NDC80

NDC80 kinetochore complex component, the group of NDC80 kinetochore complex

Basic information

Region (hg38): 18:2571556-2616635

Previous symbols: [ "KNTC2" ]

Links

ENSG00000080986 ∙ NCBI:10403 ∙ OMIM:607272 ∙ HGNC:16909 ∙ Uniprot:O14777 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDC80 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDC80 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			24	1		25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	24	1	3

Variants in NDC80

This is a list of pathogenic ClinVar variants found in the NDC80 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-2573014-G-T		not specified	Uncertain significance (Nov 10, 2022)
18-2573068-G-A		not specified	Uncertain significance (Jul 20, 2021)
18-2575030-C-T		not specified	Uncertain significance (Jun 17, 2024)
18-2575051-C-T		not specified	Uncertain significance (Dec 20, 2021)
18-2577855-C-G		not specified	Uncertain significance (Dec 01, 2022)
18-2578029-G-C		not specified	Uncertain significance (Oct 18, 2021)
18-2578932-C-A		not specified	Uncertain significance (Nov 27, 2023)
18-2578932-C-T		not specified	Uncertain significance (Nov 16, 2021)
18-2578935-T-A		not specified	Uncertain significance (Nov 08, 2022)
18-2585134-A-G		not specified	Uncertain significance (Apr 21, 2022)
18-2585158-C-A		not specified	Uncertain significance (Dec 18, 2023)
18-2587844-C-T			Benign (May 17, 2018)
18-2589218-G-A		not specified	Uncertain significance (Jan 17, 2024)
18-2590046-A-C		not specified	Uncertain significance (Apr 08, 2022)
18-2590076-A-G		not specified	Uncertain significance (Jan 04, 2022)
18-2590081-G-A		not specified	Uncertain significance (Jun 07, 2024)
18-2590087-A-G		not specified	Uncertain significance (Apr 03, 2023)
18-2590105-C-T		not specified	Uncertain significance (Feb 10, 2022)
18-2590159-G-C		not specified	Uncertain significance (Nov 29, 2023)
18-2595464-T-C		not specified	Uncertain significance (Dec 18, 2023)
18-2595531-G-T		not specified	Uncertain significance (Jun 30, 2022)
18-2595568-G-C		not specified	Uncertain significance (Sep 20, 2023)
18-2595630-T-A			Benign (Apr 02, 2018)
18-2599025-A-G		not specified	Likely benign (Aug 12, 2021)
18-2599152-A-G		not specified	Uncertain significance (Aug 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDC80	protein_coding	protein_coding	ENST00000261597	16	45125

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.14e-7	0.999	125715	0	31	125746	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	224	316	0.709	0.0000156	4239
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000502	0.000486
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000108	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.000197	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;Aurora B signaling;PLK1 signaling events (Consensus)

Recessive Scores

• pRec: 0.447

Intolerance Scores

• loftool: 0.789
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.43

Haploinsufficiency Scores

• pHI: 0.718
• hipred: Y
• hipred_score: 0.560
• ghis: 0.671

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.837

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ndc80

Zebrafish Information Network

• Gene name: ndc80
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: flat

Gene ontology

• Biological process: mitotic sister chromatid segregation;establishment of mitotic spindle orientation;mitotic cell cycle;mitotic spindle organization;chromosome segregation;attachment of spindle microtubules to kinetochore;cell division;metaphase plate congression;attachment of mitotic spindle microtubules to kinetochore;kinetochore organization;positive regulation of mitotic cell cycle spindle assembly checkpoint;positive regulation of protein localization to kinetochore
• Cellular component: chromosome, centromeric region;kinetochore;condensed chromosome kinetochore;condensed nuclear chromosome kinetochore;condensed nuclear chromosome outer kinetochore;nucleus;nucleoplasm;centrosome;cytosol;membrane;Ndc80 complex
• Molecular function: protein binding;identical protein binding