KLC1

Summary

KLC1 (kinesin light chain 1, HGNC:6387) is a protein-coding gene on chromosome 14q32.33, encoding Kinesin light chain 1 (Q07866). Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport.

Conventional kinesin is a tetrameric molecule composed of two heavy chains and two light chains, and transports various cargos along microtubules toward their plus ends. The heavy chains provide the motor activity, while the light chains bind to various cargos. This gene encodes a member of the kinesin light chain family. It associates with kinesin heavy chain through an N-terminal domain, and six tetratricopeptide repeat (TPR) motifs are thought to be involved in binding of cargos such as vesicles, mitochondria, and the Golgi complex. Thus, kinesin light chains function as adapter molecules and not motors per se. Although previously named “kinesin 2”, this gene is not a member of the kinesin-2 / kinesin heavy chain subfamily of kinesin motor proteins. Extensive alternative splicing produces isoforms with different C-termini that are proposed to bind to different cargos; however, the full-length nature and/or biological validity of most of these variants have not been determined.

Source: NCBI Gene 3831 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 111 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001394837

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6387
Approved symbol	KLC1
Name	kinesin light chain 1
Location	14q32.33
Locus type	gene with protein product
Status	Approved
Aliases	KNS2A, KLC, hKLC1S, hKLC1N, hKLC1P, hKLC1G, hKLC1R, hKLC1J, hKLC1B
Ensembl gene	ENSG00000126214
Ensembl biotype	protein_coding
OMIM	600025
Entrez	3831

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 38 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay

ENST00000246489, ENST00000334553, ENST00000347839, ENST00000348520, ENST00000380038, ENST00000389744, ENST00000445352, ENST00000452929, ENST00000535194, ENST00000537046, ENST00000538504, ENST00000553286, ENST00000553325, ENST00000553436, ENST00000553680, ENST00000554228, ENST00000554280, ENST00000555467, ENST00000555836, ENST00000555856, ENST00000556986, ENST00000557143, ENST00000557172, ENST00000557450, ENST00000557575, ENST00000557686, ENST00000634686, ENST00000881692, ENST00000881693, ENST00000881694, ENST00000881695, ENST00000881696, ENST00000881697, ENST00000881698, ENST00000881699, ENST00000881700, ENST00000881701, ENST00000881702, ENST00000881703, ENST00000881704, ENST00000920419, ENST00000920420, ENST00000950074, ENST00000950075, ENST00000950076

RefSeq mRNA: 32 — MANE Select: NM_001394837 NM_001130107, NM_001394832, NM_001394833, NM_001394834, NM_001394835, NM_001394836, NM_001394837, NM_001394838, NM_001394839, NM_001394840, NM_001394841, NM_001394842, NM_001394843, NM_001394844, NM_001394845, NM_001394846, NM_001394847, NM_001394848, NM_001394849, NM_001394850, NM_001394851, NM_001394852, NM_001394853, NM_001394854, NM_001394855, NM_001394856, NM_001394857, NM_001394858, NM_001394859, NM_001394860, NM_005552, NM_182923

CCDS: CCDS32165, CCDS41996, CCDS45168, CCDS91945, CCDS91946, CCDS91947, CCDS91948, CCDS91949, CCDS91950, CCDS91951, CCDS91952, CCDS91953

Canonical transcript exons

ENST00000334553 — 17 exons

Exon	Start	End
ENSE00002450634	103629211	103629494
ENSE00003532953	103657546	103657776
ENSE00003543885	103654564	103654825
ENSE00003545251	103675552	103675601
ENSE00003557168	103662116	103662194
ENSE00003557446	103670182	103670283
ENSE00003573691	103701201	103701544
ENSE00003608978	103675689	103675756
ENSE00003610050	103700655	103700727
ENSE00003614763	103687081	103687211
ENSE00003622688	103673014	103673187
ENSE00003628072	103677415	103677523
ENSE00003643354	103662702	103662927
ENSE00003644519	103692359	103692425
ENSE00003658971	103679384	103679545
ENSE00003688404	103673332	103673431
ENSE00003694641	103669511	103669598

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.1164 / max 1708.0801, expressed in 1821 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141762	63.6999	1820
141763	1.1244	369
141764	0.1765	41
141751	0.1110	15
141750	0.0046	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.67	gold quality
cerebellar hemisphere	UBERON:0002245	99.56	gold quality
right frontal lobe	UBERON:0002810	99.51	gold quality
cortical plate	UBERON:0005343	99.46	gold quality
cerebellar cortex	UBERON:0002129	99.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.02	gold quality
ganglionic eminence	UBERON:0004023	98.88	gold quality
spinal cord	UBERON:0002240	98.75	gold quality
tibial nerve	UBERON:0001323	98.74	gold quality
adenohypophysis	UBERON:0002196	98.66	gold quality
prefrontal cortex	UBERON:0000451	98.57	gold quality
lower esophagus	UBERON:0013473	98.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.53	gold quality
olfactory bulb	UBERON:0002264	98.52	gold quality
sural nerve	UBERON:0015488	98.51	gold quality
body of uterus	UBERON:0009853	98.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.47	gold quality
right coronary artery	UBERON:0001625	98.46	gold quality
lower esophagus mucosa	UBERON:0035834	98.45	gold quality
pituitary gland	UBERON:0000007	98.44	gold quality
endocervix	UBERON:0000458	98.43	gold quality
mucosa of stomach	UBERON:0001199	98.42	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.40	gold quality
ascending aorta	UBERON:0001496	98.31	gold quality
ectocervix	UBERON:0012249	98.30	gold quality
thoracic aorta	UBERON:0001515	98.27	gold quality
amygdala	UBERON:0001876	98.26	gold quality
aorta	UBERON:0000947	98.25	gold quality
popliteal artery	UBERON:0002250	98.25	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	43.59
E-HCAD-5	yes	15.51
E-ANND-3	yes	7.30
E-GEOD-84465	yes	6.90
E-GEOD-93593	no	11.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting KLC1, 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-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-185-5P	99.35	68.60	2497

Literature-anchored findings (GeneRIF, showing 28)

• The major binding site for kinesin light chain in kinesin heavy chain has been mapped to residues 789-813 at the C-terminal end of the heavy chain stalk domain. (PMID:12475239)
• For a single nucleotide polymorphism (G58836C in intron 13) in the kinesin light-chain 1 (KNS2) gene, the association between Alzheimer’s disease and the C allele is found to be significant. (PMID:15364413)
• KNS2 gene may play a role during early stages of Alzheimer’s disease pathogenesis. (PMID:17611642)
• KLC1 gene may be a novel susceptibility gene for age-related cataract. (PMID:17653041)
• microtubule-dependent functions of von Hippel-Lindau tumour suppressor are influenced by kinesin-2 (PMID:17825299)
• The present finding supports the involvement of the cytoskeleton and KNS2 in the development of vascular white matter damage, thereby opening up novel fields in the research into leukariois. (PMID:17977659)
• The KLC1 56836CC variant exerts a significant protective effect on the occurrence of multiple sclerosis. (PMID:17999208)
• The rs8702 variant of the kinesin light chain 1 genotype proved to exert strong amplifying effects on the occurrence and severity of leukoaraiosis in patients with long-lasting poorly controlled severe hypertension (PMID:19046961)
• Results do not convincingly support kinesin light chain 1 (KLC1) as a major susceptibility gene in any of the studied diseases, although there is a small effect of KLC1 in relation to cataract. (PMID:19911314)
• Phosphorylation of KLC1 at serine 460 modulates binding and trafficking of calsyntenin-1. (PMID:21385839)
• Data suggest that KLC1 is required for normal neural differentiation, ensuring proper metabolism of AD-associated molecules APP and Tau and for proliferation of neural precursors (NPs). (PMID:22272245)
• For the binding of cargos shared by KLC1, we propose a different site located within the groove but not involving N343. (PMID:22470497)
• study provides evidence that the combined effect of three variants within the KLC1 gene may predispose to age-related cataract. (PMID:23776437)
• Studies indicate that FEZ1 (fasciculation and elongation protein zeta 1), SCOCO (short coiled-coil protein) and kinesins (kinesin heavy chain) are involved in biological transport process. (PMID:24116125)
• The expression levels of KLC1 variant E in brain and lymphocytes were significantly higher in Alzheimer’s disease patients. (PMID:24497505)
• Dnm1L interacts with KLC1 through the tetratricopeptide repeat domains. (PMID:25082190)
• Microtubule-bound kinesin-1 and kinesin-3 motor domains were visualized at multiple steps in their ATPase cycles–including their nucleotide-free states–at approximately 7 A resolution using cryo-electron microscopy. (PMID:25209998)
• BNIP-2 is a kinesin-1 adapter involved in vesicular transportation in the cytoplasm and that association with cargos depends on interaction of the CRAL-TRIO domain with membrane phosphatidylserine. (PMID:25472445)
• The G allele and GG genotype of KLC1 rs8702 were significantly over-represented among cataract patients, as compared to healthy controls, and were associated with an odds ratio for cataract development. (PMID:25883527)
• All binary complexes (KLC1:APP, KLC1:JIP1, and APP:JIP1) contain conformations with favorable binding free energies indicating that KLC1 and JIP1 may take part in APP transport in Alzheimer’s disease patients. (PMID:27891669)
• structural plasticity of the N-terminal capping helix might represent a structural determinant for TPR domain structural versatility in cargo binding (PMID:29036226)
• these studies demonstrate that kinesin 1 regulates ciliogenesis through CCDC28B (PMID:29445114)
• extensive biochemical characterization of the KLC:JIP1 interaction, as well as identification of potential KLC1-binding partners, improves the understanding of how this growing family of cargos is recruited to kinesin1 by KLC1. (PMID:30026235)
• LMTK2 binds to KLC1 to direct axonal transport of p35 and its loss may contribute to Alzheimer’s disease. (PMID:31068217)
• TGF-beta mediated pro-invasive activity was found to be dependent on KIF5B expression. In contrast, the epithelial differentiation factor and EMT suppressor prolactin (PRL) was found to repress KIF5B gene expression and KIF5B-Snail1 nuclear accumulation, but enhanced KLC1 gene expression and KIF5B-KLC1 interaction. (PMID:31204277)
• Kinesin light chain-1 serine-460 phosphorylation is altered in Alzheimer’s disease and regulates axonal transport and processing of the amyloid precursor protein. (PMID:31806024)
• Normal levels of KIF5 but reduced KLC1 levels in both Alzheimer disease and Alzheimer disease in Down syndrome: evidence suggesting defects in anterograde transport. (PMID:33691783)
• Gene-gene functional relationships in Alzheimer’s disease: CELF1 regulates KLC1 alternative splicing. (PMID:38768546)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	klc1a	ENSDARG00000009796
mus_musculus	Klc1	ENSMUSG00000021288
rattus_norvegicus	Klc1	ENSRNOG00000011572
drosophila_melanogaster	Klc	FBGN0010235
caenorhabditis_elegans		WBGENE00002214
caenorhabditis_elegans		WBGENE00002215

Paralogs (5): APPBP2 (ENSG00000062725), KLC3 (ENSG00000104892), NPHP3 (ENSG00000113971), KLC4 (ENSG00000137171), KLC2 (ENSG00000174996)

Protein

Protein identifiers

Kinesin light chain 1 — Q07866 (reviewed: Q07866)

All UniProt accessions (13): Q07866, F8W6L3, G3V2E7, G3V2P7, G3V3H3, G3V5R9, G5E9S8, H0YG16, H0YGB8, H0YJK1, H0YJL0, H0YJT3, H0YJU9

UniProt curated annotations — full annotation on UniProt →

Function. Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport. The light chain may function in coupling of cargo to the heavy chain or in the modulation of its ATPase activity.

Subunit / interactions. Oligomeric complex composed of two heavy chains and two light chains. Interacts with SPAG9. Interacts with ATCAY; may link mitochondria to KLC1 and regulate mitochondria localization into neuron projections. Interacts (via TPR repeats) with TOR1A; the interaction associates TOR1A with the kinesin oligomeric complex. Interacts with BORCS5. Interacts with MAPK8IP3/JIP3 and NTRK2/TRKB; interaction with NTRK2/TRKB is mediated by MAPK8IP3/JIP3. Interacts with CLSTN1; phosphorylation at Ser-460 inhibits interaction with CLSTN1. (Microbial infection) Interacts with adenovirus hexon-interlacing protein; this interaction leads to capsid disruption at the nuclear pore complex during virus entry into host cell.

Subcellular location. Cell projection. Growth cone. Cytoplasmic vesicle. Cytoplasm. Cytoskeleton.

Tissue specificity. Found in a variety of tissues. Mostly abundant in brain and spine.

Post-translational modifications. Phosphorylation at Ser-460 by ERK inhibits interaction with CLSTN1 and localization to cytoplasmic vesicles.

Similarity. Belongs to the kinesin light chain family.

Isoforms (10)

UniProt ID	Names	Canonical?
Q07866-1	A	yes
Q07866-2	C, KLC1C, R, KLC1R
Q07866-3	G, KLC1G
Q07866-4	J, KLC1J
Q07866-5	K, KLC1K
Q07866-6	N, KLC1N
Q07866-7	P, KLC1P
Q07866-8	S, KLC1S, Q, KLC1Q
Q07866-9	I
Q07866-10	D, KLC1D

RefSeq proteins (32): NP_001123579, NP_001381761, NP_001381762, NP_001381763, NP_001381764, NP_001381765, NP_001381766, NP_001381767, NP_001381768, NP_001381769, NP_001381770, NP_001381771, NP_001381772, NP_001381773, NP_001381774, NP_001381775, NP_001381776, NP_001381777, NP_001381778, NP_001381779, NP_001381780, NP_001381781, NP_001381782, NP_001381783, NP_001381784, NP_001381785, NP_001381786, NP_001381787, NP_001381788, NP_001381789, NP_005543, NP_891553 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002151	Kinesin_light	Family
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR015792	Kinesin_light_repeat	Repeat
IPR019734	TPR_rpt	Repeat

Pfam: PF13374, PF13424

UniProt features (54 total): helix 13, modified residue 12, splice variant 7, repeat 6, mutagenesis site 4, sequence conflict 3, compositionally biased region 2, strand 2, region of interest 2, chain 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5OJ8	X-RAY DIFFRACTION	2.25
7AI4	X-RAY DIFFRACTION	2.79
3NF1	X-RAY DIFFRACTION	2.8
7AIE	X-RAY DIFFRACTION	3.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07866-F1	75.27	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (12): 162, 449, 460, 521, 524, 600, 631, 591, 622, 547, 578, 600

Mutagenesis-validated functional residues (4):

Position	Phenotype
460	abolished phosphorylation, leading to increased interaction with clstn1.
460	mimics clstn1, leading to decreased interaction with clstn1.
521	no effect on motor function; when associated with a/d-524.
524	no effect on motor function; when associated with a/d-521.

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-5625970	RHO GTPases activate KTN1
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-9700206	Signaling by ALK in cancer
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 188 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, KANG_FLUOROURACIL_RESISTANCE_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_KINESIN_COMPLEX, DITTMER_PTHLH_TARGETS_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, REACTOME_MEMBRANE_TRAFFICKING, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GARY_CD5_TARGETS_DN, GOBP_PROTEIN_RNA_COMPLEX_DISASSEMBLY

GO Biological Process (3): microtubule-based movement (GO:0007018), cell adhesion (GO:0007155), stress granule disassembly (GO:0035617)

GO Molecular Function (3): cytoskeletal motor activity (GO:0003774), kinesin binding (GO:0019894), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), membrane (GO:0016020), growth cone (GO:0030426), cytoplasmic vesicle (GO:0031410), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Adaptive Immune System	1
RHO GTPase Effectors	1
Golgi-to-ER retrograde transport	1
Signaling by ALK in cancer	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Vesicle-mediated transport	1
Disease	1
Membrane Trafficking	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Signal Transduction	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
microtubule-based process	1
cellular process	1
protein-RNA complex disassembly	1
organelle disassembly	1
molecular_function	1
cytoskeletal protein binding	1
binding	1
intracellular anatomical structure	1
microtubule associated complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
site of polarized growth	1
distal axon	1
intracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLC1	KIF5B	P33176	990
KLC1	MAPK8IP1	Q9UQF2	983
KLC1	MAPK8IP3	Q9UPT6	976
KLC1	CLSTN1	O94985	960
KLC1	KIF5A	Q12840	942
KLC1	KIF5C	O60282	921
KLC1	APP	P05067	875
KLC1	HAP1	P54257	875
KLC1	PLEKHM2	Q8IWE5	859
KLC1	MAPK8IP2	Q13387	795
KLC1	SPAG9	O60271	782
KLC1	ATCAY	Q86WG3	742
KLC1	ALK	Q9UM73	722
KLC1	DPYSL2	Q16555	721
KLC1	KIFAP3	Q92845	710

IntAct

136 interactions, top by confidence:

A	B	Type	Score
YWHAB	KLC1	psi-mi:“MI:0915”(physical association)	0.870
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
KLC1	KIF5B	psi-mi:“MI:0914”(association)	0.730
KIF5B	KLC1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AZIN1	OAZ2	psi-mi:“MI:0914”(association)	0.670
pipB2	KLC1	psi-mi:“MI:0915”(physical association)	0.630
pipB2	KLC1	psi-mi:“MI:0407”(direct interaction)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
N	KLC1	psi-mi:“MI:0915”(physical association)	0.600
BNIP2	KLC1	psi-mi:“MI:0915”(physical association)	0.560
KLC1	KRT31	psi-mi:“MI:0915”(physical association)	0.560
ODAD1	KLC1	psi-mi:“MI:0915”(physical association)	0.560
KRT31	KLC1	psi-mi:“MI:0915”(physical association)	0.560
KLC1	BNIP2	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560

BioGRID (366): KLC1 (Two-hybrid), KRT31 (Two-hybrid), CCDC114 (Two-hybrid), KLC1 (Affinity Capture-MS), KLC1 (Affinity Capture-MS), KLC1 (Affinity Capture-MS), KLC1 (Affinity Capture-MS), KLC1 (Affinity Capture-MS), KLC1 (Affinity Capture-MS), KLC1 (Affinity Capture-MS), KLC1 (Affinity Capture-MS), KLC1 (Two-hybrid), KIF5A (Co-fractionation), KIF5B (Co-fractionation), KIF5C (Co-fractionation)

ESM2 similar proteins: A0JNN3, A2AWA9, B1H2N3, B5DEN9, B5DGH9, O43242, O60941, O76031, P14685, P60228, P60229, Q05AY2, Q06364, Q07866, Q0IIL1, Q13330, Q1LUA8, Q28FE2, Q2KJ46, Q3B8M3, Q3T102, Q4QR03, Q4R6G8, Q503N9, Q5F428, Q5R7N3, Q5R8K9, Q5R8N4, Q5RAN1, Q5U2U0, Q5ZLA5, Q62599, Q641X8, Q6DH26, Q6DRI1, Q6GQA1, Q6P6Q9, Q6P7L9, Q7Z3J2, Q8K4B0

Diamond homologs: O88447, O88448, P37285, P46822, P46824, P46825, Q05090, Q07866, Q2HJJ0, Q2TBQ9, Q5PQM2, Q5R581, Q5R8E2, Q68G30, Q6P597, Q91W40, Q9DBS5, Q9H0B6, Q9NSK0

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
MAPK1	down-regulates	KLC1	phosphorylation
MAPK3	down-regulates	KLC1	phosphorylation
Gbeta	down-regulates	KLC1	phosphorylation
ERK1/2	down-regulates	KLC1	phosphorylation
KLC1	“up-regulates activity”	TOR1A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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
Activation of BAD and translocation to mitochondria	7	67.5×	7e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	59.5×	1e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	59.5×	1e-09
Activation of BH3-only proteins	7	44.0×	8e-09
RHO GTPases activate PKNs	7	28.1×	2e-07
Intrinsic Pathway for Apoptosis	7	25.9×	3e-07
FOXO-mediated transcription	5	21.3×	6e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	9	17.6×	9e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	22.0×	2e-04
microtubule-based movement	6	17.7×	3e-04
negative regulation of TORC1 signaling	5	16.2×	2e-03
intracellular protein localization	9	9.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	75
Likely benign	4
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625708	GRCh37/hg19 14q32.32-32.33(chr14:103804791-105677579)	Likely pathogenic

SpliceAI

8172 predictions. Top by Δscore:

Variant	Effect	Δscore
14:103562611:CTCA:C	donor_loss	1.0000
14:103562612:TCACC:T	donor_loss	1.0000
14:103562613:CA:C	donor_loss	1.0000
14:103562614:ACC:A	donor_loss	1.0000
14:103562615:C:CG	donor_loss	1.0000
14:103563120:GCGGG:G	donor_gain	1.0000
14:103563122:GGG:G	donor_gain	1.0000
14:103563123:GG:G	donor_gain	1.0000
14:103563123:GGG:G	donor_gain	1.0000
14:103563124:GG:G	donor_gain	1.0000
14:103563125:G:GG	donor_gain	1.0000
14:103563125:GTAA:G	donor_loss	1.0000
14:103563125:GTAAG:G	donor_loss	1.0000
14:103563126:T:A	donor_loss	1.0000
14:103574105:A:G	acceptor_gain	1.0000
14:103574167:TCAG:T	donor_loss	1.0000
14:103574167:TCAGG:T	donor_loss	1.0000
14:103574168:CAG:C	donor_loss	1.0000
14:103574169:AGGT:A	donor_loss	1.0000
14:103574169:AGGTT:A	donor_loss	1.0000
14:103574170:GG:G	donor_loss	1.0000
14:103574171:G:C	donor_loss	1.0000
14:103574171:G:GA	donor_loss	1.0000
14:103574497:T:G	donor_gain	1.0000
14:103587273:GGTCA:G	acceptor_gain	1.0000
14:103587361:ACAGG:A	donor_loss	1.0000
14:103587364:GGTA:G	donor_loss	1.0000
14:103590326:G:GT	donor_gain	1.0000
14:103654557:A:AG	acceptor_gain	1.0000
14:103654558:T:G	acceptor_gain	1.0000

AlphaMissense

4225 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:103654668:T:C	L35P	1.000
14:103654808:G:C	G82R	1.000
14:103654812:T:C	L83P	1.000
14:103654820:G:C	A86P	1.000
14:103657555:G:C	A91P	1.000
14:103657571:T:C	L96P	1.000
14:103657601:T:C	L106P	1.000
14:103657616:G:C	R111P	1.000
14:103657619:G:C	R112P	1.000
14:103657622:T:C	L113P	1.000
14:103657630:G:A	E116K	1.000
14:103657631:A:T	E116V	1.000
14:103657639:T:A	W119R	1.000
14:103657639:T:C	W119R	1.000
14:103657641:G:C	W119C	1.000
14:103657641:G:T	W119C	1.000
14:103657643:T:A	L120Q	1.000
14:103657643:T:C	L120P	1.000
14:103657646:G:C	R121P	1.000
14:103657655:T:C	L124P	1.000
14:103657657:G:C	A125P	1.000
14:103657676:T:C	L131P	1.000
14:103657706:T:C	L141P	1.000
14:103657727:T:C	L148P	1.000
14:103657732:T:C	F150L	1.000
14:103657733:T:C	F150S	1.000
14:103657734:T:A	F150L	1.000
14:103657734:T:G	F150L	1.000
14:103662768:T:A	L213Q	1.000
14:103662768:T:C	L213P	1.000

dbSNP variants (sampled 300 via entrez): RS1000007370 (14:103652555 G>A,C), RS1000105326 (14:103698087 C>T), RS1000173903 (14:103697623 C>T), RS1000256803 (14:103675323 T>A), RS1000310750 (14:103671415 G>C), RS1000324156 (14:103642158 G>A), RS1000326901 (14:103629122 GC>G), RS1000337510 (14:103687258 G>A), RS1000375694 (14:103693244 G>A,T), RS1000406512 (14:103681692 C>T), RS1000426846 (14:103683952 T>G), RS1000480715 (14:103654375 G>A), RS1000505145 (14:103698490 CT>C), RS1000569791 (14:103677012 C>T), RS1000577457 (14:103638644 T>G)

Disease associations

OMIM: gene MIM:600025 | disease phenotypes: MIM:167000, MIM:613972

GenCC curated gene-disease

Mondo (2): ovarian cancer (MONDO:0008170), melanoma, cutaneous malignant, susceptibility to, 6 (MONDO:0013510)

Orphanet (2): Rare ovarian cancer (Orphanet:213500), Familial melanoma (Orphanet:618)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002539_23	Schizophrenia	1.000000e-13
GCST002783_125	Body mass index	3.000000e-06
GCST002783_156	Body mass index	1.000000e-07
GCST002783_209	Body mass index	1.000000e-07
GCST004521_135	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_15	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_262	Autism spectrum disorder or schizophrenia	6.000000e-09
GCST004904_118	Body mass index	2.000000e-08
GCST008103_98	Bipolar disorder	2.000000e-06
GCST008595_89	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-13
GCST008803_9	Smoking behaviour (cigarette pack-years)	3.000000e-09
GCST008971_150	Urate levels	2.000000e-09
GCST008972_222	Urate levels	3.000000e-09
GCST010703_23	Brain morphology (MOSTest)	2.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009115	tobacco smoke exposure measurement
EFO:0004531	urate measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465389 (CHIMERIC PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs861539	Efficacy	3	fluorouracil;irinotecan;leucovorin	Colorectal Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs861539	KLC1, XRCC3	3	2.00	2	Platinum compounds;fluorouracil;irinotecan;leucovorin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Valproic Acid	decreases expression, increases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
afimoxifene	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
aflatoxin B2	decreases methylation	1
K 7174	increases expression	1
ICG 001	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dietary Carbohydrates	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5363000	Binding	Inhibition of ALK-KLC1 (unknown origin) assessed as residual activity at 1 uM relative to control	Discovery of pyrazolo[3,4-b]pyridine derivatives as novel and potent Mps1 inhibitors for the treatment of cancer. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1VB	Abcam HeLa KLC1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	PHASE3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer