KIF20A

Summary

KIF20A (kinesin family member 20A, HGNC:9787) is a protein-coding gene on chromosome 5q31.2, encoding Kinesin-like protein KIF20A (O95235). Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. It is a selective cancer dependency (DepMap: 46.9% of cell lines).

Enables protein kinase binding activity. Involved in microtubule bundle formation; midbody abscission; and regulation of cytokinesis. Located in several cellular components, including cleavage furrow; midbody; and mitotic spindle. Implicated in familial restrictive cardiomyopathy 6.

Source: NCBI Gene 10112 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial isolated restrictive cardiomyopathy (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 577 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 46.9% of screened cell lines
• MANE Select transcript: NM_005733

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9787
Approved symbol	KIF20A
Name	kinesin family member 20A
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	MKLP2
Ensembl gene	ENSG00000112984
Ensembl biotype	protein_coding
OMIM	605664
Entrez	10112

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000394894, ENST00000502338, ENST00000503417, ENST00000504621, ENST00000508792, ENST00000511638, ENST00000513276, ENST00000927193, ENST00000927194, ENST00000927195, ENST00000927196, ENST00000927197, ENST00000927198, ENST00000927199, ENST00000927200, ENST00000927201, ENST00000927202

RefSeq mRNA: 1 — MANE Select: NM_005733 NM_005733

CCDS: CCDS4199

Canonical transcript exons

ENST00000394894 — 19 exons

Exon	Start	End
ENSE00000764373	138181609	138181728
ENSE00000764374	138182323	138182461
ENSE00000764375	138182586	138182773
ENSE00000764376	138182861	138182990
ENSE00000764377	138183169	138183363
ENSE00000764378	138183470	138183581
ENSE00000764379	138183688	138183756
ENSE00000764380	138183962	138184105
ENSE00000764381	138184239	138184404
ENSE00000764383	138184512	138184676
ENSE00000764385	138184807	138184946
ENSE00000764387	138185095	138185197
ENSE00000764390	138185512	138185710
ENSE00001293914	138187096	138187723
ENSE00001419528	138179112	138179202
ENSE00003461852	138181422	138181511
ENSE00003546655	138185961	138186052
ENSE00003612780	138179660	138179845
ENSE00003617858	138186294	138186431

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 96.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8571 / max 443.1959, expressed in 1380 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58749	10.9371	1250
58750	10.0788	1275
58748	0.5143	311
58751	0.2552	120
58746	0.0423	7
58747	0.0293	9

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	96.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.60	gold quality
oocyte	CL:0000023	92.30	gold quality
embryo	UBERON:0000922	91.08	gold quality
secondary oocyte	CL:0000655	90.63	gold quality
ganglionic eminence	UBERON:0004023	89.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.65	gold quality
stromal cell of endometrium	CL:0002255	85.03	gold quality
bone marrow	UBERON:0002371	83.60	gold quality
trabecular bone tissue	UBERON:0002483	81.88	gold quality
bone marrow cell	CL:0002092	79.94	gold quality
thymus	UBERON:0002370	78.41	gold quality
sperm	CL:0000019	78.05	silver quality
tongue squamous epithelium	UBERON:0006919	77.73	silver quality
mucosa of transverse colon	UBERON:0004991	76.90	gold quality
amniotic fluid	UBERON:0000173	76.89	gold quality
adrenal tissue	UBERON:0018303	76.79	gold quality
esophagus mucosa	UBERON:0002469	76.76	gold quality
male germ cell	CL:0000015	76.62	silver quality
esophagus squamous epithelium	UBERON:0006920	76.04	gold quality
rectum	UBERON:0001052	75.98	gold quality
testis	UBERON:0000473	75.60	gold quality
right testis	UBERON:0004534	75.25	gold quality
gingival epithelium	UBERON:0001949	74.89	silver quality
left testis	UBERON:0004533	74.72	gold quality
epithelium of esophagus	UBERON:0001976	74.49	gold quality
squamous epithelium	UBERON:0006914	73.96	silver quality
vermiform appendix	UBERON:0001154	73.88	gold quality
placenta	UBERON:0001987	72.85	gold quality
lower esophagus mucosa	UBERON:0035834	72.39	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	703.26
E-GEOD-75140	yes	500.15
E-GEOD-99795	yes	459.08
E-MTAB-6911	yes	440.84
E-ANND-3	yes	4.12
E-MTAB-7037	no	331.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting KIF20A, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-496	98.66	69.80	931
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-4768-3P	98.16	66.02	2330

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 46.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• KIF20A (Rab6KIFL/MKlp2) is required for cytokinesis (PMID:11060022)
• This gene is not involved in Charcot-Marie-Tooth disease. (PMID:12469216)
• KIF20A (MKlp2) is required for targeting of the polo like kinase 1 during anaphase and telophase cells. (PMID:12939256)
• Relocation of the Aurora B/INCENP/survivin passenger protein complex requires KIF20A (MKlp2). (PMID:15263015)
• Collaboration of RAB6KIFL and disc large homologue 5 is likely to be involved in pancreatic cancer. (PMID:15665285)
• Data demonstrate that Mklp2 and the chromosomal passenger complex mutually depend on each other for microtubule midzone localization, and that the association between the CPC and Mklp2 is negatively regulated by Cdk1. (PMID:19303298)
• Primary melanomas that were positive for KIF20A showed a significantly greater thickness than those that were negative, and patients with KIF20A+ melanoma tended to develop recurrence earlier. (PMID:22854760)
• Used proteomics to identify the genistein-induced protein alterations in gastric cancer cells and found the silencing of KIF20A inhibited cell viability and induced G2/M arrest,& also increased cancer cell sensitivity to genistein inhibition. (PMID:22887948)
• targeting Aurora B to the cell cortex (or the equatorial cortex) by MKlp2 is essential for the maintenance of the ingressing furrow for successful cytokinesis (PMID:23750214)
• Authors propose that phosphoregulation of MKlp2 by Cdk1/cyclin B1 ensures that activation of MKlp2 kinesin and relocation of the CPC occur at the appropriate time and space for proper mitotic progression and genomic stability. (PMID:24656812)
• Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers. (PMID:25499221)
• Kif20a expression was upregulated in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine cancer compared with normal pancreas. Kif20a silencing resulted in inhibition of proliferation, motility, and invasion of pancreatic cancer cell lines. (PMID:25953216)
• we identify KIF20A as a direct transcriptional target of FOXM1, involved in paclitaxel action and resistance (PMID:25961928)
• High KIF20A expression is associated with hepatocellular carcinoma. (PMID:27036048)
• Study reveals the mechanism controlling abscission through integration of Aurora B kinase and B56-bound PP2A phosphatase activities on the kinesin motor protein MKlp2. MKlp2 is an essential protein for promoting abscission, which may regulate tethering and stabilizing of the PM to the microtubule cytoskeleton at the intercellular bridge through its previously uncharacterized lipid association motif. (PMID:27939310)
• elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome in early-stage cervical squamous cell carcinoma patients. (PMID:27941992)
• Study shows that the kinesin family member 20A (KIF20A) is a tumor-associated antigen involved in the glioma cell growth and cell survival, suggesting that KIF20A is an oncoantigen of gliomas. (PMID:28070829)
• KIF20A is overexpressed and may serve as an independent prognostic biomarker in Nasopharyngeal Cancer. Targeting KIF20A reduces migration and invasion of Nasopharyngeal Cancer cells. (PMID:28081138)
• Signaling cascade of the NIMA-related kinases (Neks) Nek6, Nek7, and Nek9 is required for the localization and function of two kinesins essential for cytokinesis, Mklp2 and Kif14 to properly coordinate cytokinesis. (PMID:28630147)
• While the MKLP2 neck-linker is directed towards the microtubule plus-end in an ATP-like state, it does not fully dock along the motor domain. Furthermore, the footprint of the MKLP2 motor domain on the microtubule surface is altered compared to motile kinesins, and enhanced by kinesin-6-specific sequences. (PMID:28826477)
