XRCC5

X-ray repair cross complementing 5

Basic information

Region (hg38): 2:216107463-216206303

Links

ENSG00000079246 ∙ NCBI:7520 ∙ OMIM:194364 ∙ HGNC:12833 ∙ Uniprot:P13010 ∙ 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 XRCC5 gene.

• Inborn genetic diseases (24 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XRCC5 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					2	2
missense			22	3		25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	22	3	2

Variants in XRCC5

This is a list of pathogenic ClinVar variants found in the XRCC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-216116756-C-T		not specified	Uncertain significance (Jun 03, 2022)
2-216117747-C-A		not specified	Uncertain significance (Feb 28, 2023)
2-216119091-C-G		not specified	Uncertain significance (Aug 17, 2022)
2-216122073-C-T		not specified	Uncertain significance (Oct 14, 2021)
2-216122120-C-G		not specified	Uncertain significance (Mar 29, 2022)
2-216122242-T-G		not specified	Uncertain significance (Aug 21, 2023)
2-216125936-T-C		not specified	Uncertain significance (May 23, 2023)
2-216127632-G-C		not specified	Uncertain significance (Feb 13, 2024)
2-216130957-C-T		not specified	Benign/Likely benign (-)
2-216137098-T-G		not specified	Uncertain significance (Aug 23, 2021)
2-216137193-G-A		not specified	Uncertain significance (May 24, 2023)
2-216138178-C-T			Likely benign (Feb 01, 2023)
2-216141198-A-G		not specified	Likely benign (Aug 17, 2022)
2-216141243-A-G		not specified	Uncertain significance (Sep 13, 2023)
2-216141258-C-G		not specified	Uncertain significance (Nov 15, 2021)
2-216141270-T-G		not specified	Uncertain significance (Aug 22, 2022)
2-216141316-T-C			Benign (Jul 11, 2018)
2-216148125-C-G		not specified	Uncertain significance (Jul 19, 2023)
2-216148156-A-G		not specified	Uncertain significance (Mar 11, 2022)
2-216148254-G-T			Likely benign (Jul 11, 2018)
2-216160129-G-C		not specified	Uncertain significance (Dec 01, 2022)
2-216161983-G-A		not specified	Uncertain significance (Jan 25, 2023)
2-216162010-G-A		not specified	Uncertain significance (Aug 08, 2023)
2-216190251-G-A		not specified	Uncertain significance (Mar 01, 2023)
2-216190279-C-T		not specified	Likely benign (Dec 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XRCC5	protein_coding	protein_coding	ENST00000392133	21	98840

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000508	125735	0	6	125741	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.81	233	389	0.599	0.0000193	4889
Missense in Polyphen		41	109.86	0.37319		1419
Synonymous	0.974	120	134	0.893	0.00000681	1315
Loss of Function	5.79	2	43.0	0.0466	0.00000230	511

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000469	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:20383123). The XRCC5/6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose- 5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). Plays a role in the regulation of DNA virus- mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. {ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}.
• Pathway: Non-homologous end-joining - Homo sapiens (human);Non-homologous end joining;DNA Repair;Neutrophil degranulation;Disease;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;telomeres telomerase cellular aging and immortality;HIV Life Cycle;HIV Infection;2-LTR circle formation;STING mediated induction of host immune responses;Infectious disease;Innate Immune System;Immune System;IRF3-mediated induction of type I IFN;AndrogenReceptor;Coregulation of Androgen receptor activity;Cytosolic sensors of pathogen-associated DNA ;Regulation of Telomerase;BARD1 signaling events;DNA-PK pathway in nonhomologous end joining;Integration of provirus;Early Phase of HIV Life Cycle (Consensus)

Recessive Scores

• pRec: 0.743

Intolerance Scores

• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.997
• hipred: Y
• hipred_score: 0.673
• ghis: 0.654

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.883

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xrcc5
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; vision/eye phenotype; hematopoietic system phenotype; reproductive 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); neoplasm; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: telomere maintenance;activation of innate immune response;double-strand break repair;double-strand break repair via nonhomologous end joining;DNA recombination;cellular response to DNA damage stimulus;brain development;cell population proliferation;regulation of telomere maintenance;positive regulation of telomere maintenance via telomerase;positive regulation of type I interferon production;DNA duplex unwinding;response to drug;positive regulation of catalytic activity;neutrophil degranulation;innate immune response;positive regulation of protein kinase activity;negative regulation of transcription, DNA-templated;regulation of smooth muscle cell proliferation;positive regulation of neurogenesis;positive regulation of telomerase activity;hematopoietic stem cell differentiation;protein localization to chromosome, telomeric region;cellular response to fatty acid;cellular hyperosmotic salinity response;cellular response to gamma radiation;cellular response to X-ray;establishment of integrated proviral latency;negative regulation of t-circle formation;cellular response to leukemia inhibitory factor
• Cellular component: nuclear telomere cap complex;nuclear chromosome, telomeric region;extracellular region;nucleus;nucleoplasm;nucleolus;cytosol;plasma membrane;membrane;protein-containing complex;protein-DNA complex;secretory granule lumen;Ku70:Ku80 complex;nonhomologous end joining complex;site of DNA damage;ribonucleoprotein complex
• Molecular function: DNA binding;damaged DNA binding;double-stranded DNA binding;double-stranded telomeric DNA binding;RNA binding;ATP-dependent DNA helicase activity;protein binding;ATP binding;protein C-terminus binding;enzyme activator activity;ubiquitin protein ligase binding;telomeric DNA binding;transcription regulatory region DNA binding;protein-containing complex binding;DNA end binding;5'-deoxyribose-5-phosphate lyase activity