ERCC1

ERCC excision repair 1, endonuclease non-catalytic subunit, the group of ERCC excision repair associated

Basic information

Region (hg38): 19:45407334-45478828

Links

ENSG00000012061 ∙ NCBI:2067 ∙ OMIM:126380 ∙ HGNC:3433 ∙ Uniprot:P07992 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebrooculofacioskeletal syndrome 4 (Definitive), mode of inheritance: AR
• cerebrooculofacioskeletal syndrome 4 (Strong), mode of inheritance: AR
• cerebrooculofacioskeletal syndrome 4 (Limited), mode of inheritance: AR
• COFS syndrome (Supportive), mode of inheritance: AR
• Cockayne syndrome type 2 (Supportive), mode of inheritance: AR
• cerebrooculofacioskeletal syndrome 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebrooculofacioskeletal syndrome 4	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	Craniofacial; Musculoskeletal; Neurologic; Renal	17273966; 23623389

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ERCC1 gene.

• not provided (2 variants)
• Cerebrooculofacioskeletal syndrome 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERCC1 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				26	3	29
missense			26			26
nonsense	1	3			1	5
start loss						0
frameshift		1	2			3
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region				5	3	8
non coding			27	31	30	88
Total	2	6	56	57	34

Highest pathogenic variant AF is 0.0000259

Variants in ERCC1

This is a list of pathogenic ClinVar variants found in the ERCC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-45408198-G-A		not specified	Uncertain significance (Jan 26, 2023)
19-45408204-G-A		not specified	Uncertain significance (Dec 06, 2022)
19-45408224-T-C		not specified	Uncertain significance (Aug 17, 2022)
19-45408243-C-T		not specified	Uncertain significance (Apr 07, 2023)
19-45408255-C-T		not specified	Uncertain significance (Mar 28, 2023)
19-45408273-G-A		not specified	Uncertain significance (Aug 02, 2021)
19-45408377-C-T		not specified	Uncertain significance (May 23, 2023)
19-45408417-G-A		not specified	Uncertain significance (Sep 26, 2023)
19-45408444-C-T		not specified	Uncertain significance (Mar 02, 2023)
19-45408504-T-C		not specified	Uncertain significance (Jan 23, 2024)
19-45408536-G-T		not specified	Uncertain significance (Aug 17, 2022)
19-45408593-G-A		not specified	Uncertain significance (Jan 09, 2024)
19-45408612-A-C		not specified	Uncertain significance (May 15, 2024)
19-45408645-C-G		not specified	Uncertain significance (Oct 10, 2023)
19-45408653-C-T		not specified	Uncertain significance (Apr 23, 2024)
19-45408720-A-G		not specified	Uncertain significance (Jul 13, 2022)
19-45408744-A-C			Benign (Jan 30, 2024)
19-45408812-A-G		Cerebrooculofacioskeletal syndrome 4 • not specified • ERCC1-related disorder	Benign (Oct 28, 2020)
19-45408851-G-C		not specified	Uncertain significance (Apr 04, 2023)
19-45408855-C-T		not specified	Uncertain significance (Jan 02, 2024)
19-45408960-A-G		not specified	Uncertain significance (Jan 31, 2023)
19-45408987-T-A		not specified	Uncertain significance (Dec 06, 2021)
19-45409050-G-C		not specified	Uncertain significance (Jul 06, 2022)
19-45409085-A-G			Benign (Jun 14, 2019)
19-45409092-A-G		not specified	Uncertain significance (Nov 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ERCC1	protein_coding	protein_coding	ENST00000013807	8	71496

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.59e-7	0.410	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.664	165	191	0.865	0.0000115	2056
Missense in Polyphen		35	52.338	0.66872		554
Synonymous	-0.320	88	84.3	1.04	0.00000546	658
Loss of Function	0.717	12	15.0	0.800	7.25e-7	170

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000967	0.0000967
Middle Eastern	0.000163	0.000163
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Non-catalytic component of a structure- specific DNA repair endonuclease responsible for the 5'-incision during DNA repair. Responsible, in conjunction with SLX4, for the first step in the repair of interstrand cross-links (ICL). Participates in the processing of anaphase bridge-generating DNA structures, which consist in incompletely processed DNA lesions arising during S or G2 phase, and can result in cytokinesis failure. Also required for homology-directed repair (HDR) of DNA double-strand breaks, in conjunction with SLX4.
• Disease: DISEASE: Cerebro-oculo-facio-skeletal syndrome 4 (COFS4) [MIM:610758]: 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:17273966, ECO:0000269|PubMed:23623389}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Nucleotide excision repair - Homo sapiens (human);Cyclophosphamide Pathway, Pharmacodynamics;HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);Fanconi Anemia Pathway;DNA Repair;DNA Double-Strand Break Repair;Homology Directed 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: 0.708

Intolerance Scores

• loftool: 0.861
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.829
• hipred: Y
• hipred_score: 0.637
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.918

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ercc1
• 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; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; reproductive system 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); hematopoietic system phenotype; neoplasm; embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton phenotype

Gene ontology

• Biological process: meiotic mismatch repair;pyrimidine dimer repair by nucleotide-excision repair;replicative cell aging;DNA repair;transcription-coupled nucleotide-excision repair;nucleotide-excision repair;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, DNA incision, 3'-to lesion;nucleotide-excision repair, DNA incision, 5'-to lesion;double-strand break repair via nonhomologous end joining;DNA recombination;mitotic recombination;syncytium formation;response to oxidative stress;spermatogenesis;response to nutrient;cell population proliferation;male gonad development;UV protection;response to sucrose;response to X-ray;multicellular organism aging;negative regulation of telomere maintenance;nucleotide-excision repair, DNA incision;post-embryonic hemopoiesis;multicellular organism growth;response to immobilization stress;interstrand cross-link repair;isotype switching;response to cadmium ion;oogenesis;embryonic organ development;telomeric DNA-containing double minutes formation;global genome nucleotide-excision repair;UV-damage excision repair;t-circle formation;positive regulation of t-circle formation;negative regulation of protection from non-homologous end joining at telomere
• Cellular component: nucleotide-excision repair complex;nucleotide-excision repair factor 1 complex;nuclear chromosome, telomeric region;nucleoplasm;transcription factor TFIID complex;cytosol;ERCC4-ERCC1 complex
• Molecular function: single-stranded DNA endodeoxyribonuclease activity;TFIID-class transcription factor complex binding;DNA binding;damaged DNA binding;single-stranded DNA binding;protein binding;protein C-terminus binding;protein domain specific binding;3' overhang single-stranded DNA endodeoxyribonuclease activity