KIF1C

Summary

KIF1C (kinesin family member 1C, HGNC:6317) is a protein-coding gene on chromosome 17p13.2, encoding Kinesin-like protein KIF1C (O43896). Motor required for the retrograde transport of Golgi vesicles to the endoplasmic reticulum.

The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive.

Source: NCBI Gene 10749 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spastic ataxia 2 (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 799 total — 15 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 40
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6317
Approved symbol	KIF1C
Name	kinesin family member 1C
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	SPAX2, SPG58
Ensembl gene	ENSG00000129250
Ensembl biotype	protein_coding
OMIM	603060
Entrez	10749

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 31 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000320785, ENST00000572959, ENST00000573815, ENST00000574165, ENST00000894736, ENST00000894737, ENST00000894738, ENST00000894739, ENST00000894740, ENST00000894741, ENST00000894742, ENST00000894743, ENST00000894744, ENST00000894745, ENST00000894746, ENST00000894747, ENST00000894748, ENST00000894749, ENST00000894750, ENST00000919364, ENST00000919365, ENST00000919366, ENST00000948909, ENST00000948910, ENST00000948911, ENST00000948912, ENST00000948913, ENST00000948914, ENST00000948915, ENST00000948916, ENST00000948917, ENST00000948918, ENST00000948919

RefSeq mRNA: 1 — MANE Select: NM_006612 NM_006612

CCDS: CCDS11065

Canonical transcript exons

ENST00000320785 — 23 exons

Exon	Start	End
ENSE00000905269	5007263	5007342
ENSE00000905270	5006915	5007084
ENSE00000905271	5004855	5005000
ENSE00000905272	5004567	5004645
ENSE00000905273	5003998	5004073
ENSE00000905274	5003851	5003916
ENSE00000905275	5003612	5003689
ENSE00000905276	5002731	5002842
ENSE00000905277	5002464	5002642
ENSE00000905278	5002059	5002124
ENSE00000905279	5001222	5001401
ENSE00000905280	5000772	5000848
ENSE00001281020	5022092	5022709
ENSE00001404462	5023468	5028401
ENSE00001410983	4999850	4999970
ENSE00001415034	5000220	5000352
ENSE00001488086	4997950	4998156
ENSE00001680549	5007467	5007542
ENSE00002387332	5013653	5013732
ENSE00003508182	5020492	5020678
ENSE00003549060	5014743	5014837
ENSE00003623501	5019996	5020079
ENSE00003676102	5020806	5020878

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.9576 / max 1536.4435, expressed in 1810 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159006	56.7576	1809
208039	1.3689	876
159005	1.1519	794
159008	0.5373	316
159007	0.1418	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.23	gold quality
gastrocnemius	UBERON:0001388	99.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.93	gold quality
apex of heart	UBERON:0002098	98.88	gold quality
muscle of leg	UBERON:0001383	98.58	gold quality
heart left ventricle	UBERON:0002084	98.47	gold quality
cardiac ventricle	UBERON:0002082	98.33	gold quality
spinal cord	UBERON:0002240	98.32	gold quality
right atrium auricular region	UBERON:0006631	98.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.16	gold quality
amygdala	UBERON:0001876	98.05	gold quality
olfactory bulb	UBERON:0002264	97.98	gold quality
cardiac atrium	UBERON:0002081	97.96	gold quality
descending thoracic aorta	UBERON:0002345	97.91	gold quality
heart	UBERON:0000948	97.83	gold quality
popliteal artery	UBERON:0002250	97.79	gold quality
tibial artery	UBERON:0007610	97.79	gold quality
right coronary artery	UBERON:0001625	97.76	gold quality
diaphragm	UBERON:0001103	97.74	gold quality
putamen	UBERON:0001874	97.68	gold quality
aorta	UBERON:0000947	97.65	gold quality
thoracic aorta	UBERON:0001515	97.53	gold quality
muscle organ	UBERON:0001630	97.53	gold quality
mucosa of stomach	UBERON:0001199	97.48	gold quality
ascending aorta	UBERON:0001496	97.47	gold quality
left coronary artery	UBERON:0001626	97.45	gold quality
body of tongue	UBERON:0011876	97.44	gold quality
coronary artery	UBERON:0001621	97.36	gold quality
lower esophagus	UBERON:0013473	97.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.19	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

138 targeting KIF1C, 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-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4648	99.91	67.00	710
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-3529-3P	99.90	73.55	3045
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 16)

• Hairpin RNA-based depletion of KIF1C resulted in decreased podosome dynamics and ultimately in podosome deficiency. (PMID:16554367)
• Data show that 4-oxo-4-HPR inhibited tubulin polymerization and modulated gene expression of spindle aberration associated genes Kif 1C, Kif 2A, Eg5, Tara, tankyrase-1, centractin, and TOGp. (PMID:19996280)
• findings show that the microtubule motor Kif1C contributes to persistent cell migration primarily through stabilization of an extended cell rearKif1C-mediated transport of alpha5beta1-integrins is required for the proper maturation of trailing focal adhesions and resistance to tail retraction (PMID:23237952)
• Nonsense and missense mutations in the KIF1C gene associated with hereditary spastic paraparesis and cerebellar dysfunction. (PMID:24319291)
• Identification of KIF1C as an hereditary spastic paraplegia gene supports the key role of intracellular trafficking processes in the pathogenesis of hereditary axonopathies. (PMID:24808017)
• Microtubule acetylation influences the subcellular distribution of vesicles associated with the kinesin KIF1C, as well as their directionality, velocity and run length. (PMID:25151635)
• KIF1C translocation to the cell periphery intensifies and KIF1C accumulates both in the proximity of peripheral microtubules that show enrichment for the plus-tip-associated proteins CLASPs and around podosomes. (PMID:25344256)
• Rab6A binding to KIF1C’s motor domain represents an entirely new mode of regulation for a kinesin motor, and likely has important consequences for KIF1C’s cellular functions. (PMID:25821985)
• The authors analyze the previously identified kinesin inhibitor binding sites and identify features of AZ82 that favor binding to one of the sites, the alpha4/alpha6 site. This selectivity can be explained by unique structural features of the KIFC1 alpha4/alpha6 binding site. (PMID:29123223)
• Hereditary spastic paraplegia (HSP) patients with KIF1C mutations may present with cerebellar signs and pyramidal findings may emerge later, therefore complicated HSP should be considered in the differential diagnosis of unidentified cases with cerebellar dysfunction. (PMID:29544888)
• Study demonstrates that PTPN21 activates KIF1C by binding to the stalk region. This function does not require catalytic activity of the phosphatase, and its N-terminal FERM domain alone is sufficient to stimulate the transport of KIF1C cargoes in cells as well as increasing the landing rate of KIF1C on microtubules in vitro. The cargo adapter Hook3 binds KIF1C in the same region and activates KIF1C in a similar way. (PMID:31217419)
• Whole exome sequencing identified a homozygous KIF1C variant in both patients (PMID:31413903)
• c-Src-mediated phosphorylation and activation of kinesin KIF1C promotes elongation of invadopodia in cancer cells. (PMID:35654143)
• Force generation of KIF1C is impaired by pathogenic mutations. (PMID:35961316)
• Intracellular transport: KIF1C produces force along with a few slips. (PMID:36099894)
• KIF1C and new Huntingtin-interacting protein 1 binding proteins regulate rheumatoid arthritis fibroblast-like synoviocytes’ phenotypes. (PMID:38726004)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif1cb	ENSDARG00000054448
danio_rerio	kif1ca	ENSDARG00000098655
mus_musculus	Kif1c	ENSMUSG00000020821
rattus_norvegicus	Kif1c	ENSRNOG00000031364

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), 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 KIF1C — O43896 (reviewed: O43896)

All UniProt accessions (2): O43896, I3L1B1

UniProt curated annotations — full annotation on UniProt →

Function. Motor required for the retrograde transport of Golgi vesicles to the endoplasmic reticulum. Has a microtubule plus end-directed motility.

Subunit / interactions. Monomer. Interacts with BICD2.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in all tissues examined, with most abundant expression in heart and skeletal muscle.

Post-translational modifications. Phosphorylated on tyrosine residues.

Disease relevance. Spastic ataxia 2, autosomal recessive (SPAX2) [MIM:611302] A neurologic disorder characterized by cerebellar ataxia, dysarthria, and variable spasticity of the lower limbs. Cognition is not affected. 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. Unc-104 subfamily.

RefSeq proteins (1): NP_006603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR001752	Kinesin_motor_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032405	Kinesin_assoc	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00225, PF00498, PF16183

UniProt features (46 total): strand 10, modified residue 9, compositionally biased region 6, coiled-coil region 4, region of interest 4, sequence conflict 3, helix 3, domain 2, turn 2, chain 1, binding site 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2G1L	X-RAY DIFFRACTION	2.6
9KO8	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43896-F1	68.43	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 (1): 97–104

Post-translational modifications (9): 295, 494, 674, 676, 915, 1033, 1041, 1083, 1092

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 289 (showing top): RNGTGGGC_UNKNOWN, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_VESICLE_LOCALIZATION, LFA1_Q6, AREB6_03, GOCC_KINESIN_COMPLEX, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GGGTGGRR_PAX4_03, SREBP1_02, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, GOBP_VESICLE_CYTOSKELETAL_TRAFFICKING

GO Biological Process (5): retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), vesicle-mediated transport (GO:0016192), anterograde neuronal dense core vesicle transport (GO:1990048), retrograde neuronal dense core vesicle transport (GO:1990049), microtubule-based movement (GO:0007018)

GO Molecular Function (9): RNA binding (GO:0003723), cytoskeletal motor activity (GO:0003774), ATP binding (GO:0005524), microtubule binding (GO:0008017), plus-end-directed microtubule motor activity (GO:0008574), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), microtubule motor activity (GO:0003777), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), kinesin complex (GO:0005871), microtubule (GO:0005874), axon (GO:0030424), dendrite (GO:0030425), axon cytoplasm (GO:1904115), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Golgi-to-ER retrograde transport	1
Factors involved in megakaryocyte development and platelet production	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle transport along microtubule	2
dense core granule cytoskeletal transport	2
ATP-dependent activity	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
neuron projection	2
Golgi vesicle transport	1
transport	1
cellular process	1
anterograde axonal transport	1
retrograde axonal transport	1
microtubule-based process	1
nucleic acid binding	1
molecular_function	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
microtubule motor activity	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
microtubule associated complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
dendritic tree	1
axon	1
neuron projection cytoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF1C	KIFBP	Q96EK5	888
KIF1C	ANKFY1	Q9P2R3	858
KIF1C	PTPN21	Q16825	855
KIF1C	BICDL1	Q6ZP65	792
KIF1C	RAB6A	P20340	789
KIF1C	REEP1	Q9H902	638
KIF1C	SPAST	Q9UBP0	569
KIF1C	ATL1	Q8WXF7	565
KIF1C	ARRB2	P32121	538
KIF1C	MAP2K3	P46734	531
KIF1C	PLP1	P04400	513
KIF1C	BICD2	Q8TD16	512
KIF1C	REEP2	Q9BRK0	512
KIF1C	HOOK3	Q86VS8	511
KIF1C	SPG7	Q9UQ90	507

IntAct

135 interactions, top by confidence:

A	B	Type	Score
KIF1C	YWHAG	psi-mi:“MI:0915”(physical association)	0.820
KIF1C	YWHAG	psi-mi:“MI:0914”(association)	0.820
KIF1C	YWHAQ	psi-mi:“MI:0915”(physical association)	0.810
KIF1C	YWHAQ	psi-mi:“MI:0403”(colocalization)	0.810
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
YWHAZ	KIF1C	psi-mi:“MI:0915”(physical association)	0.740
YWHAE	KIF1C	psi-mi:“MI:0915”(physical association)	0.730
KIF1C	YWHAE	psi-mi:“MI:0403”(colocalization)	0.730
KIF1C	YWHAE	psi-mi:“MI:0915”(physical association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
KIF1C	Bicdl1	psi-mi:“MI:0915”(physical association)	0.540
Bicdl1	KIF1C	psi-mi:“MI:0403”(colocalization)	0.540
Bicdl1	KIF1C	psi-mi:“MI:0915”(physical association)	0.540
KIFBP	KIF3C	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480

BioGRID (159): ANXA7 (Affinity Capture-MS), LYST (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), MYO1A (Affinity Capture-MS), POLR2G (Affinity Capture-MS), RAN (Affinity Capture-MS), ROBO2 (Affinity Capture-MS), UBE2N (Affinity Capture-MS), UTY (Affinity Capture-MS), MKNK1 (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), KIF1C (Affinity Capture-MS), KIF1C (Affinity Capture-MS), KIF1C (Affinity Capture-MS), KIF1C (Affinity Capture-MS)

ESM2 similar proteins: A0A096X8J7, A3KN19, A4IFL1, B1MTL0, B2DD29, B2RXE2, O18917, O35071, O35787, O43896, O60307, O75064, P04920, P13808, P16283, P23347, P23348, P29414, P41987, P48746, P48751, P54310, Q14940, Q3U1Y4, Q3U214, Q3UHC7, Q5RB85, Q5RD44, Q5RJI5, Q5VWQ8, Q64448, Q68J42, Q6NZR5, Q6P730, Q6SJP2, Q80UP3, Q8BTY2, Q8CIP4, Q8TDC3, Q96L34

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
KIF1C	up-regulates	“Plus-end directed sliding movement”
CSNK2A1	unknown	KIF1C	phosphorylation
CSNK2A2	unknown	KIF1C	phosphorylation
BICDL1	“up-regulates activity”	KIF1C	binding
KIF1C	“up-regulates quantity”	RAB6A	relocalization
KIF1C	“up-regulates quantity”	RAB6B	relocalization
KIF1C	“up-regulates quantity”	RAB6C	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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	8	65.5×	7e-11
Activation of BAD and translocation to mitochondria	7	65.0×	9e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	57.4×	2e-09
Activation of BH3-only proteins	7	42.4×	1e-08
RHO GTPases activate PKNs	8	30.9×	1e-08
Intrinsic Pathway for Apoptosis	7	25.0×	4e-07
Transport of Mature Transcript to Cytoplasm	5	23.2×	5e-05
FOXO-mediated transcription	5	20.5×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	18.9×	3e-04
substantia nigra development	6	18.9×	3e-04
mRNA export from nucleus	5	12.7×	5e-03
intracellular protein localization	8	7.2×	2e-03
RNA splicing	8	6.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	20
Uncertain significance	340
Likely benign	278
Benign	57

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
101066	NM_006612.6(KIF1C):c.2191C>T (p.Arg731Ter)	Pathogenic
101069	NC_000017.10:g.(4907452_4914761)_(4918508_4926045)del	Pathogenic
1027417	NM_006612.6(KIF1C):c.765del (p.Asp256fs)	Pathogenic
1075456	NM_006612.6(KIF1C):c.726_727insCC (p.Lys243fs)	Pathogenic
1180686	NM_006612.6(KIF1C):c.1996G>T (p.Glu666Ter)	Pathogenic
1406903	NM_006612.6(KIF1C):c.601_604del (p.Lys201fs)	Pathogenic
2413840	NM_006612.6(KIF1C):c.328C>T (p.Arg110Ter)	Pathogenic
265862	NM_006612.6(KIF1C):c.2478del (p.Ala828fs)	Pathogenic
2851191	NM_006612.6(KIF1C):c.1396_1397del (p.Glu466fs)	Pathogenic
3639597	NM_006612.6(KIF1C):c.238del (p.Glu80fs)	Pathogenic
3897855	NM_006612.6(KIF1C):c.182C>A (p.Ser61Ter)	Pathogenic
4738673	NM_006612.6(KIF1C):c.1039C>T (p.Gln347Ter)	Pathogenic
625205	NM_006612.6(KIF1C):c.1051_1055del (p.Asn351fs)	Pathogenic
989135	NM_006612.6(KIF1C):c.445A>T (p.Ile149Phe)	Pathogenic
989136	NM_006612.6(KIF1C):c.1019+1dup	Pathogenic
101067	NM_006612.6(KIF1C):c.505C>T (p.Arg169Trp)	Likely pathogenic
101068	NM_006612.6(KIF1C):c.183G>A (p.Ser61=)	Likely pathogenic
2444164	NM_006612.6(KIF1C):c.41C>T (p.Pro14Leu)	Likely pathogenic
2583176	NM_006612.6(KIF1C):c.647G>A (p.Arg216His)	Likely pathogenic
2847385	NM_006612.6(KIF1C):c.1491+2T>C	Likely pathogenic
3252095	NM_006612.6(KIF1C):c.2885_2895del (p.Leu962fs)	Likely pathogenic
3256747	NM_006612.6(KIF1C):c.1020-2A>G	Likely pathogenic
3357938	NM_006612.6(KIF1C):c.774_775del (p.Ala260fs)	Likely pathogenic
3375268	NM_006612.6(KIF1C):c.1166-2A>T	Likely pathogenic
423907	NM_006612.6(KIF1C):c.646C>T (p.Arg216Cys)	Likely pathogenic
4280619	NM_006612.6(KIF1C):c.64C>T (p.Gln22Ter)	Likely pathogenic
4526626	NM_006612.6(KIF1C):c.941-2A>G	Likely pathogenic
4728367	NM_006612.6(KIF1C):c.865-1G>A	Likely pathogenic
560374	NM_006612.6(KIF1C):c.864+1G>A	Likely pathogenic
987071	NM_006612.6(KIF1C):c.940+2T>G	Likely pathogenic

SpliceAI

3193 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4998154:GAGGT:G	donor_loss	1.0000
17:4998155:AGGTG:A	donor_loss	1.0000
17:4998156:GGTG:G	donor_loss	1.0000
17:4998157:G:GA	donor_loss	1.0000
17:4998158:T:A	donor_loss	1.0000
17:5000210:T:TA	acceptor_gain	1.0000
17:5000218:A:AG	acceptor_gain	1.0000
17:5000218:AGCT:A	acceptor_gain	1.0000
17:5000219:G:A	acceptor_loss	1.0000
17:5000219:G:GA	acceptor_gain	1.0000
17:5000219:GC:G	acceptor_gain	1.0000
17:5000219:GCT:G	acceptor_gain	1.0000
17:5000219:GCTG:G	acceptor_gain	1.0000
17:5000219:GCTGA:G	acceptor_gain	1.0000
17:5000350:CCT:C	donor_gain	1.0000
17:5000353:G:GG	donor_gain	1.0000
17:5000354:TGA:T	donor_gain	1.0000
17:5000355:GA:G	donor_gain	1.0000
17:5000355:GAG:G	donor_gain	1.0000
17:5000357:G:GG	donor_gain	1.0000
17:5001210:A:AG	acceptor_gain	1.0000
17:5001211:C:G	acceptor_gain	1.0000
17:5001218:CTAG:C	acceptor_loss	1.0000
17:5001219:TAGA:T	acceptor_loss	1.0000
17:5001220:A:AG	acceptor_gain	1.0000
17:5001220:AGAC:A	acceptor_gain	1.0000
17:5001220:AGACG:A	acceptor_gain	1.0000
17:5001221:G:GT	acceptor_gain	1.0000
17:5001221:GAC:G	acceptor_gain	1.0000
17:5001221:GACG:G	acceptor_gain	1.0000

AlphaMissense

7138 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:5001327:G:T	G97W	1.000
17:5001328:G:A	G97E	1.000
17:5003637:T:C	L249P	1.000
17:5003876:T:C	L275P	1.000
17:5004035:G:T	R301M	1.000
17:5004056:T:C	L308P	1.000
17:5004059:T:C	L309P	1.000
17:5004856:T:C	Y341H	1.000
17:5004860:C:A	A342D	1.000
17:5004866:G:C	R344P	1.000
17:5004932:T:C	L366P	1.000
17:5022146:T:A	W689R	1.000
17:5022146:T:C	W689R	1.000
17:5022153:T:C	L691P	1.000
17:5022156:T:A	I692N	1.000
17:5022165:T:C	L695S	1.000
17:5022192:T:A	V704D	1.000
17:5022204:T:A	V708D	1.000
17:5022321:T:C	L747P	1.000
17:5022332:G:C	A751P	1.000
17:5022340:G:C	K753N	1.000
17:5022340:G:T	K753N	1.000
17:5022349:C:G	C756W	1.000
17:5022600:T:C	L840P	1.000
17:5000281:T:A	V12D	0.999
17:5001314:C:G	C92W	0.999
17:5001322:C:A	A95D	0.999
17:5001327:G:A	G97R	0.999
17:5001327:G:C	G97R	0.999
17:5001328:G:T	G97V	0.999

dbSNP variants (sampled 300 via entrez): RS1000163811 (17:5013421 G>A), RS1000167974 (17:5013202 A>G), RS1000209201 (17:5005400 C>G), RS1000249874 (17:5023926 C>T), RS1000268517 (17:5007813 T>C), RS1000311424 (17:5019524 G>A), RS1000325184 (17:5014056 G>A), RS1000424608 (17:5003135 C>G,T), RS1000458278 (17:5019045 T>G), RS1000464490 (17:4999457 C>T), RS1000473426 (17:5003310 G>A), RS1000546495 (17:5005226 G>A,C,T), RS1000564143 (17:5027104 A>G), RS1000597577 (17:5008950 T>C), RS1000725177 (17:4999629 C>G,T)

Disease associations

OMIM: gene MIM:603060 | disease phenotypes: MIM:611302, MIM:303350, MIM:108600

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic ataxia 2	Strong	Autosomal recessive

Mondo (6): spastic ataxia 2 (MONDO:0012651), hereditary spastic paraplegia (MONDO:0019064), spastic ataxia (MONDO:0017845), microcephaly (MONDO:0001149), cerebellar ataxia (MONDO:0000437), intellectual disability (MONDO:0001071)

Orphanet (5): Autosomal spastic paraplegia type 58 (Orphanet:397946), Hereditary spastic paraplegia (Orphanet:685), Spastic ataxia (Orphanet:316226), Rare ataxia (Orphanet:102002), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000473	Torticollis
HP:0000666	Horizontal nystagmus
HP:0000668	Hypodontia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0002059	Cerebral atrophy
HP:0002066	Gait ataxia
HP:0002072	Chorea
HP:0002080	Intention tremor
HP:0002169	Clonus
HP:0002317	Unsteady gait
HP:0002359	Frequent falls
HP:0002380	Fasciculations
HP:0002395	Lower limb hyperreflexia
HP:0002497	Spastic ataxia
HP:0002500	Abnormal cerebral white matter morphology
HP:0002599	Head titubation
HP:0003487	Babinski sign
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0003693	Distal amyotrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST90002397_728	Mean spheric corpuscular volume	2.000000e-28
GCST90002405_327	Reticulocyte count	2.000000e-10
GCST90013442_27	Keratoconus	2.000000e-14
GCST90016667_11	Spleen volume	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C566969	Ataxia, Spastic, 2, Autosomal Recessive (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
Valproic Acid	affects expression, decreases expression	2
FR900359	affects phosphorylation	1
securinine	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
cobaltous chloride	decreases expression	1
cupric chloride	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Cadmium	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 1 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4EJ	HIHRSi003-A-1	Induced pluripotent stem cell	Female
CVCL_B2ZS	Abcam HEK293T KIF1C KO	Transformed cell line	Female
CVCL_SU73	HAP1 KIF1C (-) 1	Cancer cell line	Male
CVCL_SU74	HAP1 KIF1C (-) 2	Cancer cell line	Male
CVCL_SU75	HAP1 KIF1C (-) 3	Cancer cell line	Male
CVCL_SU76	HAP1 KIF1C (-) 4	Cancer cell line	Male
CVCL_SU77	HAP1 KIF1C (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT00034242	PHASE2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	PHASE2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	PHASE2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	PHASE2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	PHASE2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	PHASE2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	PHASE2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	PHASE2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT00683943	PHASE1	COMPLETED	Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064	PHASE1	UNKNOWN	An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802	PHASE1	ACTIVE_NOT_RECRUITING	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism