KIF2A

Summary

KIF2A (kinesin family member 2A, HGNC:6318) is a protein-coding gene on chromosome 5q12.1, encoding Kinesin-like protein KIF2A (O00139). Plus end-directed microtubule-dependent motor required for normal brain development. It is a selective cancer dependency (DepMap: 18.7% of cell lines).

The protein encoded by this gene is a plus end-directed motor required for normal mitotic progression. The encoded protein is required for normal spindle activity during mitosis and is necessary for normal brain development. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3796 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex cortical dysplasia with other brain malformations 3 (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 658 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 18.7% of screened cell lines
• MANE Select transcript: NM_001098511

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6318
Approved symbol	KIF2A
Name	kinesin family member 2A
Location	5q12.1
Locus type	gene with protein product
Status	Approved
Aliases	HK2
Ensembl gene	ENSG00000068796
Ensembl biotype	protein_coding
OMIM	602591
Entrez	3796

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 24 protein_coding, 7 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000381103, ENST00000401507, ENST00000407818, ENST00000504883, ENST00000506857, ENST00000509624, ENST00000512006, ENST00000512541, ENST00000514082, ENST00000673733, ENST00000674632, ENST00000674733, ENST00000674751, ENST00000674752, ENST00000674916, ENST00000675085, ENST00000675387, ENST00000675534, ENST00000676122, ENST00000676271, ENST00000676413, ENST00000908143, ENST00000908144, ENST00000908145, ENST00000908146, ENST00000908147, ENST00000908148, ENST00000908149, ENST00000927777, ENST00000927778, ENST00000927779, ENST00000927780

RefSeq mRNA: 4 — MANE Select: NM_001098511 NM_001098511, NM_001243952, NM_001243953, NM_004520

CCDS: CCDS3980, CCDS47216, CCDS58949, CCDS93716

Canonical transcript exons

ENST00000407818 — 21 exons

Exon	Start	End
ENSE00000549144	62381118	62381253
ENSE00000748339	62352588	62352710
ENSE00000748340	62353275	62353375
ENSE00000748341	62355159	62355254
ENSE00000748342	62357691	62357745
ENSE00000748343	62358137	62358299
ENSE00000748345	62361242	62361332
ENSE00000748347	62361466	62361529
ENSE00000748348	62362450	62362541
ENSE00000748349	62363178	62363320
ENSE00000748351	62363695	62363899
ENSE00000748352	62365243	62365353
ENSE00000748370	62366414	62366481
ENSE00000748401	62373687	62373837
ENSE00000748403	62377661	62377762
ENSE00001552899	62372438	62372551
ENSE00001829215	62385484	62391025
ENSE00003496543	62348048	62348167
ENSE00003502071	62350066	62350120
ENSE00003599040	62347130	62347224
ENSE00003898030	62306206	62306536

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 97.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 70.8668 / max 1176.9964, expressed in 1825 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56641	28.9135	1788
56639	18.7976	1803
56640	15.9370	1788
56637	6.0980	1556
56638	1.0897	666
56636	0.0309	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.27	gold quality
corpus callosum	UBERON:0002336	96.58	gold quality
ganglionic eminence	UBERON:0004023	95.17	gold quality
monocyte	CL:0000576	94.37	gold quality
mononuclear cell	CL:0000842	94.29	gold quality
sperm	CL:0000019	94.12	gold quality
leukocyte	CL:0000738	94.01	gold quality
ventricular zone	UBERON:0003053	93.92	gold quality
lateral globus pallidus	UBERON:0002476	93.85	gold quality
embryo	UBERON:0000922	93.82	gold quality
sural nerve	UBERON:0015488	93.42	gold quality
male germ cell	CL:0000015	93.09	gold quality
subthalamic nucleus	UBERON:0001906	92.62	gold quality
adrenal tissue	UBERON:0018303	92.61	gold quality
globus pallidus	UBERON:0001875	92.43	gold quality
substantia nigra pars compacta	UBERON:0001965	92.41	gold quality
superior vestibular nucleus	UBERON:0007227	92.36	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.27	gold quality
pons	UBERON:0000988	92.20	gold quality
medial globus pallidus	UBERON:0002477	91.92	gold quality
inferior vagus X ganglion	UBERON:0005363	91.86	gold quality
postcentral gyrus	UBERON:0002581	91.63	gold quality
entorhinal cortex	UBERON:0002728	91.58	gold quality
colonic epithelium	UBERON:0000397	91.07	gold quality
parietal lobe	UBERON:0001872	91.05	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.01	gold quality
superior frontal gyrus	UBERON:0002661	90.86	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.80	gold quality
ventral tegmental area	UBERON:0002691	90.54	gold quality
calcaneal tendon	UBERON:0003701	90.07	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	38.02
E-HCAD-4	yes	29.72
E-CURD-122	yes	23.99
E-MTAB-7316	yes	21.69
E-MTAB-9221	yes	20.51
E-HCAD-6	yes	19.38
E-MTAB-9067	yes	10.96
E-ANND-3	yes	7.04
E-HCAD-1	yes	5.34
E-CURD-55	no	841.54
E-GEOD-137537	no	3.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

139 targeting KIF2A, 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-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-10523-5P	99.91	69.22	2038

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Kif2a has a role in bipolar spindle assembly along with MCAK (PMID:15302853)
• 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)
• KIF2 gene, located at 5q12.1, is a potential schizophrenia susceptibility gene (PMID:16959419)
• kinesin-1, but not kinesin-2, contributes to the specific cytoplasmic distribution of three of the four steps of VV morphogenesis tested. (PMID:17394562)
• 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)
• DDA3 interacts with the MT depolymerase Kif2a in an microtubule-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. (PMID:18411309)
• Data show that Kif2a is regulated positively by Plk1 and negatively by Aurora A, and suggest that this antagonistic regulation confers differential stability to microtubules in the spindle versus at the pole versus in the cytosol. (PMID:19351716)
• Targeting of integrin beta1 and kinesin 2alpha by microRNA 183. (PMID:19940135)
• Data show that 4-oxo-4-HPR inhibited tubulin polymerization and modulated gene expression of spindle aberration associated genes Kif 1C, Kif 2A, Eg5, Tara, tankyrase-1, centractin, and TOGp. (PMID:19996280)
• The kinesin-2 deficiency weakened intercellular adhesion, despite the maintenance of adherens junctions and other desmosome components at the plasma membrane. (PMID:22184201)
• The distribution of Kif2A was limited to the distal ends of the central spindle through Aurora B-dependent phosphorylation and exclusion from the spindle midzone. (PMID:23960144)
• Ras regulates KIF2A to control cell migration pathways in transformed human bronchial epithelial cells. (PMID:24240690)
• Silencing Kif2a induces apoptosis and decreases the mRNA and protein level of PI3K, Akt and Bcell lymphoma 2 (Bcl2) in Tca8113 cells. (PMID:24248467)
• KIF2A may play an important role in breast cancer progression and is potentially a novel predictive and prognostic marker for breast cancer. (PMID:24950762)
• up-regulation of KIF2C and KIF2A by ERK1/2 caused aberrant lysosomal positioning and mTORC1 activity in a mutant K-Ras-dependent cancer and cancer model. (PMID:25002494)
• This study demonstrated colorectal cancer (CRC) tissue-preferred expression pattern of the KIF2A and suggested that high KIF2A expression might serve as an independent maker for poor prognosis in CRC patients. (PMID:26070867)
• TTBK2 phosphorylates KIF2A and antagonizes KIF2A-induced depolymerization at microtubules plus ends for cell migration. (PMID:26323690)
• KIF2A may be important in glioma progression. (PMID:26707290)
• Mdp3 (also known as MAP7D3) forms a complex with DDA3 (also known as PSRC1) and controls spindle dynamics at the minus end of Microtubuless by inhibiting DDA3-mediated Kif2a recruitment to the spindle. (PMID:27284004)
• The effect of Kif2A Knockdown on spreading could be rescued by expression of Kif2A-GFP or FLAG-AGAP1, but not by Kif2C-GFP. The results support the hypothesis that the Kif2A.AGAP1 complex contributes to control of cytoskeleton remodeling involved in cell movement. (PMID:27531749)
• High KIF2A expression is associated with Gastric Cancer. (PMID:27773961)
• The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1) regulate the expression of mitotic kinesins in breast cancer cells. (PMID:28061449)
• these data provide the first evidence that increased KIF2A expression predicts poor prognosis in patients with diffuse large B cell lymphoma, and a rationale for treatment of DLBCL by targeting KIF2A. (PMID:28616658)
• have identified a conserved WDR5 interaction (Win) motif, so far unique to the Mixed-lineage leukemia family (PMID:28633016)
• Study used high-resolution single-molecule microscopy to directly observe the stepping behavior of kinesin-1 and -2 family motors with different length neck-linker domains. Results provide a kinetic framework for explaining kinesin processivity and for mapping structural differences to functional differences in diverse kinesin isoforms. (PMID:28636917)
• Furthermore, silencing KIF2A inhibited cell proliferation and induced apoptosis in lung adenocarcinoma(LUAD) cells. In conclusion, KIF2A may serve as a valuable prognostic indicator and promising therapeutic target of LUAD. (PMID:29427669)
• down-regulation of KIF2A can inhibit gastric cancer cell invasion by suppressing MT1-MMP (PMID:29781531)
• the crystal structure of a catalytically active kinesin-13 monomer (Kif2A) in complex with two bent alphabeta-tubulin heterodimers in a head-to-tail array, providing a view of these interactions, is reported. (PMID:29980677)
• KIF2A expression was increased in human ovarian cancer patients and in tumor tissues and KIF2A mRNA contains two target sites for miR-206 binding and confirmed that miR-206 directly suppresses KIF2A; inhibits ovarian cancer cell proliferation, migration, and invasion; and induces apoptosis. (PMID:30352438)
• Study in mutant mice and human cerebral organoids showed that WDR62 deletion resulted in a reduction in the size of mouse brains and organoids due to the disruption of neural progenitor cells. WDR62 interacts with and promotes CEP170 localization to the basal body of primary cilium, where CEP170 recruits KIF2A to disassemble cilium. (PMID:31197141)
• KIF2A promotes the progression via AKT signaling pathway and is upregulated by transcription factor ETV4 in human gastric cancer. (PMID:32106376)
• Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy. (PMID:32386558)
• Reciprocal regulation of Aurora kinase A and ATIP3 in the control of metaphase spindle length. (PMID:32789689)
• Long Non-Coding RNA Paternally Expressed Imprinted Gene 10 (PEG10) Elevates Diffuse Large B-Cell Lymphoma Progression by Regulating Kinesin Family Member 2A (KIF2A) via Targeting MiR-101-3p. (PMID:32976381)
• Separable roles for RanGTP in nuclear and ciliary trafficking of a kinesin-2 subunit. (PMID:33234597)
• Association of kinesin family member 2A with increased disease risk, deteriorative clinical characteristics, and shorter survival profiles in acute myeloid leukemia. (PMID:33331418)
• Variants in KIF2A cause broad clinical presentation; the computational structural analysis of a novel variant in a patient with a cortical dysplasia, complex, with other brain malformations 3. (PMID:33506645)
• Clinical significance of kinesin family member 2A as a facilitating biomarker of disease surveillance and prognostication in cervical cancer patients. (PMID:33797694)
• Kinesin family member 2A links with advanced tumor stage, reduced chemosensitivity and worse prognosis in gastric cancer. (PMID:35313389)
• The minus-end depolymerase KIF2A drives flux-like treadmilling of gammaTuRC-uncapped microtubules. (PMID:37615667)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif2a	ENSDARG00000043571
danio_rerio		ENSDARG00000109770
mus_musculus	Kif2a	ENSMUSG00000021693
rattus_norvegicus	Kif2a	ENSRNOG00000014000

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), 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), KIF2C (ENSG00000142945), 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 KIF2A — O00139 (reviewed: O00139)

Alternative names: Kinesin-2

All UniProt accessions (9): O00139, A0A6Q8PFA6, A0A6Q8PG37, A0A6Q8PGG1, A0A6Q8PGH7, A0A6Q8PH57, D6R9M0, D6RD93, H0Y8H2

UniProt curated annotations — full annotation on UniProt →

Function. Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity.

Subunit / interactions. Interacts with AURKA and PLK1. Interacts with PSRC1. Interacts with MCRS1; the interaction enhances recruitment of KIF2A to the minus ends of spindle microtubules which promotes chromosome alignment.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole. Spindle.

Disease relevance. Cortical dysplasia, complex, with other brain malformations 3 (CDCBM3) [MIM:615411] A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include early-onset epilepsy, and various malformations of cortical development such as agyria, posterior or frontal pachygyria, subcortical band heterotopia, and thin corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. HeLa cells lacking KIF2A show asymmetric or monopolar mitotic spindles. Osteosarcoma cells (U2OS) lacking KIF2A or KIF2B show disorganised or monopolar mitotic spindles.

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

Isoforms (5)

UniProt ID	Names	Canonical?
O00139-3	3	yes
O00139-1	1, HK2
O00139-2	2, HK2s
O00139-4	4
O00139-5	5

RefSeq proteins (4): NP_001091981, NP_001230881, NP_001230882, NP_004511 (=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

UniProt features (54 total): helix 15, strand 11, modified residue 9, splice variant 4, region of interest 3, sequence conflict 3, sequence variant 2, turn 2, chain 1, domain 1, coiled-coil region 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9KD4	X-RAY DIFFRACTION	1.64
9JWV	X-RAY DIFFRACTION	1.8
9KD5	X-RAY DIFFRACTION	1.8
9J20	X-RAY DIFFRACTION	1.85
2GRY	X-RAY DIFFRACTION	2.35
6BBN	X-RAY DIFFRACTION	3.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00139-F1	79.37	0.45

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 (1): 313–320

Post-translational modifications (9): 97, 100, 102, 135, 140, 556, 573, 75, 78

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: 851 (showing top): AHRARNT_01, GOBP_CHROMOSOME_ORGANIZATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, HARRIS_HYPOXIA, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, ATACCTC_MIR202, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN

GO Biological Process (10): microtubule cytoskeleton organization (GO:0000226), microtubule-based movement (GO:0007018), microtubule depolymerization (GO:0007019), mitotic spindle organization (GO:0007052), nervous system development (GO:0007399), cell differentiation (GO:0030154), regulation of cell migration (GO:0030334), cell division (GO:0051301), mitotic spindle assembly (GO:0090307), mitotic sister chromatid segregation (GO:0000070)

GO Molecular Function (7): cytoskeletal motor activity (GO:0003774), microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (20): spindle pole (GO:0000922), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), spindle (GO:0005819), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), membrane (GO:0016020), nuclear body (GO:0016604), ciliary basal body (GO:0036064), mitotic spindle (GO:0072686), sperm midpiece (GO:0097225), sperm annulus (GO:0097227), sperm principal piece (GO:0097228), centriolar subdistal appendage (GO:0120103), cytoskeleton (GO:0005856), spindle microtubule (GO:0005876)

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	8
intracellular membraneless organelle	5
spindle	3
microtubule organizing center	3
sperm flagellum	3
microtubule-based process	2
mitotic nuclear division	2
ATP-dependent activity	2
nuclear lumen	2
microtubule cytoskeleton	2
cilium	2
cytoskeleton organization	1
microtubule polymerization or depolymerization	1
protein depolymerization	1
supramolecular fiber organization	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
system development	1
cellular developmental process	1
cell migration	1
regulation of cell motility	1
cellular process	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
sister chromatid segregation	1
mitotic cell cycle process	1
molecular_function	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
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
centriole	1

Protein interactions and networks

STRING

1792 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF2A	CEP170	Q5SW79	684
KIF2A	PSRC1	Q6PGN9	648
KIF2A	AURKA	O14965	635
KIF2A	TUBG1	P23258	590
KIF2A	WDR62	O43379	584
KIF2A	NEK2	P51955	548
KIF2A	DYNC1H1	Q14204	546
KIF2A	PLK1	P53350	544
KIF2A	DVL2	O14641	542
KIF2A	NDE1	Q9NXR1	531
KIF2A	CKAP5	Q14008	526
KIF2A	AURKB	Q96GD4	516
KIF2A	CCP110	O43303	511
KIF2A	RBBP5	Q15291	494
KIF2A	EML1	O00423	492

IntAct

127 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAM13C	KIF2A	psi-mi:“MI:0915”(physical association)	0.670
KIF2A	FAM13C	psi-mi:“MI:0915”(physical association)	0.670
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
CEP170	KIF2A	psi-mi:“MI:0915”(physical association)	0.650
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
LARP1B	KIF2A	psi-mi:“MI:0915”(physical association)	0.560
MRPL53	KIF2A	psi-mi:“MI:0915”(physical association)	0.560
KIF2A	LARP1B	psi-mi:“MI:0915”(physical association)	0.560
KIF2A	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
KIF2C	KIF2A	psi-mi:“MI:0914”(association)	0.530
KIF2A	KIF2A	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
SKA1	ILVBL	psi-mi:“MI:0914”(association)	0.350
TTK	IBTK	psi-mi:“MI:0914”(association)	0.350
KIF2A	GNS	psi-mi:“MI:0914”(association)	0.350
LTN1	KIF2A	psi-mi:“MI:0914”(association)	0.350
KIF2A	EIF3F	psi-mi:“MI:0914”(association)	0.350
ILK	ELOC	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (289): KIF2A (Two-hybrid), LARP1B (Two-hybrid), MRPL53 (Two-hybrid), FAM13C (Two-hybrid), KIF2A (Affinity Capture-MS), KIF2A (Affinity Capture-MS), KIF2A (Affinity Capture-MS), CHM (Co-fractionation), KIF2A (Co-fractionation), KIF2A (Affinity Capture-MS), KIF2A (Affinity Capture-MS), KIF2A (Proximity Label-MS), KIF2A (Affinity Capture-MS), KIF2A (Proximity Label-MS), KIF2A (Proximity Label-MS)

ESM2 similar proteins: A0JN40, A1ZAJ2, A8BKD1, F1M4A4, F1QN54, F4J8L3, O00139, O14782, O15066, O35066, O55165, O60333, O88658, P23678, P28740, P28741, P33173, P34540, P46867, P46871, P46873, Q12756, Q15058, Q17BU3, Q28WQ1, Q29DY1, Q2NL05, Q4R628, Q5R4H3, Q5R706, Q5R9Y9, Q5ZKV8, Q60575, Q61771, Q7PHR1, Q8LNZ2, Q8S905, Q8S950, Q91636, Q91637

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

4 interactions.

A	Effect	B	Mechanism
KIF2A	up-regulates	“Minus-end directed microtubule movement”
WDCP	“up-regulates activity”	KIF2A	binding
PLK1	“up-regulates activity”	KIF2A	phosphorylation
TTBK2	“down-regulates activity”	KIF2A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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
RHO GTPases activate PKNs	5	19.1×	2e-04
Aggrephagy	5	15.0×	5e-04
Loss of Nlp from mitotic centrosomes	7	13.4×	6e-05
Loss of proteins required for interphase microtubule organization from the centrosome	7	13.4×	6e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	13.0×	6e-05
AURKA Activation by TPX2	7	12.8×	6e-05
SARS-CoV-1-host interactions	6	12.7×	2e-04
COPI-independent Golgi-to-ER retrograde traffic	5	12.5×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of microtubule polymerization	6	37.5×	1e-05
mitotic spindle organization	6	15.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	229
Likely benign	295
Benign	89

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
65400	NM_001098511.3(KIF2A):c.961C>G (p.His321Asp)	Pathogenic
65401	NM_001098511.3(KIF2A):c.950G>A (p.Ser317Asn)	Pathogenic
800959	NM_001098511.3(KIF2A):c.283C>T (p.Arg95Ter)	Pathogenic
1031823	NM_001098511.3(KIF2A):c.217G>A (p.Glu73Lys)	Likely pathogenic
1701060	NM_001098511.3(KIF2A):c.1444A>C (p.Asn482His)	Likely pathogenic
584429	NM_001098511.3(KIF2A):c.938G>A (p.Gly313Glu)	Likely pathogenic

SpliceAI

3162 predictions. Top by Δscore:

Variant	Effect	Δscore
5:62347125:C:G	acceptor_gain	1.0000
5:62347125:CATA:C	acceptor_loss	1.0000
5:62347126:A:AG	acceptor_gain	1.0000
5:62347126:ATAG:A	acceptor_gain	1.0000
5:62347127:T:G	acceptor_gain	1.0000
5:62347127:TAGGC:T	acceptor_loss	1.0000
5:62347128:A:AG	acceptor_gain	1.0000
5:62347128:A:AT	acceptor_loss	1.0000
5:62347128:AG:A	acceptor_gain	1.0000
5:62347128:AGGCC:A	acceptor_gain	1.0000
5:62347129:G:GT	acceptor_gain	1.0000
5:62347129:G:T	acceptor_loss	1.0000
5:62347129:GG:G	acceptor_gain	1.0000
5:62347129:GGC:G	acceptor_gain	1.0000
5:62347129:GGCC:G	acceptor_gain	1.0000
5:62347129:GGCCG:G	acceptor_gain	1.0000
5:62347222:GAG:G	donor_gain	1.0000
5:62347225:G:GG	donor_gain	1.0000
5:62347225:GT:G	donor_loss	1.0000
5:62347226:T:G	donor_loss	1.0000
5:62348046:A:AG	acceptor_gain	1.0000
5:62348047:G:GG	acceptor_gain	1.0000
5:62348166:AGGT:A	donor_loss	1.0000
5:62348167:GG:G	donor_loss	1.0000
5:62348169:T:A	donor_loss	1.0000
5:62350061:CATA:C	acceptor_loss	1.0000
5:62350062:ATAG:A	acceptor_loss	1.0000
5:62350063:T:G	acceptor_gain	1.0000
5:62350063:TAG:T	acceptor_loss	1.0000
5:62350064:A:AC	acceptor_loss	1.0000

AlphaMissense

4917 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:62306522:T:G	I17S	1.000
5:62306527:C:A	R19S	1.000
5:62306527:C:T	R19C	1.000
5:62306528:G:A	R19H	1.000
5:62306528:G:C	R19P	1.000
5:62306528:G:T	R19L	1.000
5:62306533:G:C	D21H	1.000
5:62347133:G:C	R23P	1.000
5:62347151:T:A	V29E	1.000
5:62347187:T:A	V41D	1.000
5:62347192:T:A	W43R	1.000
5:62347192:T:C	W43R	1.000
5:62347193:G:C	W43S	1.000
5:62347194:G:C	W43C	1.000
5:62347194:G:T	W43C	1.000
5:62347213:A:G	K50E	1.000
5:62347215:A:C	K50N	1.000
5:62347215:A:T	K50N	1.000
5:62347216:G:C	G51R	1.000
5:62347217:G:A	G51D	1.000
5:62347220:A:T	K52I	1.000
5:62347221:A:C	K52N	1.000
5:62347221:A:T	K52N	1.000
5:62353294:T:G	C159W	1.000
5:62353314:T:C	L166P	1.000
5:62353326:G:C	R170P	1.000
5:62353335:G:C	R173T	1.000
5:62353335:G:T	R173M	1.000
5:62353336:G:C	R173S	1.000
5:62353336:G:T	R173S	1.000

dbSNP variants (sampled 300 via entrez): RS1000008205 (5:62350489 G>T), RS1000009962 (5:62309428 C>T), RS1000018556 (5:62346639 C>G), RS1000027992 (5:62304760 C>A), RS1000107834 (5:62384105 C>T), RS1000113279 (5:62316228 C>G,T), RS1000116287 (5:62381470 G>A), RS1000139609 (5:62310630 G>A), RS1000166739 (5:62317619 G>A), RS1000177827 (5:62327947 G>T), RS1000258842 (5:62373280 A>C), RS1000274556 (5:62340199 A>G), RS1000279245 (5:62381436 C>A), RS1000332390 (5:62328910 A>G), RS1000344441 (5:62374258 G>A,T)

Disease associations

OMIM: gene MIM:602591 | disease phenotypes: MIM:615411

GenCC curated gene-disease

Disease	Classification	Inheritance
complex cortical dysplasia with other brain malformations 3	Strong	Autosomal dominant

Mondo (1): complex cortical dysplasia with other brain malformations 3 (MONDO:0014170)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000639	Nystagmus
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001302	Pachygyria
HP:0001339	Lissencephaly
HP:0001511	Intrauterine growth retardation
HP:0002079	Hypoplasia of the corpus callosum
HP:0002282	Gray matter heterotopia
HP:0002510	Spastic tetraplegia
HP:0002539	Cortical dysplasia
HP:0031882	Agyria
HP:0032409	Subcortical band heterotopia
HP:0033725	Thin corpus callosum

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006630_67	Diastolic blood pressure	1.000000e-21
GCST009391_986	Metabolite levels	1.000000e-06
GCST012489_115	Heel bone mineral density x serum urate levels interaction	3.000000e-10
GCST90002392_627	Mean corpuscular volume	1.000000e-09
GCST90002396_302	Mean reticulocyte volume	2.000000e-10
GCST90002397_37	Mean spheric corpuscular volume	5.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0010475	deoxycholate measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725148 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects cotreatment, decreases expression	3
Valproic Acid	affects expression, decreases expression, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
bisphenol A	affects localization, decreases expression	2
sodium arsenite	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
tamibarotene	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
jinfukang	decreases expression	1
Lycopene	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Nickel	increases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Phenobarbital	affects expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697557	Binding	Inhibition of KIF2A (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU78	HAP1 KIF2A (-) 1	Cancer cell line	Male
CVCL_SU79	HAP1 KIF2A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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