XRCC1

X-ray repair cross complementing 1

Basic information

Region (hg38): 19:43543311-43580473

Previous symbols: [ "RCC" ]

Links

ENSG00000073050 ∙ NCBI:7515 ∙ OMIM:194360 ∙ HGNC:12828 ∙ Uniprot:P18887 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• head and neck cancer (Limited), mode of inheritance: AD
• spinocerebellar ataxia, autosomal recessive 26 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive, 26	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	28002403

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XRCC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XRCC1 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				9	5	14
missense			33	10	3	46
nonsense		1	1			2
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding				1	2	3
Total	0	1	36	20	10

Variants in XRCC1

This is a list of pathogenic ClinVar variants found in the XRCC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-43543341-CGTGT-C		Laryngeal squamous cell carcinoma	association (Jun 16, 2022)
19-43543341-CGTGTGTGTGTGTGT-C		Laryngeal squamous cell carcinoma	association (Jun 16, 2022)
19-43543398-T-C		Spinocerebellar ataxia, autosomal recessive 26	Benign (Dec 05, 2021)
19-43543402-G-A			Uncertain significance (May 01, 2024)
19-43543412-C-T		not specified	Uncertain significance (Jul 19, 2022)
19-43543472-G-A		not specified	Uncertain significance (Jun 06, 2023)
19-43543504-G-A		not specified	Uncertain significance (Jul 19, 2022)
19-43543662-G-A		Spinocerebellar ataxia, autosomal recessive 26	Uncertain significance (Feb 12, 2018)
19-43543667-C-T		not specified	Uncertain significance (Feb 07, 2023)
19-43543671-T-G		not specified	Uncertain significance (Dec 14, 2021)
19-43543687-C-T			Likely benign (Jul 01, 2024)
19-43544180-C-T			Likely benign (Jul 01, 2023)
19-43544196-A-G		not specified	Uncertain significance (Mar 28, 2024)
19-43544199-C-T		not specified	Uncertain significance (Sep 29, 2022)
19-43544243-G-C			Likely benign (Aug 15, 2018)
19-43545834-T-C		XRCC1-related disorder	Likely benign (Sep 17, 2019)
19-43545857-G-T		not specified	Uncertain significance (Jun 22, 2023)
19-43545889-C-G		not specified	Uncertain significance (Jul 14, 2021)
19-43546043-C-T		Spinocerebellar ataxia, autosomal recessive 26	Benign (Dec 05, 2021)
19-43546054-C-G		not specified	Uncertain significance (Mar 01, 2024)
19-43546079-G-T			Uncertain significance (Dec 01, 2021)
19-43546614-G-A			Likely benign (Jul 23, 2018)
19-43546628-G-A		Spinocerebellar ataxia, autosomal recessive 26	Pathogenic (Aug 22, 2017)
19-43546646-C-T			Uncertain significance (Mar 01, 2023)
19-43546711-G-A		not specified	Uncertain significance (Jul 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XRCC1	protein_coding	protein_coding	ENST00000262887	17	37434

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.34e-9	0.999	125640	0	108	125748	0.000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.715	348	388	0.898	0.0000233	4083
Missense in Polyphen		127	154.35	0.82278		1554
Synonymous	0.889	135	149	0.907	0.00000874	1277
Loss of Function	2.85	20	39.3	0.509	0.00000234	393

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00162	0.00160
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.0000937	0.0000924
European (Non-Finnish)	0.000406	0.000404
Middle Eastern	0.000381	0.000381
South Asian	0.000622	0.000588
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes. Probably during DNA repair, negatively regulates ADP-ribose levels by modulating ADP-ribosyltransferase PARP1 activity. {ECO:0000269|PubMed:28002403}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:28002403}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Base excision repair - Homo sapiens (human);HDR through MMEJ (alt-NHEJ);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Resolution of Abasic Sites (AP sites);Base Excision Repair;Resolution of AP sites via the single-nucleotide replacement pathway;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway;FOXM1 transcription factor network;E2F transcription factor network;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.455

Intolerance Scores

• loftool: 0.708
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.27

Haploinsufficiency Scores

• pHI: 0.179
• hipred: Y
• hipred_score: 0.608
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.839

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xrcc1
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); normal phenotype; neoplasm; 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: single strand break repair;double-strand break repair via homologous recombination;response to hypoxia;transcription-coupled nucleotide-excision repair;base-excision repair;base-excision repair, DNA ligation;nucleotide-excision repair, DNA gap filling;double-strand break repair via nonhomologous end joining;response to organic substance;negative regulation of protein ADP-ribosylation;cerebellum morphogenesis;hippocampus development;response to hydroperoxide;response to drug;voluntary musculoskeletal movement;telomeric DNA-containing double minutes formation;positive regulation of single strand break repair;positive regulation of DNA ligase activity;negative regulation of protection from non-homologous end joining at telomere;replication-born double-strand break repair via sister chromatid exchange
• Cellular component: nuclear chromosome, telomeric region;nuclear chromatin;nucleus;nucleoplasm;nucleolus;ERCC4-ERCC1 complex
• Molecular function: DNA ligase activity;protein binding;enzyme binding;oxidized DNA binding;3' overhang single-stranded DNA endodeoxyribonuclease activity