XRCC1

Summary

XRCC1 (X-ray repair cross complementing 1, HGNC:12828) is a protein-coding gene on chromosome 19q13.31, encoding DNA repair protein XRCC1 (P18887). Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes. In precision oncology, XRCC1 Q399R confers sensitivity to Cisplatin + Carboplatin in Cervical Cancer (CIViC Level B); 1 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 20.0% of cell lines).

The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity.

Source: NCBI Gene 7515 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia, autosomal recessive 26 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 152 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 21
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer dependency (DepMap): dependent in 20.0% of screened cell lines
• MANE Select transcript: NM_006297

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12828
Approved symbol	XRCC1
Name	X-ray repair cross complementing 1
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000073050
Ensembl biotype	protein_coding
OMIM	194360
Entrez	7515

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000262887, ENST00000543982, ENST00000594107, ENST00000594511, ENST00000595789, ENST00000597811, ENST00000598165, ENST00000598422, ENST00000599693, ENST00000865399, ENST00000865400, ENST00000865401, ENST00000865402, ENST00000865403, ENST00000865404, ENST00000865405, ENST00000934412, ENST00000934413, ENST00000953254, ENST00000953255, ENST00000953256, ENST00000953257, ENST00000953258

RefSeq mRNA: 1 — MANE Select: NM_006297 NM_006297

CCDS: CCDS12624

Canonical transcript exons

ENST00000262887 — 17 exons

Exon	Start	End
ENSE00000710543	43546884	43546977
ENSE00002216514	43545818	43545957
ENSE00002249873	43543612	43543687
ENSE00002279002	43546595	43546727
ENSE00002300711	43544144	43544234
ENSE00002488072	43546052	43546106
ENSE00003120722	43543311	43543505
ENSE00003506614	43552982	43553091
ENSE00003519093	43552017	43552275
ENSE00003520923	43552797	43552908
ENSE00003601517	43553401	43553512
ENSE00003606583	43551571	43551687
ENSE00003608314	43560910	43561020
ENSE00003611390	43553609	43553683
ENSE00003648491	43554646	43554804
ENSE00003691559	43574910	43575002
ENSE00003903235	43575408	43575527

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 94.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.5905 / max 214.7140, expressed in 1809 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181288	24.7690	1808
181290	0.4836	283
181285	0.3231	147
181286	0.0147	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	94.21	gold quality
tendon of biceps brachii	UBERON:0008188	93.27	gold quality
ganglionic eminence	UBERON:0004023	93.19	gold quality
oocyte	CL:0000023	91.46	gold quality
pituitary gland	UBERON:0000007	90.98	gold quality
adenohypophysis	UBERON:0002196	90.78	gold quality
cortical plate	UBERON:0005343	90.40	gold quality
right uterine tube	UBERON:0001302	89.88	gold quality
left ovary	UBERON:0002119	89.82	gold quality
right ovary	UBERON:0002118	89.77	gold quality
granulocyte	CL:0000094	89.27	gold quality
parotid gland	UBERON:0001831	89.22	gold quality
body of uterus	UBERON:0009853	89.09	gold quality
popliteal artery	UBERON:0002250	88.75	gold quality
tibial artery	UBERON:0007610	88.73	gold quality
endocervix	UBERON:0000458	88.57	gold quality
right lobe of thyroid gland	UBERON:0001119	88.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.40	gold quality
cerebellar hemisphere	UBERON:0002245	88.33	gold quality
stromal cell of endometrium	CL:0002255	88.26	gold quality
cerebellar cortex	UBERON:0002129	88.26	gold quality
aorta	UBERON:0000947	88.21	gold quality
ectocervix	UBERON:0012249	88.14	gold quality
left lobe of thyroid gland	UBERON:0001120	87.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.82	gold quality
apex of heart	UBERON:0002098	87.78	gold quality
ovary	UBERON:0000992	87.63	gold quality
thoracic aorta	UBERON:0001515	87.58	gold quality
descending thoracic aorta	UBERON:0002345	87.56	gold quality
ascending aorta	UBERON:0001496	87.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, E2F1, FOXM1, HR, MITF, PARP1, PLAG1, SP1, YBX1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• XRCC1 is directly involved in the dominant negative activity of a truncated variant of DNA polymerase beta, possibly leading to the genomic instability characteristic of tumor cells. (PMID:11467963)
• The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction. (PMID:11782372)
• X-ray repair cross-complementing gene I protein plays an important role in camptothecin resistance. (PMID:11809696)
• we investigated the association between the repair phenotype of ultraviolet (UV)-induced damage and genotypes of three DNA repair genes, XPC and XPD [involved in nucleotide excision repair (NER)] and XRCC1 [involved in base excision repair (BER)]. (PMID:11872635)
• Central role for the XRCC1 BRCT I domain in mammalian DNA single-strand break repair. (PMID:11909950)
• Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population. (PMID:12124811)
• polymorphism and risk of lung cancer in a Chinese population (PMID:12151350)
• When tested in CHO derived XRCC1 ‘knock out’ EM9 cells, co-expression of human papillomavirus 16 E6 with human XRCC1 reduced the ability of the latter protein to correct the methyl methane sulfate sensitivity of XRCC1 mutant CHO cell line EM9. (PMID:12198176)
• XRCC1 polymorphism is associated with gastric cancer (PMID:12359351)
• The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia (PMID:12393447)
• evaluated prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake (PMID:12433703)
• The XRCC1 variant allele did not show any effect on the p53 mutation in lung tumors. (PMID:12552590)
• Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. (PMID:12565173)
• polymorphisms and age-related diseases (PMID:12618003)
• Epidermal growth factor and ionizing radiation up-regulate the DNA repair genes XRCC1 and ERCC1 in DU145 and LNCaP prostate carcinoma through MAPK signaling. (PMID:12643788)
• Cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk. (PMID:12692111)
• the XRCC1 Gln allele is associated with AT to GC mutations in p53 in NSCLC. The XRCC1 gene may play a role in the repair of cigarette smoking-induced DNA damage. (PMID:12873719)
• data presented support a model by which X-ray repair cross complementing protein 1 (XRCC1) will pass on the DNA intermediate from DNA glycosylase hOGG1 to the endonuclease APE1 (PMID:12933815)
• High XRCC1 mRNA levels is associated with Clear cell tumors of epithelial ovarian cancer (PMID:14614013)
• XRCC1 polymorphism and risks of breast neoplasms has no apparent association in chinese women. (PMID:14693738)
• These data suggest that XRCC1 Gln399Arg polymorphism plays a limited role in lymphomagenesis. (PMID:15104288)
• XRCC1 co-localizes with proliferating cell nuclear antigen (PCNA) at DNA replication foci, observed exclusively in the S phase of undamaged HeLa cells (PMID:15107487)
• The XRCC1-DNA ligase IIIalpha heterodimer must interact with DNA polymerase beta for efficient base excision repair. (PMID:15141024)
• XRCC1 codon 194, 280, and 399 genotypes do not influence CIN risk in the Taiwanese population (PMID:15216398)
• The polymorphic DNArepair gene, XRCC1 was associated with the risk of esophageal cancer in patients with smoking. (PMID:15225899)
• XRCC1 polymorphism (Arg/94Trp) associated with susceptibility to squamous cell carcinoma of the head and neck in Korean population (PMID:15252855)
• XRCC1 gene polymorphism is associated with higher risk susceptibility of bladder cancer. (PMID:15298955)
• Polymorphism of XRCC1 is associated with colorectal cancer (PMID:15354414)
• Genetic variation in XRCC1 and sun exposure is associated with skin cancer (PMID:15381933)
• poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III utilize an alternative route for DNA double-strand breaks rejoining (PMID:15498778)
• determined the domains of APTX and XRCC1 required for their interaction; findings suggest that APTX, together with XRCC1 and PARP-1, plays an essential role in single-strand DNA break repair (PMID:15555565)
• XRCC1 gene DNA repair capacity found reduced in patients with laryngeal neoplasms. (PMID:15608415)
• exhibits preferential binding to DNA with single-strand breaks with a gap size of <5 nucleotides (PMID:15610045)
• Lack of evidence for a role of the XRCC1 polymorphism in developing breast cancer. (PMID:15665590)
• Preliminary evidence of a role for XRCC1 codon 194 and 399 polymorphisms in the genetic predisposition to breast cancer in Indian women (PMID:15666192)
• The role of a genetic polymorphism of the XRCC1 gene in risk for colorectal cancer was investigated. (PMID:15679883)
• Neither of the two genetic polymorphisms of XRCC1 directly influence breast cancer risk; however, there was a suggestive weak additive interaction between XRCC1 and polycyclic aromatic hydrocarbon-DNA adducts on breast cancer risk among never smokers. (PMID:15734955)
• investigated relationship between genetic polymorphism of XRCC1 & ERCC2 & DNA damage in polycyclic aromatic hydrocarbon exposed workers workers; findings suggest that variant allele of G27466A polymorphism of XRCC1 is associated with increased DNA damage (PMID:15764301)
• These results indicate that the Arg399Gln polymorphism, but not the Arg194Trp or Arg280His polymorphism, influences the ability of XRCC1 to repair DNA. (PMID:15797631)
• genetic variants in APEX1 and XRCC1 may alter the risk of lung cancer in a special population in China (PMID:15816625)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Xrcc1	ENSMUSG00000051768
rattus_norvegicus	Xrcc1	ENSRNOG00000019915
drosophila_melanogaster	XRCC1	FBGN0026751

Paralogs (1): XNDC1N (ENSG00000254469)

Protein

Protein identifiers

DNA repair protein XRCC1 — P18887 (reviewed: P18887)

Alternative names: X-ray repair cross-complementing protein 1

All UniProt accessions (6): P18887, F5H8D7, M0QYS5, M0QZ96, M0R0D2, M0R1U8

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes. Negatively regulates ADP-ribosyltransferase activity of PARP1 during base-excision repair in order to prevent excessive PARP1 activity. Recognizes and binds poly-ADP-ribose chains: specifically binds auto-poly-ADP-ribosylated PARP1, limiting its activity.

Subunit / interactions. Homodimer. Interacts with polynucleotide kinase (PNK), DNA polymerase-beta (POLB) and DNA ligase III (LIG3). Interacts with APTX and APLF. Interacts with APEX1; the interaction is induced by SIRT1 and increases with the acetylated form of APEX1. Interacts with (poly-ADP-ribosylated) PARP1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in fibroblasts, retinal pigmented epithelial cells and lymphoblastoid cells (at protein level).

Post-translational modifications. Phosphorylation of Ser-371 causes dimer dissociation. Phosphorylation by CK2 promotes interaction with APTX and APLF. Sumoylated.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 26 (SCAR26) [MIM:617633] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR26 is a progressive disease characterized by gait and limb ataxia, loss of independent ambulation, oculomotor apraxia, and peripheral neuropathy with distal muscle weakness and areflexia. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. Carriers of the polymorphic Gln-399 allele may be at greater risk for tobacco- and age-related DNA damage.

RefSeq proteins (1): NP_006288* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR002706	Xrcc1_N	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR045080	BRCT_XRCC1_rpt1	Domain

Pfam: PF00533, PF01834, PF16589

UniProt features (104 total): modified residue 26, sequence variant 21, strand 18, helix 16, compositionally biased region 6, mutagenesis site 5, region of interest 4, turn 3, domain 2, cross-link 2, chain 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
2W3O	X-RAY DIFFRACTION	1.85
5W7X	X-RAY DIFFRACTION	2
5W7Y	X-RAY DIFFRACTION	2.1
5E6Q	X-RAY DIFFRACTION	2.31
3LQC	X-RAY DIFFRACTION	2.35
6WH1	X-RAY DIFFRACTION	2.4
6WH2	X-RAY DIFFRACTION	2.41
3K77	X-RAY DIFFRACTION	2.6
3K75	X-RAY DIFFRACTION	2.95
1CDZ	X-RAY DIFFRACTION	3.2
1XNA	SOLUTION NMR
1XNT	SOLUTION NMR
2D8M	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18887-F1	70.71	0.41

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 (28): 140, 198, 199, 202, 204, 226, 241, 257, 259, 266, 281, 371, 408, 409, 410, 421, 446, 447, 453, 457 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
335	abolished binding to poly-adp-ribose and ability to inhibit parp1 activity; when associated with a-369.
360–361	reduced binding to poly-adp-ribose nuclear foci.
369	abolished binding to poly-adp-ribose and ability to inhibit parp1 activity; when associated with a-335.
385	strongly reduced binding to poly-adp-ribose nuclear foci.
389	reduced binding to poly-adp-ribose nuclear foci.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-110381	Resolution of AP sites via the single-nucleotide replacement pathway
R-HSA-5649702	APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway
R-HSA-5685939	HDR through MMEJ (alt-NHEJ)
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER

MSigDB gene sets: 242 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOMF_ENDONUCLEASE_ACTIVITY, TGCGCANK_UNKNOWN, GOBP_TELOMERE_CAPPING, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, MODULE_308, KAUFFMANN_DNA_REPAIR_GENES, HEIDENBLAD_AMPLICON_8Q24_DN, AAAYRNCTG_UNKNOWN, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_FOREBRAIN_DEVELOPMENT

GO Biological Process (12): single strand break repair (GO:0000012), base-excision repair (GO:0006284), double-strand break repair (GO:0006302), double-strand break repair via nonhomologous end joining (GO:0006303), negative regulation of protein ADP-ribosylation (GO:0010836), hippocampus development (GO:0021766), response to hydroperoxide (GO:0033194), telomeric DNA-containing double minutes formation (GO:0061819), regulation of base-excision repair (GO:1905051), negative regulation of protection from non-homologous end joining at telomere (GO:1905765), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (7): enzyme binding (GO:0019899), oxidized DNA binding (GO:0032356), poly-ADP-D-ribose binding (GO:0072572), ADP-D-ribose modification-dependent protein binding (GO:0160002), 3’ overhang single-stranded DNA endonuclease activity (GO:1990599), damaged DNA binding (GO:0003684), protein binding (GO:0005515)

GO Cellular Component (8): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), ERCC4-ERCC1 complex (GO:0070522), site of DNA damage (GO:0090734), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Resolution of Abasic Sites (AP sites)	2
Homology Directed Repair	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	3
cellular anatomical structure	3
chromosome	2
nuclear lumen	2
intracellular membraneless organelle	2
double-strand break repair	1
regulation of protein ADP-ribosylation	1
negative regulation of catalytic activity	1
NAD+-protein mono-ADP-ribosyltransferase activity	1
pallium development	1
limbic system development	1
anatomical structure development	1
response to oxidative stress	1
response to oxygen-containing compound	1
telomere maintenance via recombination	1
regulation of DNA repair	1
base-excision repair	1
protection from non-homologous end joining at telomere	1
negative regulation of telomere capping	1
negative regulation of telomere maintenance in response to DNA damage	1
regulation of protection from non-homologous end joining at telomere	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
protein binding	1
damaged DNA binding	1
carbohydrate derivative binding	1
modification-dependent protein binding	1
single-stranded DNA endonuclease activity	1
DNA binding	1
binding	1
chromosomal region	1
intracellular membrane-bounded organelle	1
nucleotide-excision repair complex	1

Protein interactions and networks

STRING

2028 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XRCC1	APEX1	P27695	999
XRCC1	POLB	P06746	999
XRCC1	LIG3	P49916	999
XRCC1	APTX	Q7Z2E3	999
XRCC1	PNKP	Q96T60	998
XRCC1	PARP1	P09874	996
XRCC1	OGG1	P78554	996
XRCC1	LIG1	P18858	995
XRCC1	APLF	Q8IW19	995
XRCC1	PARP2	Q9UGN5	992
XRCC1	NEIL2	Q969S2	988
XRCC1	NTHL1	P78549	976
XRCC1	ERCC2	P18074	972
XRCC1	TDP1	Q9NUW8	964
XRCC1	NEIL1	Q96FI4	956

IntAct

219 interactions, top by confidence:

A	B	Type	Score
MAX	MYC	psi-mi:“MI:0914”(association)	0.980
APLF	XRCC1	psi-mi:“MI:0915”(physical association)	0.920
XRCC1	APLF	psi-mi:“MI:0915”(physical association)	0.920
XRCC1	APLF	psi-mi:“MI:0407”(direct interaction)	0.920
XRCC1	APTX	psi-mi:“MI:0403”(colocalization)	0.880
XRCC1	APTX	psi-mi:“MI:0915”(physical association)	0.880
APTX	XRCC1	psi-mi:“MI:0915”(physical association)	0.880
APLF	PARP1	psi-mi:“MI:0914”(association)	0.870
PNKP	XRCC1	psi-mi:“MI:0915”(physical association)	0.830
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
PARP1	TP53	psi-mi:“MI:0914”(association)	0.750
XRCC1	POLB	psi-mi:“MI:0915”(physical association)	0.740
POLB	XRCC1	psi-mi:“MI:0914”(association)	0.740
LIG3	XRCC1	psi-mi:“MI:0914”(association)	0.740

BioGRID (344): XRCC1 (Affinity Capture-MS), APEX1 (Affinity Capture-Western), XRCC1 (Affinity Capture-MS), XRCC1 (Biochemical Activity), XRCC1 (Affinity Capture-MS), XRCC1 (Affinity Capture-MS), XRCC1 (Affinity Capture-MS), XRCC1 (Affinity Capture-MS), XRCC1 (Affinity Capture-MS), XRCC1 (Proximity Label-MS), C1QBP (Affinity Capture-MS), LIG3 (Affinity Capture-MS), POLB (Affinity Capture-MS), RAP1B (Affinity Capture-MS), XRCC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JV04, B5FX50, P18887, P70218, Q05AA6, Q0P5H9, Q12851, Q13474, Q14164, Q2KIM1, Q3TJ91, Q3ZBQ1, Q3ZBT2, Q4KM45, Q5BK48, Q5RCX2, Q5RD32, Q5U2X1, Q61161, Q61211, Q68FA2, Q68FV8, Q6P1M3, Q6P5E6, Q6V7V2, Q7SZE3, Q8BK06, Q8BMI3, Q8C6B2, Q8N0Z6, Q8R0H9, Q91WB7, Q92918, Q969R8, Q99LG4, Q9BST9, Q9BZF2, Q9CZT4, Q9D1K7, Q9EPA0

Diamond homologs: O54935, P18887, P32372, Q24JK4, Q60596, Q6ZNB5, Q9ESZ0, Q9R244, Q9R283, O18784, O35119, O62826, O62852, P19334, P34586, P48994, P48995, P79100, Q13507, Q61056, Q61143, Q9HCX4, Q9JMI9, Q9MYV9, Q9MYW0, Q9QUQ5, Q9QX01, Q9QX29, Q9QZC1, Q9TUN9, Q9UBN4, Q9UL62, Q9VJJ7, Q9WVC5, Q9Y210

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	XRCC1	phosphorylation
CHEK2	up-regulates	XRCC1	phosphorylation
CSNK2A2	“up-regulates activity”	XRCC1	phosphorylation
CSNK2A1	“up-regulates activity”	XRCC1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 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
Nonhomologous End-Joining (NHEJ)	8	11.2×	1e-04
Transcriptional regulation of granulopoiesis	10	10.5×	3e-05
Recognition and association of DNA glycosylase with site containing an affected purine	6	10.2×	1e-03
Cleavage of the damaged purine	6	10.2×	1e-03
FXIIa activates plasma kallikrein-kinin system	7	10.1×	4e-04
PTEN Regulation	5	9.5×	2e-03
NuRD complex assembly	8	9.4×	2e-04
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	6	9.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
base-excision repair, gap-filling	6	44.4×	1e-06
double-strand break repair via nonhomologous end joining	8	22.2×	1e-06
chromosome organization	5	19.1×	1e-03
base-excision repair	6	18.5×	2e-04
double-strand break repair	9	12.0×	2e-05
heterochromatin formation	6	10.1×	3e-03
cellular response to UV	5	9.7×	9e-03
cellular senescence	5	9.7×	9e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	80
Likely benign	19
Benign	14

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
433532	NM_006297.3(XRCC1):c.1393C>T (p.Gln465Ter)	Pathogenic
2573207	NM_006297.3(XRCC1):c.1015C>T (p.Arg339Ter)	Likely pathogenic
433531	NM_006297.3(XRCC1):c.1293G>C (p.Lys431Asn)	Likely pathogenic

SpliceAI

3267 predictions. Top by Δscore:

Variant	Effect	Δscore
19:43543684:CTCC:C	acceptor_gain	1.0000
19:43543685:TCC:T	acceptor_gain	1.0000
19:43543686:CC:C	acceptor_gain	1.0000
19:43543686:CCC:C	acceptor_gain	1.0000
19:43543686:CCCT:C	acceptor_loss	1.0000
19:43543687:CC:C	acceptor_gain	1.0000
19:43543688:C:CC	acceptor_gain	1.0000
19:43543688:C:T	acceptor_gain	1.0000
19:43543692:C:CT	acceptor_gain	1.0000
19:43543693:G:T	acceptor_gain	1.0000
19:43544140:TCA:T	donor_loss	1.0000
19:43544141:CACCC:C	donor_loss	1.0000
19:43544142:A:AC	donor_gain	1.0000
19:43544142:AC:A	donor_gain	1.0000
19:43544142:ACC:A	donor_gain	1.0000
19:43544143:C:CG	donor_gain	1.0000
19:43544143:CC:C	donor_gain	1.0000
19:43544143:CCC:C	donor_gain	1.0000
19:43544143:CCCA:C	donor_gain	1.0000
19:43544143:CCCAT:C	donor_gain	1.0000
19:43544230:GAAAT:G	acceptor_gain	1.0000
19:43544231:AAAT:A	acceptor_gain	1.0000
19:43544232:AAT:A	acceptor_gain	1.0000
19:43544233:AT:A	acceptor_gain	1.0000
19:43544235:C:CC	acceptor_gain	1.0000
19:43545814:CCACC:C	donor_loss	1.0000
19:43545815:CACCT:C	donor_loss	1.0000
19:43545817:C:CA	donor_loss	1.0000
19:43545850:T:TA	donor_gain	1.0000
19:43545864:A:AC	donor_gain	1.0000

AlphaMissense

4121 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:43551615:C:A	W385C	1.000
19:43551615:C:G	W385C	1.000
19:43551617:A:G	W385R	1.000
19:43551617:A:T	W385R	1.000
19:43551678:A:C	F364L	1.000
19:43551678:A:T	F364L	1.000
19:43551680:A:G	F364L	1.000
19:43552020:A:G	L360P	1.000
19:43574957:A:G	W33R	1.000
19:43574957:A:T	W33R	1.000
19:43543463:A:G	W611R	0.999
19:43543463:A:T	W611R	0.999
19:43543474:A:T	V607D	0.999
19:43551663:C:A	K369N	0.999
19:43551663:C:G	K369N	0.999
19:43551679:A:C	F364C	0.999
19:43551685:C:T	C362Y	0.999
19:43552017:A:T	I361N	0.999
19:43552020:A:T	L360H	0.999
19:43552042:A:G	W353R	0.999
19:43552042:A:T	W353R	0.999
19:43552083:C:G	R339P	0.999
19:43552096:G:T	R335S	0.999
19:43552109:G:C	F330L	0.999
19:43552109:G:T	F330L	0.999
19:43552110:A:G	F330S	0.999
19:43552111:A:G	F330L	0.999
19:43552113:C:T	G329D	0.999
19:43552114:C:G	G329R	0.999
19:43552115:A:C	S328R	0.999

dbSNP variants (sampled 300 via entrez): RS1000096322 (19:43568461 C>T), RS1000196241 (19:43559377 G>A,T), RS1000311454 (19:43562064 T>C,G), RS1000364833 (19:43561835 A>G), RS1000463365 (19:43570818 C>T), RS1000670795 (19:43544526 A>G), RS1000797176 (19:43555822 C>T), RS1000924101 (19:43565761 C>A,T), RS1001015323 (19:43551973 G>A,C), RS1001020021 (19:43544769 G>A), RS1001127817 (19:43561105 C>T), RS1001181763 (19:43561357 T>C), RS1001195687 (19:43562396 C>T), RS1001271371 (19:43566258 C>G), RS1001561186 (19:43545411 G>A)

Disease associations

OMIM: gene MIM:194360 | disease phenotypes: MIM:617633

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive 26	Strong	Autosomal recessive
head and neck cancer	Limited	Autosomal dominant

Mondo (3): spinocerebellar ataxia, autosomal recessive 26 (MONDO:0033116), laryngeal squamous cell carcinoma (MONDO:0005595), head and neck cancer (MONDO:0005627)

Orphanet (1): Squamous cell carcinoma of the larynx (Orphanet:494550)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000657	Oculomotor apraxia
HP:0000666	Horizontal nystagmus
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001310	Dysmetria
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002075	Dysdiadochokinesis
HP:0002317	Unsteady gait
HP:0002403	Positive Romberg sign
HP:0002460	Distal muscle weakness
HP:0003676	Progressive
HP:0006858	Impaired distal proprioception
HP:0006886	Impaired distal vibration sensation
HP:0007141	Sensorimotor neuropathy
HP:0007338	Hypermetric saccades
HP:0025710	Late young adult onset

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002359_3	Plasma amyloid beta peptide concentrations (ABx-42)	1.000000e-06
GCST008839_104	Height	6.000000e-10
GCST010204_140	Low density lipoprotein cholesterol levels	3.000000e-11
GCST010243_104	Apolipoprotein B levels	8.000000e-13
GCST010245_16	LDL cholesterol levels	9.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005660	plasma beta-amyloid 1-42 measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
XRCC1 Q399R	Cisplatin + Carboplatin	Cervical Cancer	Sensitivity/Response	CIViC B	EID673
XRCC1 R194W	Docetaxel + Gemcitabine + Vinorelbine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID659

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1799782	Efficacy	3	cisplatin;fluorouracil;radiotherapy	Carcinoma;Squamous Cell;Overall survival
rs1799782	Efficacy	3	Platinum compounds	Lung Neoplasms;Non-Small Cell Lung Carcinoma
rs25487	Efficacy	2B	Platinum compounds	Neoplasms
rs25487	Toxicity	3	cyclophosphamide;doxorubicin;fluorouracil	Breast Neoplasms
rs25487	Efficacy	3	fluorouracil	Colonic Neoplasms;Colorectal Neoplasms;Neoplasms;Rectal Neoplasms;Uterine Cervical Neoplasm
rs25487	Efficacy,Toxicity	4	cyclophosphamide	Neoplasms;Ovarian Neoplasms

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs25487	XRCC1	2B	11.25	4	Platinum compounds;fluorouracil;cyclophosphamide;cyclophosphamide;doxorubicin;fluorouracil
rs25489	XRCC1		0.00	0
rs1799782	XRCC1	3	4.50	2	cisplatin;fluorouracil;radiotherapy;Platinum compounds
rs3213239	APLF, PINLYP, XRCC1	3	2.50	1	Platinum compounds

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects cotreatment, decreases expression, increases abundance, affects expression, increases expression (+2 more)	9
Vinyl Chloride	affects mutagenesis, affects reaction, increases reaction, increases mutagenesis, increases response to substance	7
Benzene	affects response to substance, decreases response to substance, increases response to substance	5
Cisplatin	decreases response to substance, increases expression, affects cotreatment, affects response to substance	5
bisphenol A	decreases expression, affects cotreatment, increases expression, decreases reaction	4
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance, decreases reaction	4
Doxorubicin	affects expression, affects response to substance, increases phosphorylation, decreases expression, decreases phosphorylation (+3 more)	4
Hydrogen Peroxide	affects activity, affects cotreatment, increases expression, decreases activity, affects reaction (+2 more)	4
Cadmium Chloride	decreases reaction, decreases expression, increases abundance, affects cotreatment, increases activity (+1 more)	4
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases abundance, decreases reaction, affects cotreatment	3
Pesticides	affects response to substance, affects cotreatment	3
Polycyclic Aromatic Hydrocarbons	affects response to substance, increases response to substance	3
Styrene	increases response to substance, affects response to substance, increases expression	3
chromium hexavalent ion	decreases reaction, increases response to substance	2
Resveratrol	decreases expression, decreases reaction, increases expression	2
Asbestos	increases response to substance, affects response to substance	2
Ascorbic Acid	decreases expression, decreases reaction, increases response to substance	2
Benzo(a)pyrene	affects cotreatment, affects expression, increases expression	2
Bleomycin	affects response to substance, decreases response to substance	2
Cadmium	decreases expression, increases abundance, affects cotreatment, increases expression	2
Floxuridine	decreases response to substance	2
Methyl Methanesulfonate	increases expression, increases response to substance	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	affects response to substance, decreases expression	2
Asbestos, Amphibole	decreases expression, decreases response to substance	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
pradimicin-IRD	affects expression, affects response to substance	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_KU28	HeLa SilenciX XRCC1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00138827	PHASE4	COMPLETED	Mouth Care Regimes During Radiotherapy
NCT00158041	PHASE4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00198263	PHASE4	COMPLETED	Study Using the Medpulser Electroporation System With Bleomycin to Treat Head and Neck Cancer
NCT00333099	PHASE4	COMPLETED	INEC Study: Immuno-modulating Enteral Nutrition in Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00772681	PHASE4	COMPLETED	Efficacy of Chemoradiotherapy After Neoadjuvant Cisplatin and Docetaxel in the Nasopharynx Carcinoma
NCT00813631	PHASE4	UNKNOWN	The Effect on an Ionic Silver Dressing in Head and Neck Patients With Malignant Fungating Wound
NCT01317589	PHASE4	COMPLETED	Treatment of Pain in Head-and-Neck Cancer Patients: is Methadone More Effective?
NCT01418118	PHASE4	COMPLETED	Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT01553032	PHASE4	COMPLETED	Skin Changes in Head and Neck Cancer During Immuno-(Chemo-) And Radiotherapy With Erbitux® (HICARE)
NCT02015650	PHASE4	TERMINATED	Cetuximab Compared to Mitomycin-C and 5-Fluorouracil for Locally Advanced Squamous Cell Carcinomas of the Head and Neck
NCT02049112	PHASE4	COMPLETED	A New Oral salIvary equivAlent Compared to Two moisturizinG Mouth sprAys in Patients With xeRostomiA: NIAGARA Study
NCT02241083	PHASE4	COMPLETED	The Effect of Norepinephrine and Dopamine on Radial Forearm Free Flap Tissue Oxygen Pressure and Microdialysate Metabolite Measurements
NCT02241876	PHASE4	UNKNOWN	THE USE OF N-ACETYLCYSTEINE ATTENUATING CISPLATIN-INDUCED TOXICITIES BY OXIDATIVE STRESS
NCT02597582	PHASE4	COMPLETED	LigaSure Small Jaw® Versus Conventional Neck Dissection in Head and Neck Cancer Patients
NCT02622880	PHASE4	COMPLETED	Comparison of Two Immunomodulatory Formulas on the Number of Postoperative Infections in Head & Neck Cancer Patients
NCT02880072	PHASE4	COMPLETED	Absorption of Orally Ingested Phosphate in Refeeding Syndrome
NCT02926573	PHASE4	COMPLETED	Perioperative Gabapentin Use In Head And Neck Mucosal Surgery Patients
NCT03607227	PHASE4	COMPLETED	Continous Popliteal Block for Microvascular Free Flap Reconstruction in Ear, Nose and Throat Surgery
NCT03714867	PHASE4	WITHDRAWN	Pre-Operative Pregabalin for Post-Operative Pain in Head and Neck Cancer Surgery
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04246697	PHASE4	COMPLETED	Multimodal Pain Study in Free Flap Patients
NCT04292990	PHASE4	UNKNOWN	Comparison of Transdermal Fentanyl and Morphine for Oral Mucositis Pain in Nasopharyngeal Cancer Patients
NCT04507035	PHASE4	UNKNOWN	Treating Locally Advanced Head and Neck Malignant Tumor With Anlotinib and Chemoradiotherapy
NCT04977271	PHASE4	WITHDRAWN	Mood Disorders in Head and Neck Cancer Patients
NCT05046028	PHASE4	COMPLETED	Individualization of Nutritive Sensory Support Of Radiation Therapy
NCT05055726	PHASE4	COMPLETED	Benzydamine Oromucosal Solution in Oral Mucositis (BOOM)
NCT06521697	PHASE4	NOT_YET_RECRUITING	Effects of Minimal-Flow Sevoflurane and Multimodal Analgesia in Head and Neck Cancer Surgery
NCT06734598	PHASE4	RECRUITING	Efficacy of Botox Injection of the Masticatory Muscles in Head &Neck Cancer Patients with Trismus After Radiotherapy
NCT06807034	PHASE4	ACTIVE_NOT_RECRUITING	Impact of the Oral Microbiota on Relapse in HNSCC Patients
NCT06879691	PHASE4	ACTIVE_NOT_RECRUITING	A Trial of Nimotuzumab and Pinkiller Efficacy and Pain in Advanced Head and Neck Squamous Cell Carcinoma
NCT07158164	PHASE4	RECRUITING	DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
NCT07189897	PHASE4	RECRUITING	Apixaban or Enoxaparin After Head and Neck Cancer Surgery
NCT00002476	PHASE3	COMPLETED	Radiation Therapy With or Without Chemotherapy in Treating Patients With Advanced Head and Neck Cancer
NCT00002496	PHASE3	COMPLETED	Radiation Therapy With or Without Chemotherapy in Treating Patients With Advanced Cancer of the Larynx
NCT00002507	PHASE3	COMPLETED	Radiation Therapy and Chemotherapy in Treating Patients With Head and Neck Cancer
NCT00002555	PHASE3	COMPLETED	High-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With Head and Neck Cancer
NCT00002654	PHASE3	COMPLETED	Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Head and Neck Cancer
NCT00002659	PHASE3	UNKNOWN	Cisplatin Plus Epinephrine in Treating Patients With Recurrent or Refractory Head and Neck Cancer