XPA

XPA, DNA damage recognition and repair factor, the group of Xeroderma pigmentosum complementation groups

Basic information

Region (hg38): 9:97674909-97697340

Links

ENSG00000136936

∙ NCBI:7507 ∙ OMIM:611153 ∙ HGNC:12814 ∙ Uniprot:P23025 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Xeroderma pigmentosum, group A	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	286113; 2168777; 2234061; 1571258; 1372102; 8053698; 9671271; 10447254; 20301571; 20534089; 20574439; 22044607; 22081045

ClinVar

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

not_provided (270 variants)
Xeroderma_pigmentosum_group_A (114 variants)
Xeroderma_pigmentosum (41 variants)
Inborn_genetic_diseases (32 variants)
not_specified (9 variants)
XPA-related_disorder (6 variants)
Ovarian_cancer (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XPA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000380.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	111 clinvar		113
missense		10 clinvar	57 clinvar	7 clinvar	1 clinvar	75
nonsense	16 clinvar	8 clinvar	2 clinvar			26
start loss	1	3				4
frameshift	29 clinvar	28 clinvar	4 clinvar			61
splice donor/acceptor (+/-2bp)	5 clinvar	12 clinvar				17
Total	51	61	65	118	1

Highest pathogenic variant AF is 0.00016981486

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XPA	protein_coding	protein_coding	ENST00000375128	6	22449

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000787	0.929	125614	0	128	125742	0.000509

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.346	139	151	0.921	0.00000731	1783
Missense in Polyphen		29	33.528	0.86495		415
Synonymous	-0.444	57	52.9	1.08	0.00000262	484
Loss of Function	1.65	9	16.2	0.557	9.39e-7	185

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000576	0.000575
Ashkenazi Jewish	0.00	0.00
East Asian	0.000276	0.000272
Finnish	0.00300	0.00301
European (Non-Finnish)	0.000302	0.000299
Middle Eastern	0.000276	0.000272
South Asian	0.000361	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation. {ECO:0000269|PubMed:19197159}.;
Disease: DISEASE: Xeroderma pigmentosum complementation group A (XP-A) [MIM:278700]: 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. XP-A patients show the most severe skin symptoms and progressive neurological disorders. {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:1339397, ECO:0000269|PubMed:1372103, ECO:0000269|PubMed:8504220, ECO:0000269|PubMed:9671271}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Nucleotide excision repair - Homo sapiens (human);Nucleotide Excision Repair ;DNA Repair;Formation of Incision Complex in GG-NER;Dual Incision in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Formation of TC-NER Pre-Incision Complex;Dual incision in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

pRec: 0.553

Intolerance Scores

loftool: 0.735
rvis_EVS: 0.68
rvis_percentile_EVS: 84.93

Haploinsufficiency Scores

pHI: 0.292
hipred: N
hipred_score: 0.452
ghis: 0.400

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.943

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Xpa
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; neoplasm; pigmentation 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); reproductive system phenotype; hematopoietic system phenotype; vision/eye phenotype; limbs/digits/tail 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); skeleton phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland 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); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype;

Gene ontology

Biological process: nucleotide-excision repair, DNA damage recognition;DNA repair;transcription-coupled nucleotide-excision repair;base-excision repair;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, DNA incision, 5'-to lesion;response to oxidative stress;intrinsic apoptotic signaling pathway in response to DNA damage;response to toxic substance;UV protection;regulation of autophagy;response to auditory stimulus;nucleotide-excision repair, DNA incision;protein localization to nucleus;multicellular organism growth;global genome nucleotide-excision repair;UV-damage excision repair;nucleotide-excision repair involved in interstrand cross-link repair
Cellular component: nucleotide-excision repair factor 1 complex;nucleus;nucleoplasm;DNA replication factor A complex;cytoplasm;intercellular bridge
Molecular function: damaged DNA binding;protein binding;protein domain specific binding;protein homodimerization activity;metal ion binding