KIF22

Summary

KIF22 (kinesin family member 22, HGNC:6391) is a protein-coding gene on chromosome 16p11.2, encoding Kinesin-like protein KIF22 (Q14807). Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. It is a selective cancer dependency (DepMap: 16.5% of cell lines).

The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. The C-terminal half of this protein has been shown to bind DNA. Studies with the Xenopus homolog suggests its essential role in metaphase chromosome alignment and maintenance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3835 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepimetaphyseal dysplasia with multiple dislocations (Definitive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 472 total — 7 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 69
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 16.5% of screened cell lines
• MANE Select transcript: NM_007317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6391
Approved symbol	KIF22
Name	kinesin family member 22
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	Kid, OBP-1, OBP-2
Ensembl gene	ENSG00000079616
Ensembl biotype	protein_coding
OMIM	603213
Entrez	3835

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 20 protein_coding, 13 nonsense_mediated_decay, 11 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000160827, ENST00000400751, ENST00000561482, ENST00000563263, ENST00000563666, ENST00000565736, ENST00000568312, ENST00000569382, ENST00000569636, ENST00000570173, ENST00000685401, ENST00000685526, ENST00000685961, ENST00000686384, ENST00000687634, ENST00000688492, ENST00000688761, ENST00000689089, ENST00000689107, ENST00000689172, ENST00000689221, ENST00000689415, ENST00000689660, ENST00000689743, ENST00000690258, ENST00000690419, ENST00000690510, ENST00000691128, ENST00000691169, ENST00000691203, ENST00000691486, ENST00000691895, ENST00000693260, ENST00000936369, ENST00000936370, ENST00000936371, ENST00000936372, ENST00000936373, ENST00000936374, ENST00000936375, ENST00000936376, ENST00000936377, ENST00000936378, ENST00000936379, ENST00000936380

RefSeq mRNA: 3 — MANE Select: NM_007317 NM_001256269, NM_001256270, NM_007317

CCDS: CCDS10653, CCDS58444

Canonical transcript exons

ENST00000160827 — 14 exons

Exon	Start	End
ENSE00000868486	29804814	29805026
ENSE00001544520	29790751	29790829
ENSE00001643614	29803998	29804065
ENSE00003463035	29799628	29799781
ENSE00003466414	29798593	29798747
ENSE00003543999	29802769	29802937
ENSE00003566442	29805115	29805174
ENSE00003567436	29796893	29797088
ENSE00003604044	29803449	29803608
ENSE00003634076	29799264	29799494
ENSE00003650217	29798374	29798501
ENSE00003686677	29799913	29800048
ENSE00003786587	29798975	29799184
ENSE00003901322	29805263	29805384

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 98.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.8541 / max 323.0225, expressed in 1813 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153488	22.2613	1696
153489	5.8721	1118
153491	5.8383	1500
153493	3.7677	1084
153492	0.5927	337
153494	0.4083	241
153490	0.0857	14
153487	0.0280	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.39	gold quality
ganglionic eminence	UBERON:0004023	96.73	gold quality
right lobe of thyroid gland	UBERON:0001119	95.49	gold quality
left lobe of thyroid gland	UBERON:0001120	95.26	gold quality
embryo	UBERON:0000922	94.78	gold quality
apex of heart	UBERON:0002098	94.56	gold quality
mucosa of transverse colon	UBERON:0004991	94.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.41	gold quality
thyroid gland	UBERON:0002046	94.23	gold quality
granulocyte	CL:0000094	94.16	gold quality
rectum	UBERON:0001052	93.76	gold quality
right testis	UBERON:0004534	93.67	gold quality
left testis	UBERON:0004533	93.54	gold quality
right lobe of liver	UBERON:0001114	92.57	gold quality
skin of abdomen	UBERON:0001416	91.81	gold quality
testis	UBERON:0000473	91.47	gold quality
skin of leg	UBERON:0001511	91.47	gold quality
endometrium epithelium	UBERON:0004811	91.26	gold quality
transverse colon	UBERON:0001157	91.20	gold quality
right atrium auricular region	UBERON:0006631	90.80	gold quality
lower esophagus mucosa	UBERON:0035834	90.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.44	gold quality
metanephros cortex	UBERON:0010533	90.06	gold quality
adenohypophysis	UBERON:0002196	90.05	gold quality
heart left ventricle	UBERON:0002084	90.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.94	gold quality
cardiac atrium	UBERON:0002081	89.65	gold quality
esophagus mucosa	UBERON:0002469	89.65	gold quality
cardiac ventricle	UBERON:0002082	89.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	35.10
E-ANND-3	yes	17.21
E-MTAB-6678	yes	10.31
E-MTAB-8060	no	100.25

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 17)

• These results are consistent with Kid having a role in chromosome congression in vivo, where it would be responsible for the polar ejection forces acting on the chromosome arms. (PMID:12606572)
• its molecular structure and interaction with microtubules (PMID:12692123)
• These results suggest that distinct from its role in chromosome movement, Kid contributes to spindle morphogenesis by mediating spindle microtubules stabilization. (PMID:16176979)
• human Aurora B and Kid are identified as APC/C(Cdh1) substrates (PMID:17726374)
• Association of importin-beta and -alpha with hKid triggers the initial targeting of hKid to mitotic chromosomes; local Ran-GTP-mediated cargo release promotes the accumulation of hKid on chromosomes. (PMID:18268099)
• These data suggest that Kid-mediated anaphase/telophase chromosome compaction prevents formation of multinucleated cells. (PMID:18329364)
• in all breast tumor tissues analyzed, variations in the Kid/KIF22 mRNA levels mirrored those seen with SIAH-1 mRNAs. (PMID:20144232)
• Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (PMID:22152677)
• Recurrent dominant mutations affecting two adjacent residues in the motor domain of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity (PMID:22152678)
• we conclude that inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through the transcriptional upregulation of CDC25C. (PMID:24626146)
• Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules. (PMID:25743205)
• KIF22-dependent regulation of microtubule dynamics led to delayed EGFR internalization, enhanced EGFR signaling, and coordination of CAR dynamics at cell-cell junctions resulting in lung cancer. (PMID:29382784)
• We identified two candidate mutations in COL1A2 and MATN1, which might be affected by the main known mutation in B3GALT6. Our finding replicated a previously identified mutation in KIF22 to be potentially associated with spondyloepimetaphyseal dysplasia with joint laxity. We also show that our identified candidate mutation genes, COL1A2, MATN1 and KIF22, are in a direct biological interaction with B3GALT6. (PMID:30358852)
• Suppression of KIF22 Inhibits Cell Proliferation and Xenograft Tumor Growth in Colon Cancer. (PMID:31657617)
• KIF22 Promotes Development of Pancreatic Cancer by Regulating the MEK/ERK/P21 Signaling Axis. (PMID:35578724)
• KIF22 promotes the proliferation and glycolysis of melanoma by activating EGFR/STAT3 signaling. (PMID:37944197)
• KIF22 promotes multiple myeloma progression by regulating the CDC25C/CDK1/cyclinB1 pathway. (PMID:38713252)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif22	ENSDARG00000102624
mus_musculus	Kif22	ENSMUSG00000030677
rattus_norvegicus	Kif22	ENSRNOG00000020281

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF3B (ENSG00000101350), KIF20A (ENSG00000112984), KIF21B (ENSG00000116852), KIF17 (ENSG00000117245), KIF14 (ENSG00000118193), KIF18A (ENSG00000121621), KIF25 (ENSG00000125337), KIF1C (ENSG00000129250), KIF1A (ENSG00000130294), KIF3A (ENSG00000131437), KIF12 (ENSG00000136883), KIF13A (ENSG00000137177), KIF23 (ENSG00000137807), KIF11 (ENSG00000138160), CENPE (ENSG00000138778), KIF21A (ENSG00000139116), KIFC3 (ENSG00000140859), KIF2B (ENSG00000141200), KIF2C (ENSG00000142945), KIF5A (ENSG00000155980), KIF26B (ENSG00000162849), KIF15 (ENSG00000163808), KIF6 (ENSG00000164627), KIF27 (ENSG00000165115), KIF7 (ENSG00000166813), KIFC2 (ENSG00000167702), KIF5C (ENSG00000168280), KIF5B (ENSG00000170759), KIF18B (ENSG00000186185), KIF24 (ENSG00000186638), KIF19 (ENSG00000196169), KIF13B (ENSG00000197892), KIF4B (ENSG00000226650)

Protein

Protein identifiers

Kinesin-like protein KIF22 — Q14807 (reviewed: Q14807)

Alternative names: Kinesin-like DNA-binding protein, Kinesin-like protein 4

All UniProt accessions (16): Q14807, A0A8I5KQ45, A0A8I5KRF7, A0A8I5KSP6, A0A8I5KTF7, A0A8I5KW08, A0A8I5KXF2, A0A8I5KXF9, A0A8I5QJC5, A0A8I5QJF2, A0A8I5QKY3, A0A8I5QL17, H3BQB9, H3BRB3, H3BTH5, I3L306

UniProt curated annotations — full annotation on UniProt →

Function. Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Binds to microtubules and to DNA. Plays a role in congression of laterally attached chromosomes in NDC80-depleted cells.

Subunit / interactions. Interacts with FAM83D. Interacts with SIAH1.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in bone, cartilage, joint capsule, ligament, skin, and primary cultured chondrocytes.

Post-translational modifications. Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation.

Disease relevance. Spondyloepimetaphyseal dysplasia with joint laxity, 2 (SEMDJL2) [MIM:603546] A bone disease characterized by short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalized ligamentous laxity, and mild spinal deformity. Intellectual development is not impaired. Radiographic characteristics include significantly retarded epiphyseal ossification that evolves into epiphyseal dysplasia and precocious osteoarthritis, metaphyseal irregularities and vertical striations, constricted femoral neck, slender metacarpals and metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or mild platyspondyly. The most distinctive features for differential diagnosis of SEMDJL2 are the slender metacarpals and phalanges and the progressive degeneration of carpal bones; however, these 2 features are evident only in older children and young adults. The soft consistency of cartilage in the airways leads to laryngotracheomalacia with proneness to respiratory obstruction and inspiratory stridor in infancy and childhood. 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 (2)

UniProt ID	Names	Canonical?
Q14807-1	1	yes
Q14807-2	2

RefSeq proteins (3): NP_001243198, NP_001243199, NP_015556* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR003583	Hlx-hairpin-Hlx_DNA-bd_motif	Domain
IPR010994	RuvA_2-like	Homologous_superfamily
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027640	Kinesin-like_fam	Family
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00225, PF12836

UniProt features (61 total): helix 17, strand 13, sequence conflict 9, modified residue 6, sequence variant 5, turn 3, chain 1, domain 1, cross-link 1, splice variant 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6NJE	X-RAY DIFFRACTION	2.2
2EDU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14807-F1	74.70	0.39

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): 127–134

Post-translational modifications (7): 562, 581, 465, 412, 427, 452, 543

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: 456 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, HORIUCHI_WTAP_TARGETS_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, CROONQUIST_NRAS_SIGNALING_DN, GOBP_CHROMOSOME_LOCALIZATION, GOCC_KINESIN_COMPLEX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, REACTOME_MEMBRANE_TRAFFICKING, GOLDRATH_ANTIGEN_RESPONSE, GOBP_ORGANELLE_FISSION, LE_EGR2_TARGETS_UP, FISCHER_G2_M_CELL_CYCLE, GOBP_SISTER_CHROMATID_COHESION, chr16p11

GO Biological Process (7): mitotic cell cycle (GO:0000278), DNA repair (GO:0006281), microtubule-based movement (GO:0007018), sister chromatid cohesion (GO:0007062), mitotic metaphase chromosome alignment (GO:0007080), metaphase chromosome alignment (GO:0051310), microtubule-based process (GO:0007017)

GO Molecular Function (8): DNA binding (GO:0003677), 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 (11): kinetochore (GO:0000776), chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), nuclear speck (GO:0016607), mitotic spindle (GO:0072686), 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
intracellular membraneless organelle	3
cellular anatomical structure	3
ATP-dependent activity	2
microtubule cytoskeleton	2
cell cycle	1
mitotic nuclear division	1
DNA metabolic process	1
DNA damage response	1
microtubule-based process	1
cell cycle process	1
chromosome organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
mitotic cell cycle process	1
chromosome localization	1
nuclear chromosome segregation	1
cellular process	1
nucleic acid binding	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
condensed chromosome, centromeric region	1
supramolecular complex	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
microtubule associated complex	1
polymeric cytoskeletal fiber	1
nuclear ribonucleoprotein granule	1
spindle	1

Protein interactions and networks

STRING

1864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF22	OBP2B	Q9NPH6	891
KIF22	MAZ	P56270	855
KIF22	Q5T8A5	Q5T8A5	853
KIF22	LCN1	P31025	780
KIF22	APOD	P05090	727
KIF22	KCTD13	Q8WZ19	688
KIF22	HIRIP3	Q9BW71	679
KIF22	ASPHD1	Q5U4P2	653
KIF22	PAGR1	Q9BTK6	638
KIF22	SEZ6L2	Q6UXD5	631
KIF22	DOC2A	Q14183	605
KIF22	CDIPT	O14735	598
KIF22	YPEL3	P61236	586
KIF22	ZNG1A	Q9BRT8	583
KIF22	SACK1D	Q9H4H8	558

IntAct

72 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
KIF22	KPNA4	psi-mi:“MI:0914”(association)	0.730
KIF22	KPNA3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
TBC1D15	UBXN8	psi-mi:“MI:0914”(association)	0.530
TBC1D15	MYO9A	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
KIF22	CRK	psi-mi:“MI:0915”(physical association)	0.400
KIF22	H2BC12L	psi-mi:“MI:0915”(physical association)	0.400
KIF22	NPM1	psi-mi:“MI:0915”(physical association)	0.400
KIF22	H1-5	psi-mi:“MI:0915”(physical association)	0.400
KIF22	H3-4	psi-mi:“MI:0915”(physical association)	0.400
KIF22	H1-4	psi-mi:“MI:0915”(physical association)	0.400
ATXN1	KIF22	psi-mi:“MI:0915”(physical association)	0.370
SVIL	KIF22	psi-mi:“MI:0915”(physical association)	0.370
Smc3	PDS5B	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
KIF22	PSEN2	psi-mi:“MI:0914”(association)	0.350
RBM45	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXL1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXM1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
FOXQ1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (161): KIF22 (Affinity Capture-RNA), KIF22 (Affinity Capture-RNA), KIF22 (Affinity Capture-MS), KIF22 (Affinity Capture-MS), KIF22 (Affinity Capture-MS), KIF22 (Proximity Label-MS), KIF22 (Proximity Label-MS), C4A (Affinity Capture-MS), CCNB1 (Affinity Capture-MS), FUS (Affinity Capture-MS), SP110 (Affinity Capture-MS), KIF22 (Affinity Capture-MS), KIF22 (Affinity Capture-MS), KPNA3 (Affinity Capture-MS), KPNA4 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NFE2, A2AP18, A6QP29, A6QPL4, A8WFU8, B1AVH7, B5DFA1, D2H0G5, D7PF45, O15357, O43304, O75038, O75808, Q0GNC1, Q0QWG9, Q14807, Q27J81, Q3V300, Q4R918, Q5I0E8, Q5REP4, Q5VV41, Q5XI63, Q60443, Q60806, Q61152, Q61846, Q69ZT1, Q6DT37, Q6L512, Q6P3R1, Q6P549, Q6ZMV9, Q7ZYL5, Q80UW5, Q8BL80, Q8C7W7, Q99952, Q9BVG8, Q9BW19

Diamond homologs: A1ZAJ2, A6QPL4, A8BB91, A8BKD1, A8WFU8, B7EJ91, B7ZNG0, B9F7C8, B9FUF9, B9G3M6, B9GE13, F1M4A4, F1QN54, F4ICA0, F4IIS5, F4J1U4, O15066, O23826, O35071, O35231, O35787, O43093, O43896, O59751, O88658, O95239, P28741, P33173, P33174, P33176, P46863, P46867, P46869, P46871, P46872, P46873, P48467, P52732, P53086, P82266

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CDK1	“up-regulates activity”	KIF22	phosphorylation
CyclinB/CDK1	up-regulates	KIF22	phosphorylation
CHFR	“down-regulates quantity by destabilization”	KIF22	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
NS1 Mediated Effects on Host Pathways	5	23.0×	4e-04
Antimicrobial mechanism of IFN-stimulated genes	6	19.1×	2e-04
B-WICH complex positively regulates rRNA expression	8	15.7×	2e-05
Influenza Infection	5	14.2×	2e-03
Assembly of the ORC complex at the origin of replication	5	13.3×	2e-03
Deposition of new CENPA-containing nucleosomes at the centromere	5	12.8×	2e-03
Condensation of Prophase Chromosomes	5	12.6×	2e-03
ISG15 antiviral mechanism	5	12.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	8	13.2×	1e-04
protein import into nucleus	6	10.2×	3e-03
chromatin remodeling	9	7.7×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	4
Uncertain significance	227
Likely benign	143
Benign	44

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1330307	GRCh37/hg19 16p11.2(chr16:29590554-30197341)x3	Pathogenic
160918	GRCh38/hg38 16p11.2(chr16:29662633-30187279)x1	Pathogenic
2575102	NM_007317.3(KIF22):c.146G>A (p.Arg49Gln)	Pathogenic
30335	NM_007317.3(KIF22):c.446G>A (p.Arg149Gln)	Pathogenic
3243486	NC_000016.9:g.(?29814750)(29825274_?)del	Pathogenic
625603	GRCh37/hg19 16p11.2(chr16:29532264-30271237)	Pathogenic
997089	GRCh37/hg19 16p11.2(chr16:29673954-30198600)	Pathogenic
1299611	NM_007317.3(KIF22):c.752T>C (p.Leu251Pro)	Likely pathogenic
1685360	NM_007317.3(KIF22):c.1399G>A (p.Glu467Lys)	Likely pathogenic
30333	NM_007317.3(KIF22):c.442C>T (p.Pro148Ser)	Likely pathogenic
988564	NM_007317.3(KIF22):c.443C>A (p.Pro148Gln)	Likely pathogenic

SpliceAI

2269 predictions. Top by Δscore:

Variant	Effect	Δscore
16:29790826:TCAGG:T	donor_loss	1.0000
16:29790827:CAGGT:C	donor_loss	1.0000
16:29790828:AGGTA:A	donor_loss	1.0000
16:29790829:GGTAC:G	donor_loss	1.0000
16:29790830:G:GA	donor_loss	1.0000
16:29790831:T:G	donor_loss	1.0000
16:29796888:TCCAG:T	acceptor_loss	1.0000
16:29796889:CCAG:C	acceptor_loss	1.0000
16:29796890:CAG:C	acceptor_loss	1.0000
16:29796891:A:AG	acceptor_gain	1.0000
16:29796891:AG:A	acceptor_gain	1.0000
16:29796892:G:GG	acceptor_gain	1.0000
16:29796892:GG:G	acceptor_gain	1.0000
16:29796892:GGA:G	acceptor_gain	1.0000
16:29796892:GGAGC:G	acceptor_gain	1.0000
16:29797084:TACCA:T	donor_gain	1.0000
16:29797087:CA:C	donor_gain	1.0000
16:29797088:AG:A	donor_loss	1.0000
16:29797089:G:GG	donor_gain	1.0000
16:29798368:CTGCA:C	acceptor_loss	1.0000
16:29798369:TGCAG:T	acceptor_loss	1.0000
16:29798370:GCAG:G	acceptor_loss	1.0000
16:29798371:CAGGT:C	acceptor_loss	1.0000
16:29798372:A:AG	acceptor_gain	1.0000
16:29798372:AGG:A	acceptor_loss	1.0000
16:29798373:G:GG	acceptor_gain	1.0000
16:29798498:GCTG:G	donor_gain	1.0000
16:29798507:G:GT	donor_gain	1.0000
16:29798587:TCCCA:T	acceptor_loss	1.0000
16:29798588:CCCAG:C	acceptor_loss	1.0000

AlphaMissense

4278 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:29798471:A:C	S122R	0.999
16:29798473:T:A	S122R	0.999
16:29798473:T:G	S122R	0.999
16:29798487:G:A	G127E	0.999
16:29798721:T:C	S175P	0.999
16:29798728:T:C	L177P	0.999
16:29799161:A:C	S246R	0.999
16:29799162:G:T	S246I	0.999
16:29799163:T:A	S246R	0.999
16:29799163:T:G	S246R	0.999
16:29799174:T:C	L250P	0.999
16:29799319:T:C	L272P	0.999
16:29799325:A:C	D274A	0.999
16:29799325:A:G	D274G	0.999
16:29799325:A:T	D274V	0.999
16:29799326:C:A	D274E	0.999
16:29799326:C:G	D274E	0.999
16:29799328:T:C	L275S	0.999
16:29799333:G:T	G277W	0.999
16:29799394:T:A	I297N	0.999
16:29799462:T:G	Y320D	0.999
16:29799478:T:A	L325H	0.999
16:29799484:G:C	R327P	0.999
16:29799652:A:C	S339R	0.999
16:29799654:T:A	S339R	0.999
16:29799654:T:G	S339R	0.999
16:29799713:T:A	L359H	0.999
16:29798475:T:A	V123E	0.998
16:29798486:G:A	G127R	0.998
16:29798486:G:C	G127R	0.998

dbSNP variants (sampled 300 via entrez): RS1000063049 (16:29805858 T>C), RS1000107177 (16:29801029 G>A), RS1000117193 (16:29804965 T>C), RS1000310515 (16:29801326 T>C), RS1000392185 (16:29791287 C>G,T), RS1000804560 (16:29789206 T>G), RS1000847946 (16:29797088 A>G), RS1001070698 (16:29803517 C>A,T), RS1001071529 (16:29788959 T>C,G), RS1001163125 (16:29792086 A>G), RS1001215342 (16:29792412 A>C), RS1001238055 (16:29794623 C>A), RS1001513990 (16:29802432 T>G), RS1001746297 (16:29799407 G>A,C,T), RS1001777052 (16:29801732 CAGGA>C)

Disease associations

OMIM: gene MIM:603213 | disease phenotypes: MIM:128200, MIM:603546, MIM:614671, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia with multiple dislocations	Definitive	Autosomal dominant

Mondo (7): episodic kinesigenic dyskinesia (MONDO:0044202), spondyloepimetaphyseal dysplasia with multiple dislocations (MONDO:0011335), breast ductal adenocarcinoma (MONDO:0005590), skeletal dysplasia (MONDO:0018230), epilepsy (MONDO:0005027), chromosome 16p11.2 duplication syndrome (MONDO:0013847), autism (MONDO:0005260)

Orphanet (4): Paroxysmal kinesigenic dyskinesia (Orphanet:98809), Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (Orphanet:93360), Primary bone dysplasia (Orphanet:364526), Proximal 16p11.2 microduplication syndrome (Orphanet:370079)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000272	Malar flattening
HP:0000486	Strabismus
HP:0000926	Platyspondyly
HP:0000977	Soft skin
HP:0001238	Slender finger
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001290	Generalized hypotonia
HP:0001374	Congenital hip dislocation
HP:0001382	Joint hypermobility
HP:0001498	Carpal bone hypoplasia
HP:0001518	Small for gestational age
HP:0001602	Laryngeal stenosis
HP:0001832	Abnormal metatarsal morphology
HP:0002650	Scoliosis
HP:0002651	Spondyloepimetaphyseal dysplasia
HP:0002652	Skeletal dysplasia
HP:0002656	Epiphyseal dysplasia
HP:0002663	Delayed epiphyseal ossification
HP:0002751	Kyphoscoliosis
HP:0002761	Generalized joint hypermobility
HP:0002808	Kyphosis
HP:0002827	Hip dislocation
HP:0002857	Genu valgum
HP:0002970	Genu varum
HP:0002987	Elbow flexion contracture
HP:0003015	Flared metaphysis
HP:0003025	Metaphyseal irregularity
HP:0003048	Radial head subluxation

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001765_19	Red blood cell traits	6.000000e-23

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D004827	Epilepsy	C10.228.140.490
C535784	Spondyloepimetaphyseal dysplasia with multiple dislocations (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5470 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	7
bisphenol A	affects expression, decreases expression	4
Cyclosporine	decreases expression	3
Arsenic	decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
diallyl trisulfide	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects expression	1
jinfukang	increases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1026544	Binding	Inhibition of ATPase activity of kid by luminescent kinase assay	Bis(hetero)aryl derivatives as unique kinesin spindle protein inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2ZU	Abcam HEK293T KIF22 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy