KIF23

Summary

KIF23 (kinesin family member 23, HGNC:6392) is a protein-coding gene on chromosome 15q23, encoding Kinesin-like protein KIF23 (Q02241). Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

The protein encoded by this gene is a member of kinesin-like protein family. This family includes microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. This protein has been shown to cross-bridge antiparallel microtubules and drive microtubule movement in vitro. Alternate splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 9493 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital dyserythropoietic anemia type 3 (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 428 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_001367805

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6392
Approved symbol	KIF23
Name	kinesin family member 23
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	MKLP1, MKLP-1
Ensembl gene	ENSG00000137807
Ensembl biotype	protein_coding
OMIM	605064
Entrez	9493

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 21 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000260363, ENST00000352331, ENST00000395392, ENST00000558303, ENST00000558346, ENST00000558585, ENST00000559279, ENST00000559283, ENST00000559456, ENST00000559944, ENST00000560042, ENST00000560125, ENST00000561089, ENST00000643966, ENST00000647715, ENST00000679126, ENST00000902293, ENST00000902294, ENST00000902295, ENST00000902296, ENST00000933185, ENST00000933186, ENST00000933187, ENST00000933188, ENST00000933189, ENST00000933190, ENST00000933191, ENST00000933192, ENST00000933193, ENST00000963414, ENST00000963415

RefSeq mRNA: 5 — MANE Select: NM_001367805 NM_001281301, NM_001367804, NM_001367805, NM_004856, NM_138555

CCDS: CCDS32278, CCDS32279, CCDS92033

Canonical transcript exons

ENST00000679126 — 24 exons

Exon	Start	End
ENSE00000696303	69444790	69445041
ENSE00000696405	69421992	69422128
ENSE00000696409	69421647	69421752
ENSE00001358343	69414349	69414476
ENSE00002227620	69425282	69425323
ENSE00002568155	69447792	69448425
ENSE00003468860	69440308	69440487
ENSE00003472357	69422326	69422435
ENSE00003472824	69438248	69438405
ENSE00003483669	69435652	69435771
ENSE00003495108	69436564	69436722
ENSE00003526343	69417383	69417511
ENSE00003527420	69426070	69426182
ENSE00003543666	69436138	69436261
ENSE00003556163	69440768	69441079
ENSE00003566339	69446283	69446364
ENSE00003595864	69423159	69423329
ENSE00003599709	69435483	69435562
ENSE00003635147	69446009	69446091
ENSE00003635572	69439904	69440077
ENSE00003637437	69426336	69426457
ENSE00003637745	69446871	69446941
ENSE00003638899	69415994	69416063
ENSE00003639059	69429111	69429213

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 96.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4471 / max 930.7114, expressed in 1517 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147449	20.6194	1466
147448	1.7648	838
147451	1.7607	704
147450	0.7360	444
147452	0.5662	319

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.74	gold quality
secondary oocyte	CL:0000655	95.02	gold quality
ganglionic eminence	UBERON:0004023	89.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.77	gold quality
oocyte	CL:0000023	88.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.50	gold quality
stromal cell of endometrium	CL:0002255	84.51	gold quality
embryo	UBERON:0000922	84.35	gold quality
lower esophagus mucosa	UBERON:0035834	83.35	gold quality
bone marrow	UBERON:0002371	82.43	gold quality
mucosa of transverse colon	UBERON:0004991	82.19	gold quality
adrenal tissue	UBERON:0018303	81.63	gold quality
metanephros cortex	UBERON:0010533	80.50	gold quality
trabecular bone tissue	UBERON:0002483	80.49	gold quality
left testis	UBERON:0004533	80.08	gold quality
testis	UBERON:0000473	79.86	gold quality
esophagus mucosa	UBERON:0002469	79.73	gold quality
right testis	UBERON:0004534	79.54	gold quality
rectum	UBERON:0001052	79.51	gold quality
amniotic fluid	UBERON:0000173	79.06	gold quality
bone marrow cell	CL:0002092	78.02	gold quality
popliteal artery	UBERON:0002250	76.19	gold quality
tibial artery	UBERON:0007610	76.17	gold quality
right coronary artery	UBERON:0001625	76.05	gold quality
aorta	UBERON:0000947	75.02	gold quality
vermiform appendix	UBERON:0001154	74.68	gold quality
tibial nerve	UBERON:0001323	74.51	gold quality
ascending aorta	UBERON:0001496	74.03	gold quality
right adrenal gland	UBERON:0001233	73.97	gold quality
thoracic aorta	UBERON:0001515	73.94	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	569.35
E-MTAB-6678	yes	9.22
E-ANND-3	yes	5.18
E-MTAB-6142	no	803.64
E-MTAB-6911	no	416.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, E2F1, KCNIP3, TP53

miRNA regulators (miRDB)

81 targeting KIF23, 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-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-20B-5P	99.88	74.01	2621

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• MKLP1 interacts with CYK4, a GTPase activating protein for the Rho GTPase, to form the centralspindlin complex. Centralspindlin is a key regulator of Rho function and microtubule organisation during cytokinesis, and is essential for cell division. (PMID:11782313)
• CHO1 and its truncated isoform MKLP1 are coexpressed in a single cell. The sequence encoded by exon 18 possesses a capability to interact with F-actin, suggesting that CHO1 can associate with both microtubule and actin cytoskeletons. (PMID:11877456)
• Plk1 and CHO1/MKLP-1 interact to have a role in cytokinesis (PMID:15199097)
• Recruitment of MKLP1 to the midzone/midbody by INCENP is a crucial step for the midbody formation and completion of cytokinesis in mammalian cells. (PMID:15796717)
• Spatial restriction of Aurora B to the central spindle by MKlp2 regulates MKlp1 during cytokinesis in human cells. (PMID:16461284)
• Cep55 directly binds to MKLP1 in vitro and associates with the MKLP1-MgcRacGAP centralspindlin complex in vivo (PMID:16790497)
• Ectopic expression of a mutant Mklp-1 without the nuclear localization signal(s)(NLSs) leads to cell cycle arrest at cytokinesis, indicating that the NLSs are necessary for Mklp-1 to execute its normal function during cell division. (PMID:17198681)
• study reports that mitotic complex genes Ect2, RacGAP, and MKLP1 are coordinately induced in S phase in proliferating T lymphocytes as well as in epithelial cells, depending upon activity of the CUX1 and E2F1 transcription factors (PMID:19015243)
• Study shows that 14-3-3 protein binds centralspindlin when the kinesin-6 component MKLP1 is phosphorylated at S710; 14-3-3 prevents centralspindlin from clustering in vitro, and MKLP1 mutant that is unable to bind 14-3-3 forms aberrant clusters in vivo. (PMID:20451386)
• The results of this study indicated that downregulation of KIF23 decreases proliferation of glioma cells and that KIF23 may be a novel therapeutic target in malignant glioma. (PMID:21904957)
• It was shown that, during cytokinesis, Arf6 is first accumulated around the cleavage furrow and, prior to abscission, recruited onto the Flemming body via interaction with MKLP1. (PMID:22522702)
• v-Src inhibits cytokinesis through the delocalization of Mklp1 and Aurora B from the spindle midzone, resulting in binucleation. (PMID:23562843)
• KIF23 mutation is associated with congenital dyserythropoietic anemia type III. (PMID:23570799)
• Transcriptional regulation of KIF23 is mediated by TP53. (PMID:23650552)
• TRAF6 mediates ubiquitination of the midbody ring localized protein KIF23/MKLP1. (PMID:24128730)
• Phosphorylation of S716 NDR/LATS, present only in the longest Kif23 isoform, is required for phosphorylation at S814, revealing phosphorylation at these two sites, and differential regulation of Kif23-14-3-3 interaction for the two Kif23 isoforms. (PMID:25658096)
• In this study we show for the first time that KIF23 V1 and V2 have different localizations in hepatocellular carcinoma cells (PMID:26674738)
• Data show high level of KIF23 expression in the majority of primary and metastatic lung cancer tissues or cell lines and associates with poor survival. (PMID:26775597)
• Authors found that KIF23 was regulated by TCF-4 at transcriptionally level. Therefore, this evidence indicates KIF23 over-expression is associated with glioma malignancy and conferred a worse survival time in glioma. (PMID:27013586)
• Data show that p120-catenin interacts with kinesin family member 23 (MKLP1) to regulate focused rhoA GTP-binding protein (RhoA) activity during cytokinesis. (PMID:28004812)
• Results show the mitotic regulators KIF23 and MIS18BP1 to be co-modified by SUMO and ubiquitin on inhibition of the proteasome and subsequently identified as novel RNF4 targets. (PMID:28951443)
• KIF23 was found highly expressed in NSCLC (PMID:29277180)
• MiR-424 functions as a tumor-suppressor, inhibiting cell metastasis and epithelial mesenchymal transformation by targeting KIF23 in gliomas. (PMID:30338805)
• miR-424/503 cluster is silenced by DNA hypermethylation, which promotes the expression of KIF23, thereby regulating the proliferation and migration of ovarian cancer cells. (PMID:31135262)
• Study revealed that PP1beta-MYPT1 phosphatase regulates microtubule dynamics in late cytokinesis and de-phosphorylates the kinesin component MKLP1/KIF23 of the centralspindlin complex. This de-phosphorylation antagonizes Aurora B kinase to modify the functions and interactions of centralspindlin in late cytokinesis. (PMID:31586073)
• KIF23 activated Wnt/beta-catenin signaling pathway through direct interaction with Amer1 in gastric cancer. (PMID:32365332)
• Differential tissue specific expression of Kif23 alternative transcripts in mice with the human mutation causing congenital dyserythropoietic anemia type III. (PMID:32818800)
• Kinesin family member 23 (KIF23) contributes to the progression of bladder cancer cells in vitro and in vivo. (PMID:33231086)
• MiR-17-5p downregulation alleviates apoptosis and fibrosis in high glucose-induced human mesangial cells through inactivation of Wnt/beta-catenin signaling by targeting KIF23. (PMID:34014023)
• DEP domain containing 1B (DEPDC1B) exerts the tumor promoter in hepatocellular carcinoma through activating p53 signaling pathway via kinesin family member 23 (KIF23). (PMID:34983303)
• Inhibition of KIF23 Alleviates IPAH by Targeting Pyroptosis and Proliferation of PASMCs. (PMID:35457254)
• Kinesin family member 23, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/beta-catenin pathway. (PMID:35524313)
• [MicroRNA 424-5p promotes the sensitivity of hepatocellular carcinoma cells to sorafenib by targeting Kinesin family member 23]. (PMID:36727232)
• A Therapeutically Targetable TAZ-TEAD2 Pathway Drives the Growth of Hepatocellular Carcinoma via ANLN and KIF23. (PMID:36894036)
• KIF23, under regulation by androgen receptor, contributes to nasopharyngeal carcinoma deterioration by activating the Wnt/beta-catenin signaling pathway. (PMID:37010644)
• Kinesin family member 23 knockdown inhibits cell proliferation and epithelial-mesenchymal transition in esophageal carcinoma by inactivating the Wnt/beta-catenin pathway. (PMID:37162618)
• KCNQ1OT1 promotes retinoblastoma progression by targeting miR-339-3p that suppresses KIF23. (PMID:37198502)
• Identification and validation of KIF23 as a hypoxia-regulated lactate metabolism-related oncogene in uterine corpus endometrial carcinoma. (PMID:38336274)
• SIRT7 promotes the proliferation and migration of anaplastic thyroid cancer cells by regulating the desuccinylation of KIF23. (PMID:38360598)
• KIF23 promotes cervical cancer progression via inhibiting NLRP3-mediated pyroptosis. (PMID:38780518)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif23	ENSDARG00000014943
mus_musculus	Kif23	ENSMUSG00000032254
rattus_norvegicus	Kif23	ENSRNOG00000014080
drosophila_melanogaster	pav	FBGN0011692
caenorhabditis_elegans		WBGENE00006974

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), 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 KIF23 — Q02241 (reviewed: Q02241)

Alternative names: Kinesin-like protein 5, Mitotic kinesin-like protein 1

All UniProt accessions (7): A0A2R8Y531, A0A2U3TZL8, A0A7I2V5Y5, Q02241, H0YME6, H0YMJ4, H7BYN4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Essential for cytokinesis in Rho-mediated signaling. Required for the localization of ECT2 to the central spindle. Plus-end-directed motor enzyme that moves antiparallel microtubules in vitro.

Subunit / interactions. Heterotetramer of two molecules each of RACGAP1 and KIF23. Found in the centralspindlin complex. Interacts with RACGAP1; the interaction is direct. Interacts with ECT2 and PRC1. Interacts with ANXA11 during cytokinesis. Interacts with BIRC6/bruce and USP8/UBPY. Interacts with ARF6, forming heterodimers and heterotetramers.

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

Tissue specificity. Widely expressed.

Post-translational modifications. Ubiquitinated. Deubiquitinated by USP8/UBPY.

Disease relevance. Anemia, congenital dyserythropoietic, 3A (CDAN3A) [MIM:105600] An autosomal dominant blood disorder characterized by ineffective erythropoiesis, hemolytic anemia, macrocytosis in the peripheral blood, intravascular hemolysis, and giant multinucleated erythroblasts in the bone marrow. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q02241-1	1	yes
Q02241-2	2
Q02241-3	3

RefSeq proteins (5): NP_001268230, NP_001354733, NP_001354734, NP_004847, NP_612565 (=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
IPR032384	Kif23_Arf-bd	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR038105	Kif23_Arf-bd_sf	Homologous_superfamily

Pfam: PF00225, PF16540

UniProt features (50 total): cross-link 13, modified residue 11, strand 7, region of interest 5, compositionally biased region 3, splice variant 3, sequence variant 2, chain 1, domain 1, binding site 1, helix 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3VHX	X-RAY DIFFRACTION	2.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02241-F1	73.08	0.44

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): 112–119

Post-translational modifications (24): 155, 160, 605, 682, 684, 738, 814, 867, 902, 911, 927, 571, 586, 624, 647, 662, 665, 741, 823, 854 …

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-68884	Mitotic Telophase/Cytokinesis
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-1640170	Cell Cycle
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-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 502 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_MITOTIC_CYTOKINESIS, GOBP_CHROMOSOME_ORGANIZATION, HORIUCHI_WTAP_TARGETS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, PAL_PRMT5_TARGETS_UP, TGCACTT_MIR519C_MIR519B_MIR519A, GOCC_KINESIN_COMPLEX, GEORGES_CELL_CYCLE_MIR192_TARGETS, GENTILE_RESPONSE_CLUSTER_D3, REACTOME_MEMBRANE_TRAFFICKING, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (6): mitotic spindle elongation (GO:0000022), mitotic cytokinesis (GO:0000281), microtubule-based movement (GO:0007018), positive regulation of cytokinesis (GO:0032467), mitotic spindle midzone assembly (GO:0051256), cell division (GO:0051301)

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

GO Cellular Component (19): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), focal adhesion (GO:0005925), midbody (GO:0030496), mitotic spindle (GO:0072686), Flemming body (GO:0090543), centralspindlin complex (GO:0097149), sperm midpiece (GO:0097225), sperm annulus (GO:0097227), sperm principal piece (GO:0097228), cytoskeleton (GO:0005856), intercellular bridge (GO:0045171)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Adaptive Immune System	1
Golgi-to-ER retrograde transport	1
M Phase	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Cell Cycle, Mitotic	1
Cell Cycle	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	9
mitotic cell cycle process	3
sperm flagellum	3
mitotic cell cycle	2
ATP-dependent activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle elongation	1
cytoskeleton-dependent cytokinesis	1
microtubule-based process	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
mitotic spindle elongation	1
spindle midzone assembly	1
mitotic spindle assembly	1
mitotic nuclear division	1
cellular process	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
microtubule associated complex	1
polymeric cytoskeletal fiber	1
cell-substrate junction	1

Protein interactions and networks

STRING

4018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF23	RACGAP1	Q9H0H5	999
KIF23	ECT2	Q9H8V3	970
KIF23	ANLN	Q9NQW6	946
KIF23	PRC1	O43663	918
KIF23	PLK1	P53350	837
KIF23	AURKB	Q96GD4	833
KIF23	INCENP	Q9NQS7	825
KIF23	CEP55	Q53EZ4	820
KIF23	RASA1	P20936	813
KIF23	SLC5A7	Q9GZV3	782
KIF23	STARD13	Q9Y3M8	777
KIF23	NME7	Q9Y5B8	760
KIF23	CIT	O14578	750
KIF23	AURKA	O14965	749
KIF23	CDCA8	Q53HL2	737

IntAct

198 interactions, top by confidence:

A	B	Type	Score
RACGAP1	KIF23	psi-mi:“MI:0914”(association)	0.920
KIF23	YWHAZ	psi-mi:“MI:0915”(physical association)	0.920
YWHAG	KIF23	psi-mi:“MI:0915”(physical association)	0.920
YWHAZ	KIF23	psi-mi:“MI:0915”(physical association)	0.920
KIF23	RACGAP1	psi-mi:“MI:0915”(physical association)	0.920
RACGAP1	KIF23	psi-mi:“MI:0915”(physical association)	0.920
KIF23	YWHAZ	psi-mi:“MI:0914”(association)	0.920
YWHAG	KIF23	psi-mi:“MI:0914”(association)	0.920
RACGAP1	KIF23	psi-mi:“MI:0403”(colocalization)	0.920
KIF23	RACGAP1	psi-mi:“MI:0403”(colocalization)	0.920
KIF23	YWHAB	psi-mi:“MI:0915”(physical association)	0.900
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
STK11	HSP90AA1	psi-mi:“MI:0914”(association)	0.740
AMPH	BIN1	psi-mi:“MI:0914”(association)	0.740
KIF23	ARF6	psi-mi:“MI:0403”(colocalization)	0.670
ARF6	KIF23	psi-mi:“MI:0915”(physical association)	0.670
KIF23	ARF6	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (1166): KIF23 (Affinity Capture-RNA), KIF23 (Affinity Capture-RNA), KIF23 (Affinity Capture-RNA), Arf6 (Co-crystal Structure), Arf6 (Reconstituted Complex), ARF6 (Affinity Capture-Western), KIF23 (Co-fractionation), KIF23 (Co-fractionation), KIF23 (Co-fractionation), KIF23 (Co-fractionation), LIG3 (Co-fractionation), RACGAP1 (Co-fractionation), SMNDC1 (Co-fractionation), TCEA1 (Co-fractionation), KIF23 (Affinity Capture-MS)

ESM2 similar proteins: A4FVD8, A5D7H2, O14795, O43237, O55047, O70585, O75446, O88574, P58405, P84060, Q02241, Q0VA03, Q13033, Q14161, Q28H91, Q2TAD4, Q4KUS2, Q4R5P6, Q5EA89, Q5HYJ3, Q5R7U7, Q5RE09, Q5SQF8, Q5ZJ65, Q62768, Q6NYV5, Q6PBM7, Q6PDL0, Q80XP8, Q80YA9, Q811S7, Q86UE8, Q8BIK4, Q8C0V0, Q8CBY8, Q8TAV0, Q8WXI2, Q90ZY6, Q922G2, Q96EZ8

Diamond homologs: A8BB91, B1AVY7, B3H6Z8, B7EJ91, B7ZC32, B7ZNG0, B9EY52, B9FL70, B9FTR1, B9FUF9, B9G8P1, B9GE13, D3YXS5, E9Q5G3, F4HZF0, F4IAR2, F4IL57, F4J1U4, F4JX00, F4K0J3, F8WLE0, O14343, O23826, O35231, O43093, O45935, O59751, O60282, O81635, O95235, O95239, P17119, P17210, P21613, P23678, P24339, P28738, P28739, P33174, P33175

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRC1	“up-regulates activity”	KIF23	binding
AURKB	“down-regulates quantity”	KIF23	phosphorylation
YAP1	“up-regulates quantity by expression”	KIF23	“transcriptional regulation”
YAP/TAZ	“up-regulates quantity by expression”	KIF23	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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	9	65.0×	1e-12
Activation of BAD and translocation to mitochondria	7	57.3×	2e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	50.6×	5e-09
Activation of BH3-only proteins	7	37.4×	4e-08
RHO GTPases activate PKNs	7	23.9×	8e-07
Intrinsic Pathway for Apoptosis	7	22.0×	1e-06
FOXO-mediated transcription	6	21.7×	8e-06
SARS-CoV-1-host interactions	8	15.1×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	14.9×	4e-03
negative regulation of TORC1 signaling	5	13.2×	5e-03
mitotic spindle organization	5	11.1×	8e-03
intracellular protein localization	10	8.5×	2e-04
RNA splicing	8	5.7×	8e-03
protein phosphorylation	9	5.0×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	234
Likely benign	117
Benign	28

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1344522	NM_001367805.3(KIF23):c.2875del (p.Leu959fs)	Pathogenic
1344521	NM_001367805.3(KIF23):c.2789C>G (p.Pro930Arg)	Likely pathogenic
402143	NM_001367805.3(KIF23):c.797T>A (p.Leu266His)	Likely pathogenic
4278021	NM_001367805.3(KIF23):c.2866G>A (p.Gly956Arg)	Likely pathogenic

SpliceAI

2963 predictions. Top by Δscore:

Variant	Effect	Δscore
15:69414475:GC:G	donor_gain	1.0000
15:69414477:G:GG	donor_gain	1.0000
15:69414481:G:GG	donor_gain	1.0000
15:69415981:A:AG	acceptor_gain	1.0000
15:69415987:T:G	acceptor_gain	1.0000
15:69417381:A:T	acceptor_loss	1.0000
15:69417381:AG:A	acceptor_gain	1.0000
15:69417382:GG:G	acceptor_gain	1.0000
15:69417382:GGT:G	acceptor_gain	1.0000
15:69417382:GGTA:G	acceptor_gain	1.0000
15:69417382:GGTAT:G	acceptor_gain	1.0000
15:69417508:GGAG:G	donor_gain	1.0000
15:69417509:GAG:G	donor_gain	1.0000
15:69417509:GAGG:G	donor_gain	1.0000
15:69417509:GAGGT:G	donor_loss	1.0000
15:69417510:AGG:A	donor_loss	1.0000
15:69417511:GGTAA:G	donor_loss	1.0000
15:69417512:G:C	donor_loss	1.0000
15:69417513:T:G	donor_loss	1.0000
15:69421642:CACA:C	acceptor_loss	1.0000
15:69421643:ACAG:A	acceptor_loss	1.0000
15:69421644:CA:C	acceptor_loss	1.0000
15:69421645:A:AG	acceptor_gain	1.0000
15:69421645:A:AT	acceptor_loss	1.0000
15:69421646:G:GG	acceptor_gain	1.0000
15:69421646:GA:G	acceptor_gain	1.0000
15:69421646:GAC:G	acceptor_gain	1.0000
15:69421646:GACT:G	acceptor_gain	1.0000
15:69421646:GACTC:G	acceptor_gain	1.0000
15:69421749:AATGG:A	donor_loss	1.0000

AlphaMissense

6440 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:69426336:G:A	G283D	1.000
15:69429154:T:C	L338P	1.000
15:69440372:T:C	L651P	1.000
15:69440381:T:C	L654P	1.000
15:69444989:T:C	L860P	1.000
15:69446046:T:A	V890D	1.000
15:69446052:T:C	F892S	1.000
15:69421995:T:C	L107P	0.999
15:69422009:G:C	G112R	0.999
15:69422010:G:A	G112D	0.999
15:69422021:A:C	S116R	0.999
15:69422023:T:A	S116R	0.999
15:69422023:T:G	S116R	0.999
15:69422028:A:T	K118I	0.999
15:69423254:T:A	V220D	0.999
15:69423256:T:C	S221P	0.999
15:69423293:T:C	L233P	0.999
15:69426093:G:C	R253P	0.999
15:69426120:T:A	V262D	0.999
15:69426182:G:C	G283R	0.999
15:69426356:G:C	A290P	0.999
15:69426373:T:A	N295K	0.999
15:69426373:T:G	N295K	0.999
15:69426380:T:C	S298P	0.999
15:69426383:A:C	S299R	0.999
15:69426385:C:A	S299R	0.999
15:69426385:C:G	S299R	0.999
15:69426386:C:A	R300S	0.999
15:69426389:T:C	S301P	0.999
15:69426394:T:A	H302Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000013192 (15:69444534 T>A), RS1000072330 (15:69436980 C>G), RS1000218024 (15:69430067 T>C), RS1000284116 (15:69430466 A>C), RS1000437287 (15:69424277 A>G), RS1000447457 (15:69423060 A>G,T), RS1000491164 (15:69424638 C>T), RS1000548067 (15:69435011 C>T), RS1000625842 (15:69428835 T>C), RS1000793288 (15:69420883 G>A), RS1000860607 (15:69422904 G>A), RS1000898201 (15:69435267 C>A), RS1001184557 (15:69421310 C>T), RS1001187468 (15:69445293 A>G), RS1001215061 (15:69437871 C>T)

Disease associations

OMIM: gene MIM:605064 | disease phenotypes: MIM:105600

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital dyserythropoietic anemia type 3	Moderate	Autosomal dominant

Mondo (2): congenital dyserythropoietic anemia type 3 (MONDO:0007109), microcephaly (MONDO:0001149)

Orphanet (1): Congenital dyserythropoietic anemia type III (Orphanet:98870)

HPO phenotypes

29 total (30 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000225	Gingival bleeding
HP:0000952	Jaundice
HP:0000980	Pallor
HP:0001877	Abnormal erythrocyte morphology
HP:0001903	Anemia
HP:0001972	Macrocytic anemia
HP:0002249	Melena
HP:0002315	Headache
HP:0002904	Hyperbilirubinemia
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003452	Increased circulating iron concentration
HP:0004322	Short stature
HP:0004447	Poikilocytosis
HP:0004810	Congenital hypoplastic anemia
HP:0005518	Increased mean corpuscular volume
HP:0010972	Anemia of inadequate production
HP:0011273	Anisocytosis
HP:0011891	Post-partum hemorrhage
HP:0012130	Abnormal erythroid lineage cell morphology
HP:0012378	Fatigue
HP:0012543	Hemosiderinuria
HP:0020181	Reduced haptoglobin level
HP:0025035	Abnormal proerythroblast morphology
HP:0025196	Increased total iron binding capacity
HP:0025354	Abnormal cellular phenotype
HP:0025435	Increased circulating lactate dehydrogenase concentration
HP:0030140	Oral cavity bleeding
HP:0034278	Multinucleated erythroblast
HP:0000252	Microcephaly

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006048_17	Rheumatoid arthritis (ACPA-positive)	5.000000e-14
GCST90002396_637	Mean reticulocyte volume	2.000000e-27

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5899 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 150 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1829433	AZD-4877	2	150

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance	3
Doxorubicin	decreases expression, affects response to substance, decreases response to substance	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
bisphenol A	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Quercetin	affects cotreatment, increases expression, decreases expression	2
Cyclosporine	decreases expression	2
Vitamin K 3	affects expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
echimidine	increases expression, increases metabolic processing	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
lasiocarpine	affects expression, increases metabolic processing	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1
riddelliine	decreases expression, increases metabolic processing	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ochratoxin A	decreases expression	1
cupric oxide	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1020050	Binding	Inhibition of cloned human MKLP1	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)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.