• Results suggest that coupling between actin and microtubule cytoskeletons driven by Myosin II and KIF20A ensures the spatial coordination between RAB6-positive vesicles fission from Golgi/trans-Golgi network membranes and their exit along microtubules. (PMID:29093437)
• Identification of a novel autosomal recessive congenital restrictive cardiomyopathy, caused by a near complete loss-of-function of KIF20A. (PMID:29357359)
• High expression of KIF20A is associated with recurrence in pancreatic cancer. (PMID:29500859)
• In conclusion, our findings indicated that FOXM1 was highly expressed in lung cancer cells after exposure to ionizing radiation (IR). We also found that FOXM1 promoted radioresistance, invasion, migration, and EMT of lung cancer cells after IR, partly through upregulating KIF20A. (PMID:29704495)
• Although the present study was preliminary, these data indicate the possible involvement of KIF20A in the proliferation of clearcell carcinoma (CCC), suggesting that targeting this molecule may contribute to reversing the malignant potential consequently affecting the oncologic outcome of CCC patients. (PMID:29749467)
• our study demonstrated that KIF20A might confer malignant phenotype to LUAD by regulating cell proliferation and apoptosis, providing a new potential biomarker for clinical treatment of LUAD. (PMID:30105795)
• KIF20A-knockdown exhibits a suppressive effect on the cell cycle and has an inhibitory effect on the terminal cell division process (cytokinesis) leading to partial multinuclearity of the cells. (PMID:30182171)
• KIF20A promotes the proliferation and metastasis of bladder cancer cells. Bladder cancer patients with a high KIF20A expression have a worse tumour differentiation and a poor prognosis. (PMID:31093305)
• a novel circ_0005576/miR-153-3p/KIF20A axis promoting cervical cancer progression, is reported. (PMID:31545253)
• Bladder urothelial cells soften with an increasing cancer grade. Inhibiting KIF20A makes the intracellular environment softer for both high- and low-grade bladder cancer cells. Upon inhibition of KIF20A, cortical stiffness also decreases in lower grade cells, while it surprisingly increases in higher grade malignant cells. (PMID:31565944)
• KIF20A promotes cellular malignant behavior and enhances resistance to chemotherapy in colorectal cancer through regulation of the JAK/STAT3 signaling pathway. (PMID:31841120)
• Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle. (PMID:32356865)
• Characterization of KIF20A as a prognostic biomarker and therapeutic target for different subtypes of breast cancer. (PMID:32467984)
• MKLP2 Is a Motile Kinesin that Transports the Chromosomal Passenger Complex during Anaphase. (PMID:32502404)
• Cyclin F and KIF20A, FOXM1 target genes, increase proliferation and invasion of ovarian cancer cells. (PMID:32771525)
• Upregulation of KIF20A promotes tumor proliferation and invasion in renal clear cell carcinoma and is associated with adverse clinical outcome. (PMID:33232285)
• The SUN2-nesprin-2 LINC complex and KIF20A function in the Golgi dispersal. (PMID:33686165)
• Low expression of KIF20A suppresses cell proliferation, promotes chemosensitivity and is associated with better prognosis in HCC. (PMID:34491228)
• The kinesin KIF20A promotes progression to castration-resistant prostate cancer through autocrine activation of the androgen receptor. (PMID:35418689)
• MKLP2 functions in early mitosis to ensure proper chromosome congression. (PMID:35638575)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif20a	ENSDARG00000044491
mus_musculus	Kif20a	ENSMUSG00000003779
rattus_norvegicus	Kif20a	ENSRNOG00000024428

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF22 (ENSG00000079616), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF3B (ENSG00000101350), 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 KIF20A — O95235 (reviewed: O95235)

Alternative names: GG10_2, Mitotic kinesin-like protein 2, Rab6-interacting kinesin-like protein, Rabkinesin-6

All UniProt accessions (4): O95235, D6R9E4, D6RBN1, H0YAC9

UniProt curated annotations — full annotation on UniProt →

Function. Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility.

Subcellular location. Golgi apparatus. Cytoplasm. Cytoskeleton. Spindle.

Post-translational modifications. Phosphorylated by PLK1 at Ser-528 during mitosis, creating a docking site for PLK1 and recruiting PLK1 at central spindle.

Disease relevance. Cardiomyopathy, familial restrictive 6 (RCM6) [MIM:619433] A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. RCM6 is an autosomal recessive, severe form characterized by prenatal onset, irreversible heart failure and early death. 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?
O95235-1	1	yes
O95235-2	2

RefSeq proteins (1): NP_005724* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR047149	KIF11-like	Family

Pfam: PF00225

Enzyme classification (BRENDA):

• EC 5.6.1.3 — plus-end-directed kinesin ATPase (BRENDA: 34 organisms, 94 substrates, 257 inhibitors, 53 Km, 52 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	—	45
ALEXA FLUOR 647 ATP	0.032	1
METHYLANTHRANILOYL-ATP	0.0004	1
ADP	—	0
PHOSPHATE	—	0

UniProt features (27 total): modified residue 14, sequence variant 3, region of interest 2, initiator methionine 1, chain 1, domain 1, splice variant 1, mutagenesis site 1, helix 1, coiled-coil region 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6YIP	X-RAY DIFFRACTION	1.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95235-F1	67.22	0.10

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): 160–167

Post-translational modifications (14): 21, 528, 532, 662, 668, 685, 825, 857, 867, 878, 883, 2, 7, 14

Mutagenesis-validated functional residues (1):

Position	Phenotype
528	impairs phosphorylation by plk1 and recruitment of plk1 to the spindle.

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: 408 (showing top): GNF2_CKS1B, GOBP_MITOTIC_CYTOKINESIS, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_KINESIN_COMPLEX, TATTATA_MIR374, GHO_ATF5_TARGETS_DN, FOXO4_01, REACTOME_MEMBRANE_TRAFFICKING, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_DN, KONG_E2F3_TARGETS, GOBP_CYTOKINETIC_PROCESS, PRAMOONJAGO_SOX4_TARGETS_DN, GOLDRATH_ANTIGEN_RESPONSE

GO Biological Process (6): mitotic cytokinesis (GO:0000281), microtubule bundle formation (GO:0001578), microtubule-based movement (GO:0007018), protein transport (GO:0015031), regulation of cytokinesis (GO:0032465), midbody abscission (GO:0061952)

GO Molecular Function (8): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), ATP hydrolysis activity (GO:0016887), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), spindle (GO:0005819), kinesin complex (GO:0005871), microtubule (GO:0005874), midbody (GO:0030496), cleavage furrow (GO:0032154), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), cytoskeleton (GO:0005856)

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	4
ATP-dependent activity	2
intracellular membrane-bounded organelle	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
microtubule cytoskeleton organization	1
microtubule-based process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
membrane organization	1
mitotic cytokinetic 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
kinase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
microtubule associated complex	1
polymeric cytoskeletal fiber	1
cell division site	1
plasma membrane region	1
spindle	1

Protein interactions and networks

STRING

3870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF20A	RAB6A	P20340	992
KIF20A	INCENP	Q9NQS7	986
KIF20A	KIF4A	O95239	854
KIF20A	CIT	O14578	853
KIF20A	AURKB	Q96GD4	847
KIF20A	PLK1	P53350	830
KIF20A	CEP55	Q53EZ4	783
KIF20A	CDC20	Q12834	782
KIF20A	ASPM	Q8IZT6	766
KIF20A	BUB1B	O60566	752
KIF20A	TOP2A	P11388	751
KIF20A	NCAPG	Q9BPX3	746
KIF20A	DLGAP5	Q15398	741
KIF20A	CDK1	P06493	738
KIF20A	TPX2	Q9ULW0	734

IntAct

70 interactions, top by confidence:

A	B	Type	Score
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
ATOSB	KIF20A	psi-mi:“MI:0915”(physical association)	0.670
KIF20A	ATOSB	psi-mi:“MI:0915”(physical association)	0.670
Mad2l1	BUB1B	psi-mi:“MI:0915”(physical association)	0.560
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
MAD2L1BP	KIF20A	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
E2	KIF20A	psi-mi:“MI:0403”(colocalization)	0.440
LONRF1	KIF20A	psi-mi:“MI:0915”(physical association)	0.400
KIF20A	Kif20a	psi-mi:“MI:0915”(physical association)	0.400
KIF20A	ZRANB2	psi-mi:“MI:0915”(physical association)	0.370
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
KIF20A	NEURL4	psi-mi:“MI:0914”(association)	0.350
Msn	ELOC	psi-mi:“MI:0914”(association)	0.350
Haus1	LTF	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
PCM1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
BTRC	ACOT7	psi-mi:“MI:0914”(association)	0.350
MAP7D2	ECI2	psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350
CDK5RAP2	PDHX	psi-mi:“MI:0914”(association)	0.350

BioGRID (1106): FAM214B (Two-hybrid), KIF20A (Affinity Capture-MS), KIF20A (Reconstituted Complex), KIF20A (Affinity Capture-MS), KIF20A (Affinity Capture-MS), KIF20A (Affinity Capture-MS), KIF20A (Affinity Capture-MS), KIF20A (Proximity Label-MS), KIF20A (Affinity Capture-MS), KIF20A (Affinity Capture-Western), KIF20A (Affinity Capture-MS), FAM214B (Two-hybrid), KIF20A (Affinity Capture-MS), CENPB (Affinity Capture-MS), INPP5B (Affinity Capture-MS)

ESM2 similar proteins: A2ZRG4, A6H750, B9EUM5, B9EY52, B9FMJ3, B9FS33, F4I1T9, F4IGL2, F4J2M6, F4J394, F4JUI9, L0N7N1, O00139, O59751, O95235, P28740, P70096, P97329, Q10MN5, Q29RT6, Q2NL05, Q5R9Y9, Q5T7B8, Q5XI51, Q5ZKV8, Q5ZLK6, Q62909, Q651Z7, Q6H638, Q6NWW5, Q6Z9D2, Q7X7H4, Q7XKR9, Q80TF6, Q8C0N1, Q8LNZ2, Q8N4N8, Q8S949, Q8W0Y9, Q91636

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
AURKB	“down-regulates activity”	KIF20A	phosphorylation
PPP2R5B	“up-regulates activity”	KIF20A	dephosphorylation
NEK6	“down-regulates activity”	KIF20A	phosphorylation
PLK1	“up-regulates activity”	KIF20A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
Regulation of PLK1 Activity at G2/M Transition	5	12.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	351
Likely benign	193
Benign	18

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1179003	NM_005733.3(KIF20A):c.1909del (p.Tyr637fs)	Pathogenic
3367014	NM_005733.3(KIF20A):c.1423C>T (p.Arg475Ter)	Likely pathogenic

SpliceAI

2065 predictions. Top by Δscore:

Variant	Effect	Δscore
5:138179658:A:AG	acceptor_gain	1.0000
5:138179659:G:GG	acceptor_gain	1.0000
5:138179841:AGCAG:A	donor_loss	1.0000
5:138179842:GCAG:G	donor_gain	1.0000
5:138179843:CAGG:C	donor_loss	1.0000
5:138179844:AGGT:A	donor_loss	1.0000
5:138179845:GG:G	donor_loss	1.0000
5:138179846:G:C	donor_loss	1.0000
5:138179847:T:A	donor_loss	1.0000
5:138181605:TCA:T	acceptor_loss	1.0000
5:138181607:A:AC	acceptor_loss	1.0000
5:138181607:A:AG	acceptor_gain	1.0000
5:138181607:AG:A	acceptor_gain	1.0000
5:138181607:AGG:A	acceptor_gain	1.0000
5:138181608:G:GG	acceptor_gain	1.0000
5:138181608:GG:G	acceptor_gain	1.0000
5:138181608:GGG:G	acceptor_gain	1.0000
5:138181608:GGGT:G	acceptor_gain	1.0000
5:138181608:GGGTT:G	acceptor_gain	1.0000
5:138181726:CAGG:C	donor_loss	1.0000
5:138181728:GGTAT:G	donor_loss	1.0000
5:138181729:G:A	donor_loss	1.0000
5:138182318:TCTA:T	acceptor_loss	1.0000
5:138182319:CTA:C	acceptor_loss	1.0000
5:138182321:A:AC	acceptor_loss	1.0000
5:138182321:A:AG	acceptor_gain	1.0000
5:138182322:G:GG	acceptor_gain	1.0000
5:138182322:G:GT	acceptor_loss	1.0000
5:138182462:G:A	donor_loss	1.0000
5:138182462:G:GG	donor_gain	1.0000

AlphaMissense

5831 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:138182411:T:C	L155P	0.999
5:138182426:G:A	G160E	0.999
5:138182441:G:A	G165E	0.999
5:138182444:A:T	K166I	0.999
5:138182604:G:A	G178E	0.999
5:138183283:T:C	L316P	0.999
5:138183527:G:A	G362D	0.999
5:138183577:C:A	R379S	0.999
5:138183578:G:C	R379P	0.999
5:138183974:T:G	C407W	0.999
5:138183976:A:C	D408A	0.999
5:138183976:A:G	D408G	0.999
5:138183976:A:T	D408V	0.999
5:138183979:T:A	L409Q	0.999
5:138183979:T:C	L409P	0.999
5:138184032:G:C	A427P	0.999
5:138184054:T:C	L434P	0.999
5:138184063:T:C	L437P	0.999
5:138184071:T:C	C440R	0.999
5:138184073:T:G	C440W	0.999
5:138184264:C:A	R460S	0.999
5:138184270:A:C	S462R	0.999
5:138184272:C:A	S462R	0.999
5:138184272:C:G	S462R	0.999
5:138184283:G:C	R466P	0.999
5:138184397:C:A	A504D	0.999
5:138181466:G:C	R70S	0.998
5:138181466:G:T	R70S	0.998
5:138181646:T:C	L98P	0.998
5:138181715:T:C	F121S	0.998

dbSNP variants (sampled 300 via entrez): RS1000082651 (5:138186697 A>AT), RS1000818590 (5:138186699 A>G), RS1001042088 (5:138179912 G>A), RS1001623027 (5:138178892 A>G), RS1001886168 (5:138185395 G>A,T), RS1002256390 (5:138185821 A>G), RS1002365074 (5:138186612 G>C), RS1002763028 (5:138177327 C>T), RS1003582311 (5:138177116 A>C), RS10038448 (5:138180092 G>A,C,T), RS10051112 (5:138177701 A>C), RS1005487516 (5:138187638 A>G), RS1005785331 (5:138182090 A>G), RS1006046938 (5:138180027 C>A), RS1006347630 (5:138187837 C>T)

Disease associations

OMIM: gene MIM:605664 | disease phenotypes: MIM:619433

GenCC curated gene-disease

Disease	Classification	Inheritance
familial isolated restrictive cardiomyopathy	Supportive	Autosomal dominant
congenital heart disease	Limited	Autosomal recessive
cardiomyopathy, familial restrictive, 6	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Limited	AR

Mondo (3): cardiomyopathy, familial restrictive, 6 (MONDO:0030330), congenital heart disease (MONDO:0005453), (MONDO:0019150)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001279	Syncope
HP:0001297	Stroke
HP:0001522	Death in infancy
HP:0001541	Ascites
HP:0001639	Hypertrophic cardiomyopathy
HP:0001642	Pulmonic stenosis
HP:0001653	Mitral regurgitation
HP:0001723	Restrictive cardiomyopathy
HP:0001789	Hydrops fetalis
HP:0001907	Thromboembolism
HP:0002094	Dyspnea
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0005110	Atrial fibrillation
HP:0005115	Supraventricular arrhythmia
HP:0005162	Abnormal left ventricular function
HP:0005180	Tricuspid regurgitation
HP:0008897	Postnatal growth retardation
HP:0010444	Pulmonic regurgitation
HP:0011461	Fetal onset
HP:0012398	Peripheral edema
HP:0012764	Orthopnea
HP:0030718	Right atrial enlargement
HP:0030950	Pulmonary venous hypertension
HP:0031295	Left atrial enlargement
HP:0031329	Interstitial cardiac fibrosis
HP:0034548	Portal vein hypoplasia
HP:0100598	Pulmonary edema
HP:4000148	Hepatic artery hyperplasia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004521_66	Autism spectrum disorder or schizophrenia	1.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2021753 (SINGLE PROTEIN)

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

ChEMBL bioactivities

14 potent at pChembl≥5 of 25 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.64	IC50	230	nM	CHEMBL3754608
6.08	IC50	830	nM	CHEMBL3753955
5.92	IC50	1200	nM	CHEMBL3754608
5.89	IC50	1300	nM	CHEMBL3753380
5.87	IC50	1350	nM	CHEMBL3753955
5.48	IC50	3300	nM	CHEMBL3753782
5.44	IC50	3600	nM	CHEMBL3752100
5.38	IC50	4200	nM	CHEMBL3753782
5.29	IC50	5100	nM	CHEMBL3752687
5.27	IC50	5400	nM	CHEMBL3753970
5.25	IC50	5600	nM	CHEMBL3753970
5.05	IC50	8900	nM	CHEMBL3752869
5.00	IC50	1.01e+04	nM	CHEMBL3752869
5.00	IC50	1e+04	nM	CHEMBL3752100

PubChem BioAssay actives

13 with measured affinity, of 147 total; 8 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
(Z)-2-(5-methoxy-1H-indol-3-yl)-3-pyridin-3-ylprop-2-enenitrile	1272834: Inhibition of microtubule-stimulated N-terminal MKLP-2 (56 to 505 residues) ATPase activity isolated from human hepatocellular carcinoma cells by pyruvate kinase/lactate dehydrogenase enzyme linked assay	ic50	0.2300	uM
(Z)-2-(1H-indol-3-yl)-3-pyridin-3-ylprop-2-enenitrile	1272834: Inhibition of microtubule-stimulated N-terminal MKLP-2 (56 to 505 residues) ATPase activity isolated from human hepatocellular carcinoma cells by pyruvate kinase/lactate dehydrogenase enzyme linked assay	ic50	0.8300	uM
(Z)-2-(5-phenylmethoxy-1H-indol-3-yl)-3-pyridin-3-ylprop-2-enenitrile	1272834: Inhibition of microtubule-stimulated N-terminal MKLP-2 (56 to 505 residues) ATPase activity isolated from human hepatocellular carcinoma cells by pyruvate kinase/lactate dehydrogenase enzyme linked assay	ic50	1.3000	uM
(Z)-2-(4-methoxy-1H-indol-3-yl)-3-pyridin-3-ylprop-2-enenitrile	1272834: Inhibition of microtubule-stimulated N-terminal MKLP-2 (56 to 505 residues) ATPase activity isolated from human hepatocellular carcinoma cells by pyruvate kinase/lactate dehydrogenase enzyme linked assay	ic50	3.3000	uM
(Z)-3-(3,5-dimethoxyphenyl)-2-(1H-indol-3-yl)prop-2-enenitrile	1272832: Inhibition of N-terminal MKLP2 (56 to 505 residues) ATPase basal activity isolated from human hepatocellular carcinoma cells by pyruvate kinase/lactate dehydrogenase enzyme linked assay	ic50	3.6000	uM
(Z)-3-(1,3-benzodioxol-5-yl)-2-(1H-indol-3-yl)prop-2-enenitrile	1272834: Inhibition of microtubule-stimulated N-terminal MKLP-2 (56 to 505 residues) ATPase activity isolated from human hepatocellular carcinoma cells by pyruvate kinase/lactate dehydrogenase enzyme linked assay	ic50	5.1000	uM
(Z)-2-(6-methoxy-1H-indol-3-yl)-3-pyridin-3-ylprop-2-enenitrile	1272834: Inhibition of microtubule-stimulated N-terminal MKLP-2 (56 to 505 residues) ATPase activity isolated from human hepatocellular carcinoma cells by pyruvate kinase/lactate dehydrogenase enzyme linked assay	ic50	5.4000	uM
(Z)-3-(4-chlorophenyl)-2-(1H-indol-3-yl)prop-2-enenitrile	1272834: Inhibition of microtubule-stimulated N-terminal MKLP-2 (56 to 505 residues) ATPase activity isolated from human hepatocellular carcinoma cells by pyruvate kinase/lactate dehydrogenase enzyme linked assay	ic50	8.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, increases expression	5
bisphenol A	affects expression, decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression	4
Valproic Acid	decreases methylation, affects expression, decreases expression	4
Cyclosporine	decreases expression	4
Air Pollutants	increases abundance, decreases expression	3
Cisplatin	affects cotreatment, increases expression, decreases expression, decreases reaction	3
Doxorubicin	affects response to substance, decreases expression	3
arsenite	affects binding, decreases reaction, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Zoledronic Acid	decreases expression	2
Fulvestrant	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Cadmium	decreases expression	2
Coumestrol	affects cotreatment, increases expression, increases reaction	2
Polychlorinated Biphenyls	increases expression, affects expression	2
Progesterone	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tunicamycin	decreases expression	2
Zinc	affects cotreatment, affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Genistein	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
3,4-dichloroaniline	decreases expression	1
beta-lapachone	decreases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2024985	Binding	Inhibition of MKLP2 ATPase activity	Triphenylbutanamines: kinesin spindle protein inhibitors with in vivo antitumor activity. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2ZT	Abcam HEK293T KIF20A KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE