N4BP2
protein-codingNEDD4 binding protein 2
Gene summary
This gene encodes a protein containing a polynucleotide kinase domain (PNK) near the N-terminal region, and a Small MutS Related (Smr) domain near the C-terminal region. The encoded protein can bind to both B-cell leukemia/lymphoma 3 (BCL-3) and neural precursor cell expressed, developmentally downregulated 4, (Nedd4) proteins. This protein binds and hydrolyzes ATP, may function as a 5'-polynucleotide kinase, and has the capacity to be a ubiquitylation substrate. This protein may play a role in transcription-coupled DNA repair or genetic recombination. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~101.5 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 N4BP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018177.6. 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 | 2 | 2 | 4 | |||
| missense | 213 | 20 | 2 | 235 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 215 | 22 | 2 | 239 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060647.2 | 16 | MANE Select | |
| Ensembl | ENSP00000261435.6 | 16 | MANE Select | |
| RefSeq | NP_001305288.1 | 15 | Standard | |
| Ensembl | ENSP00000422436.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- phosphorylation
- nucleic acid phosphodiester bond hydrolysis
Molecular Function
- endonuclease activity
- protein binding
- ATP binding
- ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261435
- Coding exons
- 16
- Length
- 101427
- Individuals with no LoFs
- 125708
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 125748
- p
- 0.000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.803 | 825 | 893 | 0.924 | 0.0000435 | 11783 |
| Missense (PolyPhen) | 233 | 275.59 | 0.84547 | 3708 | ||
| Synonymous | 0.0250 | 320 | 321 | 0.998 | 0.0000170 | 3235 |
| Loss of Function | 4.16 | 29 | 65.2 | 0.445 | 0.00000295 | 957 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00070 | 0.00068 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00024 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has 5'-polynucleotide kinase and nicking endonuclease activity. May play a role in DNA repair or recombination. {ECO:0000269|PubMed:12730195}.;
Recessive Scores
- pRec
- 0.0933
Intolerance Scores
- LoFtool
- 0.918
- RVIS EVS
- 0.95
- RVIS percentile EVS
- 89.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.932
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |