XPC

XPC complex subunit, DNA damage recognition and repair factor, the group of Xeroderma pigmentosum complementation groups

Basic information

Region (hg38): 3:14145145-14178621

Links

ENSG00000154767

∙ NCBI:7508 ∙ OMIM:613208 ∙ HGNC:12816 ∙ Uniprot:Q01831 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

xeroderma pigmentosum group C (Definitive), mode of inheritance: AR
xeroderma pigmentosum group C (Definitive), mode of inheritance: AR
xeroderma pigmentosum group C (Strong), mode of inheritance: AR
xeroderma pigmentosum group C (Strong), mode of inheritance: AR
xeroderma pigmentosum (Supportive), mode of inheritance: AR
xeroderma pigmentosum group C (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Xeroderma pigmentosum, group C	AR	Dermatologic; Oncologic; Ophthalmologic	Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial	Dermatologic; Neurologic; Oncologic; Ophthalmologic	7389185; 6696469; 8298653; 9804340; 10766188; 11511294; 14662655; 20301571; 21482201; 22211393; 23143338; 23173980; 23436679

ClinVar

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

not provided (73 variants)
Xeroderma pigmentosum, group C (33 variants)
Xeroderma pigmentosum (12 variants)
XPC-related disorder (2 variants)
See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XPC gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

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 clinvar	362 clinvar	7 clinvar	371
missense		2 clinvar	130 clinvar	15 clinvar	6 clinvar	153
nonsense	27 clinvar	24 clinvar	2 clinvar			53
start loss		4				4
frameshift	54 clinvar	42 clinvar	2 clinvar			98
splice donor/acceptor (+/-2bp)	5 clinvar	43 clinvar	2 clinvar			50
Total	86	115	138	377	13

Highest pathogenic variant AF is 0.0000591281

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XPC	protein_coding	protein_coding	ENST00000285021	16	33637

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.69e-11	0.996	124669	0	86	124755	0.000345

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.695	483	528	0.915	0.0000304	6115
Missense in Polyphen		153	183.91	0.83194		2051
Synonymous	0.125	200	202	0.989	0.0000116	1846
Loss of Function	2.70	24	43.2	0.556	0.00000236	526

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00111	0.00110
Ashkenazi Jewish	0.000797	0.000795
East Asian	0.0000556	0.0000554
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000359	0.000345
Middle Eastern	0.0000556	0.0000554
South Asian	0.000427	0.000425
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA- binding activity.;
Disease: DISEASE: Xeroderma pigmentosum complementation group C (XP-C) [MIM:278720]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:10766188, ECO:0000269|PubMed:17355181, ECO:0000269|PubMed:17682058, ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:8298653}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Nucleotide excision repair - Homo sapiens (human);DNA Repair;SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;SUMOylation;DNA Damage Recognition in GG-NER;Formation of Incision Complex in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

pRec: 0.484

Intolerance Scores

loftool: 0.960
rvis_EVS: 0.45
rvis_percentile_EVS: 78.04

Haploinsufficiency Scores

pHI: 0.282
hipred: Y
hipred_score: 0.608
ghis: 0.483

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.808

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Xpc
Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); vision/eye 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);

Gene ontology

Biological process: nucleotide-excision repair, DNA damage recognition;DNA repair;nucleotide-excision repair;nucleotide-excision repair, preincision complex assembly;mismatch repair;response to UV-B;response to auditory stimulus;intra-S DNA damage checkpoint;response to drug;global genome nucleotide-excision repair;UV-damage excision repair;regulation of mitotic cell cycle phase transition
Cellular component: nucleotide-excision repair complex;nucleotide-excision repair factor 2 complex;nucleus;nucleoplasm;nucleolus;cytoplasm;mitochondrion;plasma membrane;intracellular membrane-bounded organelle;XPC complex
Molecular function: heteroduplex DNA loop binding;bubble DNA binding;damaged DNA binding;single-stranded DNA binding;protein binding;protein-containing complex binding