ERCC5

ERCC excision repair 5, endonuclease, the group of ERCC excision repair associated|Xeroderma pigmentosum complementation groups

Basic information

Region (hg38): 13:102845831-102875995

Previous symbols: [ "ERCM2", "XPGC" ]

Links

ENSG00000134899 ∙ NCBI:2073 ∙ OMIM:133530 ∙ HGNC:3437 ∙ Uniprot:P28715 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• xeroderma pigmentosum group G (Definitive), mode of inheritance: AR
• xeroderma pigmentosum group G (Strong), mode of inheritance: AR
• cerebrooculofacioskeletal syndrome 3 (Limited), mode of inheritance: AR
• xeroderma pigmentosum group G (Definitive), mode of inheritance: AR
• COFS syndrome (Supportive), mode of inheritance: AR
• xeroderma pigmentosum (Supportive), mode of inheritance: AR
• xeroderma pigmentosum-Cockayne syndrome complex (Supportive), mode of inheritance: AR
• cerebrooculofacioskeletal syndrome 3 (Strong), mode of inheritance: AR
• xeroderma pigmentosum group G (Strong), mode of inheritance: AR
• xeroderma pigmentosum group G (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Xeroderma pigmentosum, complementation group G; Xeroderma pigmentosum, complementation group G/Cockayne syndrome	AR	Dermatologic; Oncologic	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 for dermatologic manifestations can be beneficial	Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	492197; 11219864; 3620347; 8317483; 8818951; 9096355; 11228268; 11841555; 20301571; 24700531

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ERCC5 gene.

• not provided (6 variants)
• Xeroderma pigmentosum (5 variants)
• Xeroderma pigmentosum, group G (4 variants)
• Cerebrooculofacioskeletal syndrome 3 (2 variants)
• Xeroderma pigmentosum-Cockayne syndrome complex (1 variants)
• ERCC5-related disorder (1 variants)
• Xeroderma pigmentosum group G/Cockayne syndrome (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERCC5 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			7	60	5	72
missense		4	124	13	8	149
nonsense	2	5	1			8
start loss						0
frameshift	11	10	3			24
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	2				3
splice region		1	6	3	1	11
non coding			12	24	38	74
Total	14	21	148	97	51

Highest pathogenic variant AF is 0.0000394

Variants in ERCC5

This is a list of pathogenic ClinVar variants found in the ERCC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-102845848-A-G		Xeroderma pigmentosum, group G	Benign (Nov 11, 2018)
13-102845887-C-T		Xeroderma pigmentosum, group G	Uncertain significance (Jan 12, 2018)
13-102846025-T-C		Xeroderma pigmentosum, group G	Benign (Nov 11, 2018)
13-102846026-G-C		Xeroderma pigmentosum, group G	Uncertain significance (Jan 13, 2018)
13-102846067-G-C		Xeroderma pigmentosum, group G	Benign/Likely benign (Jun 01, 2023)
13-102846075-A-C		Xeroderma pigmentosum, group G	Uncertain significance (Apr 27, 2017)
13-102846111-C-A		Xeroderma pigmentosum, group G	Uncertain significance (Jan 12, 2018)
13-102846121-A-G		Xeroderma pigmentosum, group G	Uncertain significance (Jan 12, 2018)
13-102846141-A-G		Xeroderma pigmentosum, group G	Uncertain significance (Jan 13, 2018)
13-102846193-G-A		Xeroderma pigmentosum, group G	Benign (Apr 03, 2019)
13-102846195-C-T		Xeroderma pigmentosum, group G	Benign (Nov 11, 2018)
13-102846266-C-G		not specified	not provided (Sep 19, 2013)
13-102846266-C-T		not specified	not provided (Sep 19, 2013)
13-102846272-G-A			Likely benign (Sep 01, 2023)
13-102846277-A-C		Ovarian cancer	Likely pathogenic (Jan 01, 2022)
13-102846298-A-C		Xeroderma pigmentosum, group G	Uncertain significance (Jan 15, 2018)
13-102846314-G-A			Likely benign (Sep 01, 2022)
13-102846322-C-T		not specified • Xeroderma pigmentosum, group G • Cerebrooculofacioskeletal syndrome 3 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 07, 2024)
13-102846328-C-G			Uncertain significance (Nov 03, 2021)
13-102846342-A-G		Xeroderma pigmentosum, group G • Hereditary cancer-predisposing syndrome • ERCC5-related disorder	Likely benign (Dec 21, 2020)
13-102846344-C-G			Uncertain significance (Nov 03, 2021)
13-102846349-C-A		Xeroderma pigmentosum, group G	Pathogenic (Mar 01, 2013)
13-102846357-A-G			Likely pathogenic (Apr 15, 2023)
13-102846367-C-CCGCCTTAAGTCCTAA			Likely benign (Jan 09, 2024)
13-102846556-G-A			Likely benign (Jul 27, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ERCC5	protein_coding	protein_coding	ENST00000355739	15	31152

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.73e-13	0.992	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.118	628	636	0.987	0.0000359	7798
Missense in Polyphen		220	225	0.97779		2766
Synonymous	-0.151	251	248	1.01	0.0000157	2258
Loss of Function	2.64	28	47.7	0.587	0.00000243	580

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000301	0.000300
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.000272	0.000272
South Asian	0.000621	0.000621
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Single-stranded structure-specific DNA endonuclease involved in DNA excision repair. Makes the 3'incision in DNA nucleotide excision repair (NER). Acts as a cofactor for a DNA glycosylase that removes oxidized pyrimidines from DNA. May also be involved in transcription-coupled repair of this kind of damage, in transcription by RNA polymerase II, and perhaps in other processes too.
• Disease: DISEASE: Xeroderma pigmentosum complementation group G (XP-G) [MIM:278780]: 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. Some XP-G patients present features of Cockayne syndrome, cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex. {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:11228268, ECO:0000269|PubMed:11841555, ECO:0000269|PubMed:12060391, ECO:0000269|PubMed:23255472, ECO:0000269|PubMed:7951246, ECO:0000269|PubMed:9096355}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cerebro-oculo-facio-skeletal syndrome 3 (COFS3) [MIM:616570]: A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome. {ECO:0000269|PubMed:24700531}. 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);Dual incision in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.493

Intolerance Scores

• loftool: 0.898
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.13

Haploinsufficiency Scores

• pHI: 0.0814
• hipred: Y
• hipred_score: 0.572
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.843

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ercc5
• Phenotype: digestive/alimentary phenotype; immune system phenotype; liver/biliary system phenotype; hematopoietic system 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); 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: transcription-coupled nucleotide-excision repair;nucleotide-excision repair;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, DNA incision, 3'-to lesion;nucleotide-excision repair, DNA incision, 5'-to lesion;response to UV;UV protection;response to UV-C;nucleotide-excision repair, DNA incision;negative regulation of apoptotic process
• Cellular component: nucleotide-excision repair complex;nucleus;nucleoplasm;DNA replication factor A complex
• Molecular function: bubble DNA binding;RNA polymerase II complex binding;double-stranded DNA binding;single-stranded DNA binding;endodeoxyribonuclease activity;protein binding;protein homodimerization activity;protein-containing complex binding;metal ion binding;protein N-terminus binding