EME1
protein-codingessential meiotic structure-specific endonuclease 1
Gene summary
This gene encodes a protein that complexes with methyl methanesulfonate-sensitive UV-sensitive 81 protein to form an endonuclease complex. The encoded protein interacts with specifc DNA structures including nicked Holliday junctions, 3'-flap structures and aberrant replication fork structures. This protein may be involved in repairing DNA damage and in maintaining genomic stability. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.3 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 EME1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152463.4. 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 | 1 | 1 | ||||
| missense | 65 | 7 | 1 | 73 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 70 | 7 | 1 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689676.2 | 8 | MANE Select | |
| Ensembl | ENSP00000339897.4 | 8 | MANE Select | |
| RefSeq | NP_001159603.1 | 8 | Standard | |
| Ensembl | ENSP00000376952.2 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fanconi anemia pathway - Homo sapiens (human)
- Homologous recombination - Homo sapiens (human)
- HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
- Fanconi Anemia Pathway
- DNA Repair
Biological Process
- resolution of meiotic recombination intermediates
- double-strand break repair
- replication fork processing
- intra-S DNA damage checkpoint
- interstrand cross-link repair
Molecular Function
- DNA binding
- endodeoxyribonuclease activity
- protein binding
- crossover junction endodeoxyribonuclease activity
- metal ion binding
Cellular Component
- nuclear chromatin
- nucleoplasm
- nuclear heterochromatin
- nucleolus
- Holliday junction resolvase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393271
- Coding exons
- 8
- Length
- 8264
- Individuals with no LoFs
- 125612
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 136
- Defined
- 125748
- p
- 0.000541
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0797 | 306 | 310 | 0.987 | 0.0000158 | 3795 |
| Missense (PolyPhen) | 80 | 76.728 | 1.0426 | 1018 | ||
| Synonymous | 0.422 | 115 | 121 | 0.951 | 0.00000634 | 1164 |
| Loss of Function | 0.630 | 23 | 26.5 | 0.868 | 0.00000130 | 304 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00051 | 0.00049 | rare |
| Latino/Admixed American | 0.00067 | 0.00064 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.0017 | 0.0016 | notable |
| European (Non-Finnish) | 0.00047 | 0.00044 | rare |
| South Asian | 0.00056 | 0.00056 | rare |
| Other | 0.00070 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'- flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks. {ECO:0000269|PubMed:12686547, ECO:0000269|PubMed:12721304, ECO:0000269|PubMed:14617801, ECO:0000269|PubMed:17289582}.;
Recessive Scores
- pRec
- 0.0974
Intolerance Scores
- LoFtool
- 0.990
- RVIS EVS
- 1
- RVIS percentile EVS
- 90.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.866
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |