ERCC6
ERCC excision repair 6, chromatin remodeling factor, the group of ERCC excision repair associated|B-WICH chromatin-remodelling complex subunits
Basic information
Region (hg38): 10:49454167-49539538
Previous symbols: [ "CKN2" ]
Links
Phenotypes
GenCC
Source:
- Cockayne syndrome type 2 (Definitive), mode of inheritance: AR
- Cockayne syndrome type 2 (Strong), mode of inheritance: AR
- UV-sensitive syndrome 1 (Strong), mode of inheritance: AR
- Cockayne syndrome type 2 (Strong), mode of inheritance: AR
- Cockayne syndrome type 2 (Definitive), mode of inheritance: AR
- COFS syndrome (Supportive), mode of inheritance: AR
- Cockayne syndrome type 2 (Supportive), mode of inheritance: AR
- UV-sensitive syndrome (Supportive), mode of inheritance: AR
- Cockayne syndrome type 2 (Strong), mode of inheritance: AR
- premature ovarian failure 11 (Limited), mode of inheritance: Unknown
- Cockayne spectrum with or without cerebrooculofacioskeletal syndrome (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Premature ovarian failure 11; Xeroderma Pigmentosum-Cockayne Syndrome; De Sanctis-Cacchione syndrome | AD/AR | Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Obstetric; Oncologic | In Cockayne syndrome, periodic surveillance for manifestations affecting the audiologic, ophthalmologic, hepatic, and other systems can be beneficial; Metronidazole should be avoided due to concerns of hepatic failure; Some individuals with Xeroderma Pigmentosum-Cockayne Syndromecan have predisposition to skin cancer; 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; For Premature ovarian failure, genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency | Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Obstetric; Oncologic; Ophthalmologic | 14246158; 5560051; 4211825; 4431498; 7264357; 3545087; 1372469; 9443879; 9777763; 10196384; 10767341; 10739753; 15486090; 18446857; 18628313;20456449; 20301571; 22466610; 26204423; 26218421 |
| Individuals with Cockayne syndrome without skin sensitivity have been described |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (1372 variants)
- Cockayne syndrome type 2 (272 variants)
- Cerebrooculofacioskeletal syndrome 1 (177 variants)
- Age related macular degeneration 5 (151 variants)
- Inborn genetic diseases (83 variants)
- Cockayne syndrome (53 variants)
- not specified (50 variants)
- COFS syndrome (37 variants)
- Macular degeneration (37 variants)
- Cerebrooculofacioskeletal syndrome 1;Cockayne syndrome type 2;DE SANCTIS-CACCHIONE SYNDROME (31 variants)
- 7 conditions (28 variants)
- Cockayne syndrome type 2;DE SANCTIS-CACCHIONE SYNDROME;Cerebrooculofacioskeletal syndrome 1 (27 variants)
- DE SANCTIS-CACCHIONE SYNDROME (21 variants)
- DE SANCTIS-CACCHIONE SYNDROME;Cerebrooculofacioskeletal syndrome 1;Cockayne syndrome type 2 (17 variants)
- ERCC6-Related Disorders (9 variants)
- UV-sensitive syndrome 1 (8 variants)
- Cerebrooculofacioskeletal syndrome 1;DE SANCTIS-CACCHIONE SYNDROME;Cockayne syndrome type 2 (3 variants)
- Premature ovarian failure 11 (2 variants)
- Cockayne syndrome type 2;Cerebrooculofacioskeletal syndrome 1;DE SANCTIS-CACCHIONE SYNDROME (2 variants)
- DE SANCTIS-CACCHIONE SYNDROME;Cockayne syndrome type 2;Cerebrooculofacioskeletal syndrome 1 (1 variants)
- See cases (1 variants)
- - (1 variants)
- Hereditary breast ovarian cancer syndrome (1 variants)
- Genetic non-acquired premature ovarian failure (1 variants)
- ERCC6-related condition (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERCC6 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 | 482 | 498 | ||||
| missense | 377 | 47 | 440 | |||
| nonsense | 42 | 52 | 98 | |||
| start loss | 0 | |||||
| frameshift | 67 | 57 | 127 | |||
| inframe indel | 17 | 17 | ||||
| splice donor/acceptor (+/-2bp) | 35 | 40 | ||||
| splice region ? | 2 | 3 | 15 | 55 | 5 | 80 |
| non coding ? | 45 | 108 | 58 | 211 | ||
| Total | 116 | 148 | 455 | 637 | 75 |
Highest pathogenic variant AF is 0.0000919
Variants in ERCC6
This is a list of pathogenic ClinVar variants found in the ERCC6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 10-49454607-T-C | Cockayne syndrome type 2 • Age related macular degeneration 5 • Cerebrooculofacioskeletal syndrome 1 | Likely benign (Jan 13, 2018) | ||
| 10-49454725-C-T | Age related macular degeneration 5 • Cerebrooculofacioskeletal syndrome 1 • Cockayne syndrome type 2 | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 10-49454796-T-C | Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 • Cockayne syndrome type 2 | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 10-49454890-T-C | Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 | Uncertain significance (Jan 12, 2018) | ||
| 10-49454894-T-C | Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 | Likely benign (Jan 12, 2018) | ||
| 10-49454992-A-G | Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 | Benign (Jan 12, 2018) | ||
| 10-49455095-A-G | Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 | Uncertain significance (Jan 13, 2018) | ||
| 10-49455111-G-A | Cerebrooculofacioskeletal syndrome 1 • Cockayne syndrome type 2 • Age related macular degeneration 5 | Uncertain significance (Jan 15, 2018) | ||
| 10-49455131-T-C | Age related macular degeneration 5 • Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 | Uncertain significance (Jan 13, 2018) | ||
| 10-49455420-T-G | Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 • Cockayne syndrome type 2 | Benign (Jan 12, 2018) | ||
| 10-49455449-C-T | Cockayne syndrome type 2 • Age related macular degeneration 5 • Cerebrooculofacioskeletal syndrome 1 | Uncertain significance (Jan 13, 2018) | ||
| 10-49455459-G-A | Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 | Uncertain significance (Jan 13, 2018) | ||
| 10-49455535-T-C | Age related macular degeneration 5 • Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 10-49455598-A-C | Cerebrooculofacioskeletal syndrome 1 • Cockayne syndrome type 2 • Age related macular degeneration 5 | Uncertain significance (Jan 12, 2018) | ||
| 10-49455842-G-C | Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 | Uncertain significance (Jan 13, 2018) | ||
| 10-49455869-G-A | Cerebrooculofacioskeletal syndrome 1 • Cockayne syndrome type 2 • Age related macular degeneration 5 | Benign (Jan 13, 2018) | ||
| 10-49456049-A-C | Cockayne syndrome type 2 • Age related macular degeneration 5 • Cerebrooculofacioskeletal syndrome 1 | Conflicting classifications of pathogenicity (Mar 01, 2023) | ||
| 10-49456086-C-T | Age related macular degeneration 5 • Cerebrooculofacioskeletal syndrome 1 • Cockayne syndrome type 2 | Conflicting classifications of pathogenicity (Jun 01, 2023) | ||
| 10-49456135-T-G | Age related macular degeneration 5 • Cerebrooculofacioskeletal syndrome 1 • Cockayne syndrome type 2 | Uncertain significance (Jan 13, 2018) | ||
| 10-49456153-A-G | Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 | Uncertain significance (Jan 13, 2018) | ||
| 10-49456213-T-C | Age related macular degeneration 5 • Cockayne syndrome type 2 • Cerebrooculofacioskeletal syndrome 1 | Uncertain significance (Jan 12, 2018) | ||
| 10-49456275-C-A | Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 • Cockayne syndrome type 2 | Uncertain significance (Mar 30, 2018) | ||
| 10-49456355-A-G | Cerebrooculofacioskeletal syndrome 1 • Age related macular degeneration 5 • Cockayne syndrome type 2 | Uncertain significance (Jan 13, 2018) | ||
| 10-49456478-T-G | Macular degeneration • Cockayne syndrome • COFS syndrome | Likely benign (Jun 14, 2016) | ||
| 10-49456578-G-A | Age related macular degeneration 5 • Cerebrooculofacioskeletal syndrome 1 • Cockayne syndrome type 2 | Conflicting classifications of pathogenicity (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ERCC6 | protein_coding | protein_coding | ENST00000355832 | 20 | 84171 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 5.16e-22 | 0.992 | 125530 | 0 | 218 | 125748 | 0.000867 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0981 | 772 | 780 | 0.990 | 0.0000441 | 9799 |
| Missense in Polyphen | 180 | 230.32 | 0.78152 | 2861 | ||
| Synonymous | -0.851 | 318 | 299 | 1.06 | 0.0000175 | 2876 |
| Loss of Function | 2.96 | 46 | 73.3 | 0.627 | 0.00000459 | 852 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00156 | 0.00156 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000489 | 0.000489 |
| Finnish | 0.00153 | 0.00153 |
| European (Non-Finnish) | 0.00104 | 0.00104 |
| Middle Eastern | 0.000489 | 0.000489 |
| South Asian | 0.000621 | 0.000621 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Essential factor involved in transcription-coupled nucleotide excision repair which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA. It is required for transcription-coupled repair complex formation. It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the at sites of RNA polymerase II- blocking lesions. {ECO:0000269|PubMed:15548521, ECO:0000269|PubMed:16916636, ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22483866}.;
- Disease
- DISEASE: Cockayne syndrome B (CSB) [MIM:133540]: A rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer. {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:19894250, ECO:0000269|PubMed:9443879}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cerebro-oculo-facio-skeletal syndrome 1 (COFS1) [MIM:214150]: 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:19894250}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: De Sanctis-Cacchione syndrome (DSC) [MIM:278800]: An autosomal recessive syndrome consisting of xeroderma pigmentosum associated with severe neurological and developmental involvement. In addition to the clinical signs of xeroderma pigmentosum, patients present with mental retardation, dwarfism, gonadal hypoplasia, microcephaly and various neurologic complications of early onset. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Macular degeneration, age-related, 5 (ARMD5) [MIM:613761]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:16754848}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: UV-sensitive syndrome 1 (UVSS1) [MIM:600630]: An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors. {ECO:0000269|PubMed:15486090}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Nucleotide excision repair - Homo sapiens (human);B-WICH complex positively regulates rRNA expression;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;Positive epigenetic regulation of rRNA expression;DNA Repair;Epigenetic regulation of gene expression;Gene expression (Transcription);RNA Polymerase I Promoter Clearance;RNA Polymerase I Transcription;RNA Polymerase I Transcription Initiation;Formation of TC-NER Pre-Incision Complex;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair
(Consensus)
Recessive Scores
- pRec
- 0.469
Intolerance Scores
- loftool
- 0.0666
- rvis_EVS
- 1.49
- rvis_percentile_EVS
- 95.32
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.652
- ghis
- 0.499
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.826
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ercc6
- 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; hearing/vestibular/ear 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); vision/eye phenotype; hematopoietic 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); neoplasm; 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; skeleton phenotype; limbs/digits/tail phenotype;
Zebrafish Information Network
- Gene name
- ercc6
- Affected structure
- post-vent region
- Phenotype tag
- abnormal
- Phenotype quality
- curved
Gene ontology
- Biological process
- response to superoxide;transcription-coupled nucleotide-excision repair;base-excision repair;pyrimidine dimer repair;transcription elongation from RNA polymerase I promoter;transcription by RNA polymerase II;response to oxidative stress;activation of JNKK activity;activation of JUN kinase activity;intrinsic apoptotic signaling pathway in response to DNA damage;response to UV;response to toxic substance;response to X-ray;response to UV-B;response to gamma radiation;DNA duplex unwinding;regulation of DNA-templated transcription, elongation;positive regulation of DNA-templated transcription, elongation;multicellular organism growth;photoreceptor cell maintenance;positive regulation of DNA repair;positive regulation of gene expression, epigenetic;positive regulation of protein tyrosine kinase activity
- Cellular component
- nucleus;nucleoplasm;nucleolus;transcription elongation factor complex
- Molecular function
- DNA binding;DNA helicase activity;chromatin binding;protein binding;ATP binding;protein C-terminus binding;DNA-dependent ATPase activity;protein tyrosine kinase activator activity;protein-containing complex binding;protein N-terminus binding