ERCC6L
protein-codingERCC excision repair 6 like, spindle assembly checkpoint helicase
Gene summary
This gene encodes a member of the SWItch/Sucrose Non-Fermentable (SWI/SNF2) family of proteins, and contains a SNF2-like ATPase domain and a PICH family domain. One distinguishing feature of this SWI/SNF protein family member is that during interphase, the protein is excluded from the nucleus, and only associates with chromatin after the nuclear envelope has broken down. This protein is a DNA translocase that is thought to bind double-stranded DNA that is exposed to stretching forces, such as those exerted by the mitotic spindle. This protein associates with ribosomal DNA and ultra-fine DNA bridges (UFBs), fine structures that connect sister chromatids during anaphase at some sites such as fragile sites, telomeres and centromeres. This gene is required for the faithful segregation of sister chromatids during mitosis, and the ATPase activity of this protein required for the resolution of UFBs before cytokinesis. [provided by RefSeq, May 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ERCC6L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017669.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 14 | 2 | 1 | 17 | ||
| missense | 107 | 7 | 2 | 116 | ||
| nonsense | 9 | 9 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 136 | 9 | 3 | 148 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060139.2 | 2 | MANE Select | |
| Ensembl | ENSP00000334675.3 | 2 | MANE Select | |
| RefSeq | NP_001009954.1 | 1 | Standard | |
| Ensembl | ENSP00000362761.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
- Amplification of signal from the kinetochores
- Mitotic Spindle Checkpoint
- Cell Cycle Checkpoints
Biological Process
- cell cycle
- cell division
Molecular Function
- DNA binding
- helicase activity
- protein binding
- ATP binding
- DNA translocase activity
Cellular Component
- condensed chromosome kinetochore
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334463
- Coding exons
- 2
- Length
- 34388
- Individuals with no LoFs
- 125619
- Homozygous LoFs
- 6
- Heterozygous LoFs
- 17
- Defined
- 125642
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.89 | 267 | 437 | 0.611 | 0.0000310 | 8275 |
| Missense (PolyPhen) | 43 | 125.58 | 0.34241 | 2351 | ||
| Synonymous | 1.41 | 142 | 165 | 0.860 | 0.0000120 | 2400 |
| Loss of Function | 4.72 | 2 | 29.9 | 0.0670 | 0.00000241 | 538 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00023 | 0.00018 | rare |
| Latino/Admixed American | 0.00026 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000063 | 0.000046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00011 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00022 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA helicase that acts as an essential component of the spindle assembly checkpoint. Contributes to the mitotic checkpoint by recruiting MAD2 to kinetochores and monitoring tension on centromeric chromatin (PubMed:17218258). Acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}.;
Recessive Scores
- pRec
- 0.0974
Intolerance Scores
- LoFtool
- 0.0101
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.583
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |