CUEDC2
protein-codingCUE domain containing 2
Gene summary
Predicted to enable ubiquitin binding activity. Acts upstream of or within negative regulation of cytokine production involved in inflammatory response and negative regulation of macrophage cytokine production. Located in cytosol; nuclear membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]
- C10orf66
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.3 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 CUEDC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024040.3. 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 | 0 | |||||
| missense | 39 | 1 | 40 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 45 | 1 | 0 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_076945.2 | 8 | MANE Select | |
| Ensembl | ENSP00000358953.4 | 8 | MANE Select | |
| Ensembl | ENSP00000558837.1 | 8 | Standard | |
| Ensembl | ENSP00000558838.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of toll-like receptor signaling pathway
Biological Process
- negative regulation of macrophage cytokine production
- negative regulation of cytokine production involved in inflammatory response
Molecular Function
- protein binding
Cellular Component
- nucleoplasm
- cytosol
- nuclear membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369937
- Coding exons
- 8
- Length
- 9417
- Individuals with no LoFs
- 124784
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 124791
- p
- 0.0000280
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.38 | 117 | 167 | 0.700 | 0.00000937 | 1881 |
| Missense (PolyPhen) | 34 | 62.647 | 0.54272 | 759 | ||
| Synonymous | 0.482 | 63 | 68.1 | 0.926 | 0.00000405 | 559 |
| Loss of Function | 2.59 | 5 | 16.3 | 0.307 | 8.71e-7 | 176 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Down-regulates ESR1 protein levels through the ubiquitination-proteasome pathway, regardless of the presence of 17 beta-estradiol. Also involved in 17 beta-estradiol-induced ESR1 degradation. Controls PGR protein levels through a similar mechanism. {ECO:0000269|PubMed:17347654, ECO:0000269|PubMed:21572428}.;
- Disease
- DISEASE: Note=May predict the clinical outcome of tamoxifen therapy of breast cancer patients. Patients with tumors that highly express CUEDC2 do not respond to tamoxifen treatment as effectively as those with tumors with low expression.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.352
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |