NSMCE1
protein-codingNSE1 homolog, SMC5-SMC6 complex component, the group of SMC5-6 protein complex|Ring finger proteins
Gene summary
Enables protein dimerization activity and ubiquitin protein ligase activity. Involved in DNA damage response. Located in nucleoplasm. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.8 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 NSMCE1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145080.4. 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 | 2 | |||
| missense | 38 | 2 | 40 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 40 | 3 | 0 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_659547.2 | 7 | MANE Select | |
| Ensembl | ENSP00000355077.4 | 7 | MANE Select | |
| Ensembl | ENSP00000457893.1 | 3 | Standard | |
| Ensembl | ENSP00000458859.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- SUMOylation of DNA damage response and repair proteins
- Post-translational protein modification
- SUMO E3 ligases SUMOylate target proteins
- Metabolism of proteins
- SUMOylation
Biological Process
- double-strand break repair via homologous recombination
- postreplication repair
- protein ubiquitination
- intracellular signal transduction
- positive regulation of response to DNA damage stimulus
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- metal ion binding
- protein dimerization activity
Cellular Component
- chromosome, telomeric region
- nucleus
- nucleoplasm
- Smc5-Smc6 complex
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361439
- Coding exons
- 7
- Length
- 43804
- Individuals with no LoFs
- 124726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 82
- Defined
- 124808
- p
- 0.000329
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.558 | 141 | 161 | 0.876 | 0.00000973 | 1762 |
| Missense (PolyPhen) | 48 | 65.668 | 0.73095 | 760 | ||
| Synonymous | 0.0236 | 69 | 69.3 | 0.996 | 0.00000483 | 472 |
| Loss of Function | 1.10 | 9 | 13.3 | 0.675 | 6.52e-7 | 161 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.00073 | 0.00072 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.0012 | 0.0012 | notable |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RING-type zinc finger-containing E3 ubiquitin ligase that assembles with melanoma antigen protein (MAGE) to catalyze the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. Within MAGE-RING ubiquitin ligase complex, MAGE stimulates and specifies ubiquitin ligase activity likely through recruitment and/or stabilization of the E2 ubiquitin-conjugating enzyme at the E3:substrate complex. Involved in maintenance of genome integrity, DNA damage response and DNA repair (PubMed:29225034, PubMed:20864041). NSMCE3/MAGEG1 and NSMCE1 ubiquitin ligase are components of SMC5-SMC6 complex and may positively regulate homologous recombination-mediated DNA repair (PubMed:18086888). MAGEF1-NSMCE1 ubiquitin ligase promotes proteasomal degradation of MMS19, a key component of the cytosolic iron-sulfur protein assembly (CIA) machinery. Down-regulation of MMS19 impairs the activity of several DNA repair and metabolism enzymes such as ERCC2/XPD, FANCJ, RTEL1 and POLD1 that require iron-sulfur clusters as cofactors (PubMed:29225034). {ECO:0000269|PubMed:18086888, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:29225034}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.496
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 53.51
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.350
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |