XRCC1

protein-coding

X-ray repair cross complementing 1

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_006297.3

Inheritance

AR, AD

ClinVar variants

P:4U:94B:35

Top phenotype

Spinocerebellar ataxia, autosomal recessive, 26

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr19:43,543,311-43,580,473

External References & Databases

Ensembl (ENSG00000073050)

Transcript & Mutation Effects

hg38 • Region Span ~37.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spinocerebellar ataxia, autosomal recessive 26STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033116

Submitter: PanelApp Australia

head and neck cancerLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005627

Submitter: Ambry Genetics

spinocerebellar ataxia, autosomal recessive 26LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033116

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spinocerebellar ataxia, autosomal recessive, 26AR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 28002403

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to XRCC1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 80

not providedTotal: 49

Spinocerebellar ataxia, autosomal recessive 26Total: 10

XRCC1-related disorderTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006297.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	19 clinvar	2 clinvar	22
missense		1 clinvar	86 clinvar	12 clinvar	2 clinvar	101
nonsense	1 clinvar	2 clinvar	2 clinvar			5
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	3	94	31	4	133

Highest pathogenic variant AF is 0.000034203236

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006297.3	RefSeq	NP_006288.2	17	MANE Select
ENST00000262887.10	Ensembl	ENSP00000262887.5	17	MANE Select
ENST00000543982.5	Ensembl	ENSP00000443671.1	16	Standard
ENST00000543982.6	Ensembl	ENSP00000443671.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Base excision repair - Homo sapiens (human)
HDR through MMEJ (alt-NHEJ)
DNA Repair
DNA Double-Strand Break Repair
Homology Directed Repair

Biological Process

single strand break repair
double-strand break repair via homologous recombination
response to hypoxia
transcription-coupled nucleotide-excision repair
base-excision repair

Molecular Function

DNA ligase activity
protein binding
enzyme binding
oxidized DNA binding
3' overhang single-stranded DNA endodeoxyribonuclease activity

Cellular Component

nuclear chromosome, telomeric region
nuclear chromatin
nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262887
Coding exons: 17
Length: 37434
Individuals with no LoFs: 125640
Homozygous LoFs: 0
Heterozygous LoFs: 108
Defined: 125748
p: 0.000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.715	348	388	0.898	0.0000233	4083
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.00043	0.00043	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00041	0.00040	rare
South Asian	0.00062	0.00059	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.455

Intolerance Scores

LoFtool: 0.708
RVIS EVS: 0.19
RVIS percentile EVS: 66.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.839

Gene Damage Prediction

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