KIF14

Summary

KIF14 (kinesin family member 14, HGNC:19181) is a protein-coding gene on chromosome 1q32.1, encoding Kinesin-like protein KIF14 (Q15058). Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity. It is a selective cancer dependency (DepMap: 51.4% of cell lines).

This gene encodes a member of the kinesin-3 superfamily of microtubule motor proteins. These proteins are involved in numerous processes including vesicle transport, chromosome segregation, mitotic spindle formation, and cytokinesis. In human HeLa-S3 and 293T cells, this protein is localized to the cytoplasm during interphase, to the spindle poles and spindle microtubules during mitosis, and to the midbody during cytokinesis. An internal motor domain displays microtubule-dependent ATPase activity, consistent with its function as a microtubule motor protein. Knockdown of this gene results in failed cytokinesis with endoreplication, which results in multinucleated cells. This gene has been identified as a likely oncogene in breast, lung and ovarian cancers, as well as retinoblastomas and gliomas. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9928 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive primary microcephaly (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 523 total — 16 pathogenic, 25 likely-pathogenic
• Phenotypes (HPO): 55
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 51.4% of screened cell lines
• MANE Select transcript: NM_014875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19181
Approved symbol	KIF14
Name	kinesin family member 14
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0042
Ensembl gene	ENSG00000118193
Ensembl biotype	protein_coding
OMIM	611279
Entrez	9928

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000367350, ENST00000614960, ENST00000928795, ENST00000928796, ENST00000928797

RefSeq mRNA: 2 — MANE Select: NM_014875 NM_001305792, NM_014875

CCDS: CCDS30963

Canonical transcript exons

ENST00000367350 — 30 exons

Exon	Start	End
ENSE00000796389	200554468	200554606
ENSE00000796390	200555380	200555454
ENSE00000796391	200559330	200559452
ENSE00000796392	200560722	200560880
ENSE00000796393	200565069	200565253
ENSE00000796394	200565445	200565669
ENSE00000796395	200569911	200570005
ENSE00000796396	200575591	200575691
ENSE00000796397	200580254	200580383
ENSE00000796398	200581201	200581294
ENSE00000796399	200586101	200586227
ENSE00000796400	200589217	200589369
ENSE00000796401	200590125	200590272
ENSE00000796402	200592080	200592240
ENSE00000796403	200593667	200593769
ENSE00000796404	200598237	200598421
ENSE00000796405	200600050	200600113
ENSE00000796406	200600356	200600503
ENSE00000796409	200603839	200603955
ENSE00000796410	200605283	200605390
ENSE00000796411	200606746	200606798
ENSE00000796412	200608830	200608928
ENSE00000796413	200614318	200614405
ENSE00000796414	200615355	200615609
ENSE00001042854	200605864	200605894
ENSE00001444293	200551500	200553767
ENSE00001444294	200601896	200602068
ENSE00001444295	200603226	200603341
ENSE00001444296	200617612	200618838
ENSE00001444297	200620411	200620751

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 92.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6404 / max 48.7986, expressed in 962 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16584	2.2454	807
16583	1.0140	553
16585	0.3810	237

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.60	gold quality
endometrium epithelium	UBERON:0004811	88.49	gold quality
trabecular bone tissue	UBERON:0002483	86.42	gold quality
oocyte	CL:0000023	85.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.99	gold quality
ventricular zone	UBERON:0003053	83.97	gold quality
buccal mucosa cell	CL:0002336	83.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.62	gold quality
embryo	UBERON:0000922	80.11	gold quality
bone marrow	UBERON:0002371	79.99	gold quality
thymus	UBERON:0002370	77.45	gold quality
ganglionic eminence	UBERON:0004023	77.14	gold quality
stromal cell of endometrium	CL:0002255	72.64	gold quality
cartilage tissue	UBERON:0002418	72.51	gold quality
tibia	UBERON:0000979	72.04	gold quality
bone marrow cell	CL:0002092	71.27	gold quality
oral cavity	UBERON:0000167	69.65	gold quality
vermiform appendix	UBERON:0001154	67.73	gold quality
jejunal mucosa	UBERON:0000399	67.64	silver quality
esophagus squamous epithelium	UBERON:0006920	65.38	gold quality
endometrium	UBERON:0001295	65.33	gold quality
caecum	UBERON:0001153	65.23	gold quality
placenta	UBERON:0001987	64.73	gold quality
adrenal tissue	UBERON:0018303	63.80	gold quality
duodenum	UBERON:0002114	63.78	gold quality
epithelium of esophagus	UBERON:0001976	63.34	gold quality
colonic mucosa	UBERON:0000317	63.24	gold quality
rectum	UBERON:0001052	63.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	63.05	silver quality
lymph node	UBERON:0000029	62.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	445.21
E-GEOD-81383	yes	287.18
E-ANND-3	yes	6.49
E-GEOD-99795	no	135.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

104 targeting KIF14, 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-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
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-3924	100.00	72.09	2394
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-539-5P	99.93	70.30	2855

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 51.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Overexpressed in primary retinoblastoma and lung cancer, and in medulloblastoma and breast cancer cell lines. Low expression in normal adult tissue; highly expressed in fetal liver and thymus. (PMID:15897902)
• Primary non-small-cell lung carcinoma overexpressing KIF14 showed a trend toward decreased survival. (PMID:15897902)
• During cytokinesis, the localization of KIF14 and citron kinase to the central spindle and midbody is codependent, and they form a complex depending on the activation state of citron kinase. (PMID:16431929)
• KIF14 is overexpressed in primary breast cancer; predicts disease-free and overall survival (PMID:16570270)
• RNA interference-mediated silencing of KIF14 disrupts cell cycle progression and induces cytokinesis failure. (PMID:16648480)
• The KIF14 gene is amplified in retinoblastoma; likely an early genomic change in this cancer. (PMID:17099872)
• KIF14 is expressed most highly in squamous cell carcinoma, then in large-cell undifferentiated carcinoma, then adenocarcinoma (PMID:17545527)
• KIF14 mRNA expression is prognostic for disease-free survival in non-small-cell lung cancer. Knockdown inhibits colony formation ability. (PMID:17545527)
• Overexpression of KIF14 was confirmed in primary human retinoblastoma and showed that patients with an older age at diagnosis express significantly higher levels of KIF14. (PMID:17962437)
• KIF14 overexpression is associated with papillary renal cell tumors with chromosome 1q duplication. (PMID:19123481)
• report confirms significant mRNA overexpression of KIF14 and E2F3 together in a large cohort of retinoblastoma tumors (PMID:19190782)
• Results show that the established nerve invasion model and the consensus signature of perineural invasion could be instrumental in the identification of novel therapeutic targets of pancreatic cancer as exemplified by KIF14 and ARHGDIbeta. (PMID:19509238)
• Four genes previously not examined in that respect in laryngeal carcinoma, occurred to be good markers of the neoplasm. They are: metal-proteinase ADAM12, cyclin-dependent kinase 2-CDK2, kinesin 14-KIF14, suppressor 1 of checkpoint-CHES1. (PMID:19609547)
• Findings indicate that KIF14 mRNA is an independent prognostic marker in serous ovarian cancer. (PMID:21618518)
• KIF14 expression in gliomas is tumor-specific and increased in more aggressive tumors. KIF14 might function as a candidate prognostic marker for human gliomas. (PMID:22999822)
• It was shown that the kinesin KIF14 associates with the PDZ domain of Radil and negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. (PMID:23209302)
• Suppression of KIF14 not only decreases cancer cell migration but also induces apoptosis of cells. (PMID:23414349)
• Data indicate that KIF14 and TLN1 loss-of-function significantly enhanced chemosensitivity in four triple-negative breast cancer (TNBC) cell lines. (PMID:23479679)
• KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma. (PMID:23626713)
• Mutations in KIF14 identified as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype. (PMID:24128419)
• analysis of epigenetic regulation of KIF14 overexpression in ovarian cancer (PMID:24626475)
• critical role for KIF14 in the tumorigenic potential of triple-negative breast cancer (PMID:24784001)
• KIF14 knockdown downregulates the expression of Skp2 and Cks1, leading to accumulation of p27Kip1. (PMID:24854087)
• High KIF14 expression is associated with hepatocellular carcinoma. (PMID:25106407)
• Kinesin-14 blocks microtubule nucleation in yeast and reveal that this inhibition is countered by the kinesin-5 protein, Cut7.[Cut7, Pkl1] (PMID:25348260)
• High-grade serous ovarian cancer cells may depend on KIF14 for in vitro proliferation. (PMID:25528264)
• Data indicate that three genes, KIF14, NCAPG and CENPE that were upregulated in Pediatric high-grade gliomas (pHGGs) and were direct miR-137 or miR-6500-3p targets. (PMID:26933822)
• study suggests that KIF14 may serve as a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer. (PMID:27128470)
• The mechanochemical cycle of kinesin-14 has been reported. (PMID:27729532)
• Studied overexpression of KIF14 which showed the tight correlation between KIF14 upregulation and inferior clinical outcome in medulloblastoma (MB), suggesting KIF14 is a potential negative prognostic marker in MB. Transient, siRNAs-mediated downregulation of KIF14 suppressed cell proliferation and induced apoptosis in two MB cell lines. (PMID:28504687)
• KIF14 is upregulated in PCa cell lines and clinical PCa tissues. Inhibition of KIF14 suppresses cell proliferation, induces G2 arrest and apoptosis. (PMID:28525372)
• Signaling cascade of the NIMA-related kinases (Neks) Nek6, Nek7, and Nek9 is required for the localization and function of two kinesins essential for cytokinesis, Mklp2 and Kif14 to properly coordinate cytokinesis. (PMID:28630147)
• In particular, counteracting forces between minus-end-directed kinesin-14 and plus-end-directed kinesin-5 motors have recently been implicated in the regulation of microtubule nucleation. (PMID:28668932)
• This study identified the mutations in KIF14 as a new cause of primary microcephaly and using cellular experiments demonstrate that impaired cytokinesis, increased apoptosis, and reduced cell motility are features of the associated pathogenesis. (PMID:28892560)
• KIF14 missense and loss of function variants were identified in intellectual disability with microcephaly patients. (PMID:29343805)
• SNP rs10800708 within the KIF14 miRNA binding site is linked with breast cancer. (PMID:30092718)
• our results demonstrate that KIF14 mutations result in a severe syndrome associating microcephaly and RHD through its conserved function in cytokinesis during kidney and brain development. (PMID:30388224)
• that KIF14 is overexpressed in gastric cancer, is correlated with poor prognosis and plays a crucial role in the progression and metastasis of gastric cancer. (PMID:30404039)
• Study confirms a high expression level of KIF14 in glioma tissues and cells. Its expression is regulated by LncRNA PAXIP1-AS1 which could upregulate its promoter activity by recruiting transcription factor ETS1. (PMID:31823805)
• KIF14 controls ciliogenesis via regulation of Aurora A and is important for Hedgehog signaling. (PMID:32348467)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif14	ENSDARG00000062187
mus_musculus	Kif14	ENSMUSG00000041498
rattus_norvegicus	Kif14	ENSRNOG00000037211
drosophila_melanogaster	neb	FBGN0004374

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), 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 KIF14 — Q15058 (reviewed: Q15058)

All UniProt accessions (1): Q15058

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity. Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis. During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively. Regulates cell growth through regulation of cell cycle progression and cytokinesis. During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1. During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division. Also is required for chromosome congression and alignment during mitotic cell cycle process. Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules.

Subunit / interactions. Directly interacts with PRC1 within a complex also containing KIF4A, KIF20A and KIF23; targets to the central spindle. Directly interacts with CIT depending on the activation state of the kinase (stronger interaction with the kinase-dead form); targets to the midbody. Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with AKT1; the interaction is detected in the plasma membrane upon INS stimulation and promotes AKT1 phosphorylation. Interacts with SVIL; at midbody during cytokinesis. Interacts with RADIL (via PDZ domain); recruits RADIL to the microtubule network restricting RADIL from interaction with activated RAP1A.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle. Midbody.

Disease relevance. Meckel syndrome 12 (MKS12) [MIM:616258] A form of Meckel syndrome, a disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. The disease is caused by variants affecting the gene represented in this entry. Microcephaly 20, primary, autosomal recessive (MCPH20) [MIM:617914] A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH20 features include mild to moderate intellectual disability, autistic features, poor speech. Disease severity is highly variable. The disease is caused by variants affecting the gene represented in this entry. The disease-causing variant NM_014875.2:c.263T>A, which produces a premature truncation of the protein at Leu-88 (p.Leu88Ter), may also partly result in the deletion of 372 bp of exon 2 of KIF14 by activation of a cryptic splice site. This in-frame deletion predicts a protein that lacks 124 aa (p.Gly58-Leu181del). The disease-causing mutation NM_014875.2:c.3662G>T, resulting in the missence variant p.Gly1221Val, may also induce the skipping of exon 24, resulting in a protein that misses 76 aa (p.Gly1221_ Lys1296delinsVal).

Domain organisation. The kinesin motor domain binds to microtubules with high affinity and has a robust ATPase activity but a very slow motility. The kinesin motor domain protects microtubules from cold depolymerization. Binds to each tubulin heterodimer resulting in a microtubule complexes. Binds at the tubulin intradimer interface, at the crest of the protofilament, and orients slightly toward the next protofilament.

Induction. Up-regulated in cells progressing through G2/M phase.

Miscellaneous. It is resistant to docetaxel anhydrous.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.

RefSeq proteins (2): NP_001292721, NP_055690* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR001752	Kinesin_motor_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032405	Kinesin_assoc	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR056523	4HB_KIF14	Domain

Pfam: PF00225, PF00498, PF16183, PF23313

UniProt features (29 total): modified residue 7, sequence variant 7, region of interest 5, coiled-coil region 4, domain 2, chain 1, compositionally biased region 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15058-F1	65.68	0.17

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): 447–454

Post-translational modifications (7): 12, 272, 277, 346, 915, 937, 1292

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5625900	RHO GTPases activate CIT
R-HSA-9696270	RND2 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 517 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_CHROMOSOME_ORGANIZATION, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_REGULATION_OF_CELL_MATURATION, GOBP_METENCEPHALON_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_BUB1, GOBP_REGULATION_OF_PHOSPHORYLATION, AAGTCCA_MIR422B_MIR422A, GOBP_CHROMOSOME_LOCALIZATION, BOYAULT_LIVER_CANCER_SUBCLASS_G2

GO Biological Process (29): regulation of cell growth (GO:0001558), microtubule-based movement (GO:0007018), mitotic metaphase chromosome alignment (GO:0007080), positive regulation of cell population proliferation (GO:0008284), regulation of G2/M transition of mitotic cell cycle (GO:0010389), cerebellar granular layer structural organization (GO:0021685), cerebellar Purkinje cell layer structural organization (GO:0021693), cerebellar cortex development (GO:0021695), hippocampus development (GO:0021766), olfactory bulb development (GO:0021772), cell proliferation in forebrain (GO:0021846), cerebral cortex development (GO:0021987), regulation of cell adhesion (GO:0030155), regulation of cell migration (GO:0030334), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), regulation of myelination (GO:0031641), activation of protein kinase activity (GO:0032147), positive regulation of cytokinesis (GO:0032467), regulation of Rap protein signal transduction (GO:0032487), negative regulation of integrin activation (GO:0033624), substrate adhesion-dependent cell spreading (GO:0034446), negative regulation of apoptotic process (GO:0043066), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), regulation of neuron apoptotic process (GO:0043523), negative regulation of neuron apoptotic process (GO:0043524), establishment of protein localization (GO:0045184), cell division (GO:0051301), regulation of cell maturation (GO:1903429), regulation of G1/S transition of mitotic cell cycle (GO:2000045)

GO Molecular Function (10): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), plus-end-directed microtubule motor activity (GO:0008574), tubulin binding (GO:0015631), ATP hydrolysis activity (GO:0016887), protein kinase binding (GO:0019901), PDZ domain binding (GO:0030165), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), membrane (GO:0016020), midbody (GO:0030496), spindle midzone (GO:0051233), Flemming body (GO:0090543), spindle (GO:0005819), cytoskeleton (GO:0005856), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	2
Signaling by Rho GTPases	2
RHO GTPase Effectors	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
anatomical structure development	4
cerebellar cortex structural organization	2
anatomical structure arrangement	2
pallium development	2
regulation of cellular process	2
ATP-dependent activity	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
microtubule-based process	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
mitotic cell cycle process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
G2/M transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
cerebellar granular layer morphogenesis	1
cerebellar Purkinje cell layer morphogenesis	1
cerebellum development	1
limbic system development	1
olfactory lobe development	1
forebrain development	1
neural precursor cell proliferation	1
cell adhesion	1
cell migration	1
regulation of cell motility	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
myelination	1
regulation of nervous system development	1
positive regulation of protein kinase activity	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1

Protein interactions and networks

STRING

4760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF14	CIT	O14578	905
KIF14	CENPF	P49454	692
KIF14	RACGAP1	Q9H0H5	690
KIF14	DLGAP5	Q15398	683
KIF14	PRC1	O43663	674
KIF14	NCAPG	Q9BPX3	660
KIF14	KIF20A	O95235	655
KIF14	NCAPH	Q15003	653
KIF14	CEP55	Q53EZ4	630
KIF14	KIF4A	O95239	619
KIF14	ASPM	Q8IZT6	618
KIF14	AURKB	Q96GD4	597
KIF14	SVIL	O95425	589
KIF14	SMC4	Q9NTJ3	563
KIF14	TOP2A	P11388	557

IntAct

177 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
GORASP2	GOLGA2	psi-mi:“MI:0914”(association)	0.880
CD68	TTI1	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
TEX28	TMCC2	psi-mi:“MI:0914”(association)	0.640
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SVIL	KIF14	psi-mi:“MI:0915”(physical association)	0.560
KIF14	SVIL	psi-mi:“MI:0403”(colocalization)	0.560
KIF14	SVIL	psi-mi:“MI:0407”(direct interaction)	0.560
SCGN	SNAP23	psi-mi:“MI:0914”(association)	0.550
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
KIFBP	KIF3C	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
VSIG2	TTI1	psi-mi:“MI:0914”(association)	0.530
CLMP	UTP20	psi-mi:“MI:0914”(association)	0.530
CCDC89	ZMYM6	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CA14	EXOC5	psi-mi:“MI:0914”(association)	0.530

BioGRID (1931): KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), KIF14 (Proximity Label-MS), KIF14 (Proximity Label-MS), KIF14 (Biochemical Activity), KIF14 (Proximity Label-MS), KIF14 (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, A0JN40, A1ZAJ2, A8BB91, A8BKD1, B1AVY7, B2GU58, B7EJ91, B7ZNG0, B9F7C8, B9FAF3, B9FUF9, F1M4A4, F1QN54, F4IIS5, F4K0J3, O14782, O15066, O23826, O35066, O35071, O35787, O43093, O43896, O55165, O60333, O88658, O95239, P17120, P17210, P23678, P28025, P28741, P28742, P33173, P33174, P46863, P46867, P46869, P46871

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
NEK7	“up-regulates activity”	KIF14	phosphorylation
KIF14	up-regulates	Cilium_assembly
KIF14	“up-regulates activity”	CIT	binding
PRC1	“up-regulates activity”	KIF14	binding
CIT	“up-regulates activity”	KIF14	binding
KIF14	up-regulates	“Plus-end directed sliding movement”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	43.3×	2e-10
Activation of BAD and translocation to mitochondria	7	43.0×	4e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	37.9×	1e-08
Activation of BH3-only proteins	7	28.0×	1e-07
Loss of Nlp from mitotic centrosomes	16	20.5×	5e-15
Loss of proteins required for interphase microtubule organization from the centrosome	16	20.5×	5e-15
AURKA Activation by TPX2	16	19.6×	8e-15
RHO GTPases activate PKNs	7	17.9×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	6	24.7×	7e-05
non-motile cilium assembly	8	13.1×	7e-05
intracellular protein localization	12	7.1×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	25
Uncertain significance	253
Likely benign	121
Benign	66

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
183396	NM_014875.3(KIF14):c.1750_1751del (p.Glu584fs)	Pathogenic
183397	NM_014875.3(KIF14):c.1780A>T (p.Arg594Ter)	Pathogenic
2573572	NM_014875.3(KIF14):c.2354_2355del (p.Lys785fs)	Pathogenic
2639725	NM_014875.3(KIF14):c.521_522del (p.Phe174fs)	Pathogenic
2966528	NM_014875.3(KIF14):c.2362C>T (p.Gln788Ter)	Pathogenic
3902527	NM_014875.3(KIF14):c.3910C>T (p.Gln1304Ter)	Pathogenic
4732924	NM_014875.3(KIF14):c.834_835insGGGGGGATTGAGCCAAGATGGCCGAATAGGAACAGCTCCGGTCTACAGCTCCCAGCGTGAGCAACGCAGAAGACGGTGANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAGAAAAAAGAACACCT (p.Thr279delinsGlyGlyIleGluProArgTrpProAsnArgAsnSerSerGlyLeuGlnLeuProAlaTer)	Pathogenic
4735470	NM_014875.3(KIF14):c.1936C>T (p.Gln646Ter)	Pathogenic
4735483	NM_014875.3(KIF14):c.4059_4060insACTTACAA (p.Leu1354fs)	Pathogenic
4761892	NM_014875.3(KIF14):c.374_375dup (p.Lys126fs)	Pathogenic
4806579	NM_014875.3(KIF14):c.246_247insG (p.Asn83fs)	Pathogenic
503565	NM_014875.3(KIF14):c.263T>A (p.Leu88Ter)	Pathogenic
503566	NM_014875.3(KIF14):c.2480_2482del (p.Val827del)	Pathogenic
503568	NM_014875.3(KIF14):c.2545C>G (p.His849Asp)	Pathogenic
503570	NM_014875.3(KIF14):c.246del (p.Asn83fs)	Pathogenic
503571	NM_014875.3(KIF14):c.4432del (p.Ser1478fs)	Pathogenic
1484531	NM_014875.3(KIF14):c.3661+1G>T	Likely pathogenic
1518661	NM_014875.3(KIF14):c.1734_1746+49del	Likely pathogenic
1722429	NM_014875.3(KIF14):c.1921dup (p.Ser641fs)	Likely pathogenic
2429248	NM_014875.3(KIF14):c.8dup (p.Leu3fs)	Likely pathogenic
2429249	NM_014875.3(KIF14):c.2765_2766del (p.Lys922fs)	Likely pathogenic
2664235	NM_014875.3(KIF14):c.2813+2dup	Likely pathogenic
3242257	NM_014875.3(KIF14):c.4475del (p.Asp1492fs)	Likely pathogenic
3374951	NM_014875.3(KIF14):c.1712_1746+27del	Likely pathogenic
3576534	NM_014875.3(KIF14):c.4428+1G>T	Likely pathogenic
3576537	NM_014875.3(KIF14):c.4094del (p.Ser1364_Ser1365insTer)	Likely pathogenic
3576539	NM_014875.3(KIF14):c.4069C>T (p.Gln1357Ter)	Likely pathogenic
3576543	NM_014875.3(KIF14):c.3887-8_3930delinsAAA	Likely pathogenic
3576547	NM_014875.3(KIF14):c.3640_3641del (p.Leu1214fs)	Likely pathogenic
3576554	NM_014875.3(KIF14):c.3619C>T (p.Gln1207Ter)	Likely pathogenic

SpliceAI

3508 predictions. Top by Δscore:

Variant	Effect	Δscore
1:200553772:A:C	acceptor_gain	1.0000
1:200554519:A:C	donor_gain	1.0000
1:200554602:CTTTT:C	acceptor_gain	1.0000
1:200554607:C:CC	acceptor_gain	1.0000
1:200555378:A:AC	donor_gain	1.0000
1:200555379:C:CC	donor_gain	1.0000
1:200555379:CA:C	donor_gain	1.0000
1:200555379:CAA:C	donor_gain	1.0000
1:200555379:CAAT:C	donor_gain	1.0000
1:200555453:ACCTA:A	acceptor_loss	1.0000
1:200555454:CCTA:C	acceptor_loss	1.0000
1:200555456:T:A	acceptor_loss	1.0000
1:200559324:TCTTA:T	donor_loss	1.0000
1:200559325:CTTA:C	donor_loss	1.0000
1:200559326:TTA:T	donor_loss	1.0000
1:200559327:TA:T	donor_loss	1.0000
1:200559328:A:AC	donor_gain	1.0000
1:200559328:A:T	donor_loss	1.0000
1:200559329:C:CC	donor_gain	1.0000
1:200559329:C:CT	donor_loss	1.0000
1:200559329:CCT:C	donor_gain	1.0000
1:200559448:TCCTC:T	acceptor_gain	1.0000
1:200559449:CCTCC:C	acceptor_gain	1.0000
1:200559450:CTC:C	acceptor_gain	1.0000
1:200559451:TC:T	acceptor_gain	1.0000
1:200559451:TCC:T	acceptor_loss	1.0000
1:200559452:CC:C	acceptor_gain	1.0000
1:200559452:CCTAG:C	acceptor_loss	1.0000
1:200559453:C:CC	acceptor_gain	1.0000
1:200560773:C:CA	donor_gain	1.0000

AlphaMissense

10974 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:200575638:C:A	W1173C	0.998
1:200575638:C:G	W1173C	0.998
1:200575640:A:G	W1173R	0.998
1:200575640:A:T	W1173R	0.998
1:200580307:A:G	W1138R	0.998
1:200580307:A:T	W1138R	0.998
1:200581247:C:G	A1097P	0.998
1:200603900:A:G	L601P	0.998
1:200580291:A:G	F1143S	0.996
1:200602011:A:C	S679R	0.996
1:200602011:A:T	S679R	0.996
1:200602013:T:G	S679R	0.996
1:200602021:G:T	A676D	0.996
1:200603911:A:C	S597R	0.996
1:200603911:A:T	S597R	0.996
1:200603913:T:G	S597R	0.996
1:200606761:A:T	V531D	0.996
1:200617633:C:G	R364P	0.996
1:200580305:C:A	W1138C	0.995
1:200580305:C:G	W1138C	0.995
1:200603891:A:G	L604P	0.995
1:200615364:T:A	K453I	0.995
1:200581246:G:T	A1097D	0.994
1:200603894:T:C	D603G	0.994
1:200603894:T:G	D603A	0.994
1:200605311:A:T	V573D	0.994
1:200615388:G:T	A445D	0.994
1:200615394:A:G	L443P	0.994
1:200617634:G:T	R364S	0.994
1:200580279:A:G	L1147P	0.993

dbSNP variants (sampled 300 via entrez): RS1000101974 (1:200578960 G>A), RS1000109036 (1:200583091 C>G), RS1000147212 (1:200592536 C>T), RS1000204222 (1:200567187 C>G), RS1000246011 (1:200576896 G>A), RS1000257655 (1:200585775 T>A), RS1000357430 (1:200569630 T>C), RS1000364915 (1:200592324 A>G), RS1000371823 (1:200554381 A>G), RS1000389054 (1:200597886 T>A), RS1000641707 (1:200563116 C>T), RS1000705577 (1:200553097 C>A), RS1000734262 (1:200598716 G>A), RS1000760112 (1:200603531 C>T), RS1000782693 (1:200600409 T>A)

Disease associations

OMIM: gene MIM:611279 | disease phenotypes: MIM:617914, MIM:616258

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive primary microcephaly	Definitive	Autosomal recessive
lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome	Strong	Autosomal recessive
microcephaly 20, primary, autosomal recessive	Strong	Autosomal recessive

Mondo (4): microcephaly 20, primary, autosomal recessive (MONDO:0054761), lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome (MONDO:0014552), Joubert syndrome and related disorders (MONDO:0015369), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (2): Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome (Orphanet:439897), Joubert syndrome and related disorders (Orphanet:140874)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000122	Unilateral renal agenesis
HP:0000148	Vaginal atresia
HP:0000193	Bifid uvula
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000568	Microphthalmia
HP:0000582	Upslanted palpebral fissure
HP:0000609	Optic nerve hypoplasia
HP:0000618	Blindness
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001290	Generalized hypotonia
HP:0001302	Pachygyria
HP:0001321	Cerebellar hypoplasia
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001562	Oligohydramnios
HP:0001838	Rocker bottom foot

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003055_3	Tandem gait	3.000000e-07
GCST008830_1	Neurofibrillary tangles	9.000000e-06
GCST010002_373	Refractive error	1.000000e-52
GCST012490_119	Femur bone mineral density x serum urate levels interaction	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006797	neurofibrillary tangles measurement
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C579935	Autosomal Recessive Primary Microcephaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5576 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
sodium arsenite	affects expression, increases expression	2
Cisplatin	increases reaction, decreases expression	2
Coumestrol	affects cotreatment, increases expression, increases reaction	2
Estradiol	increases expression	2
Testosterone	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
propionaldehyde	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
diallyl trisulfide	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1020055	Binding	Inhibition of cloned human Kif14	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

Clinical trials (associated diseases)

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