XRRA1

Summary

XRRA1 (X-ray radiation resistance associated 1, HGNC:18868) is a protein-coding gene on chromosome 11q13.4, encoding X-ray radiation resistance-associated protein 1 (Q6P2D8). May be involved in the response of cells to X-ray radiation.

Involved in response to X-ray. Located in cytoplasm and nuclear body.

Source: NCBI Gene 143570 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 143 total
• MANE Select transcript: NM_001378157

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18868
Approved symbol	XRRA1
Name	X-ray radiation resistance associated 1
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00225
Ensembl gene	ENSG00000166435
Ensembl biotype	protein_coding
OMIM	609788
Entrez	143570

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 8 protein_coding, 7 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000321448, ENST00000340360, ENST00000431210, ENST00000524430, ENST00000525407, ENST00000526047, ENST00000527087, ENST00000528219, ENST00000528819, ENST00000529400, ENST00000529926, ENST00000530280, ENST00000530562, ENST00000531449, ENST00000531849, ENST00000531852, ENST00000533598, ENST00000533990, ENST00000534041, ENST00000534798, ENST00000684022, ENST00000705661

RefSeq mRNA: 23 — MANE Select: NM_001378157 NM_001270380, NM_001270381, NM_001378157, NM_001378158, NM_001378159, NM_001378160, NM_001378161, NM_001378162, NM_001378163, NM_001378164, NM_001378165, NM_001378166, NM_001378167, NM_001378168, NM_001378169, NM_001378170, NM_001378171, NM_001378172, NM_001378173, NM_001378174, NM_001378175, NM_001378176, NM_182969

CCDS: CCDS44680, CCDS58159, CCDS58160, CCDS91535

Canonical transcript exons

ENST00000684022 — 19 exons

Exon	Start	End
ENSE00001242559	74862981	74863021
ENSE00001470150	74945018	74945085
ENSE00001549403	74859158	74859283
ENSE00001705069	74840910	74843453
ENSE00002180994	74948928	74949091
ENSE00003473450	74930300	74930372
ENSE00003474061	74848115	74848462
ENSE00003496123	74921214	74921347
ENSE00003504981	74927391	74927488
ENSE00003535437	74907145	74907273
ENSE00003537031	74851088	74851203
ENSE00003557327	74843854	74843959
ENSE00003574045	74936884	74937068
ENSE00003603215	74906239	74906456
ENSE00003614024	74845073	74845271
ENSE00003652614	74844168	74844283
ENSE00003662008	74933801	74933872
ENSE00003684932	74851989	74852082
ENSE00003993947	74940785	74940882

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 92.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0364 / max 143.4450, expressed in 1779 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121331	8.7504	1757
121332	3.2861	1272

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	92.23	gold quality
left testis	UBERON:0004533	91.75	gold quality
right testis	UBERON:0004534	91.07	gold quality
testis	UBERON:0000473	89.25	gold quality
bone marrow cell	CL:0002092	87.78	gold quality
calcaneal tendon	UBERON:0003701	87.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.65	gold quality
smooth muscle tissue	UBERON:0001135	81.98	gold quality
colonic epithelium	UBERON:0000397	81.81	gold quality
right uterine tube	UBERON:0001302	80.97	gold quality
corpus callosum	UBERON:0002336	80.92	gold quality
islet of Langerhans	UBERON:0000006	80.50	gold quality
granulocyte	CL:0000094	80.18	gold quality
muscle of leg	UBERON:0001383	79.74	gold quality
gall bladder	UBERON:0002110	79.70	gold quality
gastrocnemius	UBERON:0001388	79.42	gold quality
adrenal tissue	UBERON:0018303	79.30	gold quality
right lobe of liver	UBERON:0001114	78.85	gold quality
pancreas	UBERON:0001264	78.60	gold quality
sperm	CL:0000019	78.55	gold quality
body of pancreas	UBERON:0001150	78.53	gold quality
ventricular zone	UBERON:0003053	78.52	gold quality
prefrontal cortex	UBERON:0000451	78.21	gold quality
left ovary	UBERON:0002119	78.08	gold quality
right adrenal gland cortex	UBERON:0035827	78.06	gold quality
right coronary artery	UBERON:0001625	77.98	gold quality
stromal cell of endometrium	CL:0002255	77.95	gold quality
body of uterus	UBERON:0009853	77.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.00
E-MTAB-6386	no	638.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting XRRA1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3934-3P	99.76	65.51	1351

Literature-anchored findings (GeneRIF, showing 3)

• Molecular cloning and gene expression patterns of XRRA1. (PMID:12908878)
• our results identify a novel link between XRRA1 and the ATM/CHK1/2 pathway and suggest that XRRA1 is involved in a DNA damage response that drives radio- and chemoresistance by regulating the ATM/CHK1/2 pathway. (PMID:29082250)
• Genetic architecture of asthma in African American patients. (PMID:36089080)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	xrra1	ENSDARG00000089578
mus_musculus	Xrra1	ENSMUSG00000035211
rattus_norvegicus	Xrra1	ENSRNOG00000026503

Protein

Protein identifiers

X-ray radiation resistance-associated protein 1 — Q6P2D8 (reviewed: Q6P2D8)

All UniProt accessions (9): A0A804HIK0, A0A994J5L1, E9PIR2, Q6P2D8, E9PJ58, E9PL06, E9PMT6, E9PP69, H0YD10

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the response of cells to X-ray radiation.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed predominantly in testis followed by prostate and ovary. Low levels found in other tissues including peripheral blood leukocytes, spleen, thymus, small intestine and colon. Also expressed in neuroblastoma, glioma, breast, lung, leukemia, renal, ovarian, prostate and colorectal cancer cell lines.

Induction. By X-ray irradiation immediately after exposure and is then down-regulated two-fold in an X-ray radiation-resistant cell clone. Responds differently to X-ray radiation in clones of varying radiation responses.

Miscellaneous. Gene model based on mouse cDNA data.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6P2D8-1	1	yes
Q6P2D8-2	2
Q6P2D8-3	3
Q6P2D8-4	4
Q6P2D8-5	5

RefSeq proteins (23): NP_001257309, NP_001257310, NP_001365086, NP_001365087, NP_001365088, NP_001365089, NP_001365090, NP_001365091, NP_001365092, NP_001365093, NP_001365094, NP_001365095, NP_001365096, NP_001365097, NP_001365098, NP_001365099, NP_001365100, NP_001365101, NP_001365102, NP_001365103, NP_001365104, NP_001365105, NP_892014 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

UniProt features (24 total): splice variant 7, repeat 6, sequence conflict 3, region of interest 3, sequence variant 2, chain 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P2D8-F1	55.86	0.10

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): GOBP_RESPONSE_TO_IONIZING_RADIATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, chr11q13, GOBP_RESPONSE_TO_RADIATION, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOBP_RESPONSE_TO_X_RAY, GOCC_NUCLEAR_BODY, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_IFNG_KO_DN, GSE14415_NATURAL_TREG_VS_TCONV_DN, CIITA_TARGET_GENES, DYRK1A_TARGET_GENES, E2F5_TARGET_GENES, ID1_TARGET_GENES

GO Biological Process (1): response to X-ray (GO:0010165)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
response to ionizing radiation	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

673 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XRRA1	XRCC5	P13010	775
XRRA1	SPCS2	Q15005	470
XRRA1	GPALPP1	Q8IXQ4	454
XRRA1	CLLU1-AS1	Q5K130	447
XRRA1	MAN2C1	Q9NTJ4	405
XRRA1	SLFN5	Q08AF3	398
XRRA1	CHRDL2	Q6WN34	381
XRRA1	C2orf74	A8MZ97	377
XRRA1	SAMD10	Q9BYL1	377
XRRA1	CCDC126	Q96EE4	370
XRRA1	ARMCX2	Q7L311	368
XRRA1	ANKRD30B	Q9BXX2	355
XRRA1	ZNF502	Q8TBZ5	349
XRRA1	ZNF880	Q6PDB4	349
XRRA1	METTL27	Q8N6F8	348

IntAct

6 interactions, top by confidence:

A	B	Type	Score
XRRA1	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
XRRA1	H1-2	psi-mi:“MI:0915”(physical association)	0.400
	XRRA1	psi-mi:“MI:0915”(physical association)	0.400
DYRK2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
XRRA1	HSPA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): XRRA1 (Affinity Capture-RNA), XRRA1 (Affinity Capture-MS), XRRA1 (Synthetic Lethality), XRRA1 (Proximity Label-MS), XRRA1 (Proximity Label-MS), KIAA0232 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), XRRA1 (Affinity Capture-MS), PPM1K (Cross-Linking-MS (XL-MS)), XRRA1 (Cross-Linking-MS (XL-MS)), XRRA1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A2AGB2, A2ALV5, A3KMW7, A6NM62, A8MT70, A9JRX0, D3Z987, P15975, P56716, P70347, Q0P5X5, Q0VET5, Q28FY7, Q2M2Z5, Q3MHT3, Q3U0P1, Q3U3V8, Q3UXL4, Q3V089, Q5SXH7, Q5T1N1, Q5T4T6, Q5VXU9, Q68CR7, Q6NZK5, Q6P2D8, Q7M6U3, Q7Z4H7, Q7Z572, Q7ZYI3, Q7ZZH7, Q80VP2, Q86T90, Q86YC2, Q8BG34, Q8BL06, Q8CCC3, Q8MJ03

Diamond homologs: Q15813, Q32KS0, Q3U3V8, Q5FVQ9, Q5RBD9, Q6P2D8, Q7PCK7, Q8CIV8, Q8GRL7, Q95LL2, A1Z6J5, B9EHT4, Q5R686, Q5U243, Q5U378, Q5U508, Q96DZ5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4295 predictions. Top by Δscore:

Variant	Effect	Δscore
11:74810182:AGCT:A	acceptor_gain	1.0000
11:74810183:GCT:G	acceptor_gain	1.0000
11:74810183:GCTG:G	acceptor_gain	1.0000
11:74817713:GG:G	donor_gain	1.0000
11:74817714:GG:G	donor_gain	1.0000
11:74818043:G:GT	donor_gain	1.0000
11:74835541:TTCA:T	acceptor_loss	1.0000
11:74835542:TCAG:T	acceptor_loss	1.0000
11:74835543:CAGGT:C	acceptor_loss	1.0000
11:74836678:G:GT	donor_gain	1.0000
11:74844131:AGGGG:A	donor_gain	1.0000
11:74844281:TTC:T	acceptor_gain	1.0000
11:74844282:TC:T	acceptor_gain	1.0000
11:74844283:CC:C	acceptor_gain	1.0000
11:74844283:CCTA:C	acceptor_loss	1.0000
11:74844284:C:A	acceptor_loss	1.0000
11:74844284:C:CC	acceptor_gain	1.0000
11:74844285:T:A	acceptor_loss	1.0000
11:74844290:C:CT	acceptor_gain	1.0000
11:74845070:TACC:T	donor_loss	1.0000
11:74845071:AC:A	donor_gain	1.0000
11:74845072:C:CA	donor_loss	1.0000
11:74845072:CC:C	donor_gain	1.0000
11:74845267:CTCAC:C	acceptor_gain	1.0000
11:74848110:GGTAC:G	donor_loss	1.0000
11:74848112:TACC:T	donor_loss	1.0000
11:74848113:A:T	donor_loss	1.0000
11:74848114:C:CA	donor_loss	1.0000
11:74851203:CCTGG:C	acceptor_gain	1.0000
11:74851211:C:CT	acceptor_gain	1.0000

AlphaMissense

5209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:74859162:T:A	N381I	0.998
11:74906445:A:G	L258S	0.998
11:74859177:A:G	L376P	0.997
11:74906430:T:A	N263I	0.997
11:74907208:A:G	L233P	0.997
11:74852011:G:C	N406K	0.996
11:74852011:G:T	N406K	0.996
11:74852051:G:T	A393D	0.996
11:74859161:G:C	N381K	0.996
11:74859161:G:T	N381K	0.996
11:74859186:A:G	L373P	0.996
11:74907169:A:G	F246S	0.996
11:74859163:T:A	N381Y	0.995
11:74859173:G:C	S377R	0.995
11:74859173:G:T	S377R	0.995
11:74859175:T:G	S377R	0.995
11:74859186:A:T	L373Q	0.995
11:74907192:G:C	N238K	0.995
11:74907192:G:T	N238K	0.995
11:74852036:A:T	L398H	0.994
11:74852045:A:G	F395S	0.994
11:74859177:A:T	L376H	0.994
11:74859195:A:G	F370S	0.994
11:74906429:G:C	N263K	0.994
11:74906429:G:T	N263K	0.994
11:74906431:T:A	N263Y	0.994
11:74906431:T:G	N263H	0.994
11:74907202:A:G	L235P	0.994
11:74907208:A:T	L233Q	0.994
11:74921271:A:G	L192P	0.994

dbSNP variants (sampled 300 via entrez): RS1000003493 (11:74900279 T>C), RS1000011833 (11:74949044 C>G), RS1000060760 (11:74867575 G>A), RS1000074357 (11:74861626 T>C), RS1000135373 (11:74914725 G>A,T), RS1000144931 (11:74843064 G>T), RS1000171144 (11:74942992 C>T), RS1000172663 (11:74890142 C>T), RS1000174159 (11:74935030 C>A,G), RS1000191311 (11:74854991 A>G), RS1000232757 (11:74885749 G>A), RS1000264116 (11:74885943 A>C), RS1000313094 (11:74935820 T>C,G), RS1000326374 (11:74884840 A>G,T), RS1000354914 (11:74899971 C>T)

Disease associations

OMIM: gene MIM:609788 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects splicing, increases abundance	2
trichostatin A	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
Sunitinib	decreases expression	1
Arsenic	affects splicing, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Methotrexate	increases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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