KIF15

Summary

KIF15 (kinesin family member 15, HGNC:17273) is a protein-coding gene on chromosome 3p21.31, encoding Kinesin-like protein KIF15 (Q9NS87). Plus-end directed kinesin-like motor enzyme involved in mitotic spindle assembly.

Predicted to enable ATP hydrolysis activity; microtubule binding activity; and plus-end-directed microtubule motor activity. Predicted to be involved in centrosome separation; microtubule-based movement; and mitotic spindle assembly. Located in membrane.

Source: NCBI Gene 56992 — RefSeq curated summary.

At a glance

• Gene–disease (curated): braddock-carey syndrome 2 (Limited, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 247 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 69
• Druggable target: yes
• MANE Select transcript: NM_020242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17273
Approved symbol	KIF15
Name	kinesin family member 15
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	HKLP2, NY-BR-62
Ensembl gene	ENSG00000163808
Ensembl biotype	protein_coding
OMIM	617569
Entrez	56992

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000326047, ENST00000422209, ENST00000425755, ENST00000438321, ENST00000453693, ENST00000481166, ENST00000493134, ENST00000917495, ENST00000917496, ENST00000917497, ENST00000917498, ENST00000917499, ENST00000917500, ENST00000917501, ENST00000917502

RefSeq mRNA: 1 — MANE Select: NM_020242 NM_020242

CCDS: CCDS33744

Canonical transcript exons

ENST00000326047 — 35 exons

Exon	Start	End
ENSE00001078466	44774395	44774437
ENSE00001770852	44761794	44761884
ENSE00003460428	44794217	44794426
ENSE00003479247	44852673	44853256
ENSE00003479356	44780885	44780922
ENSE00003482265	44801765	44801974
ENSE00003483639	44852208	44852339
ENSE00003489906	44828214	44828300
ENSE00003497681	44801450	44801526
ENSE00003504712	44851787	44851952
ENSE00003505448	44843125	44843234
ENSE00003506649	44775254	44775437
ENSE00003511318	44841074	44841238
ENSE00003526857	44812182	44812289
ENSE00003528164	44814911	44815076
ENSE00003543180	44848521	44848558
ENSE00003544682	44813075	44813180
ENSE00003545963	44838275	44838421
ENSE00003554866	44797834	44797956
ENSE00003564468	44800314	44800437
ENSE00003565101	44797551	44797676
ENSE00003565899	44827459	44827528
ENSE00003581902	44840355	44840456
ENSE00003624505	44829971	44830075
ENSE00003624963	44810846	44811043
ENSE00003639043	44805027	44805168
ENSE00003640940	44802814	44802991
ENSE00003641335	44778115	44778191
ENSE00003654514	44826039	44826189
ENSE00003671355	44805845	44805986
ENSE00003672674	44847985	44848057
ENSE00003677999	44786395	44786574
ENSE00003686096	44826375	44826460
ENSE00003690585	44784845	44784942
ENSE00003694572	44830896	44831018

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 96.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.9422 / max 162.0174, expressed in 995 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36344	4.7008	987
36345	0.2230	125
36348	0.0082	3
36347	0.0076	3
36346	0.0027	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.56	gold quality
ganglionic eminence	UBERON:0004023	93.93	gold quality
left testis	UBERON:0004533	88.23	gold quality
testis	UBERON:0000473	87.98	gold quality
right testis	UBERON:0004534	87.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.88	gold quality
bone marrow	UBERON:0002371	81.44	gold quality
mucosa of transverse colon	UBERON:0004991	81.13	gold quality
bone marrow cell	CL:0002092	77.43	gold quality
endometrium	UBERON:0001295	76.05	gold quality
stromal cell of endometrium	CL:0002255	75.50	gold quality
rectum	UBERON:0001052	75.33	gold quality
lymph node	UBERON:0000029	75.29	gold quality
vermiform appendix	UBERON:0001154	73.48	gold quality
esophagus mucosa	UBERON:0002469	73.19	gold quality
lower esophagus mucosa	UBERON:0035834	73.00	gold quality
adrenal tissue	UBERON:0018303	72.39	gold quality
placenta	UBERON:0001987	71.87	gold quality
duodenum	UBERON:0002114	71.38	gold quality
cortical plate	UBERON:0005343	70.73	gold quality
colonic epithelium	UBERON:0000397	69.11	silver quality
smooth muscle tissue	UBERON:0001135	68.14	gold quality
transverse colon	UBERON:0001157	67.84	gold quality
tonsil	UBERON:0002372	67.56	gold quality
esophagus	UBERON:0001043	66.87	gold quality
spleen	UBERON:0002106	66.84	gold quality
intestine	UBERON:0000160	66.03	gold quality
small intestine	UBERON:0002108	65.97	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-17	yes	262.97
E-GEOD-124858	yes	39.03
E-ANND-3	yes	3.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TCF7L2

miRNA regulators (miRDB)

24 targeting KIF15, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-4438	97.96	63.70	947
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-200C-5P	97.71	67.73	596
HSA-MIR-4794	96.47	65.53	1063
HSA-MIR-3135A	96.41	65.30	494
HSA-MIR-6888-5P	95.89	63.78	831
HSA-MIR-664A-5P	95.84	64.93	949
HSA-MIR-3677-5P	93.16	64.62	393

Literature-anchored findings (GeneRIF, showing 39)

• Kif15 can replace all essential functions of Eg5 in bipolar spindle assembly. (PMID:19818618)
• Hklp2 participates in the assembly and stabilization of the bipolar spindle. (PMID:19818619)
• Pole separation depends on Hklp2/Kif15, an otherwise dispensable plus end-directed spindle motor and results in spindles with two centrosomal poles. (PMID:22024925)
• By examining Kif15 activity in two cellular contexts, it was found that Kif15 bound to kinetochore fibers antagonizes centrosome separation while Kif15 bound to nonkinetochore MTs mediates centrosome separation. (PMID:23791727)
• Although Kif15 contains ADP in the catalytic site, its motor-domain structure was captured in the ;ATP-like’ configuration, with the neck linker docked to the catalytic core. (PMID:24419385)
• regulates alpha2 integrin internalization (PMID:24659801)
• These data reveal that hKif15 is a plus-end-directed processive homotetramer that can step against loads of up to 3.5 pN. (PMID:24668168)
• Eg5, Kif15, and dynein work together to build a bipolar spindle and reveal an important role for antagonistic motors in chromosome segregation. (PMID:25127142)
• When intersecting microtubules are parallel, Kif15 motors can drive (biased) parallel sliding because the motor simultaneously steps on both microtubules that it cross-links. (PMID:26969727)
• KIF15 is involved in alternative spindle assembly pathways. (PMID:27091450)
• To our knowledge, KIF15 is the first kinesin to be associated with congenital thrombocytopenia. (PMID:28150392)
• Both Kif15 and KBP are required for the alignment of all the chromosomes to the metaphase plate and the assembly of stable kinetochore fibers of the correct length. (PMID:28445502)
• This study identified KIF15 as a critical regulator that promotes pancreatic cancer proliferation, broadening our understanding of KIF15 function in tumorigenesis. (PMID:28595260)
• The non-motor microtubule-binding tail domain interacts with the microtubule’s E-hook tail with a rupture force higher than the stall force of the motor. This allows Kif15 dimers to productively and efficiently generate forces that could potentially slide microtubules apart. (PMID:28918951)
• KIF15 knockdown using short hairpin RNA in two human lung adenocarcinoma cell lines induced G1/S phase cell cycle arrest and inhibited cell growth. (PMID:30439711)
• Our results suggest that KIF15 plays a positive role in the tumorigenicity of melanoma and it may serve as a novel diagnostic and therapeutic target for melanoma, especially uveal melanoma. (PMID:30797758)
• KIF15 high expression is associated with Triple-Negative Breast Cancer. (PMID:30854965)
• We identified and replicated three new genome-wide significant signals of association with idiopathic pulmonary fibrosis susceptibility (associated with altered gene expression of KIF15, MAD1L1, and DEPTOR). New signals of association implicating KIF15 and MAD1L1 suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility. (PMID:31710517)
• Kinesin family member 15 promotes cancer stem cell phenotype and malignancy via reactive oxygen species imbalance in hepatocellular carcinoma. (PMID:31733289)
• KIF15 Expression in Tumor-associated Monocytes Is a Prognostic Biomarker in Hepatocellular Carcinoma. (PMID:32108036)
• Identification of KIF15 as a potential therapeutic target and prognostic factor for glioma. (PMID:32323839)
• KIF15 promotes the evolution of gastric cancer cells through inhibition of reactive oxygen species-mediated apoptosis. (PMID:32342525)
• GSG2 (Haspin) promotes development and progression of bladder cancer through targeting KIF15 (Kinase-12). (PMID:32439830)
• ZNF367-induced transcriptional activation of KIF15 accelerates the progression of breast cancer. (PMID:32549756)
• KIF15 contributes to cell proliferation and migration in breast cancer. (PMID:32578050)
• B7-H3 regulates KIF15-activated ERK1/2 pathway and contributes to radioresistance in colorectal cancer. (PMID:33011740)
• KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer. (PMID:33277366)
• KIF15 upregulation promotes leiomyosarcoma cell growth via promoting USP15-mediated DEK deubiquitylation. (PMID:34280614)
• Kinesin 12 (KIF15) contributes to the development and tumorigenicity of prostate cancer. (PMID:34474246)
• K-fiber bundles in the mitotic spindle are mechanically reinforced by Kif15. (PMID:34668719)
• KIF15 knockdown suppresses gallbladder cancer development. (PMID:34781077)
• Downregulation of KIF15 inhibits the tumorigenesis of non-small-cell lung cancer via inactivating Raf/MEK/ERK signaling. (PMID:34908156)
• Rare and Common Variants in KIF15 Contribute to Genetic Risk of Idiopathic Pulmonary Fibrosis. (PMID:35417304)
• PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer. (PMID:36137220)
• Dynamic regulation of KIF15 phosphorylation and acetylation promotes focal adhesions disassembly in pancreatic cancer. (PMID:36280663)
• KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer. (PMID:36807568)
• KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis. (PMID:37777755)
• Antiparallel microtubule bundling supports KIF15-driven mitotic spindle assembly. (PMID:38598297)
• KIF15 promotes human glioblastoma progression under the synergistic transactivation of REST and P300. (PMID:39430242)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif15	ENSDARG00000012073
mus_musculus	Kif15	ENSMUSG00000036768
rattus_norvegicus	Kif15	ENSRNOG00000060356
drosophila_melanogaster	ncd	FBGN0002924
caenorhabditis_elegans		WBGENE00002228

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), KIF2C (ENSG00000142945), KIF5A (ENSG00000155980), KIF26B (ENSG00000162849), 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 KIF15 — Q9NS87 (reviewed: Q9NS87)

Alternative names: Kinesin-like protein 2, Kinesin-like protein 7, Serologically defined breast cancer antigen NY-BR-62

All UniProt accessions (6): C9JKA9, D6RCT7, Q9NS87, F8WC33, H7BZT2, H7C1K7

UniProt curated annotations — full annotation on UniProt →

Function. Plus-end directed kinesin-like motor enzyme involved in mitotic spindle assembly.

Subunit / interactions. Interacts with MKI67 and TPX2.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle.

Tissue specificity. Expressed in testis, colon, thymus and in breast cancer.

Disease relevance. Braddock-Carey syndrome 2 (BRDCS2) [MIM:619981] An autosomal recessive disease characterized by microcephaly, congenital thrombocytopenia, and facial dysmorphisms including Pierre-Robin sequence. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KLP2 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NS87-1	1	yes
Q9NS87-2	2
Q9NS87-3	3
Q9NS87-4	4

RefSeq proteins (1): NP_064627* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031794	HMMR_C	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR044986	KIF15/KIN-12	Family

Pfam: PF00225, PF15908

UniProt features (48 total): strand 16, helix 10, modified residue 5, sequence variant 5, splice variant 4, region of interest 2, chain 1, domain 1, sequence conflict 1, coiled-coil region 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4BN2	X-RAY DIFFRACTION	2.69
6ZPI	ELECTRON MICROSCOPY	4.5
7RYP	ELECTRON MICROSCOPY	4.8
6ZPH	ELECTRON MICROSCOPY	6.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS87-F1	72.23	0.13

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): 109–116

Post-translational modifications (5): 1141, 1169, 399, 568, 1009

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 413 (showing top): GOBP_CHROMOSOME_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GNF2_CENPF, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_KINESIN_COMPLEX, REACTOME_MEMBRANE_TRAFFICKING, YY1_Q6, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_MITOTIC_SPINDLE_ASSEMBLY, E2F_Q3, GOBP_ORGANELLE_FISSION, YY1_02, FISCHER_G2_M_CELL_CYCLE, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOCC_CENTROSOME

GO Biological Process (4): mitotic cell cycle (GO:0000278), microtubule-based movement (GO:0007018), centrosome separation (GO:0051299), mitotic spindle assembly (GO:0090307)

GO Molecular Function (8): cytoskeletal motor activity (GO:0003774), microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), plus-end-directed microtubule motor activity (GO:0008574), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (10): spindle pole (GO:0000922), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), kinesin complex (GO:0005871), plus-end kinesin complex (GO:0005873), microtubule (GO:0005874), membrane (GO:0016020), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Adaptive Immune System	1
Golgi-to-ER retrograde transport	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
mitotic nuclear division	2
ATP-dependent activity	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
cell cycle	1
microtubule-based process	1
centrosome cycle	1
cell cycle process	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	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
microtubule motor activity	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
spindle	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
microtubule associated complex	1
kinesin complex	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

1910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF15	TPX2	Q9ULW0	750
KIF15	ASPM	Q8IZT6	743
KIF15	KIFBP	Q96EK5	720
KIF15	NUF2	Q9BZD4	674
KIF15	TTK	P33981	640
KIF15	AURKB	Q96GD4	636
KIF15	CENPF	P49454	616
KIF15	NUSAP1	Q9BXS6	611
KIF15	CCNB2	O95067	591
KIF15	TOP2A	P11388	591
KIF15	PLK4	O00444	587
KIF15	CCNB1	P14635	566
KIF15	ZWINT	O95229	558
KIF15	DLGAP5	Q15398	556
KIF15	CENPM	Q9NSP4	553

IntAct

34 interactions, top by confidence:

A	B	Type	Score
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
MKI67	KIF15	psi-mi:“MI:0915”(physical association)	0.530
KIF15	MKI67	psi-mi:“MI:0407”(direct interaction)	0.530
KIFBP	KIF3C	psi-mi:“MI:0914”(association)	0.530
PHYHIP	TRIP6	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
KIF15	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
KIF15	DEK	psi-mi:“MI:0915”(physical association)	0.400
KIF15	CANX	psi-mi:“MI:0915”(physical association)	0.400
KIF15	PISD	psi-mi:“MI:0914”(association)	0.350
CUL4B	GPS1	psi-mi:“MI:0914”(association)	0.350
KIF15	DMD	psi-mi:“MI:0914”(association)	0.350
DGCR8	HNRNPUL1	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
SYNC	NDC80	psi-mi:“MI:0914”(association)	0.350
CUL4A	DDX39A	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
MCC	CIBAR1	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
ISCA1	BACH1	psi-mi:“MI:0914”(association)	0.350
KIFBP	STK25	psi-mi:“MI:0914”(association)	0.350
PPM1B	KARS1	psi-mi:“MI:2364”(proximity)	0.270
KIF15	CEP126	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (119): KIF15 (Affinity Capture-MS), KIF15 (Affinity Capture-MS), DMD (Affinity Capture-MS), FANCG (Affinity Capture-MS), MED6 (Affinity Capture-MS), CD2AP (Affinity Capture-MS), PISD (Affinity Capture-MS), UPF2 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), KIF15 (Affinity Capture-MS), KIF15 (Affinity Capture-MS), KIAA1143 (Affinity Capture-MS), MRPL44 (Affinity Capture-MS), ELMO3 (Affinity Capture-MS), MRI1 (Affinity Capture-MS)

ESM2 similar proteins: A3BFT0, A8BB91, A8BKD1, B9F2Y7, F4IJK6, F4JGP4, F4K0J3, G5EGS3, O15066, O35066, O43093, O60282, P17210, P20480, P21613, P28738, P28739, P28741, P33175, P33176, P34540, P35978, P45962, P46864, P46873, P46875, P48467, P56536, P79955, Q07970, Q0J9V3, Q0WN69, Q12840, Q2PQA9, Q498L9, Q4R628, Q5JKW1, Q5R4H3, Q5R9K7, Q61768

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	174
Likely benign	16
Benign	13

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1698455	NM_020242.3(KIF15):c.1501C>T (p.Arg501Ter)	Pathogenic
3065669	NM_020242.3(KIF15):c.1830-2A>C	Likely pathogenic
4849463	NM_020242.3(KIF15):c.2410C>T (p.Arg804Ter)	Likely pathogenic

SpliceAI

6041 predictions. Top by Δscore:

Variant	Effect	Δscore
3:44761882:AAA:A	donor_gain	1.0000
3:44761882:AAAGT:A	donor_loss	1.0000
3:44761883:AA:A	donor_gain	1.0000
3:44761883:AAG:A	donor_loss	1.0000
3:44761885:G:C	donor_loss	1.0000
3:44761885:G:GG	donor_gain	1.0000
3:44774394:GCTGA:G	acceptor_gain	1.0000
3:44775245:T:A	acceptor_gain	1.0000
3:44775252:A:AG	acceptor_gain	1.0000
3:44775253:G:GT	acceptor_gain	1.0000
3:44775253:GT:G	acceptor_gain	1.0000
3:44775253:GTA:G	acceptor_gain	1.0000
3:44775253:GTAA:G	acceptor_gain	1.0000
3:44775253:GTAAT:G	acceptor_gain	1.0000
3:44775434:TCAGG:T	donor_loss	1.0000
3:44775435:CAGGT:C	donor_loss	1.0000
3:44775436:AGG:A	donor_loss	1.0000
3:44775437:GGTA:G	donor_loss	1.0000
3:44775439:T:G	donor_loss	1.0000
3:44778187:GCATA:G	donor_gain	1.0000
3:44778190:TA:T	donor_gain	1.0000
3:44778192:G:GG	donor_gain	1.0000
3:44780883:A:AG	acceptor_gain	1.0000
3:44780884:G:GG	acceptor_gain	1.0000
3:44786393:A:AG	acceptor_gain	1.0000
3:44786393:AGGCT:A	acceptor_gain	1.0000
3:44786394:G:GG	acceptor_gain	1.0000
3:44786394:GGCT:G	acceptor_gain	1.0000
3:44786394:GGCTG:G	acceptor_gain	1.0000
3:44786499:G:GT	donor_gain	1.0000

AlphaMissense

9229 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:44797928:C:A	A357D	1.000
3:44780886:G:A	G109R	0.999
3:44780886:G:C	G109R	0.999
3:44780887:G:A	G109E	0.999
3:44780887:G:T	G109V	0.999
3:44784884:G:A	G134E	0.999
3:44794281:G:T	R235M	0.999
3:44794293:T:A	V239D	0.999
3:44794379:G:A	G268R	0.999
3:44794379:G:C	G268R	0.999
3:44794380:G:A	G268E	0.999
3:44797564:T:A	I288K	0.999
3:44797606:T:C	L302P	0.999
3:44797644:T:G	Y315D	0.999
3:44797648:G:C	R316T	0.999
3:44797649:A:C	R316S	0.999
3:44797649:A:T	R316S	0.999
3:44797672:T:C	L324P	0.999
3:44797919:T:C	L354P	0.999
3:44797924:T:C	F356L	0.999
3:44797926:T:A	F356L	0.999
3:44797926:T:G	F356L	0.999
3:44797936:G:C	A360P	0.999
3:44797937:C:A	A360D	0.999
3:44778167:G:A	G100D	0.998
3:44780901:G:T	G114W	0.998
3:44780902:G:A	G114E	0.998
3:44780904:A:C	K115Q	0.998
3:44780922:G:A	G121R	0.998
3:44780922:G:C	G121R	0.998

dbSNP variants (sampled 300 via entrez): RS1000034324 (3:44806321 A>G), RS1000061986 (3:44790130 A>G,T), RS1000066467 (3:44794026 T>C), RS1000090556 (3:44808569 T>C), RS1000091888 (3:44813541 T>G), RS1000151852 (3:44835906 G>A,T), RS1000171793 (3:44855569 G>A), RS1000171822 (3:44778917 T>A,G), RS1000208728 (3:44847419 G>A), RS1000266672 (3:44855284 A>G), RS1000268069 (3:44822463 A>G), RS1000340220 (3:44801214 G>A,C,T), RS1000408109 (3:44799121 T>C), RS1000494196 (3:44764799 G>A), RS1000494985 (3:44829549 T>C)

Disease associations

OMIM: gene MIM:617569 | disease phenotypes: MIM:619981

GenCC curated gene-disease

Disease	Classification	Inheritance
braddock-carey syndrome 2	Limited	Unknown

Mondo (2): pulmonary fibrosis (MONDO:0002771), braddock-carey syndrome 2 (MONDO:0859570)

Orphanet (0):

HPO phenotypes

69 total (30 of 69 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000201	Pierre-Robin sequence
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000413	Atresia of the external auditory canal
HP:0000414	Bulbous nose
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000568	Microphthalmia
HP:0000678	Dental crowding
HP:0000708	Atypical behavior
HP:0000752	Hyperactivity
HP:0000958	Dry skin
HP:0000960	Sacral dimple
HP:0001106	Periorbital hyperpigmentation
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002481_7	Acne (severe)	3.000000e-06
GCST003123_9	Severe influenza A (H1N1) infection	9.000000e-14
GCST006444_7	Bone mineral density (hip)	1.000000e-06
GCST006629_89	Pulse pressure	1.000000e-11
GCST007269_28	Pulse pressure	1.000000e-11
GCST008103_52	Bipolar disorder	3.000000e-07
GCST009309_1	Face memory	4.000000e-08
GCST009758_1	Idiopathic pulmonary fibrosis	4.000000e-14
GCST011598_2	Sepsis (hospital admission)	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0007702	hip bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0004874	memory performance
EFO:0000768	idiopathic pulmonary fibrosis

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011658	Pulmonary Fibrosis	C08.381.483.652; C23.550.355.644

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3632454 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	CHEMBL4540278
6.12	IC50	750	nM	CHEMBL73157
6.09	IC50	820	nM	CHEMBL73157
5.76	IC50	1720	nM	CHEMBL4540278
5.60	IC50	2500	nM	CHEMBL72365

PubChem BioAssay actives

5 with measured affinity, of 55 total; 3 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
ethyl 2-[[(2S)-2-(2,4-dioxo-1H-quinazolin-3-yl)-3-methylbutanoyl]amino]-4-methyl-1,3-thiazole-5-carboxylate	1574597: Inhibition of recombinant His6-tagged Kif15 (N700 residues) (unknown origin) expressed in HeLa cells assessed as reduction in Alexa-594 labelled microtubule gliding measured every 2 secs for 20 secs by epifluorescence microscopic analysis	ic50	0.2000	uM
(3Z)-3-[(3,5-dichloro-4-hydroxyphenyl)methylidene]-5-(furan-2-carbonyl)-1H-indol-2-one	1574597: Inhibition of recombinant His6-tagged Kif15 (N700 residues) (unknown origin) expressed in HeLa cells assessed as reduction in Alexa-594 labelled microtubule gliding measured every 2 secs for 20 secs by epifluorescence microscopic analysis	ic50	0.7500	uM
(3Z)-3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1H-indol-2-one	1574596: Inhibition of recombinant His6-tagged Kif15 ATPase activity (N420 residues) (unknown origin) expressed in HeLa cells using microtubule as substrate preincubated for 15 mins followed by ATP addition and measured after 20 mins by ADP-Glo luminescence assay	ic50	2.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases methylation	5
Valproic Acid	affects expression, decreases expression, decreases methylation	5
bisphenol A	increases expression, affects expression, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Tetrachlorodibenzodioxin	decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Cadmium	decreases expression, increases abundance	2
Drugs, Chinese Herbal	decreases expression, affects cotreatment, increases expression	2
Estradiol	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
tert-Butylhydroperoxide	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
caffeic acid	affects cotreatment, increases expression	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3636406	Binding	Inhibition of microtubule-stimulated KIF15 motor domain (1 to 372) (unknown origin) ATPase activity at 6.3 uM	Structure-Guided Design of Novel l-Cysteine Derivatives as Potent KSP Inhibitors. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU70	HAP1 KIF15 (-) 1	Cancer cell line	Male
CVCL_SU71	HAP1 KIF15 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04619680	PHASE4	COMPLETED	The Study of the Use of Nintedanib in Slowing Lung Disease in Patients With Fibrotic or Non-Fibrotic Interstitial Lung Disease Related to COVID-19
NCT07570888	PHASE4	NOT_YET_RECRUITING	This is a Trial Designed to Evaluate the Combination of Nerandomilast With Mycophenolate Across a Wide Variety of Pulmonary Fibrosis Subtypes, With the Aim of Providing Clinicians With Assurance That This is an Appropriate Therapeutic Combination.
NCT00004563	PHASE3	COMPLETED	Scleroderma Lung Disease
NCT00052039	PHASE3	TERMINATED	A Randomized, Double-Blind, Three-Arm, Phase 3b Study Comparing the Safety and Efficacy of Interferon Gamma-1b With Azathioprine, and Azathioprine Alone in Patients With IPF Receiving Prednisone
NCT00075998	PHASE3	TERMINATED	The INSPIRE Trial: A Study of Interferon Gamma-1b for Idiopathic Pulmonary Fibrosis (IPF)
NCT00076635	PHASE3	TERMINATED	An Open-Label Study of the Safety of Interferon Gamma-1b in Patients With IPF
NCT00517933	PHASE3	COMPLETED	Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis
NCT00639496	PHASE3	COMPLETED	Study of the Effects of High-dose N-acetylcysteine (NAC) in Idiopathic Pulmonary Fibrosis (IPF)
NCT00650091	PHASE3	COMPLETED	Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in Patients With IPF
NCT00896155	PHASE3	UNKNOWN	Trial of Concurrent Versus Sequential Tamoxifen With Radiotherapy in Breast Cancer Patients
NCT01335464	PHASE3	COMPLETED	Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients
NCT01335477	PHASE3	COMPLETED	Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients II
NCT01570764	PHASE3	COMPLETED	Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease
NCT03267108	PHASE3	TERMINATED	A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension
NCT04905693	PHASE3	ENROLLING_BY_INVITATION	Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease
NCT04979884	PHASE3	COMPLETED	Safety and Effectiveness of Cyclosporin in the Management of COVID19 ARDS Patients in Alexandria University Hospital
NCT05943535	PHASE3	RECRUITING	Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
NCT06025578	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis
NCT06238622	PHASE3	RECRUITING	A Follow-up Study to Test Long-term Treatment With Nerandomilast in People With Pulmonary Fibrosis Who Took Part in a Previous Study With Nerandomilast
NCT07201922	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Can Help Slow Down Changes in the Lung in People With a Family History of Pulmonary Fibrosis
NCT07441408	PHASE3	NOT_YET_RECRUITING	Long-term Extension Study to Evaluate Safety and Tolerability of Admilparant in Participants With Pulmonary Fibrosis
NCT07503587	PHASE3	NOT_YET_RECRUITING	Evaluating the Efficacy and Safety of of HSK44459 in People With Progressive Pulmonary Fibrosis
NCT00000596	PHASE2	COMPLETED	Diffuse Fibrotic Lung Disease
NCT00001596	PHASE2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
NCT00052052	PHASE2	COMPLETED	An Open-Label Study of the Safety and Efficacy of Subcutaneous Recombinant Interferon-Gamma 1b (IFN-Gamma 1b) in Patients With Idiopathic Pulmonary Fibrosis (IPF)
NCT00063869	PHASE2	COMPLETED	Study Evaluating the Safety and Efficacy of Etanercept in Patients With Idiopathic Pulmonary Fibrosis
NCT00080223	PHASE2	COMPLETED	Safety Study of Oral Pirfenidone in Patients With Pulmonary Fibrosis/Idiopathic Pulmonary Fibrosis
NCT00109681	PHASE2	COMPLETED	Inhaled Iloprost in Adults With Abnormal Pulmonary Pressure and Associated With Idiopathic Pulmonary Fibrosis
NCT00352482	PHASE2	COMPLETED	Sildenafil to Increase Exercise Capacity in Individuals With Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension
NCT00455767	PHASE2	COMPLETED	Safety and Efficacy Study of Depelestat in Acute Respiratory Distress Syndrome (ARDS) Patients
NCT00514683	PHASE2	COMPLETED	Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis
NCT00690885	PHASE2	TERMINATED	Interferon-alpha Treatment of Chronic Cough in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis
NCT00786201	PHASE2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of CNTO 888 Administered Intravenously (IV) in Participants With Idiopathic Pulmonary Fibrosis (IPF)
NCT01135199	PHASE2	WITHDRAWN	Pomalidomide for Cough in Patients With Idiopathic Pulmonary Fibrosis
NCT01170065	PHASE2	COMPLETED	Roll Over Study From 1199.30 BIBF 1120 in Idiopathic Pulmonary Fibrosis (IPF)
NCT01203943	PHASE2	TERMINATED	A Study to Characterize the Safety, PK and Biological Activity of CC-930 in Idiopathic Pulmonary Fibrosis (IPF)
NCT01417156	PHASE2	COMPLETED	Safety and PK Study of BIBF 1120 in Japanese Patients With IPF: Follow up Study From 1199.31(NCT01136174)
NCT01442779	PHASE2	COMPLETED	Clinical Trial of Low Dose Oral Interferon Alpha in Idiopathic Pulmonary Fibrosis
NCT01917877	PHASE2	UNKNOWN	Efficiency Study for Acute Radiation-induced and Chemotherapy-induced Pulmonary Fibrosis With Bevasizumab
NCT02603068	PHASE2	WITHDRAWN	Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis