NUF2
protein-codingNUF2 component of NDC80 kinetochore complex, the group of NDC80 kinetochore complex
Gene summary
This gene encodes a protein that is highly similar to yeast Nuf2, a component of a conserved protein complex associated with the centromere. Yeast Nuf2 disappears from the centromere during meiotic prophase when centromeres lose their connection to the spindle pole body, and plays a regulatory role in chromosome segregation. The encoded protein is found to be associated with centromeres of mitotic HeLa cells, which suggests that this protein is a functional homolog of yeast Nuf2. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]
- CDCA1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~89.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0100038
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NUF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145697.3. 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 | 2 | 2 | ||||
| missense | 1 | 60 | 2 | 63 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 1 | 0 | 67 | 2 | 0 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_663735.2 | 13 | MANE Select | |
| Ensembl | ENSP00000271452.3 | 13 | MANE Select | |
| RefSeq | NP_113611.2 | 13 | Standard | |
| Ensembl | ENSP00000356875.3 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nuf2 | Danio rerio | Structure: head Quality: flat abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
- Amplification of signal from the kinetochores
- Mitotic Spindle Checkpoint
- Cell Cycle Checkpoints
Biological Process
- mitotic spindle organization
- chromosome segregation
- meiotic chromosome segregation
- cell division
- attachment of mitotic spindle microtubules to kinetochore
Molecular Function
- molecular_function
- protein binding
- protein-containing complex binding
Cellular Component
- chromosome, centromeric region
- condensed nuclear chromosome kinetochore
- nucleus
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000271452
- Coding exons
- 13
- Length
- 89189
- Individuals with no LoFs
- 125625
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 94
- Defined
- 125719
- p
- 0.000374
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.37 | 173 | 232 | 0.747 | 0.0000118 | 3073 |
| Missense (PolyPhen) | 40 | 57.535 | 0.69523 | 781 | ||
| Synonymous | 0.865 | 71 | 80.9 | 0.878 | 0.00000434 | 776 |
| Loss of Function | 2.71 | 12 | 27.3 | 0.440 | 0.00000131 | 372 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.0011 | 0.0011 | notable |
| European (Non-Finnish) | 0.00050 | 0.00050 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a component of the essential kinetochore- associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:12438418, PubMed:14654001, PubMed:15062103, PubMed:15235793, PubMed:15239953, PubMed:15548592, PubMed:17535814). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:15548592). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020). {ECO:0000269|PubMed:12438418, ECO:0000269|PubMed:14654001, ECO:0000269|PubMed:15062103, ECO:0000269|PubMed:15235793, ECO:0000269|PubMed:15239953, ECO:0000269|PubMed:15548592, ECO:0000269|PubMed:17535814, ECO:0000269|PubMed:23085020}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.907
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.69
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.906
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |