NUCKS1
protein-codingnuclear casein kinase and cyclin dependent kinase substrate 1
Gene summary
This gene encodes a nuclear protein that is highly conserved in vertebrates. The conserved regions of the protein contain several consensus phosphorylation sites for casein kinase II and cyclin-dependent kinases, two putative nuclear localization signals, and a basic DNA-binding domain. It is phosphorylated in vivo by Cdk1 during mitosis of the cell cycle. [provided by RefSeq, Aug 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.4 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 NUCKS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022731.5. 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 | 16 | 16 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 18 | 1 | 0 | 19 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073568.2 | 7 | MANE Select | |
| Ensembl | ENSP00000356110.4 | 7 | MANE Select | |
| Ensembl | ENSP00000545276.1 | 7 | Standard | |
| Ensembl | ENSP00000545277.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- double-strand break repair via homologous recombination
- cellular glucose homeostasis
- regulation of DNA replication
- chromatin organization
- regulation of transcription by RNA polymerase II
Molecular Function
- DNA-binding transcription activator activity, RNA polymerase II-specific
- chromatin binding
- double-stranded DNA binding
- single-stranded DNA binding
- RNA binding
Cellular Component
- chromatin
- nuclear chromatin
- nucleus
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367142
- Coding exons
- 7
- Length
- 37458
- Individuals with no LoFs
- 120217
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 120218
- p
- 0.00000416
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.09 | 66 | 134 | 0.492 | 0.00000720 | 1613 |
| Missense (PolyPhen) | 7 | 26.579 | 0.26337 | 298 | ||
| Synonymous | 0.382 | 47 | 50.4 | 0.932 | 0.00000304 | 418 |
| Loss of Function | 3.37 | 1 | 15.2 | 0.0658 | 8.77e-7 | 179 |
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) | 0.0000091 | 0.0000091 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.133
Intolerance Scores
- LoFtool
- 0.301
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |