NEDD8
protein-codingNEDD8 ubiquitin like modifier
Gene summary
Enables ubiquitin protein ligase binding activity. Acts upstream of or within protein neddylation. Located in nucleoplasm. Biomarker of Parkinson's disease; alcohol-associated liver disease; and malignant astrocytoma. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.5 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 NEDD8 variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 0 | 0 | 0 | 0 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006147.1 | 4 | MANE Select | |
| Ensembl | ENSP00000250495.5 | 4 | MANE Select | |
| Ensembl | ENSP00000380040.4 | 3 | Standard | |
| Ensembl | ENSP00000448192.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- regulation of p27 phosphorylation during cell cycle progression
- EGF-EGFR Signaling Pathway
- Signal Transduction
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- regulation of transcription by RNA polymerase II
- cellular protein modification process
- proteolysis
- ubiquitin-dependent protein catabolic process
- cellular iron ion homeostasis
Molecular Function
- protein binding
- protein tag
- ubiquitin protein ligase binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250495
- Coding exons
- 4
- Length
- 15603
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.03 | 6 | 43.8 | 0.137 | 0.00000229 | 517 |
| Missense (PolyPhen) | 1 | 13.768 | 0.072635 | 178 | ||
| Synonymous | 1.01 | 10 | 15.0 | 0.667 | 7.29e-7 | 155 |
| Loss of Function | 2.31 | 0 | 6.22 | 0.00 | 3.47e-7 | 69 |
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 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C- APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins. {ECO:0000269|PubMed:10318914, ECO:0000269|PubMed:10597293, ECO:0000269|PubMed:11953428}.;
Recessive Scores
- pRec
- 0.171
Intolerance Scores
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 60.96
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.997