NDC80

Summary

NDC80 (NDC80 kinetochore complex component, HGNC:16909) is a protein-coding gene on chromosome 18p11.32, encoding Kinetochore protein NDC80 homolog (O14777). Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

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.

Source: NCBI Gene 10403 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 66 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_006101

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16909
Approved symbol	NDC80
Name	NDC80 kinetochore complex component
Location	18p11.32
Locus type	gene with protein product
Status	Approved
Aliases	HEC, HEC1, hsNDC80, TID3
Ensembl gene	ENSG00000080986
Ensembl biotype	protein_coding
OMIM	607272
Entrez	10403

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000261597, ENST00000574096, ENST00000574567, ENST00000575515, ENST00000576274, ENST00000887758, ENST00000929146, ENST00000929147

RefSeq mRNA: 1 — MANE Select: NM_006101 NM_006101

CCDS: CCDS11827

Canonical transcript exons

ENST00000261597 — 17 exons

Exon	Start	End
ENSE00000521757	2574989	2575066
ENSE00000521765	2585113	2585202
ENSE00000664889	2589204	2589310
ENSE00000664890	2590018	2590162
ENSE00000664891	2595416	2595621
ENSE00000799508	2572977	2573086
ENSE00001016867	2601396	2601485
ENSE00001016868	2606415	2606507
ENSE00001016869	2608700	2608830
ENSE00001147432	2599019	2599171
ENSE00001147512	2571557	2571683
ENSE00001276649	2610759	2610861
ENSE00001276765	2616437	2616635
ENSE00002709622	2587830	2587923
ENSE00003517673	2577746	2577869
ENSE00003706737	2577969	2578141
ENSE00003706940	2578927	2579029

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 96.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2913 / max 354.5567, expressed in 1403 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169099	9.3161	1298
169100	7.9751	1205

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.88	gold quality
ganglionic eminence	UBERON:0004023	92.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.31	gold quality
endometrium epithelium	UBERON:0004811	90.33	gold quality
embryo	UBERON:0000922	90.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.90	gold quality
trabecular bone tissue	UBERON:0002483	86.51	gold quality
amniotic fluid	UBERON:0000173	85.62	gold quality
bone marrow	UBERON:0002371	85.40	gold quality
secondary oocyte	CL:0000655	83.88	gold quality
oocyte	CL:0000023	83.71	gold quality
sperm	CL:0000019	83.29	gold quality
seminal vesicle	UBERON:0000998	82.60	gold quality
esophagus squamous epithelium	UBERON:0006920	81.60	gold quality
mucosa of transverse colon	UBERON:0004991	81.59	gold quality
rectum	UBERON:0001052	81.51	gold quality
male germ cell	CL:0000015	81.25	gold quality
gingival epithelium	UBERON:0001949	80.89	gold quality
buccal mucosa cell	CL:0002336	80.67	silver quality
testis	UBERON:0000473	80.67	gold quality
vermiform appendix	UBERON:0001154	80.33	gold quality
squamous epithelium	UBERON:0006914	79.83	gold quality
left testis	UBERON:0004533	79.61	gold quality
tibia	UBERON:0000979	79.49	gold quality
gingiva	UBERON:0001828	79.42	gold quality
right testis	UBERON:0004534	79.42	gold quality
bone marrow cell	CL:0002092	79.02	gold quality
stromal cell of endometrium	CL:0002255	78.95	gold quality
lower esophagus mucosa	UBERON:0035834	78.67	gold quality
adrenal tissue	UBERON:0018303	77.97	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-99795	yes	303.08
E-MTAB-6678	yes	9.04
E-ANND-3	yes	4.95
E-CURD-11	no	301.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, CREB1, E2F4

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• role in spindle checkpoint signaling; required for the recruitment of Mps1 kinase and Mad1/Mad2 complexes to kinetochores (PMID:12351790)
• cell cycle-regulated serine phosphorylation of Hec1 by Nek2 is essential for faithful chromosome segregation (PMID:12386167)
• HEC1 is a core component of the kinetochore outer plate essential for organizing microtubule attachment sites. (PMID:15548592)
• Altered expression is associated with therapy failure and death in patients with multiple types of cancer. (PMID:15931389)
• the Spc24, Spc25, Nuf2, and Ndc80/Hec1 complex is a faithful copy of the endogenous Ndc80 complex (PMID:15961401)
• These findings reveal a key role for the Hec1 N terminus in controlling dynamic behavior of kinetochore microtubules. (PMID:17129782)
• Study describes the crystal structure of the most conserved region of HEC1, which lies at one end of the rod and near the N terminus of the polypeptide chain, it folds into a calponin-homology domain. (PMID:17195848)
• overexpression of either CREB or ATF4 enhanced the activation of the HEC1 promoter and overexpression of both of them had an additive effect on the activation of the HEC1 transcription. (PMID:17822787)
• that Hec1 binds to microtubule in low affinity and phosphorylation by NEK2A, which prevents aberrant kinetochore-microtubule connections in vivo, increases the affinity of the Ndc80 complex for microtubules in vitro (PMID:18297113)
• The 180 kDa Ndc80 complex is a direct point of contact between kinetochores and microtubules; its four subunits contain coiled coils and form an elongated rod structure with functional globular domains at either end. (PMID:18455984)
• Hec 1 was highhy expressed in cancer tissues with lymph node metastasis and poor differentiation. (PMID:18782526)
• Results suggest that the globular domain of the Ndc80 subunit binds strongly at the interface between tubulin dimers and weakly at the adjacent intradimer interface along the microtubule protofilament axis. (PMID:18794333)
• Data show that the kinetochore localization of PinX1 is dependent on Hec1 and CENP-E. (PMID:19553660)
• Results suggest that Hec1, through cooperation with Hice1, contributes to centrosome-directed microtubule growth to facilitate establishing a proper mitotic spindle. (PMID:19776357)
• cell growths of colorectal and gastric cancers after the siRNA-mediated knockdown of either CDCA1 or KNTC2 were significantly suppressed. (PMID:19878654)
• subnanometre-resolution cryo-electron microscopy reconstruction of the human Ndc80 complex bound to microtubules (PMID:20944740)
• Data provide evidence for a functional link between Hec1 expression and the pRb pathway. (PMID:20948316)
• CENP-U is a novel microtubule binding protein and plays an important role in kinetochore-microtubule attachment through its interaction with Hec1 (PMID:21056971)
• Hec1 phosphorylation control kinetochore-microtubule attachment stability during mitosis. (PMID:21266467)
• These data suggest that the CH and tail domains of Hec1 generate essential contacts between kinetochores and microtubules in cells, whereas the Nuf2 CH domain does not. (PMID:21270439)
• N-terminally modified Hec1 promotes spindle pole fragmentation by CENP-E-mediated plus-end directed kinetochore pulling forces that disrupt the fine balance of kinetochore- and centrosome-associated forces regulating spindle bipolarity (PMID:21297979)
• In vertebrates there is a tripartite attachment point facilitating the interaction between Hec1/Ndc80 and microtubules. (PMID:21325630)
• Alteration in NDC80, were also detected in benign breast tumors. (PMID:21352579)
• Hec1 serine 165 (S165) is preferentially phosphorylated at kinetochores by Nek2 and it serves as an important mechanism in modulating spindle assemble checkpoint signaling and chromosome alignment. (PMID:21832156)
• The Ndc80 internal loop is essential for end-on microtubule attachment to kinetochores. (PMID:22454517)
• results reveal the molecular function of CENP-T proteins and demonstrate how the Ndc80 complex is anchored to centromeres in a manner that couples chromosome movement to spindle dynamics (PMID:22561346)
• results support the conclusion that Cdt1 binding to Hec1 is essential for an extended Ndc80 configuration and stable kinetochore-microtubule attachment (PMID:22581055)
• The Ndc80 kinetochore complex directly modulates microtubule dynamics. (PMID:22908300)
• NDC80, NUF2 and PTN were significantly aberrantly overexpressed in serous adenocarcinomas. (PMID:23056589)
• Ndc80’s interaction with either growing or shrinking microtubule ends can be tuned by the phosphorylation state of its tail. (PMID:23085714)
• Hec1 expression was highest in paclitaxel-resistant A2780/Taxol cells. (PMID:23474708)
• Hec1 is critical in maintaining the in vitro and in vivo growth of gastric cancer cells; elevated Hec1 levels may occur at the early stage of gastric tumorigenesis (PMID:23591767)
• these findings demonstrated that three buried glutamic acid-lysine pairs, in concert with hydrophobic interactions of core residues, provide the major specificity and stability requirements for Hec1-Nuf2 dimerization (PMID:24129578)
• a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis (PMID:24187132)
• Growth inhibition following knockdown of NDC80, CDK1 and PLK1. (PMID:24327015)
• The Ndc80 complex binds straight microtubules by recognizing the dimeric interface of tubulin. (PMID:24413531)
• Certain clinical subtypes of breast cancer more likely to respond to Hec1-targeted therapy were identified and these subtypes are the ones associated with poor prognosis. (PMID:24694948)
• N-terminus-modified Hec1 suppresses tumour growth by interfering with kinetochore-microtubule dynamics (PMID:25132262)
• Overproduction of Ndc80 in cancer cells may unfavourably absorb protein interactors through the internal loop domain and lead to a change in the equilibrium of microtubule-associated proteins. [Review] (PMID:25557589)
• Mechanisms of mitosis-specific assembly of the checkpoint platform Knl1/MIS12/NDC80 at human kinetochores. (PMID:25601404)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndc80	ENSDARG00000071694
mus_musculus	Ndc80	ENSMUSG00000024056
rattus_norvegicus	Ndc80	ENSRNOG00000013727
caenorhabditis_elegans		WBGENE00003576

Protein

Protein identifiers

Kinetochore protein NDC80 homolog — O14777 (reviewed: O14777)

Alternative names: Highly expressed in cancer protein, Kinetochore protein Hec1, Kinetochore-associated protein 2, Retinoblastoma-associated protein HEC

All UniProt accessions (5): O14777, A8K031, I3L0P0, I3L4G3, V9GYM9

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules. Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spindle microtubules.

Subunit / interactions. Component of the NDC80 complex, which consists of NDC80/HEC1, CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24-SPBC25. Each subcomplex is formed by parallel interactions through the coiled-coil domains of individual subunits. Formation of a tetrameric complex is mediated by interactions between the C-terminal regions of both subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 complex has an elongated rod-like structure with globular domains at either end. Interacts with isoform 1 of NEK2 and ZWINT specifically during mitosis. Interacts with CENPH and MIS12. May interact with AURKB, PSMC2, PSMC5 and SMC1A. May interact with RB1 during G2 phase and mitosis. Interacts with CKAP5. Interacts with CDT1; leading to kinetochore localization of CDT1.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Post-translational modifications. Phosphorylation begins in S phase of the cell cycle and peaks in mitosis. Phosphorylated by NEK2. Also phosphorylated by AURKA and AURKB. Acetylated at Lys-53 and Lys-59 by KAT5 during mitosis, promoting robust kinetochore-microtubule attachment. Deacetylated by SIRT1.

Similarity. Belongs to the NDC80/HEC1 family.

RefSeq proteins (1): NP_006092* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005550	Kinetochore_Ndc80	Family
IPR038273	Ndc80_sf	Homologous_superfamily
IPR040967	DUF5595	Domain
IPR055260	Ndc80_CH	Domain
IPR057091	NDC80_loop	Domain

Pfam: PF03801, PF18077, PF24487

UniProt features (45 total): helix 11, modified residue 9, region of interest 8, mutagenesis site 5, turn 4, sequence variant 3, coiled-coil region 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2IGP	X-RAY DIFFRACTION	1.8
8G0P	X-RAY DIFFRACTION	2
2VE7	X-RAY DIFFRACTION	2.88
9N9G	ELECTRON MICROSCOPY	3
3IZ0	ELECTRON MICROSCOPY	8.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14777-F1	78.41	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (9): 44, 53, 55, 59, 62, 69, 165, 242, 527

Mutagenesis-validated functional residues (5):

Position	Phenotype
53	mimics acetylation, leading to increased kinetochore-microtubule attachment; when associated with q-59.
53	impaired acetylation, leading to reduced kinetochore-microtubule attachment; when associated with r-59.
59	mimics acetylation, leading to increased kinetochore-microtubule attachment; when associated with q-53.
59	impaired acetylation, leading to reduced kinetochore-microtubule attachment; when associated with r-53.
234	abrogates binding to rb1.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 421 (showing top): GNF2_CKS1B, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GNF2_MSH2, HORIUCHI_WTAP_TARGETS_DN, GNF2_CENPF, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, MORF_BUB1, GOBP_REGULATION_OF_NUCLEAR_DIVISION, CROONQUIST_NRAS_SIGNALING_DN, GOBP_SPINDLE_LOCALIZATION

GO Biological Process (21): mitotic sister chromatid segregation (GO:0000070), establishment of mitotic spindle orientation (GO:0000132), mitotic cell cycle (GO:0000278), mitotic spindle organization (GO:0007052), spindle assembly involved in female meiosis I (GO:0007057), chromosome segregation (GO:0007059), mitotic spindle assembly checkpoint signaling (GO:0007094), G2/MI transition of meiotic cell cycle (GO:0008315), attachment of spindle microtubules to kinetochore (GO:0008608), skeletal muscle satellite cell proliferation (GO:0014841), regulation of protein stability (GO:0031647), centrosome duplication (GO:0051298), cell division (GO:0051301), metaphase chromosome alignment (GO:0051310), attachment of mitotic spindle microtubules to kinetochore (GO:0051315), kinetochore organization (GO:0051383), positive regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090267), nuclear division (GO:0000280), spindle organization (GO:0007051), chromosome organization (GO:0051276), nuclear chromosome segregation (GO:0098813)

GO Molecular Function (5): microtubule binding (GO:0008017), cyclin binding (GO:0030332), identical protein binding (GO:0042802), kinetochore adaptor activity (GO:0140483), protein binding (GO:0005515)

GO Cellular Component (12): chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), outer kinetochore (GO:0000940), nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), membrane (GO:0016020), nuclear speck (GO:0016607), Ndc80 complex (GO:0031262), chromosome (GO:0005694), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Cell Cycle	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell cycle process	4
cellular anatomical structure	4
mitotic cell cycle	3
mitotic nuclear division	2
mitotic cell cycle process	2
protein binding	2
intracellular membraneless organelle	2
protein-containing complex	2
sister chromatid segregation	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
spindle assembly involved in female meiosis	1
female meiosis I	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
meiotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
meiosis I cell cycle process	1
microtubule binding	1
metaphase chromosome alignment	1
skeletal muscle cell proliferation	1
regulation of biological quality	1
centrosome cycle	1
cellular process	1
chromosome localization	1
nuclear chromosome segregation	1
mitotic metaphase chromosome alignment	1
attachment of spindle microtubules to kinetochore	1
chromosome organization	1
mitotic spindle assembly checkpoint signaling	1
positive regulation of cell cycle process	1
positive regulation of spindle checkpoint	1
regulation of mitotic cell cycle spindle assembly checkpoint	1
organelle fission	1
microtubule cytoskeleton organization	1
organelle organization	1

Protein interactions and networks

STRING

2570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDC80	SPC24	Q8NBT2	998
NDC80	NUF2	Q9BZD4	998
NDC80	SPC25	Q9HBM1	943
NDC80	KNL1	Q8NG31	937
NDC80	AURKB	Q96GD4	856
NDC80	BUB1	O43683	854
NDC80	NEK2	P51955	854
NDC80	MIS12	Q9H081	836
NDC80	CENPE	Q02224	835
NDC80	BUB1B	O60566	794
NDC80	HAUS6	Q7Z4H7	794
NDC80	CENPC	Q03188	793
NDC80	DSN1	Q9H410	788
NDC80	CENPU	Q71F23	774
NDC80	ZW10	O43264	770
NDC80	HAUS8	Q9BT25	770

IntAct

361 interactions, top by confidence:

A	B	Type	Score
NDC80	NUF2	psi-mi:“MI:0915”(physical association)	0.950
NUF2	NDC80	psi-mi:“MI:0915”(physical association)	0.950
NDC80	SPC25	psi-mi:“MI:0915”(physical association)	0.940
SPC25	NDC80	psi-mi:“MI:0915”(physical association)	0.940
ZWINT	NDC80	psi-mi:“MI:0914”(association)	0.940
NDC80	ZWINT	psi-mi:“MI:0915”(physical association)	0.940
ZWINT	NDC80	psi-mi:“MI:0403”(colocalization)	0.940
ZWINT	NDC80	psi-mi:“MI:0915”(physical association)	0.940
NDC80	ZWINT	psi-mi:“MI:0403”(colocalization)	0.940
SPC25	NDC80	psi-mi:“MI:0914”(association)	0.940
NDC80	SPC24	psi-mi:“MI:0915”(physical association)	0.920
NDC80	SPC24	psi-mi:“MI:0914”(association)	0.920
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
WASHC3	NDC80	psi-mi:“MI:0915”(physical association)	0.870
NDC80	WASHC3	psi-mi:“MI:0915”(physical association)	0.870

BioGRID (471): NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), NDC80 (Two-hybrid), TFIP11 (Two-hybrid), MED4 (Two-hybrid), CCDC53 (Two-hybrid), CCHCR1 (Two-hybrid)

ESM2 similar proteins: A0A1L8GVF0, A0A1L8GXM0, A0A8M9PQ61, A2ZAC2, G0SHW7, G5EG17, O14777, O44199, O94383, O95347, P12753, P38989, P41003, P48996, P53692, P70388, Q09591, Q10173, Q12267, Q12749, Q196W6, Q336R3, Q4R630, Q503N2, Q54PK4, Q5U4X5, Q6DRJ7, Q6GQ71, Q6P9I7, Q6Q1P4, Q76I89, Q76I90, Q7ZW63, Q802R8, Q8AWF4, Q8AWF5, Q8CG48, Q90988, Q924W5, Q92878

Diamond homologs: O14777, Q4R630, Q5U4X5, Q6DRJ7, Q76I89, Q8AWF5, Q9D0F1, Q8SUE9, Q17635, Q4WXP0

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
AURKB	down-regulates	NDC80	phosphorylation
NEK2	up-regulates	NDC80	phosphorylation
NDC80	“form complex”	“Ndc80 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Amplification of signal from the kinetochores	11	38.7×	1e-13
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	18	37.5×	8e-22
Mitotic Spindle Checkpoint	11	31.2×	2e-12
EML4 and NUDC in mitotic spindle formation	18	29.8×	3e-20
Resolution of Sister Chromatid Cohesion	18	27.8×	8e-20
RHO GTPases Activate Formins	18	25.0×	4e-19
Mitotic Prometaphase	18	22.2×	3e-18
Separation of Sister Chromatids	19	20.6×	1e-18

GO biological processes:

GO term	Partners	Fold	FDR
attachment of spindle microtubules to kinetochore	8	102.6×	1e-12
attachment of mitotic spindle microtubules to kinetochore	5	72.1×	6e-07
mitotic spindle assembly checkpoint signaling	8	61.6×	6e-11
mitotic sister chromatid segregation	6	39.6×	7e-07
establishment of mitotic spindle orientation	5	33.0×	2e-05
chromosome segregation	12	28.6×	2e-12
mitotic spindle organization	6	22.3×	2e-05
cell division	22	13.9×	7e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

66 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2567 predictions. Top by Δscore:

Variant	Effect	Δscore
18:2571584:G:GT	donor_gain	1.0000
18:2571625:A:G	donor_gain	1.0000
18:2571679:AAAAG:A	donor_loss	1.0000
18:2571680:AAAGG:A	donor_loss	1.0000
18:2571681:AAGGT:A	donor_loss	1.0000
18:2571682:AGG:A	donor_loss	1.0000
18:2571734:G:GT	donor_gain	1.0000
18:2574984:TAAA:T	acceptor_loss	1.0000
18:2574985:A:AG	acceptor_gain	1.0000
18:2574985:AAAGC:A	acceptor_loss	1.0000
18:2574986:A:G	acceptor_gain	1.0000
18:2574986:AAGCA:A	acceptor_loss	1.0000
18:2574987:A:AC	acceptor_loss	1.0000
18:2574987:A:AG	acceptor_gain	1.0000
18:2574988:G:GA	acceptor_gain	1.0000
18:2574988:GC:G	acceptor_gain	1.0000
18:2574988:GCA:G	acceptor_gain	1.0000
18:2574988:GCAA:G	acceptor_gain	1.0000
18:2574988:GCAAA:G	acceptor_gain	1.0000
18:2574990:A:AG	acceptor_gain	1.0000
18:2575062:AAAAG:A	donor_loss	1.0000
18:2575067:G:GC	donor_loss	1.0000
18:2575068:T:G	donor_loss	1.0000
18:2577742:CCAG:C	acceptor_loss	1.0000
18:2577743:CA:C	acceptor_loss	1.0000
18:2577744:A:AG	acceptor_gain	1.0000
18:2577744:AGAA:A	acceptor_loss	1.0000
18:2577745:G:GA	acceptor_gain	1.0000
18:2577745:GA:G	acceptor_gain	1.0000
18:2577745:GAA:G	acceptor_gain	1.0000

AlphaMissense

4266 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:2578976:C:G	H176D	0.999
18:2578982:T:A	W178R	0.999
18:2578982:T:C	W178R	0.999
18:2578968:G:A	G173E	0.998
18:2578971:C:A	A174D	0.998
18:2578946:A:G	K166E	0.997
18:2578948:A:C	K166N	0.997
18:2578948:A:T	K166N	0.997
18:2579009:T:A	W187R	0.997
18:2579009:T:C	W187R	0.997
18:2577818:A:C	R84S	0.996
18:2577818:A:T	R84S	0.996
18:2578965:T:A	V172E	0.996
18:2579001:C:A	A184D	0.996
18:2579013:T:C	L188P	0.996
18:2578984:G:C	W178C	0.995
18:2578984:G:T	W178C	0.995
18:2577817:G:C	R84T	0.994
18:2578947:A:T	K166I	0.994
18:2578949:A:C	S167R	0.994
18:2578951:C:A	S167R	0.994
18:2578951:C:G	S167R	0.994
18:2577832:A:T	K89I	0.993
18:2577833:A:C	K89N	0.993
18:2577833:A:T	K89N	0.993
18:2577862:T:C	L99P	0.993
18:2577973:T:C	L103P	0.993
18:2578024:C:A	P120H	0.993
18:2578928:T:G	Y160D	0.993
18:2578967:G:A	G173R	0.993

dbSNP variants (sampled 300 via entrez): RS1000138505 (18:2572914 A>G), RS1000150520 (18:2616244 C>T), RS1000267845 (18:2585596 C>G,T), RS1000285319 (18:2592325 T>C), RS1000330970 (18:2577327 G>A), RS1000343710 (18:2591836 C>T), RS1000454659 (18:2598736 T>C), RS1000499740 (18:2572885 C>T), RS1000598463 (18:2571477 A>G), RS1000776896 (18:2585306 C>A,T), RS1000839994 (18:2605300 G>T), RS1000840904 (18:2583612 G>A), RS1000932719 (18:2604961 T>C,G), RS1001011260 (18:2605217 T>C), RS1001152152 (18:2614825 A>G)

Disease associations

OMIM: gene MIM:607272 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008361_4	Response to cognitive-behavioural therapy in major depressive disorder	3.000000e-06
GCST009391_1604	Metabolite levels	4.000000e-06
GCST009391_1726	Metabolite levels	7.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0010377	phosphatidylcholine 34:3 measurement
EFO:0010374	phosphatidylcholine 32:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4802034 (PROTEIN-PROTEIN INTERACTION), CHEMBL5660 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

111 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects expression	6
bisphenol A	decreases expression, increases expression	5
Estradiol	increases expression, decreases expression	5
Benzo(a)pyrene	decreases expression	3
Cyclosporine	decreases expression	3
trichostatin A	decreases expression, affects cotreatment	2
sodium arsenite	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	increases abundance, decreases expression	2
Cisplatin	decreases expression, increases expression, affects reaction	2
Doxorubicin	decreases expression, affects response to substance	2
Quercetin	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance	2
ginger extract	decreases expression, increases abundance	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
deoxynivalenol	increases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(k)fluoranthene	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
1,2,5,6-dibenzanthracene	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4685608	Binding	Inhibition of Hec1-Nek2 protein-protein interaction in human K562 cells at 100 nM measured after 6 hrs by coimmunoprecipitation assay	Discovery of T-1101 tosylate as a first-in-class clinical candidate for Hec1/Nek2 inhibition in cancer therapy. — Eur J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.