KIF5C

Summary

KIF5C (kinesin family member 5C, HGNC:6325) is a protein-coding gene on chromosome 2q23.1-q23.2, encoding Kinesin heavy chain isoform 5C (O60282). Microtubule-associated force-producing protein that may play a role in organelle transport.

The protein encoded by this gene is a kinesin heavy chain subunit involved in the transport of cargo within the central nervous system. The encoded protein, which acts as a tetramer by associating with another heavy chain and two light chains, interacts with protein kinase CK2. Mutations in this gene have been associated with complex cortical dysplasia with other brain malformations-2. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene.

Source: NCBI Gene 3800 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex cortical dysplasia with other brain malformations 2 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 304 total — 1 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_004522

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6325
Approved symbol	KIF5C
Name	kinesin family member 5C
Location	2q23.1-q23.2
Locus type	gene with protein product
Status	Approved
Aliases	NKHC2
Ensembl gene	ENSG00000168280
Ensembl biotype	protein_coding
OMIM	604593
Entrez	3800

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 16 retained_intron, 10 protein_coding, 7 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000435030, ENST00000450621, ENST00000460377, ENST00000464066, ENST00000482151, ENST00000676503, ENST00000676677, ENST00000676805, ENST00000676852, ENST00000676875, ENST00000677080, ENST00000677122, ENST00000677280, ENST00000677443, ENST00000677465, ENST00000677474, ENST00000677563, ENST00000677705, ENST00000677747, ENST00000677773, ENST00000677843, ENST00000677862, ENST00000677891, ENST00000678056, ENST00000678133, ENST00000678160, ENST00000678184, ENST00000678291, ENST00000678363, ENST00000678636, ENST00000678720, ENST00000678856, ENST00000678891, ENST00000679018, ENST00000679129, ENST00000679156, ENST00000679236

RefSeq mRNA: 1 — MANE Select: NM_004522 NM_004522

CCDS: CCDS74586

Canonical transcript exons

ENST00000435030 — 26 exons

Exon	Start	End
ENSE00001434139	149023078	149026759
ENSE00001752993	148929281	148929354
ENSE00002218531	148875227	148875743
ENSE00002349201	148937284	148937388
ENSE00002380753	148941935	148941990
ENSE00002391368	148941610	148941658
ENSE00002422526	148942673	148942760
ENSE00002534992	148946899	148947023
ENSE00002576645	148922137	148922227
ENSE00003469041	149000423	149000524
ENSE00003512375	149011570	149011683
ENSE00003523642	149000722	149000782
ENSE00003534713	148978922	148978990
ENSE00003548091	149005393	149005464
ENSE00003564949	149007963	149008067
ENSE00003571231	149010135	149010351
ENSE00003591170	148949839	148949943
ENSE00003615060	148950314	148950462
ENSE00003619567	148997264	148997340
ENSE00003627603	148981355	148981561
ENSE00003630846	148998400	148998509
ENSE00003673715	148991010	148991198
ENSE00003675974	148973336	148973511
ENSE00003678294	148994421	148994538
ENSE00003680455	148983620	148983766
ENSE00003694594	148961971	148962119

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 99.94.

FANTOM5 (CAGE): breadth broad, TPM avg 56.0478 / max 34844.0063, expressed in 808 samples.

FANTOM5 promoters (39 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22962	24.5895	698
202433	8.0083	317
202430	6.8578	292
202429	2.3369	161
22967	2.2827	167
22971	1.7893	150
22963	1.5020	251
202432	1.4102	134
22969	1.3466	109
22972	1.0081	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	99.94	gold quality
paraflocculus	UBERON:0005351	99.93	gold quality
frontal pole	UBERON:0002795	99.91	gold quality
cerebellar vermis	UBERON:0004720	99.88	gold quality
middle frontal gyrus	UBERON:0002702	99.83	gold quality
middle temporal gyrus	UBERON:0002771	99.83	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.83	gold quality
postcentral gyrus	UBERON:0002581	99.82	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.81	gold quality
orbitofrontal cortex	UBERON:0004167	99.79	gold quality
parietal lobe	UBERON:0001872	99.78	gold quality
endothelial cell	CL:0000115	99.74	gold quality
CA1 field of hippocampus	UBERON:0003881	99.71	gold quality
superior frontal gyrus	UBERON:0002661	99.70	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.67	gold quality
entorhinal cortex	UBERON:0002728	99.65	gold quality
corpus callosum	UBERON:0002336	99.56	gold quality
occipital lobe	UBERON:0002021	99.55	gold quality
primary visual cortex	UBERON:0002436	99.51	gold quality
inferior olivary complex	UBERON:0002127	99.47	gold quality
medial globus pallidus	UBERON:0002477	99.41	gold quality
temporal lobe	UBERON:0001871	99.39	gold quality
globus pallidus	UBERON:0001875	99.36	gold quality
pons	UBERON:0000988	99.34	gold quality
medulla oblongata	UBERON:0001896	99.31	gold quality
inferior vagus X ganglion	UBERON:0005363	99.31	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.28	gold quality
superior vestibular nucleus	UBERON:0007227	99.27	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.25	gold quality
subthalamic nucleus	UBERON:0001906	99.24	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1552.08
E-HCAD-5	yes	50.29
E-GEOD-125970	yes	8.33
E-GEOD-93593	yes	7.94
E-HCAD-10	yes	4.64
E-ANND-3	yes	4.19
E-MTAB-5061	no	3.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

196 targeting KIF5C, 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-8485	100.00	77.57	4731
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 14)

• analysis of the GRIF-1 binding domain of the kinesin, KIF5C, which substantiates a role for GRIF-1 as an adaptor protein in the anterograde trafficking of cargoes (PMID:16835241)
• binding of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function (PMID:17887960)
• KIF5C, a member of the kinesin 1 heavy chain family, is a substrate for protein kinase CK2. (PMID:18682247)
• Results identified the motor neuron protein KIF5C as a new binding partner for the protein kinase CK2alpha’. (PMID:19011756)
• Genetic association of KIF4A and KIF5C mutations in intellectual disability and synaptic function. (PMID:24812067)
• Study found that in peripheral blood mononuclear cells the median expression of KIFC3, KIF1B, and KIF5C was much lower than the expression of dynactin subunits DCTN1 and DCTN3, in both sporadic amyotrophic lateral sclerosis and healthy cases (PMID:26954557)
• KIF5C mutations are associated with a neurodevelopmental disorder characterized by infantile onset epilepsy, and subtle but recognizable types of brain malformations. (PMID:29048727)
• Findings point to a role for Kinesin-2 in the long-range movement of RAB5 endosomes during interphase. At the onset of mitosis, Kinesin-2 mediated transport controls timing of nuclear envelope breakdown and localization of RAB5 endosomes at spindle. (PMID:30200238)
• The adaptor proteins HAP1a and GRIP1 collaborate to activate the kinesin-1 isoform KIF5C. (PMID:31757889)
• Reduced miR-203 predicts metastasis and poor survival in esophageal carcinoma. (PMID:31844033)
• Deletion of the Pseudorabies Virus gE/gI-US9p complex disrupts kinesin KIF1A and KIF5C recruitment during egress, and alters the properties of microtubule-dependent transport in vitro. (PMID:32511265)
• KIF5C deficiency causes abnormal cortical neuronal migration, dendritic branching, and spine morphology in mice. (PMID:34966180)
• Abnormal course of the corticospinal tracts in KIF5C-related encephalopathy. (PMID:36122673)
• LncRNA ZNF667-AS1 Targets miR-523-3p/KIF5C Axis to Hinder Colon Cancer Progression. (PMID:37322260)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kif5c	ENSMUSG00000026764
rattus_norvegicus	Kif5c	ENSRNOG00000004680

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF22 (ENSG00000079616), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF3B (ENSG00000101350), KIF20A (ENSG00000112984), KIF21B (ENSG00000116852), KIF17 (ENSG00000117245), KIF14 (ENSG00000118193), KIF18A (ENSG00000121621), KIF25 (ENSG00000125337), KIF1C (ENSG00000129250), KIF1A (ENSG00000130294), KIF3A (ENSG00000131437), KIF12 (ENSG00000136883), KIF13A (ENSG00000137177), KIF23 (ENSG00000137807), KIF11 (ENSG00000138160), CENPE (ENSG00000138778), KIF21A (ENSG00000139116), KIFC3 (ENSG00000140859), KIF2B (ENSG00000141200), KIF2C (ENSG00000142945), KIF5A (ENSG00000155980), KIF26B (ENSG00000162849), KIF15 (ENSG00000163808), KIF6 (ENSG00000164627), KIF27 (ENSG00000165115), KIF7 (ENSG00000166813), KIFC2 (ENSG00000167702), KIF5B (ENSG00000170759), KIF18B (ENSG00000186185), KIF24 (ENSG00000186638), KIF19 (ENSG00000196169), KIF13B (ENSG00000197892), KIF4B (ENSG00000226650)

Protein

Protein identifiers

Kinesin heavy chain isoform 5C — O60282 (reviewed: O60282)

Alternative names: Kinesin heavy chain neuron-specific 2, Kinesin-1

All UniProt accessions (9): A0A7I2V352, A0A7I2V3N5, A0A7I2V3V4, A0A7I2V492, A0A7I2V4K6, A0A7I2V581, A0A7I2YQB4, A0A7I2YQQ7, O60282

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-associated force-producing protein that may play a role in organelle transport. Has ATPase activity. Involved in synaptic transmission. Mediates dendritic trafficking of mRNAs. Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation.

Subunit / interactions. Oligomer composed of two heavy chains and two light chains. Interacts with GRIP1 and KLC3. Interacts with TRAK1. Interacts with ZFYVE27.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Dendrite.

Tissue specificity. Highest expression in brain, prostate and testis, and moderate expression in kidney, small intestine and ovary.

Disease relevance. Cortical dysplasia, complex, with other brain malformations 2 (CDCBM2) [MIM:615282] A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include intrauterine growth retardation, fetal akinesia, seizures, microcephaly, lack of psychomotor development, and arthrogryposis. Brain imaging shows malformations of cortical development, including polymicrogyria, gyral simplification, and thin corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O60282-1	1	yes
O60282-2	2

RefSeq proteins (1): NP_004513* (*=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
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR059182	Khc_C	Domain

Pfam: PF00225

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (20 total): binding site 8, region of interest 3, splice variant 2, sequence variant 2, sequence conflict 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60282-F1	78.70	0.25

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 (8): 92; 93; 94; 99; 87; 89; 90; 91

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-264876	Insulin processing
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 375 (showing top): GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GNF2_RTN1, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_KINESIN_COMPLEX, GOBP_NEUROGENESIS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MODULE_66, GOBP_MOTOR_NEURON_AXON_GUIDANCE, KOYAMA_SEMA3B_TARGETS_UP, MCLACHLAN_DENTAL_CARIES_DN, DOANE_RESPONSE_TO_ANDROGEN_DN, SMID_BREAST_CANCER_LUMINAL_B_UP, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY

GO Biological Process (10): organelle organization (GO:0006996), axon guidance (GO:0007411), motor neuron axon guidance (GO:0008045), intracellular mRNA localization (GO:0008298), synaptic vesicle transport (GO:0048489), mRNA transport (GO:0051028), anterograde dendritic transport of messenger ribonucleoprotein complex (GO:0098964), anterograde dendritic transport of neurotransmitter receptor complex (GO:0098971), anterograde axonal protein transport (GO:0099641), microtubule-based movement (GO:0007018)

GO Molecular Function (10): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), plus-end-directed microtubule motor activity (GO:0008574), ATP hydrolysis activity (GO:0016887), apolipoprotein receptor binding (GO:0034190), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (15): cytoplasm (GO:0005737), kinesin complex (GO:0005871), microtubule (GO:0005874), dendrite cytoplasm (GO:0032839), ciliary rootlet (GO:0035253), neuronal cell body (GO:0043025), axonal growth cone (GO:0044295), GABA-ergic synapse (GO:0098982), postsynaptic cytosol (GO:0099524), distal axon (GO:0150034), axon cytoplasm (GO:1904115), cytoskeleton (GO:0005856), dendrite (GO:0030425), cell projection (GO:0042995), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide hormone metabolism	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
anterograde dendritic transport	2
ATP-dependent activity	2
neuron projection cytoplasm	2
axon	2
cellular component organization	1
axonogenesis	1
neuron projection guidance	1
axon guidance	1
RNA localization	1
transport	1
cellular process	1
establishment of vesicle localization	1
synaptic vesicle localization	1
RNA transport	1
receptor localization to synapse	1
anterograde axonal transport	1
axo-dendritic protein transport	1
protein localization to presynapse	1
microtubule-based 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
microtubule motor activity	1
ribonucleoside triphosphate phosphatase activity	1
signaling receptor binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
microtubule associated complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
dendrite	1
cytoskeleton	1
cilium	1

Protein interactions and networks

STRING

2674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF5C	RANBP2	P49792	990
KIF5C	KLC2	Q9H0B6	940
KIF5C	KLC3	Q6P597	934
KIF5C	KLC4	Q9NSK0	924
KIF5C	KLC1	Q07866	921
KIF5C	TRAK2	O60296	789
KIF5C	TRAK1	Q9UPV9	761
KIF5C	CSNK2A2	P19784	755
KIF5C	DYNC1H1	Q14204	734
KIF5C	DCTN1	Q14203	574
KIF5C	COX11	Q9Y6N1	570
KIF5C	TUBG1	P23258	566
KIF5C	RPGRIP1	Q96KN7	557
KIF5C	TUBB2B	Q9BVA1	555
KIF5C	GRIP1	Q9Y3R0	543
KIF5C	LYPD6B	Q8NI32	543

IntAct

111 interactions, top by confidence:

A	B	Type	Score
CSNK2A2	KIF5C	psi-mi:“MI:0915”(physical association)	0.650
KIF5C	CSNK2A2	psi-mi:“MI:0915”(physical association)	0.650
KIF5C	CSNK2A2	psi-mi:“MI:0407”(direct interaction)	0.650
CSNK2A2	KIF5C	psi-mi:“MI:0403”(colocalization)	0.650
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
KIF5C	CSNK2A1	psi-mi:“MI:0915”(physical association)	0.600
CSNK2A1	KIF5C	psi-mi:“MI:0915”(physical association)	0.600
KIF5C	CSNK2A1	psi-mi:“MI:0403”(colocalization)	0.600
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
TRIP6	WTIP	psi-mi:“MI:0914”(association)	0.530
COG6	EXOC5	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
KLC1	KIF5C	psi-mi:“MI:0914”(association)	0.530
RHOT1	KIF5C	psi-mi:“MI:0915”(physical association)	0.520
KIF5C	RHOT1	psi-mi:“MI:0915”(physical association)	0.520
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
KIF5C	CSNK2B	psi-mi:“MI:0915”(physical association)	0.460
CSNK2B	KIF5C	psi-mi:“MI:0403”(colocalization)	0.460
	KIF5C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
ANKRD27	KIF5C	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (115): KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS), KIF5C (Co-fractionation), KIF5C (Co-fractionation), KIF5C (Co-fractionation), KIF5C (Co-fractionation), KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS), KIF5C (Affinity Capture-MS)

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

Diamond homologs: A0A068FIK2, A0JN40, A1ZAJ2, A8BB91, A8BKD1, B1AVY7, B7EJ91, B7ZNG0, B9F2Y7, B9GE13, F1M4A4, F1M5N7, F1QN54, F4IIS5, F4J1U4, F4K0J3, G5EGS3, O14343, O14782, O15066, O23826, O35066, O35071, O35787, O43896, O45935, O55165, O60282, O60333, O75037, O88658, O95239, P17210, P21613, P23678, P28738, P28741, P33173, P33174, P33175

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
GRIP1	“up-regulates activity”	KIF5C	binding
HAP1	“up-regulates activity”	KIF5C	binding
JNK	“up-regulates activity”	KIF5C	phosphorylation
KIF5C	“up-regulates activity”	TRAK2	binding
KIF5C	up-regulates	Organelle_transport
KIF5C	up-regulates	“Plus-end directed sliding movement”
MAPK10	“down-regulates activity”	KIF5C	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 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	6	57.6×	1e-07
Activation of BAD and translocation to mitochondria	5	54.4×	1e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	48.0×	3e-06
Activation of BH3-only proteins	5	35.5×	1e-05
RHO GTPases activate PKNs	5	22.7×	9e-05
Intrinsic Pathway for Apoptosis	5	20.9×	1e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	17.6×	1e-06
Apoptosis	6	14.4×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
early endosome to late endosome transport	5	35.2×	1e-04
protein targeting	6	23.9×	1e-04
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	21.8×	7e-04
intracellular protein localization	8	9.1×	7e-04
protein phosphorylation	9	6.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	6
Uncertain significance	106
Likely benign	109
Benign	66

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1878628	NM_004522.3(KIF5C):c.265T>C (p.Ser89Pro)	Pathogenic
2443686	NM_004522.3(KIF5C):c.275A>G (p.Lys92Arg)	Likely pathogenic
2498166	NM_004522.3(KIF5C):c.710A>G (p.Glu237Gly)	Likely pathogenic
3384044	NM_004522.3(KIF5C):c.404A>G (p.Tyr135Cys)	Likely pathogenic
3385394	NM_004522.3(KIF5C):c.1666A>T (p.Lys556Ter)	Likely pathogenic
3385396	NM_004522.3(KIF5C):c.2385dup (p.Gln796fs)	Likely pathogenic
65402	NM_004522.3(KIF5C):c.710A>T (p.Glu237Val)	Likely pathogenic

SpliceAI

4217 predictions. Top by Δscore:

Variant	Effect	Δscore
2:148875742:GG:G	donor_gain	1.0000
2:148875743:GG:G	donor_gain	1.0000
2:148875744:G:C	donor_loss	1.0000
2:148875745:T:G	donor_loss	1.0000
2:148877356:A:T	donor_gain	1.0000
2:148922121:T:TA	acceptor_gain	1.0000
2:148922132:TTTA:T	acceptor_loss	1.0000
2:148922134:TA:T	acceptor_loss	1.0000
2:148922135:A:AG	acceptor_gain	1.0000
2:148922136:G:GG	acceptor_gain	1.0000
2:148922136:GC:G	acceptor_gain	1.0000
2:148922136:GCA:G	acceptor_gain	1.0000
2:148922136:GCAA:G	acceptor_gain	1.0000
2:148922224:AAAGG:A	donor_loss	1.0000
2:148922225:AAG:A	donor_gain	1.0000
2:148922226:AG:A	donor_gain	1.0000
2:148922227:GG:G	donor_gain	1.0000
2:148922227:GGTA:G	donor_loss	1.0000
2:148922228:G:GG	donor_gain	1.0000
2:148929272:T:TA	acceptor_gain	1.0000
2:148929279:A:AG	acceptor_gain	1.0000
2:148929279:A:AT	acceptor_loss	1.0000
2:148929279:AGAT:A	acceptor_gain	1.0000
2:148929280:G:GA	acceptor_gain	1.0000
2:148929280:GA:G	acceptor_gain	1.0000
2:148929280:GAT:G	acceptor_gain	1.0000
2:148929280:GATG:G	acceptor_gain	1.0000
2:148929280:GATGT:G	acceptor_gain	1.0000
2:148929353:AGG:A	donor_loss	1.0000
2:148929355:GT:G	donor_loss	1.0000

AlphaMissense

6380 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:148929292:G:C	G77R	1.000
2:148929293:G:A	G77D	1.000
2:148929301:G:A	G80R	1.000
2:148929301:G:C	G80R	1.000
2:148929301:G:T	G80W	1.000
2:148929302:G:A	G80E	1.000
2:148929316:T:C	Y85H	1.000
2:148929319:G:A	G86R	1.000
2:148929319:G:C	G86R	1.000
2:148929319:G:T	G86W	1.000
2:148929320:G:A	G86E	1.000
2:148929320:G:T	G86V	1.000
2:148929334:G:A	G91R	1.000
2:148929334:G:C	G91R	1.000
2:148929335:G:A	G91E	1.000
2:148929335:G:T	G91V	1.000
2:148929337:A:C	K92Q	1.000
2:148929338:A:T	K92I	1.000
2:148929339:A:C	K92N	1.000
2:148929339:A:T	K92N	1.000
2:148937284:G:A	G98R	1.000
2:148937284:G:C	G98R	1.000
2:148937284:G:T	G98W	1.000
2:148937285:G:A	G98E	1.000
2:148937311:G:A	G107R	1.000
2:148937311:G:C	G107R	1.000
2:148937311:G:T	G107W	1.000
2:148937312:G:A	G107E	1.000
2:148937377:T:C	F129L	1.000
2:148937379:T:A	F129L	1.000

dbSNP variants (sampled 300 via entrez): RS1000004934 (2:148931745 C>T), RS1000016870 (2:148881152 C>T), RS1000071698 (2:148942327 A>G), RS1000077647 (2:148884037 T>C), RS1000082876 (2:148873958 G>A,C), RS1000086773 (2:149011586 C>T), RS1000102353 (2:149018675 A>G), RS1000120883 (2:149014128 G>A), RS1000129828 (2:148884383 A>G), RS1000164718 (2:148899660 G>A), RS1000197170 (2:148903208 C>T), RS1000246293 (2:148993149 T>C), RS1000248050 (2:148958169 T>C), RS1000257121 (2:148910069 G>A), RS1000258406 (2:148912987 T>C)

Disease associations

OMIM: gene MIM:604593 | disease phenotypes: MIM:615282, MIM:123100, MIM:126800, MIM:154600

GenCC curated gene-disease

Disease	Classification	Inheritance
complex cortical dysplasia with other brain malformations 2	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex cortical dysplasia with other brain malformations 2	Moderate	AD

Mondo (7): glioblastoma (MONDO:0018177), complex cortical dysplasia with other brain malformations 2 (MONDO:0014116), craniosynostosis (MONDO:0015469), Duane retraction syndrome (MONDO:0007473), jaw-winking syndrome (MONDO:0007946), cerebral cortical dysplasia (MONDO:0017094), intellectual disability (MONDO:0001071)

Orphanet (6): Glioblastoma (Orphanet:360), Craniosynostosis (Orphanet:1531), Duane retraction syndrome (Orphanet:233), Marcus-Gunn syndrome (Orphanet:91412), Cerebral cortical dysplasia (Orphanet:268950), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

21 total (23 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000733	Motor stereotypy
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001344	Absent speech
HP:0001511	Intrauterine growth retardation
HP:0001773	Short foot
HP:0001989	Fetal akinesia sequence
HP:0002079	Hypoplasia of the corpus callosum
HP:0002126	Polymicrogyria
HP:0002510	Spastic tetraplegia
HP:0002539	Cortical dysplasia
HP:0002804	Arthrogryposis multiplex congenita
HP:0005484	Secondary microcephaly
HP:0010864	Severe intellectual disability
HP:0011461	Fetal onset
HP:0020221	Clonic seizure
HP:0100716	Self-injurious behavior
HP:0200055	Small hand
HP:0012174	Glioblastoma multiforme
HP:0100843

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001877_62	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	8.000000e-06
GCST007576_44	Chronotype	2.000000e-09
GCST90026416_19	Mild age-related type 2 diabetes	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D004370	Duane Retraction Syndrome	C10.292.562.700.375.500; C11.270.235; C11.590.436.400.500; C16.320.290.235
D005909	Glioblastoma	C04.557.465.625.600.380.080.335; C04.557.470.670.380.080.335; C04.557.580.625.600.380.080.335
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D054220	Malformations of Cortical Development	C10.500.507; C16.131.666.507
C535908	Marcus Gunn phenomenon (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2029194 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
Doxorubicin	increases expression	2
aristolochic acid I	decreases expression, increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
enzalutamide	decreases expression	1
picoxystrobin	decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Panobinostat	affects cotreatment, affects expression	1
Acetaminophen	increases expression	1
Aldehydes	increases expression	1
Antimycin A	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2033192	Binding	Inhibition of human Kif5C ATPase activity by pyruvate kinase/lactate dehydrogenase-linked assay	Receptor-ligand interaction-based virtual screening for novel Eg5/kinesin spindle protein inhibitors. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00686725	PHASE4	COMPLETED	Standard Temodal (Temozolomide) Regimen Versus Standard Regimen Plus Early Postsurgery Temodal for Newly Diagnosed Glioblastoma Multiforme (Study P05572)
NCT01756729	PHASE4	TERMINATED	Post-approval Study of NovoTTF-100A in Recurrent GBM Patients
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT05342883	PHASE4	ACTIVE_NOT_RECRUITING	GammaTile and Stupp in Newly Diagnosed GBM
NCT05900908	PHASE4	WITHDRAWN	Post-operative Adjuvant Therapy w/wo GammaTile + Systemic Therapy
NCT06625047	PHASE4	COMPLETED	Comparing Telehealth and In-person Assessments in Glioma Patients Receiving Oral Chemotherapy
NCT07546669	PHASE4	NOT_YET_RECRUITING	Efficacy of Zoster Vaccination in Glioblastoma Patients
NCT00045968	PHASE3	UNKNOWN	Study of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer
NCT00068952	PHASE3	COMPLETED	Study of IV Edotecarin Vs Temozolomide or Carmustine (BCNU) or Lomustine (CCNU) in Patients With Glioblastoma Multiforme
NCT00076986	PHASE3	COMPLETED	The PRECISE Trial: Study of IL13-PE38QQR Compared to GLIADEL Wafer in Patients With Recurrent Glioblastoma Multiforme
NCT00083447	PHASE3	WITHDRAWN	Study of Therapy With TransMID™ Compared to Best Standard of Care in Patients With Glioblastoma Multiforme
NCT00088400	PHASE3	COMPLETED	Comparison of TransMID vs Standard Treatment of Cancerous Brain Tumors
NCT00154375	PHASE3	COMPLETED	Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
NCT00224978	PHASE3	COMPLETED	Chloroquine for Treatment of Glioblastoma Multiforme
NCT00295815	PHASE3	COMPLETED	Enzastaurin Versus Lomustine in Glioblastoma
NCT00335075	PHASE3	COMPLETED	Efficacy and Safety of Temodal vs Semustine in Subjects With Recurrent Glioblastoma or Anaplastic Astrocytoma (Study P03644)
NCT00379470	PHASE3	COMPLETED	Effect of NovoTTF-100A in Recurrent Glioblastoma Multiforme (GBM)
NCT00430911	PHASE3	COMPLETED	Radiotherapy for Malignant Astrocytomas in the Elderly
NCT00615186	PHASE3	TERMINATED	Glioblastoma Multiforme (GBM) Locoregional Agent Survival Study - Anti-tenascin Radiolabeled Antibody Therapy
NCT00689221	PHASE3	COMPLETED	Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status
NCT00761280	PHASE3	TERMINATED	Efficacy and Safety of AP 12009 in Patients With Recurrent or Refractory Anaplastic Astrocytoma or Secondary Glioblastoma
NCT00777153	PHASE3	COMPLETED	Cediranib in Combination With Lomustine Chemotherapy in Recurrent Glioblastoma
NCT00807027	PHASE3	COMPLETED	Clinical Trial to Assess the Efficacy and Safety of ‘Immuncell-LC’ With Temozolomide in Newly Diagnosed Glioblastoma of Korea
NCT00884741	PHASE3	COMPLETED	Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma
NCT00916409	PHASE3	COMPLETED	Effect of NovoTTF-100A Together With Temozolomide in Newly Diagnosed Glioblastoma Multiforme (GBM)
NCT00943826	PHASE3	COMPLETED	A Study of Bevacizumab (Avastin®) in Combination With Temozolomide and Radiotherapy in Participants With Newly Diagnosed Glioblastoma
NCT01149109	PHASE3	COMPLETED	Efficacy and Safety Study of Lomustine/Temozolomide Combination Therapy vs. Standard Therapy for Glioblastoma Patients
NCT01290939	PHASE3	COMPLETED	Bevacizumab and Lomustine for Recurrent GBM
NCT01364064	PHASE3	COMPLETED	Conventional Adjuvant Temozolomide With Dose Intensive Temozolomide in Patients With Newly Diagnosed Glioblastoma
NCT01450449	PHASE3	COMPLETED	Short Course vs. Standard Course Radiotherapy in Elderly and/or Frail Patients With Glioblastoma Multiforme
NCT01480479	PHASE3	COMPLETED	Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma
NCT01502241	PHASE3	COMPLETED	Phase III Trial of Primary Radio- or Chemotherapy in Malignant Astrocytoma of the Elderly
NCT01507506	PHASE3	TERMINATED	Phase III Study Comparing 2 Brain Conformational Radiotherapy in Combination With Chemotherapy in the Treatment of Glioblastoma
NCT01656980	PHASE3	UNKNOWN	Safety and Efficacy Study of Intracranially Implanted Carmustine to Treat Newly Diagnosed Malignant Glioma
NCT01765088	PHASE3	UNKNOWN	A Phase III Trial on Adjuvant Temozolomide With or Without Interferon-alpha in Newly Diagnosed High-grade Gliomas
NCT01811121	PHASE3	COMPLETED	MEDICO-ECONOMIC EVALUATION OF SURGERY GUIDED BY FLUORESCENCE FOR THE OPTIMIZATION OF RESECTION OF GLIOBLASTOMAS
NCT01830101	PHASE3	WITHDRAWN	A Phase III Study of Re-Irradiation in Recurrent Glioblastoma
NCT02017717	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients
NCT02511405	PHASE3	COMPLETED	A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE)
NCT02546102	PHASE3	SUSPENDED	Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma