KIF2C

Summary

KIF2C (kinesin family member 2C, HGNC:6393) is a protein-coding gene on chromosome 1p34.1, encoding Kinesin-like protein KIF2C (Q99661). In complex with KIF18B, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells. It is a selective cancer dependency (DepMap: 23.7% of cell lines).

This gene encodes a kinesin-like protein that functions as a microtubule-dependent molecular motor. The encoded protein can depolymerize microtubules at the plus end, thereby promoting mitotic chromosome segregation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11004 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 113 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 23.7% of screened cell lines
• MANE Select transcript: NM_006845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6393
Approved symbol	KIF2C
Name	kinesin family member 2C
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	MCAK, CT139
Ensembl gene	ENSG00000142945
Ensembl biotype	protein_coding
OMIM	604538
Entrez	11004

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000372217, ENST00000372224, ENST00000423289, ENST00000452259, ENST00000455186, ENST00000472235, ENST00000480574, ENST00000493027, ENST00000858636, ENST00000927009, ENST00000927010, ENST00000927011, ENST00000927012, ENST00000927013, ENST00000927014, ENST00000927015

RefSeq mRNA: 4 — MANE Select: NM_006845 NM_001297655, NM_001297656, NM_001297657, NM_006845

CCDS: CCDS512, CCDS72774

Canonical transcript exons

ENST00000372224 — 21 exons

Exon	Start	End
ENSE00001457243	44767097	44767767
ENSE00001631477	44753132	44753254
ENSE00001652465	44755929	44755983
ENSE00001662209	44761916	44761983
ENSE00001678770	44758049	44758140
ENSE00001689958	44759206	44759348
ENSE00001712066	44760592	44760702
ENSE00001726373	44766826	44766949
ENSE00001747875	44762346	44762451
ENSE00001770471	44760280	44760484
ENSE00001945221	44739837	44740002
ENSE00002151499	44756075	44756237
ENSE00003509550	44750442	44750564
ENSE00003532176	44747384	44747485
ENSE00003579853	44740913	44741007
ENSE00003583659	44757556	44757646
ENSE00003589423	44754750	44754845
ENSE00003591723	44762545	44762658
ENSE00003629091	44753733	44753833
ENSE00003646073	44747652	44747700
ENSE00003784908	44757908	44757971

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 96.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.4772 / max 435.9345, expressed in 1383 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2629	19.8748	1338
2630	1.9365	796
2631	1.1973	575
2628	1.0722	541
2632	0.3043	161
2634	0.0672	5
2633	0.0250	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.88	gold quality
ventricular zone	UBERON:0003053	96.18	gold quality
right testis	UBERON:0004534	95.99	gold quality
left testis	UBERON:0004533	95.82	gold quality
sperm	CL:0000019	95.54	gold quality
oocyte	CL:0000023	95.27	gold quality
male germ cell	CL:0000015	93.48	gold quality
testis	UBERON:0000473	93.41	gold quality
embryo	UBERON:0000922	91.67	gold quality
ganglionic eminence	UBERON:0004023	91.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.34	gold quality
bone marrow	UBERON:0002371	85.82	gold quality
trabecular bone tissue	UBERON:0002483	83.91	gold quality
amniotic fluid	UBERON:0000173	83.60	gold quality
stromal cell of endometrium	CL:0002255	81.74	gold quality
bone marrow cell	CL:0002092	81.34	gold quality
mucosa of transverse colon	UBERON:0004991	80.37	gold quality
endometrium epithelium	UBERON:0004811	79.97	gold quality
esophagus squamous epithelium	UBERON:0006920	79.53	gold quality
rectum	UBERON:0001052	78.92	gold quality
squamous epithelium	UBERON:0006914	78.48	gold quality
thymus	UBERON:0002370	78.05	gold quality
ileal mucosa	UBERON:0000331	77.97	gold quality
epithelium of esophagus	UBERON:0001976	77.70	gold quality
esophagus mucosa	UBERON:0002469	77.61	gold quality
gingival epithelium	UBERON:0001949	77.31	gold quality
vermiform appendix	UBERON:0001154	77.09	gold quality
lower esophagus mucosa	UBERON:0035834	76.90	gold quality
cervix squamous epithelium	UBERON:0006922	76.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	252.51
E-MTAB-6678	yes	7.77
E-ANND-3	yes	4.53
E-GEOD-99795	no	347.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, SP1, TP53

miRNA regulators (miRDB)

21 targeting KIF2C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-3059-3P	96.71	67.08	606
HSA-MIR-3162-5P	95.67	67.53	794
HSA-MIR-6075	93.03	64.73	45

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• identification as a candidate gene for the testis-specific KRPs and its specific expression in the testis was correlated with spermatogenesis and may be correlated with male infertility (PMID:12383881)
• MCAK has a role in bipolar spindle assembly along with Kif2a (PMID:15302853)
• MCAK is a microtubule-catastrophe promoting factor in vitro, and may serve as a catastrophe-promoting factor in cells. (PMID:15304328)
• We propose that tip tracking is a mechanism by which MCAK is preferentially localized to regions of the cell that modulate the plus ends of MTs. (PMID:15883193)
• Spindles in human mitotic cells depleted of the kinesin-13 proteins Kif2a and MCAK lack detectable flux and that such cells frequently fail to segregate all chromosomes appropriately at anaphase. (PMID:16243029)
• MCAK moves along the microtubule lattice in a one-dimensional (1D) random walk (PMID:16672973)
• These data demonstrate that Kif2b function is required for spindle assembly and chromosome movement and that the microtubule depolymerase activities of Kif2a, Kif2b, and MCAK fulfill distinct functions during mitosis in human cells. (PMID:17538014)
• Elevated expression of MCAK may be associated with lymphatic invasion, lymph node metastasis, and poor prognosis in gastric cancer. (PMID:17653072)
• KIF2C/MCAK expression was significantly suppressed by ectopic introduction of p53. Findings suggest that overexpression of KIF2C/MCAK might be involved in breast carcinogenesis (PMID:17944972)
• MCAK is held in an inactive conformation when associated with EB1 (PMID:17968321)
• Sp1-binding to the GC-motifs was crucial for promoter activation, but the E2F1-binding to the E2F-motif was crucial for promoter repression. (PMID:18440323)
• MCAK expression was higher in colorectal cancer tissue than in corresponding normal tissue; elevated expression level was markedly associated with factors such as lymph node metastasis, venous invasion, peritoneal dissemination & Dukes’ classification (PMID:18506187)
• A novel function of Aurora-A, the regulation of ch-TOG and MCAK localization, in a common pathway in control of spindle pole integrity. (PMID:18663358)
• ch-Tog has at least two distinct roles in spindle formation: it protects kinetochore microtubules from depolymerization by MCAK, and ch-Tog plays an essential role in centrosomal microtubule assembly, a function independent of MCAK activity. (PMID:18809577)
• These studies indicate that MCAK activity is limited during the latter stages of mitosis by protein degradation, and argue against a role for the protein in anaphase chromosome movement. (PMID:18843200)
• A point mutation of the kinesin-13 family member mitotic centromere-associated kinesin/Kif2C (E491A) isolates the tubulin-removal conformation of the motor (PMID:19001124)
• Here we show that two microtubule-depolymerizing kinesins, Kif2b and MCAK, stimulate kinetochore-microtubule dynamics during distinct phases of mitosis to correct mal-orientations. (PMID:19060894)
• TIP150 facilitates the EB1-dependent loading of MCAK onto MT plus ends and orchestrates the dynamics at the plus end of MTs. (PMID:19543227)
• Mitotic cells deficient in MCAK fail to maintain spindle bipolarity in the absence of Eg5 activity. (PMID:19931454)
• Data show that Cdk1 regulates the localization and activity of mitotic centromere-associated kinesin (MCAK) in mitosis by directly phosphorylating the catalytic core domain of MCAK. (PMID:20368358)
• MCAK appears to possess a unique distribution and function in oocyte maturation. (PMID:20406800)
• identified the phosphorylation of hSgo2 by Aurora B at the N-terminal coiled-coil region and the middle region, and showed that these phosphorylations separately promote binding of hSgo2 to PP2A and MCAK (PMID:20889715)
• dynamic regulation of MCAK phosphorylation by PLK1 is required to orchestrate faithful cell division (PMID:21078677)
• The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer. (PMID:21165574)
• MCAK and CENP-E are involved in DDA3-mediated chromosome congression (PMID:21426902)
• Mitotic centromere-associated kinesin (MCAK)has the ability to stimulate microtubule depolymerization. (PMID:21471284)
• Abeta impairs the assembly and maintenance of the mitotic spindle. Mechanistically, these defects result from Abeta’s inhibition of mitotic motor kinesins, including Eg5, KIF4A and MCAK. (PMID:21566458)
• Results provide a simple model for the generation of driving force and the regulation of chromosome segregation by the activity of MCAK at both kinetochores and spindle poles through a ‘side-sliding, end-catching’ mechanism. (PMID:21602793)
• Results uncover a novel role for Aurora A/B kinases in regulating spindle MT dynamics through Kif18b-MCAK and suggest that the Kif18b-MCAK complex constitutes the major MT plus-end depolymerizing activity in mitotic cells. (PMID:21820309)
• The mitotic centromere-associated kinesin (MCAK) was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple castration-resistant prostate cancer gene-expression datasets. (PMID:22363599)
• a mechanism in which, in the first step, the specificity of ATP-bound Kif2C for soluble tubulin causes it to stabilize a curved conformation of tubulin heterodimers at the ends of microtubules. (PMID:22403406)
• study identifed and defined a mitotic function specific to the microtubule tip-associated population of MCAK: negative regulation of microtubule length within the assembling bipolar spindle. (PMID:22492725)
• PAK1 phosphorylates MCAK and regulates both its localization and function. (PMID:23055517)
• Results suggest that MCAK/Kif2C plays an important role in the regulation of cellular senescence through a p53-dependent pathway and might contribute to tissue/organism aging and protection of cellular transformation. (PMID:23098759)
• result suggested E403K mutation in mitotic centromere-associated kinesin protein as highly damaging and showed strong concordance to the previously observed colorectal cancer mutations aggregation tendency and energy value changes (PMID:23564489)
• expression has no effect on the level of the TRAIL receptors DR4 and DR5. These findings might have clinical implications since the combination of TRAIL therapy with administration of Pgp modulators might sensitize TRAIL resistant tumors. (PMID:23830822)
• A CENP-E mediated wall-tethering event and a MCAK-mediated wall-removing event show that human chromosome-microtubule attachment is achieved through a set of deterministic sequential events rather than stochastic direct capture of microtubule ends. (PMID:23891108)
• Ras regulates KIF2C to control cell migration pathways in transformed human bronchial epithelial cells. (PMID:24240690)
• A dynamic interaction of MCAK-TIP150 orchestrated by Aurora A-mediated phosphorylation governs entosis via regulating microtubule plus-end dynamics and cell rigidity. (PMID:24847103)
• this study suggests a new mechanism by which Plk1 regulates MCAK: by regulating its degradation and hence controlling its turnover in mitosis. (PMID:24931513)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kif2c	ENSMUSG00000028678
rattus_norvegicus	Kif2c	ENSRNOG00000019100
drosophila_melanogaster	Klp10A	FBGN0030268
drosophila_melanogaster	Klp59C	FBGN0034824
drosophila_melanogaster	Klp59D	FBGN0034827
caenorhabditis_elegans		WBGENE00002219

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF22 (ENSG00000079616), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF3B (ENSG00000101350), KIF20A (ENSG00000112984), KIF21B (ENSG00000116852), KIF17 (ENSG00000117245), KIF14 (ENSG00000118193), KIF18A (ENSG00000121621), KIF25 (ENSG00000125337), KIF1C (ENSG00000129250), KIF1A (ENSG00000130294), KIF3A (ENSG00000131437), KIF12 (ENSG00000136883), KIF13A (ENSG00000137177), KIF23 (ENSG00000137807), KIF11 (ENSG00000138160), CENPE (ENSG00000138778), KIF21A (ENSG00000139116), KIFC3 (ENSG00000140859), KIF2B (ENSG00000141200), KIF5A (ENSG00000155980), KIF26B (ENSG00000162849), KIF15 (ENSG00000163808), KIF6 (ENSG00000164627), KIF27 (ENSG00000165115), KIF7 (ENSG00000166813), KIFC2 (ENSG00000167702), KIF5C (ENSG00000168280), KIF5B (ENSG00000170759), KIF18B (ENSG00000186185), KIF24 (ENSG00000186638), KIF19 (ENSG00000196169), KIF13B (ENSG00000197892), KIF4B (ENSG00000226650)

Protein

Protein identifiers

Kinesin-like protein KIF2C — Q99661 (reviewed: Q99661)

Alternative names: Kinesin-like protein 6, Mitotic centromere-associated kinesin

All UniProt accessions (5): Q99661, A0A140VKF1, H0Y5Z9, Q5JR89, Q5JR91

UniProt curated annotations — full annotation on UniProt →

Function. In complex with KIF18B, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells. Regulates the turnover of microtubules at the kinetochore and functions in chromosome segregation during mitosis. Plays a role in chromosome congression and is required for the lateral to end-on conversion of the chromosome-microtubule attachment.

Subunit / interactions. Interacts with CENPH. Interacts with MTUS2/TIP150; the interaction is direct. Interacts with MAPRE1; the interaction is direct, regulated by phosphorylation and is probably required for targeting to growing microtubule plus ends. Interacts with KIF18B at microtubule tips; this interaction increases the affinity of both partners for microtubule plus ends and is required for robust microtubule depolymerization. Phosphorylation by AURKA or AURKB strongly reduces KIF18B-binding.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus. Chromosome. Centromere. Kinetochore.

Tissue specificity. Expressed at high levels in thymus and testis, at low levels in small intestine, the mucosal lining of colon, and placenta, and at very low levels in spleen and ovary; expression is not detected in prostate, peripheral blood Leukocytes, heart, brain, lung, liver, skeletal muscle, kidney or pancreas. Isoform 2 is testis-specific.

Post-translational modifications. Phosphorylation by AURKB, regulates association with centromeres and kinetochores and the microtubule depolymerization activity. Ubiquitinated.

Domain organisation. The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. MCAK/KIF2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99661-1	1	yes
Q99661-2	2, tsMCAK

RefSeq proteins (4): NP_001284584, NP_001284585, NP_001284586, NP_006836* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027640	Kinesin-like_fam	Family
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR054473	KIF2A-like_N	Domain

Pfam: PF00225, PF22923

Enzyme classification (BRENDA):

• EC 5.6.1.3 — plus-end-directed kinesin ATPase (BRENDA: 34 organisms, 94 substrates, 257 inhibitors, 53 Km, 52 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	—	45
ALEXA FLUOR 647 ATP	0.032	1
METHYLANTHRANILOYL-ATP	0.0004	1
ADP	—	0
PHOSPHATE	—	0

UniProt features (67 total): strand 17, modified residue 15, helix 15, mutagenesis site 4, region of interest 3, binding site 2, turn 2, short sequence motif 2, initiator methionine 1, chain 1, domain 1, splice variant 1, sequence variant 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2HEH	X-RAY DIFFRACTION	2.15
4Y05	X-RAY DIFFRACTION	2.59
4UBF	X-RAY DIFFRACTION	3
5MIO	X-RAY DIFFRACTION	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99661-F1	74.61	0.40

Functional residue map

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

Ligand- & substrate-binding residues (2): 348–355; 264

Post-translational modifications (15): 2, 6, 22, 95, 106, 109, 111, 115, 166, 175, 187, 192, 519, 621, 633

Mutagenesis-validated functional residues (4):

Position	Phenotype
95	alters interaction with mapre1 and association with microtubule growing ends; when associated with e-109 and e-111.
100–101	loss of interaction with mapre1 and association with microtubule growing ends.
109	alters interaction with mapre1 and association with microtubule growing ends; when associated with e-95 and e-111.
111	alters interaction with mapre1 and association with microtubule growing ends; when associated with e-95 and e-109.

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2132295	MHC class II antigen presentation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
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-8856688	Golgi-to-ER retrograde transport
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 403 (showing top): GNF2_CKS1B, RNGTGGGC_UNKNOWN, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, HORIUCHI_WTAP_TARGETS_DN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_BUB1, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, CROONQUIST_NRAS_SIGNALING_DN, OHASHI_AURKB_TARGETS, GOBP_CHROMOSOME_LOCALIZATION, GOCC_KINESIN_COMPLEX, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (12): microtubule-based movement (GO:0007018), microtubule depolymerization (GO:0007019), mitotic metaphase chromosome alignment (GO:0007080), establishment or maintenance of microtubule cytoskeleton polarity (GO:0030951), cell division (GO:0051301), metaphase chromosome alignment (GO:0051310), attachment of mitotic spindle microtubules to kinetochore (GO:0051315), regulation of chromosome segregation (GO:0051983), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696), postsynaptic cytoskeleton organization (GO:0099188), mitotic sister chromatid segregation (GO:0000070), chromosome segregation (GO:0007059)

GO Molecular Function (9): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), ATP hydrolysis activity (GO:0016887), centromeric DNA binding (GO:0019237), microtubule plus-end binding (GO:0051010), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), protein binding (GO:0005515)

GO Cellular Component (18): chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), microtubule plus-end (GO:0035371), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), chromosome (GO:0005694), cytoskeleton (GO:0005856), cytoplasmic microtubule (GO:0005881)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Adaptive Immune System	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Golgi-to-ER retrograde transport	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	4
mitotic cell cycle process	3
synapse	3
ATP-dependent activity	2
microtubule cytoskeleton	2
cytoplasm	2
microtubule-based process	1
microtubule polymerization or depolymerization	1
protein depolymerization	1
supramolecular fiber organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
microtubule cytoskeleton organization	1
establishment or maintenance of cytoskeleton polarity	1
cellular process	1
chromosome localization	1
nuclear chromosome segregation	1
mitotic metaphase chromosome alignment	1
attachment of spindle microtubules to kinetochore	1
chromosome segregation	1
regulation of cell cycle process	1
regulation of biological quality	1
neurotransmitter receptor localization to postsynaptic specialization membrane	1
regulation of protein localization to synapse	1
regulation of receptor localization to synapse	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
cytoskeleton organization	1
postsynapse organization	1
sister chromatid segregation	1
mitotic nuclear division	1
cell cycle process	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
ribonucleoside triphosphate phosphatase activity	1

Protein interactions and networks

STRING

2096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF2C	AURKB	Q96GD4	975
KIF2C	BUB1	O43683	964
KIF2C	CENPA	P49450	924
KIF2C	CENPF	P49454	907
KIF2C	SGO2	Q562F6	888
KIF2C	BUB1B	O60566	863
KIF2C	KIF18B	Q86Y91	845
KIF2C	AURKA	O14965	834
KIF2C	INCENP	Q9NQS7	832
KIF2C	HASPIN	Q8TF76	827
KIF2C	BIRC5	O15392	810
KIF2C	CDCA8	Q53HL2	810
KIF2C	CDC20	Q12834	788
KIF2C	MAPRE1	Q15691	784
KIF2C	PLK1	P53350	778

IntAct

111 interactions, top by confidence:

A	B	Type	Score
MAPRE1	KIF2C	psi-mi:“MI:0915”(physical association)	0.890
KIF2C	MAPRE1	psi-mi:“MI:0407”(direct interaction)	0.890
MAPRE1	KIF2C	psi-mi:“MI:0407”(direct interaction)	0.890
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
RELL2	OXSR1	psi-mi:“MI:0914”(association)	0.830
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
KIF2C	SGF29	psi-mi:“MI:0915”(physical association)	0.620
MAPRE1	MTUS2	psi-mi:“MI:0914”(association)	0.620
MTUS2	KIF2C	psi-mi:“MI:0914”(association)	0.560
KIF2C	MTUS2	psi-mi:“MI:0914”(association)	0.560
KIF2C	MTUS2	psi-mi:“MI:0407”(direct interaction)	0.560
KIF2C	KIF2A	psi-mi:“MI:0914”(association)	0.530
KLHL40	CBX4	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
KIF2B	BACH1	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530
DUSP3	ERLIN1	psi-mi:“MI:0914”(association)	0.530
FBXO11	LONP1	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
SGO2	PPP1CA	psi-mi:“MI:0914”(association)	0.460
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
VHL	KIF2C	psi-mi:“MI:0915”(physical association)	0.370
ZNF566	KIF2C	psi-mi:“MI:0915”(physical association)	0.370
CSNK2B	KIF2C	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (229): KIF2C (Affinity Capture-RNA), KIF2C (Affinity Capture-RNA), KIF2C (Reconstituted Complex), KIF2C (Affinity Capture-Western), KIF2C (Affinity Capture-MS), KIF2C (Affinity Capture-MS), PLK1 (Affinity Capture-Western), KIF2C (Biochemical Activity), GOT1 (Co-fractionation), HSPA14 (Co-fractionation), KIF2C (Co-fractionation), KIF2C (Co-fractionation), KIF2C (Co-fractionation), KIF2C (Co-fractionation), PCBP2 (Co-fractionation)

ESM2 similar proteins: A2ZRG4, A6H750, B9EUM5, B9EY52, B9FMJ3, B9FS33, F4I1T9, F4IGL2, F4J2M6, F4J394, F4JUI9, L0N7N1, O00139, O59751, O95235, P28740, P70096, P97329, Q10MN5, Q29RT6, Q2NL05, Q5R9Y9, Q5T7B8, Q5XI51, Q5ZKV8, Q5ZLK6, Q62909, Q651Z7, Q6H638, Q6NWW5, Q6Z9D2, Q7X7H4, Q7XKR9, Q80TF6, Q8C0N1, Q8LNZ2, Q8N4N8, Q8S949, Q8W0Y9, Q91636

Diamond homologs: A0A068FIK2, A1ZAJ2, A6H750, A8BKD1, B7EJ91, B7ZNG0, B9EY52, B9F2Y7, B9F7C8, B9FMJ3, E2RTQ2, F1M4A4, F4ICA0, F4IIS5, F4K0J3, L0N7N1, O00139, O14343, O15066, O23826, O35071, O35787, O43896, O45935, O59751, O60282, O95239, P21613, P23678, P28740, P28741, P33173, P33174, P33176, P46863, P46867, P46874, P53086, P70096, P82266

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
AURKB	up-regulates	KIF2C	phosphorylation
AURKB	down-regulates	KIF2C	phosphorylation
CDK1	down-regulates	KIF2C	phosphorylation
PAK1	down-regulates	KIF2C	phosphorylation
KIF2C	up-regulates	“Plus-end directed sliding movement”
KIF2C	up-regulates	“Minus-end directed microtubule movement”
PLK1	“up-regulates activity”	KIF2C	phosphorylation
PLK1	“down-regulates quantity by destabilization”	KIF2C	phosphorylation
APC-c	“down-regulates quantity by destabilization”	KIF2C	ubiquitination
AURKA	“down-regulates activity”	KIF2C	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 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	6	11.7×	8e-04
SARS-CoV-1-host interactions	6	10.4×	1e-03
Mitotic Spindle Checkpoint	6	9.4×	2e-03
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	8	9.2×	2e-04
SARS-CoV-1 Infection	6	8.5×	3e-03
EML4 and NUDC in mitotic spindle formation	9	8.3×	2e-04
SARS-CoV-2-host interactions	7	8.2×	1e-03
Cell Cycle Checkpoints	9	7.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	7	14.8×	2e-04
canonical NF-kappaB signal transduction	5	14.2×	4e-03
mRNA transport	6	12.2×	2e-03
mRNA splicing, via spliceosome	9	6.4×	2e-03
cell division	17	6.1×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2469 predictions. Top by Δscore:

Variant	Effect	Δscore
1:44747378:TTGCA:T	acceptor_loss	1.0000
1:44747379:TGCA:T	acceptor_loss	1.0000
1:44747380:GCAG:G	acceptor_loss	1.0000
1:44747381:CA:C	acceptor_loss	1.0000
1:44747382:A:AG	acceptor_gain	1.0000
1:44747382:AG:A	acceptor_loss	1.0000
1:44747382:AGATT:A	acceptor_gain	1.0000
1:44747383:G:GA	acceptor_gain	1.0000
1:44747383:GAT:G	acceptor_gain	1.0000
1:44747383:GATT:G	acceptor_gain	1.0000
1:44747383:GATTG:G	acceptor_gain	1.0000
1:44747482:CCAGG:C	donor_loss	1.0000
1:44747486:G:GA	donor_loss	1.0000
1:44747487:T:G	donor_loss	1.0000
1:44747646:TTTCA:T	acceptor_loss	1.0000
1:44747647:TTCA:T	acceptor_loss	1.0000
1:44747648:TCA:T	acceptor_loss	1.0000
1:44747649:CAGA:C	acceptor_loss	1.0000
1:44747650:A:AG	acceptor_gain	1.0000
1:44747651:G:GG	acceptor_gain	1.0000
1:44747651:GA:G	acceptor_gain	1.0000
1:44747651:GAA:G	acceptor_gain	1.0000
1:44747651:GAAA:G	acceptor_gain	1.0000
1:44747651:GAAAC:G	acceptor_gain	1.0000
1:44747696:AGAAA:A	donor_gain	1.0000
1:44747697:GAAA:G	donor_gain	1.0000
1:44747697:GAAAG:G	donor_gain	1.0000
1:44747698:A:T	donor_gain	1.0000
1:44747698:AAA:A	donor_gain	1.0000
1:44747698:AAAGT:A	donor_loss	1.0000

AlphaMissense

4806 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:44760390:T:C	L493P	1.000
1:44760480:T:C	L523P	1.000
1:44760484:G:C	K524N	1.000
1:44760484:G:T	K524N	1.000
1:44760597:C:G	C526W	1.000
1:44760634:T:C	F539L	1.000
1:44760636:C:A	F539L	1.000
1:44760636:C:G	F539L	1.000
1:44761968:T:C	L579P	1.000
1:44740975:T:A	W45R	0.999
1:44740975:T:C	W45R	0.999
1:44740977:G:C	W45C	0.999
1:44740977:G:T	W45C	0.999
1:44755951:T:A	V261D	0.999
1:44755957:T:A	V263D	0.999
1:44755960:G:C	R264T	0.999
1:44755960:G:T	R264M	0.999
1:44755961:G:C	R264S	0.999
1:44755961:G:T	R264S	0.999
1:44755965:C:A	R266S	0.999
1:44757608:T:C	C344R	0.999
1:44757612:T:C	F345S	0.999
1:44757621:G:A	G348D	0.999
1:44757621:G:T	G348V	0.999
1:44757630:G:A	G351E	0.999
1:44757632:A:C	S352R	0.999
1:44757634:T:A	S352R	0.999
1:44757634:T:G	S352R	0.999
1:44757636:G:A	G353D	0.999
1:44757638:A:C	K354Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000155121 (1:44766177 G>C,T), RS1000274274 (1:44741404 G>A,T), RS1000300933 (1:44755150 G>A,T), RS1000320123 (1:44747667 T>C,G), RS1000479307 (1:44765461 TAAAAAA>T,TAA,TAAAAA), RS1000495067 (1:44742821 G>A), RS1000583779 (1:44741664 G>A,C), RS1000836485 (1:44765727 C>T), RS1000895058 (1:44742067 T>C), RS1000946525 (1:44740245 G>T), RS1001033336 (1:44742585 G>A), RS1001276080 (1:44767393 G>A), RS1001470632 (1:44759504 A>G), RS1001504331 (1:44742733 AAAAAC>A), RS1001528386 (1:44752638 G>A)

Disease associations

OMIM: gene MIM:604538 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5967 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	Kd	20.01	nM	CHEMBL3752910
7.70	ED50	20.01	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 25 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149876: Binding affinity to human KIF2C incubated for 45 mins by Kinobead based pull down assay	kd	0.0200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, affects cotreatment	4
sodium arsenite	increases abundance, increases expression, decreases expression	3
Valproic Acid	affects expression, decreases expression	3
Cyclosporine	decreases expression	3
cobaltous chloride	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Estradiol	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
propionaldehyde	decreases expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
caffeic acid	decreases reaction, increases expression	1
diallyl trisulfide	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1020056	Binding	Inhibition of cloned human MCAK	Kinesin spindle protein (KSP) inhibitors. 9. Discovery of (2S)-4-(2,5-difluorophenyl)-n-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the treatment of taxane-refractory cancer. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SU80	HAP1 KIF2C (-) 1	Cancer cell line	Male
CVCL_SU81	HAP1 KIF2C (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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