XRCC6

X-ray repair cross complementing 6, the group of DNA helicases

Basic information

Region (hg38): 22:41621162-41664048

Previous symbols: [ "G22P1" ]

Links

ENSG00000196419 ∙ NCBI:2547 ∙ OMIM:152690 ∙ HGNC:4055 ∙ Uniprot:P12956 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XRCC6 gene.

• Inborn genetic diseases (11 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XRCC6 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						0
missense			8	3		11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	8	3	2

Variants in XRCC6

This is a list of pathogenic ClinVar variants found in the XRCC6 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-41621350-G-A			Benign (Jan 21, 2021)
22-41636188-G-A		not specified	Likely benign (Feb 02, 2022)
22-41636210-A-C		not specified	Uncertain significance (Mar 01, 2024)
22-41636581-A-G		not specified	Uncertain significance (May 31, 2023)
22-41636681-T-C		not specified	Uncertain significance (May 09, 2023)
22-41636752-G-A		not specified	Uncertain significance (Dec 19, 2022)
22-41637677-T-C		not specified	Uncertain significance (Jul 25, 2023)
22-41637686-T-C		not specified	Uncertain significance (Aug 14, 2023)
22-41646923-A-G		not specified	Uncertain significance (Feb 17, 2024)
22-41647092-G-A			Benign (Dec 31, 2019)
22-41650806-G-A		not specified	Likely benign (Sep 01, 2021)
22-41650817-C-A		not specified	Uncertain significance (Dec 16, 2023)
22-41650864-G-A		not specified	Uncertain significance (May 06, 2022)
22-41653558-A-C		not specified	Uncertain significance (Dec 07, 2021)
22-41653559-T-C		not specified	Likely benign (Jul 20, 2022)
22-41653610-G-T		not specified	Uncertain significance (Jan 19, 2024)
22-41658274-G-A		not specified	Uncertain significance (Sep 17, 2021)
22-41663654-G-C		not specified	Uncertain significance (Sep 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XRCC6	protein_coding	protein_coding	ENST00000359308	12	42922

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000963	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.10	173	332	0.521	0.0000174	4043
Missense in Polyphen		30	85.498	0.35089		1193
Synonymous	0.419	121	127	0.953	0.00000680	1115
Loss of Function	4.64	2	28.9	0.0691	0.00000155	362

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000585	0.0000585
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000547	0.0000544
South Asian	0.0000332	0.0000327
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. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. Required for osteocalcin gene expression. 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. 5'-dRP lyase activity 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. 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:20493174, ECO:0000269|PubMed:2466842, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}.
• 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;Signaling events mediated by HDAC Class III;DNA-PK pathway in nonhomologous end joining;Integration of provirus;Early Phase of HIV Life Cycle (Consensus)

Recessive Scores

• pRec: 0.763

Intolerance Scores

• loftool: 0.0649
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.62

Haploinsufficiency Scores

• pHI: 0.0783
• hipred: Y
• hipred_score: 0.802
• ghis: 0.681

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xrcc6
• Phenotype: reproductive system phenotype; hematopoietic system phenotype; neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system 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); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: xrcc6
• Affected structure: response to ionizing radiation
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: telomere maintenance;activation of innate immune response;DNA ligation;double-strand break repair via nonhomologous end joining;DNA recombination;brain development;positive regulation of type I interferon production;DNA duplex unwinding;neutrophil degranulation;innate immune response;positive regulation of protein kinase activity;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of smooth muscle cell proliferation;protein heterotetramerization;cellular hyperosmotic salinity response;cellular response to gamma radiation;cellular response to X-ray;establishment of integrated proviral latency;double-strand break repair via classical nonhomologous end joining
• Cellular component: nuclear telomere cap complex;nuclear chromosome, telomeric region;extracellular region;nucleus;nucleoplasm;transcription factor complex;nucleolus;cytosol;membrane;protein-containing complex;protein-DNA complex;secretory granule lumen;Ku70:Ku80 complex;nonhomologous end joining complex;ficolin-1-rich granule lumen
• 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;cyclin binding;telomeric DNA binding;transcription regulatory region DNA binding;protein-containing complex binding;5'-deoxyribose-5-phosphate lyase activity