NDC80
protein-codingNDC80 kinetochore complex component, the group of NDC80 kinetochore complex
Gene summary
This gene encodes a component of the NDC80 kinetochore complex. The encoded protein consists of an N-terminal microtubule binding domain and a C-terminal coiled-coiled domain that interacts with other components of the complex. This protein functions to organize and stabilize microtubule-kinetochore interactions and is required for proper chromosome segregation. [provided by RefSeq, Oct 2011]
- KNTC2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.1 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 NDC80 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006101.3. 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 | 59 | 1 | 60 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 60 | 1 | 2 | 63 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006092.1 | 16 | MANE Select | |
| Ensembl | ENSP00000261597.4 | 16 | MANE Select | |
| Ensembl | ENSP00000458236.1 | 2 | Standard | |
| Ensembl | ENSP00000461227.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ndc80 | 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 sister chromatid segregation
- establishment of mitotic spindle orientation
- mitotic cell cycle
- mitotic spindle organization
- chromosome segregation
Molecular Function
- protein binding
- identical protein binding
Cellular Component
- chromosome, centromeric region
- kinetochore
- condensed chromosome kinetochore
- condensed nuclear chromosome kinetochore
- condensed nuclear chromosome outer kinetochore
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261597
- Coding exons
- 16
- Length
- 45125
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125746
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.84 | 224 | 316 | 0.709 | 0.0000156 | 4239 |
| Missense (PolyPhen) | 30 | 54.618 | 0.54927 | 681 | ||
| Synonymous | 1.08 | 99 | 114 | 0.872 | 0.00000567 | 1112 |
| Loss of Function | 3.03 | 18 | 38.2 | 0.471 | 0.00000193 | 492 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00038 | 0.00037 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00020 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
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:9315664, PubMed:12351790, PubMed:14654001, PubMed:14699129, PubMed:15062103, PubMed:15235793, PubMed:15239953, PubMed:15548592, PubMed:16732327). 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). Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spindle microtubules (PubMed:25743205, PubMed:23891108). {ECO:0000269|PubMed:12351790, ECO:0000269|PubMed:14654001, ECO:0000269|PubMed:14699129, ECO:0000269|PubMed:15062103, ECO:0000269|PubMed:15235793, ECO:0000269|PubMed:15239953, ECO:0000269|PubMed:15548592, ECO:0000269|PubMed:16732327, ECO:0000269|PubMed:23085020, ECO:0000269|PubMed:23891108, ECO:0000269|PubMed:25743205, ECO:0000269|PubMed:9315664}.;
Recessive Scores
- pRec
- 0.447
Intolerance Scores
- LoFtool
- 0.789
- RVIS EVS
- -0.22
- RVIS percentile EVS
- 37.43
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.837
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |