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7SRK	X-RAY DIFFRACTION	2.5
7STG	X-RAY DIFFRACTION	2.7
8U5Y	ELECTRON MICROSCOPY	3.01
8U61	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NSI4-F1	76.40	0.48

Antibody-complex structures (SAbDab): 2 — 7SRK, 7STG

Functional residue map

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

Mutagenesis-validated functional residues (7):

Position	Phenotype
240	decreased binding to single-stranded dna; when associated with e-248; 252-e–e-256; a-279; e-304; e-310 and a-327.
248	decreased binding to single-stranded dna; when associated with e-240; 252-e–e-256; a-279; e-304; e-310 and a-327.
252–256	decreased binding to single-stranded dna; when associated with e-240; e-248; a-279; e-304; e-310 and a-327.
279	decreased binding to single-stranded dna; when associated with e-240; e-248; 252-e–e-256; e-304; e-310 and a-327.
304	decreased binding to single-stranded dna; when associated with e-240; e-248; 252-e–e-256; a-279; e-310 and a-327.
310	decreased binding to single-stranded dna; when associated with e-240; e-248; 252-e–e-256; a-279; e-304 and a-327.
327	decreased binding to single-stranded dna; when associated with e-240; e-248; 252-e–e-256; a-279; e-304 and e-310.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 92 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, TAATGTG_MIR323, GOBP_RECOMBINATIONAL_REPAIR, HAN_SATB1_TARGETS_DN, GOMF_SINGLE_STRANDED_DNA_BINDING

GO Biological Process (2): regulation of DNA repair (GO:0006282), negative regulation of double-strand break repair via homologous recombination (GO:2000042)

GO Molecular Function (4): single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): replication fork (GO:0005657), nuclear speck (GO:0016607), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	2
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
DNA binding	1
binding	1
chromosome	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RADX	SMARCAL1	Q9NZC9	759
RADX	ZRANB3	Q5FWF4	725
RADX	FBH1	Q8NFZ0	664
RADX	BOD1L1	Q8NFC6	623
RADX	HLTF	Q14527	607
RADX	DNA2	P51530	601
RADX	MUS81	Q96NY9	587
RADX	RAD51	Q06609	580
RADX	BRCA2	P51587	575
RADX	MRNIP	Q6NTE8	531
RADX	PAXIP1	Q6ZW49	521
RADX	RECQL5	O94762	519
RADX	FANCD2	Q9BXW9	506
RADX	MMS22L	Q6ZRQ5	495
RADX	RECQL	P46063	495

IntAct

39 interactions, top by confidence:

A	B	Type	Score
MLH1	RADX	psi-mi:“MI:0915”(physical association)	0.870
RADX	MLH1	psi-mi:“MI:0915”(physical association)	0.870
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
DNAJA4	DNAJA2	psi-mi:“MI:0914”(association)	0.710
	TOMM70	psi-mi:“MI:0914”(association)	0.690
RAB8B	GDI1	psi-mi:“MI:0914”(association)	0.640
AIPL1	SUPT5H	psi-mi:“MI:0914”(association)	0.510
NUDCD3	RADX	psi-mi:“MI:0915”(physical association)	0.500
RADX	RADX	psi-mi:“MI:0915”(physical association)	0.370
PLEKHF2	RADX	psi-mi:“MI:0915”(physical association)	0.370
MAPK6		psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CTDP1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DNAJC7	HSPA8	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
DPP8	KRBA1	psi-mi:“MI:0914”(association)	0.350
RADX	DNAJA2	psi-mi:“MI:0914”(association)	0.350
DNAJA2	QSOX1	psi-mi:“MI:0914”(association)	0.350
SLC12A3	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC6A15	EI24	psi-mi:“MI:0914”(association)	0.350
SLC9A3	ESYT3	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): CXorf57 (Two-hybrid), CXorf57 (Two-hybrid), CXorf57 (Affinity Capture-MS), CXorf57 (Two-hybrid), PLEKHF2 (Two-hybrid), AIPL1 (Affinity Capture-MS), CXorf57 (Two-hybrid), CXorf57 (Affinity Capture-MS), CXorf57 (Affinity Capture-MS), CXorf57 (Affinity Capture-MS), CXorf57 (Affinity Capture-MS), CXorf57 (Proximity Label-MS), CXorf57 (Proximity Label-MS), CXorf57 (Affinity Capture-MS), CXorf57 (Affinity Capture-MS)

ESM2 similar proteins: A0JMF1, A2CI97, A3KNA7, A6NE52, B2GV47, E7FAW3, P60330, Q06ZW3, Q0VDN7, Q12769, Q1M161, Q2NKJ3, Q2YDQ5, Q3SYW0, Q3T1I9, Q3U6Q4, Q4FZR5, Q5EE38, Q5PNP6, Q5RDX3, Q5SUQ9, Q5TYP4, Q5ZIB8, Q6AYM1, Q6DG91, Q6IRN0, Q6NSI4, Q6NYX6, Q6P4K6, Q6PH58, Q6ZNJ1, Q6ZPG2, Q6ZQA0, Q7T006, Q7ZVM9, Q80TE0, Q80VA5, Q8BJW5, Q8BMG1, Q8C779

Diamond homologs: B2GV47, Q6NSI4, Q8C779

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	5	15.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2226 predictions. Top by Δscore:

Variant	Effect	Δscore
X:106622643:T:G	acceptor_gain	1.0000
X:106622790:TCAG:T	donor_loss	1.0000
X:106622791:CAGGT:C	donor_loss	1.0000
X:106622792:AG:A	donor_loss	1.0000
X:106622793:GG:G	donor_loss	1.0000
X:106622794:GT:G	donor_loss	1.0000
X:106625282:GGT:G	donor_gain	1.0000
X:106632619:TTTCA:T	acceptor_loss	1.0000
X:106632620:TTCA:T	acceptor_loss	1.0000
X:106632621:TCAG:T	acceptor_loss	1.0000
X:106632623:A:AG	acceptor_gain	1.0000
X:106632624:G:GT	acceptor_gain	1.0000
X:106632624:GA:G	acceptor_gain	1.0000
X:106632624:GAA:G	acceptor_gain	1.0000
X:106632624:GAAAT:G	acceptor_gain	1.0000
X:106632927:TTTA:T	acceptor_loss	1.0000
X:106632929:TAG:T	acceptor_loss	1.0000
X:106632930:A:AG	acceptor_gain	1.0000
X:106632931:G:GA	acceptor_gain	1.0000
X:106632931:GGTC:G	acceptor_gain	1.0000
X:106632931:GGTCA:G	acceptor_gain	1.0000
X:106633019:GAAAG:G	donor_gain	1.0000
X:106633021:AAGG:A	donor_loss	1.0000
X:106633022:AGGT:A	donor_loss	1.0000
X:106633023:GGT:G	donor_loss	1.0000
X:106633024:G:GG	donor_gain	1.0000
X:106633024:GTAA:G	donor_loss	1.0000
X:106633025:T:A	donor_loss	1.0000
X:106633112:A:AG	acceptor_gain	1.0000
X:106633115:A:AG	acceptor_gain	1.0000

AlphaMissense

5621 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:106612654:T:A	W192R	0.997
X:106612654:T:C	W192R	0.997
X:106612684:T:A	W202R	0.995
X:106612684:T:C	W202R	0.995
X:106633009:G:C	R389P	0.995
X:106662149:A:C	S705R	0.994
X:106662151:T:A	S705R	0.994
X:106662151:T:G	S705R	0.994
X:106612308:G:C	R76S	0.993
X:106612308:G:T	R76S	0.993
X:106612301:T:A	V74D	0.992
X:106612402:T:C	C108R	0.992
X:106625138:T:A	W279R	0.992
X:106625138:T:C	W279R	0.992
X:106633157:G:C	R403P	0.992
X:106612297:G:C	A73P	0.991
X:106612307:G:C	R76T	0.991
X:106612366:G:C	D96H	0.991
X:106625105:G:C	A268P	0.991
X:106633159:T:A	W404R	0.991
X:106633159:T:C	W404R	0.991
X:106632990:T:C	F383L	0.990
X:106632992:T:A	F383L	0.990
X:106632992:T:G	F383L	0.990
X:106612367:A:G	D96G	0.989
X:106612376:T:A	I99N	0.989
X:106625140:G:C	W279C	0.989
X:106625140:G:T	W279C	0.989
X:106625190:T:C	L296P	0.989
X:106632696:T:A	W351R	0.989

dbSNP variants (sampled 300 via entrez): RS1000081101 (X:106614521 C>A,T), RS1000213973 (X:106634633 C>T), RS1000321538 (X:106631195 A>G), RS1000335469 (X:106661316 T>C), RS1000366615 (X:106662077 G>A), RS1000376226 (X:106644594 T>C,G), RS1000428892 (X:106644105 C>A), RS1000509913 (X:106652422 C>G), RS1000574780 (X:106669606 C>T), RS1000586012 (X:106656661 G>A), RS1000590174 (X:106614879 G>C), RS1000664921 (X:106642648 A>G), RS1000712416 (X:106672086 C>T), RS1000716649 (X:106643095 C>A,T), RS1000795130 (X:106668790 C>T)

Disease associations

OMIM: gene MIM:301146 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004860_31	Alcoholic chronic pancreatitis	5.000000e-06
GCST008839_302	Height	2.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	9
trichostatin A	affects cotreatment, increases expression	3
Cyclosporine	decreases expression, increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
butyraldehyde	increases expression	1
ochratoxin A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Copper	affects binding, increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases expression, affects response to substance	1
Melphalan	decreases expression	1
Methotrexate	increases expression	1

Clinical trials (associated diseases)

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