XRCC3

X-ray repair cross complementing 3

Basic information

Region (hg38): 14:103697609-103715504

Links

ENSG00000126215 ∙ NCBI:7517 ∙ OMIM:600675 ∙ HGNC:12830 ∙ Uniprot:O43542 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XRCC3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XRCC3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	1	4
missense			30	3	6	39
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	31	6	8

Variants in XRCC3

This is a list of pathogenic ClinVar variants found in the XRCC3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-103698819-T-G		XRCC3-related disorder	Likely benign (Jul 10, 2019)
14-103698827-G-A		Familial cancer of breast	Uncertain significance (Jul 06, 2022)
14-103698901-C-T		not specified	Uncertain significance (Jan 23, 2024)
14-103698914-C-T		Ovarian cancer	Benign (Jan 01, 2022)
14-103698934-C-T		XRCC3-related disorder	Likely benign (Jun 11, 2019)
14-103698935-G-A		not specified	Uncertain significance (Mar 23, 2022)
14-103698941-G-A		not specified	Uncertain significance (Jul 06, 2021)
14-103699003-C-T		not specified	Uncertain significance (Dec 14, 2023)
14-103699007-C-T		not specified	Uncertain significance (Jun 24, 2022)
14-103699010-C-A		not specified	Uncertain significance (Oct 12, 2022)
14-103699143-C-T		Ovarian cancer	Benign (Jan 01, 2022)
14-103699152-C-T		not specified	Uncertain significance (Jul 05, 2023)
14-103699153-G-A		XRCC3-related disorder	Likely benign (Aug 14, 2019)
14-103699161-C-T		not specified	Uncertain significance (Mar 23, 2022)
14-103699345-A-C			Benign (Dec 07, 2023)
14-103699410-C-T			Benign (Mar 29, 2018)
14-103699411-G-A		not specified	Uncertain significance (May 24, 2023)
14-103699416-G-A		Melanoma, cutaneous malignant, susceptibility to, 6 • XRCC3-related disorder	Benign (Sep 08, 2023)
14-103699453-C-T		not specified	Uncertain significance (Jan 19, 2024)
14-103699469-A-C		not specified	Uncertain significance (Nov 09, 2022)
14-103699472-T-G		not specified	Uncertain significance (Dec 08, 2023)
14-103699479-C-T		not specified	Uncertain significance (Jul 06, 2021)
14-103699515-C-T		not specified	Uncertain significance (May 31, 2023)
14-103699521-A-C		not specified	Uncertain significance (Oct 03, 2023)
14-103699558-C-T		not specified	Uncertain significance (Jun 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XRCC3	protein_coding	protein_coding	ENST00000553264	7	17896

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.91e-10	0.0354	125721	0	17	125738	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.386	192	208	0.925	0.0000153	2136
Missense in Polyphen		54	58.865	0.91735		593
Synonymous	-0.462	103	97.2	1.06	0.00000739	742
Loss of Function	-0.425	14	12.4	1.13	6.28e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000918	0.0000916
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000707	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the RAD21 paralog protein complex CX3 which acts in the BRCA1-BRCA2- dependent HR pathway. Upon DNA damage, CX3 acts downstream of RAD51 recruitment; the complex binds predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junctions of replication forks. Involved in HJ resolution and thus in processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex and seems to involve GEN1 during mitotic cell cycle progression. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C. {ECO:0000269|PubMed:14716019, ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:23108668, ECO:0000269|PubMed:23149936}.
• Disease: DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:12023982}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Melanoma, cutaneous malignant 6 (CMM6) [MIM:613972]: A malignant neoplasm of melanocytes, arising de novo or from a pre- existing benign nevus, which occurs most often in the skin but also may involve other sites. {ECO:0000269|PubMed:11059748}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Fluoropyrimidine Pathway, Pharmacodynamics;Homologous recombination - Homo sapiens (human);Fluoropyrimidine Activity;Integrated Breast Cancer Pathway;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Fanconi anemia pathway;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.405

Intolerance Scores

• loftool: 0.671
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.37

Haploinsufficiency Scores

• pHI: 0.632
• hipred: N
• hipred_score: 0.458
• ghis: 0.539

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Xrcc3
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Gene ontology

• Biological process: telomere maintenance via recombination;double-strand break repair via homologous recombination;DNA repair;DNA recombination;cellular response to DNA damage stimulus;response to organic substance;regulation of centrosome duplication;interstrand cross-link repair;double-strand break repair via synthesis-dependent strand annealing;resolution of mitotic recombination intermediates;positive regulation of mitotic cell cycle spindle assembly checkpoint;t-circle formation;telomeric loop disassembly;telomere maintenance via telomere trimming
• Cellular component: nuclear chromosome, telomeric region;nucleus;nucleoplasm;replication fork;cytoplasm;mitochondrion;cytosol;Rad51C-XRCC3 complex;perinuclear region of cytoplasm
• Molecular function: four-way junction DNA binding;protein binding;ATP binding;DNA-dependent ATPase activity;crossover junction endodeoxyribonuclease activity