KIF1A

Summary

KIF1A (kinesin family member 1A, HGNC:888) is a protein-coding gene on chromosome 2q37.3, encoding Kinesin-like protein KIF1A (Q12756). Kinesin motor with a plus-end-directed microtubule motor activity.

The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 547 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 3,466 total — 83 pathogenic, 97 likely-pathogenic
• Phenotypes (HPO): 100
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001244008

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:888
Approved symbol	KIF1A
Name	kinesin family member 1A
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	UNC104
Ensembl gene	ENSG00000130294
Ensembl biotype	protein_coding
OMIM	601255
Entrez	547

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 31 protein_coding, 12 protein_coding_CDS_not_defined, 10 retained_intron, 2 nonsense_mediated_decay

ENST00000320389, ENST00000404283, ENST00000415042, ENST00000428768, ENST00000431776, ENST00000448728, ENST00000460788, ENST00000463388, ENST00000465813, ENST00000488776, ENST00000492812, ENST00000494452, ENST00000498729, ENST00000647572, ENST00000647731, ENST00000647885, ENST00000648047, ENST00000648129, ENST00000648364, ENST00000648534, ENST00000648680, ENST00000648854, ENST00000649064, ENST00000649096, ENST00000649190, ENST00000649306, ENST00000649381, ENST00000650053, ENST00000650130, ENST00000650430, ENST00000650542, ENST00000674530, ENST00000674607, ENST00000674664, ENST00000674793, ENST00000674907, ENST00000674958, ENST00000674975, ENST00000675126, ENST00000675152, ENST00000675314, ENST00000675421, ENST00000675450, ENST00000675465, ENST00000675644, ENST00000675932, ENST00000675940, ENST00000676050, ENST00000676130, ENST00000676135, ENST00000676368, ENST00000715177, ENST00000942881, ENST00000942882, ENST00000942883

RefSeq mRNA: 24 — MANE Select: NM_001244008 NM_001244008, NM_001320705, NM_001330289, NM_001330290, NM_001379631, NM_001379632, NM_001379633, NM_001379634, NM_001379635, NM_001379636, NM_001379637, NM_001379638, NM_001379639, NM_001379640, NM_001379641, NM_001379642, NM_001379645, NM_001379646, NM_001379648, NM_001379649, NM_001379650, NM_001379651, NM_001379653, NM_004321

CCDS: CCDS46561, CCDS58757, CCDS92987, CCDS92988, CCDS92989, CCDS92990, CCDS92991, CCDS92992, CCDS92993

Canonical transcript exons

ENST00000498729 — 49 exons

Exon	Start	End
ENSE00000894087	240740058	240740142
ENSE00000894094	240746039	240746177
ENSE00000894098	240760665	240760843
ENSE00000894103	240763166	240763346
ENSE00000894105	240765710	240765793
ENSE00000894106	240766915	240767021
ENSE00000894110	240769133	240769208
ENSE00000894112	240769627	240769706
ENSE00000894116	240773114	240773256
ENSE00000894128	240784989	240785100
ENSE00000894130	240786335	240786513
ENSE00001038722	240770971	240771104
ENSE00001074196	240747236	240747321
ENSE00001074199	240737063	240737168
ENSE00001074202	240742929	240742984
ENSE00001074208	240740298	240740364
ENSE00001074215	240758360	240758497
ENSE00001074224	240726826	240726940
ENSE00001074251	240741269	240741377
ENSE00001074254	240761229	240761377
ENSE00001074255	240750429	240750547
ENSE00001162253	240783739	240783816
ENSE00001162271	240789236	240789312
ENSE00001261008	240775851	240775926
ENSE00001414796	240820122	240820219
ENSE00001460115	240725271	240725404
ENSE00001460157	240787251	240787316
ENSE00001460158	240788051	240788230
ENSE00001525123	240797647	240797812
ENSE00001551924	240783044	240783109
ENSE00001626039	240774183	240774261
ENSE00002245046	240745738	240745909
ENSE00002280618	240745427	240745517
ENSE00002284802	240743942	240744060
ENSE00002297767	240763019	240763091
ENSE00002318009	240762719	240762812
ENSE00002411311	240767266	240767345
ENSE00002534810	240782590	240782607
ENSE00003464589	240723413	240723558
ENSE00003566543	240721807	240721884
ENSE00003573426	240720914	240721038
ENSE00003578385	240722456	240722656
ENSE00003585614	240719006	240719198
ENSE00003613493	240719774	240719926
ENSE00003628920	240723975	240724036
ENSE00003642600	240718050	240718168
ENSE00004026006	240713767	240717406
ENSE00004026008	240757319	240757594
ENSE00004026021	240772570	240772596

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 99.26.

FANTOM5 (CAGE): breadth broad, TPM avg 62.1120 / max 2032.2034, expressed in 585 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34861	60.7677	575
34863	0.1882	89
34850	0.1835	109
34856	0.1827	82
34858	0.1762	103
34860	0.1214	71
34857	0.1182	65
34845	0.1147	61
34862	0.0870	59
34844	0.0835	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	99.26	gold quality
postcentral gyrus	UBERON:0002581	99.17	gold quality
parietal lobe	UBERON:0001872	99.13	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.02	gold quality
cerebellar vermis	UBERON:0004720	99.00	gold quality
pons	UBERON:0000988	98.95	gold quality
anterior cingulate cortex	UBERON:0009835	98.88	gold quality
substantia nigra pars compacta	UBERON:0001965	98.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.83	gold quality
cingulate cortex	UBERON:0003027	98.80	gold quality
amygdala	UBERON:0001876	98.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.69	gold quality
nucleus accumbens	UBERON:0001882	98.67	gold quality
entorhinal cortex	UBERON:0002728	98.67	gold quality
cerebellar cortex	UBERON:0002129	98.65	gold quality
cerebellar hemisphere	UBERON:0002245	98.64	gold quality
ventral tegmental area	UBERON:0002691	98.61	gold quality
temporal lobe	UBERON:0001871	98.59	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.59	gold quality
superior vestibular nucleus	UBERON:0007227	98.52	gold quality
inferior vagus X ganglion	UBERON:0005363	98.51	gold quality
prefrontal cortex	UBERON:0000451	98.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.32	gold quality
caudate nucleus	UBERON:0001873	98.28	gold quality
neocortex	UBERON:0001950	98.22	gold quality
lateral globus pallidus	UBERON:0002476	98.19	gold quality
primary visual cortex	UBERON:0002436	98.16	gold quality
subthalamic nucleus	UBERON:0001906	98.15	gold quality
cerebellum	UBERON:0002037	98.12	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	13.00
E-CURD-114	yes	11.78
E-ANND-3	yes	7.99
E-GEOD-84465	yes	6.99
E-CURD-7	no	346.73
E-CURD-53	no	307.97
E-MTAB-6524	no	117.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFE2L2, NRF1

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• KIF1A mediates neuronal transport at a high velocity and processivity in vivo (PMID:12435738)
• Results suggest that the intramolecular FHA-CC2 interaction negatively regulates KIF1A activity by inhibiting MT binding and dimerization of KIF1A, and point to a novel role of the FHA domain in the regulation of kinesin motors. (PMID:15014437)
• cryo-electron microscopy structures of the monomeric kinesin KIF1A-microtubule complex in two nucleotide states at about 10 A resolution, sufficient to reveal the secondary structure (PMID:16946706)
• Promoter hypermethylation of KIF1A and EDNRB is a frequent event in primary HNSCC, and these genes are preferentially methylated in salivary rinses from HNSCC patients. (PMID:20162572)
• A mutation in KIF1A is associated with a pure form of hereditary spastic paraparesis. (HSP) cases in a single inbred family. (PMID:21487076)
• Mutations in KIF1A are a rare cause of hereditary sensory and autonomic neuropathy type 2. (PMID:21820098)
• The authors find that Arl8B is required for kinesin-1 recruitment to Salmonella-containing vacuoles, migration of the vacuoles to the cell periphery 24 h after infection and for cell-to-cell transfer of bacteria to neighbouring cells. (PMID:21824248)
• mutations in the KIF1A gene are responsible for SPG30 in two autosomal recessive HSP families (PMID:22258533)
• The CC1-FHA tandem likely functions as a hub for controlling the dimerization and activation of KIF1A. (PMID:22863567)
• Cytoplasmic dynein is active during minus- and plus-end directed motion, whereas kinesin is only active in the plus direction. (PMID:23404705)
• This study establishes an essential role of the CC1-FHA dimer for KIF1A/unc-104-mediated neuronal transport. (PMID:23669038)
• Data demonstrated that KIF1A promoter methylation can distinguish breast cancer cases from controls in plasma and was inversely associated with DNA repair capacity. (PMID:24927296)
• Findings provide evidence that de novo missense mutations in the motor domain of KIF1A cause a more severe phenotype that overlaps with that associated with recessive mutations in the same gene. (PMID:25265257)
• KIF1A should be considered a candidate gene for hereditary paraplegias regardless of inheritance pattern. (PMID:25585697)
• This study further delineates clinical features of de novo KIF1A mutations (PMID:26354034)
• KIF1A variants in dominant and sporadic forms of hereditary spastic paraparesis. (PMID:26410750)
• De novo missense variant affecting the motor domain of KIF1A was identified as a cause of PEHO syndrome. (PMID:26486474)
• BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bbeta and KIF1A). (PMID:27851960)
• Mutations outside the motor domain of the gene can cause (recessive) SPG30 and extends the genotype-phenotype association for KIF1A-related diseases. (PMID:28332297)
• These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated hereditary spastic paraplegia accompanying intellectual disability transmitted in autosomal dominant inheritance (PMID:28970574)
• We report a child with a de novo KIF1A gene mutation who was found to have bilateral optic nerve hypoplasia and atrophy. (PMID:28985824)
• Consistent with the differential clinical and structural impact, TUBB2AA248V does not drastically affect TUBB2A binding to KIF1A, nor mitotic spindle bipolarity. Overall, our data demonstrate a pathogenic role of the p.D417N substitution that is different from previously reported TUBB2A mutations and expand the phenotypic spectrum associated with mutations in this gene. (PMID:29547997)
• Mechanochemical Model of the Power Stroke of the Single-Headed Motor Protein KIF1A (PMID:30179486)
• These results suggest a new mechanism to regulate KIF1A motility via pauses mediated by K-loop/polyglutamylated C-terminal tail interactions, providing further insight into KIF1A’s role in axonal transport. (PMID:30770469)
• KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia. (PMID:31488895)
• Pathogenic variants of KIF1A are associated with Rett and Rett-like syndrome. (PMID:31512412)
• All-atom molecular dynamics simulations reveal how kinesin transits from one-head-bound to two-heads-bound state. (PMID:31589786)
• Mobility Characteristics of Children with Spastic Paraplegia Due to a Mutation in the KIF1A Gene. (PMID:31805580)
• Breaking of buckled microtubules is mediated by kinesins. (PMID:31983434)
• Kif1a recruitment complex facilitates axonal sorting of human herpes simplex virus 1. (PMID:31995633)
• Generation of a human induced pluripotent stem cell line (SDUBMSi001-A) from a hereditary spastic paraplegia patient carrying kif1a c.773C>T missense mutation. (PMID:32045731)
• KIF1A-related disorders in children: A wide spectrum of central and peripheral nervous system involvement. (PMID:32096284)
• 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)
• Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A). (PMID:32652677)
• Heterozygous KIF1A variants underlie a wide spectrum of neurodevelopmental and neurodegenerative disorders. (PMID:32737135)
• Phenotypic expansion in KIF1A-related dominant disorders: A description of novel variants and review of published cases. (PMID:32935419)
• Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review. (PMID:34487232)
• KLF5 promotes KIF1A expression through transcriptional repression of microRNA-338 in the development of pediatric neuroblastoma. (PMID:35033353)
• A neuropathy-associated kinesin KIF1A mutation hyper-stabilizes the motor-neck interaction during the ATPase cycle. (PMID:35132656)
• A kinesin-1 variant reveals motor-induced microtubule damage in cells. (PMID:35504282)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif1aa	ENSDARG00000061817
mus_musculus	Kif1a	ENSMUSG00000014602
rattus_norvegicus	Kif1a	ENSRNOG00000023993

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), 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 KIF1A — Q12756 (reviewed: Q12756)

Alternative names: Axonal transporter of synaptic vesicles, Microtubule-based motor KIF1A, Unc-104- and KIF1A-related protein

All UniProt accessions (23): Q12756, A0A3B3IT28, A0A3B3ITE5, A0A3B3ITF7, A0A3B3ITK3, A0A3B3ITW4, A0A3B3ITW6, A0A3B3IU40, A0A3B3IUA1, A0A3F2YNW9, A0A6Q8PFE9, A0A6Q8PFJ8, A0A6Q8PFL2, A0A6Q8PFR1, A0A6Q8PFR5, A0A6Q8PGE4, A0A6Q8PGW8, A0A6Q8PH56, A0A6Q8PHQ5, A0AAQ5BID6, C9JBH1, H7C0K6, H7C3Y8

UniProt curated annotations — full annotation on UniProt →

Function. Kinesin motor with a plus-end-directed microtubule motor activity. It is required for anterograde axonal transport of synaptic vesicle precursors. Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons. The interaction calcium-dependent with CALM1 increases vesicle motility and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites.

Subunit / interactions. Dimeric motor; dimerization is required for ATP-driven processive motility. Monomer in vitro. Interacts with PPFIA1 and PPFIA4. Interacts with CALM1; the interaction is increased in presence of calcium and increases neuronal dense core vesicles motility. Interacts with PPFIA2 and TANC2; both interactions allow the recruitment of neuronal dense core vesicles to dendritic spines and decrease in presence of calcium. Interacts with SYT4 (unphosphorylated) and SYT11; both interactions increase in presence of calcium. Interacts with MADD.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Neuron projection. Axon. Perinuclear region. Synapse. Cytoplasmic vesicle. Secretory vesicle. Neuronal dense core vesicle membrane.

Tissue specificity. Expressed in neurons.

Disease relevance. Spastic paraplegia 30A, autosomal dominant (SPG30A) [MIM:610357] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG30A patients have a pure form of the disorder, limited to spastic paraplegia, whereas others may have a complicated form that includes additional features such as cognitive dysfunction, learning disabilities, peripheral sensorimotor neuropathy, urinary sphincter problems, and/or cerebellar atrophy. SPG30A is characterized by onset in the first or second decades of unsteady spastic gait and hyperreflexia of the lower limbs. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Spastic paraplegia 30B, autosomal recessive (SPG30B) [MIM:620607] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG30B patients have a pure form of the disorder, limited to spastic paraplegia, whereas others may have a complicated form that includes additional features such as cognitive dysfunction, learning disabilities, peripheral sensorimotor neuropathy, urinary sphincter problems, and/or cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry. Neuropathy, hereditary sensory, 2C (HSN2C) [MIM:614213] A neurodegenerative disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs. The disease is caused by variants affecting the gene represented in this entry. NESCAV syndrome (NESCAVS) [MIM:614255] An autosomal dominant neurodegenerative disorder with variable manifestations. Main features are delayed psychomotor development, progressive spasticity, intellectual disability, speech delay, and learning disabilities. Some patients never achieve ambulation. Additional variable features are cortical visual impairment, often associated with optic atrophy, axonal peripheral neuropathy, seizures, dysautonomia, ataxia, and dystonia. Brain imaging often shows progressive cerebellar atrophy and thin corpus callosum. Disease onset is in infancy or early childhood. The disease is caused by variants affecting the gene represented in this entry. KIF1A dysfunction is associated with a large spectrum of neurologic disorders, including HSN2C, SPG30 and NESCAVS. It has been proposed to collectively name them KIF1A-Associated Neurological Disorder (KAND). Some variants reported here are based on this broad classification.

Domain organisation. Composed of an N-terminal active core containing the motor domain (MD) and a neck coil (NC), a central regulatory center containing the FHA domain and coiled coils (CC1 and CC2) and required for dimerization and activation, and a cargo-recognition region containing a coiled coil (CC3), an undefined region (UDR) and the C-terminal PH domain.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Unc-104 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q12756-1	1	yes
Q12756-2	2
Q12756-3	3

RefSeq proteins (24): NP_001230937, NP_001307634, NP_001317218, NP_001317219, NP_001366560, NP_001366561, NP_001366562, NP_001366563, NP_001366564, NP_001366565, NP_001366566, NP_001366567, NP_001366568, NP_001366569, NP_001366570, NP_001366571, NP_001366574, NP_001366575, NP_001366577, NP_001366578, NP_001366579, NP_001366580, NP_001366582, NP_004312 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR001752	Kinesin_motor_dom	Domain
IPR001849	PH_domain	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019821	Kinesin_motor_CS	Conserved_site
IPR022140	Kinesin-like_KIF1-typ	Domain
IPR022164	Kinesin-like	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032405	Kinesin_assoc	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR049779	FHA_KIF1A	Domain
IPR049780	PH_KIFIA_KIFIB	Domain

Pfam: PF00169, PF00225, PF00498, PF12423, PF12473, PF16183

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

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

UniProt features (197 total): sequence variant 95, strand 37, helix 16, modified residue 14, sequence conflict 11, binding site 6, turn 4, coiled-coil region 4, domain 3, splice variant 3, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
4EJQ	X-RAY DIFFRACTION	1.89
4EGX	X-RAY DIFFRACTION	2.51
8UTS	ELECTRON MICROSCOPY	2.7
9YA5	ELECTRON MICROSCOPY	2.95
8UTU	ELECTRON MICROSCOPY	3
8UTV	ELECTRON MICROSCOPY	3
8UTN	ELECTRON MICROSCOPY	3.1
8UTQ	ELECTRON MICROSCOPY	3.1
8UTT	ELECTRON MICROSCOPY	3.1
9YAI	ELECTRON MICROSCOPY	3.12
8UTO	ELECTRON MICROSCOPY	3.2
8UTP	ELECTRON MICROSCOPY	3.2
9YAB	ELECTRON MICROSCOPY	3.21
9YA7	ELECTRON MICROSCOPY	3.29
8UTR	ELECTRON MICROSCOPY	3.3
8UTY	ELECTRON MICROSCOPY	3.3
8UTW	ELECTRON MICROSCOPY	3.4
4UXO	ELECTRON MICROSCOPY	6.3
4UXP	ELECTRON MICROSCOPY	6.3
4UXR	ELECTRON MICROSCOPY	7
4UXS	ELECTRON MICROSCOPY	7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12756-F1	71.38	0.20

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 (6): 102; 103; 104; 104; 105; 215

Post-translational modifications (14): 416, 418, 419, 607, 612, 932, 937, 1310, 1337, 1519, 1523, 1528, 1532, 1548

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: 356 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_VESICLE_LOCALIZATION, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOCC_KINESIN_COMPLEX, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELL_JUNCTION_ORGANIZATION, MODULE_205, GOBP_VESICLE_CYTOSKELETAL_TRAFFICKING

GO Biological Process (9): anterograde axonal transport (GO:0008089), vesicle-mediated transport (GO:0016192), regulation of dendritic spine development (GO:0060998), regulation of dendritic spine morphogenesis (GO:0061001), dense core granule cytoskeletal transport (GO:0099519), anterograde neuronal dense core vesicle transport (GO:1990048), retrograde neuronal dense core vesicle transport (GO:1990049), microtubule-based movement (GO:0007018), transport along microtubule (GO:0010970)

GO Molecular Function (12): 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), identical protein binding (GO:0042802), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), microtubule motor activity (GO:0003777), protein binding (GO:0005515), hydrolase activity (GO:0016787), isomerase activity (GO:0016853)

GO Cellular Component (16): cytoplasm (GO:0005737), kinesin complex (GO:0005871), microtubule (GO:0005874), axon (GO:0030424), dendrite (GO:0030425), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), neuronal dense core vesicle (GO:0098992), neuronal dense core vesicle membrane (GO:0099012), axon cytoplasm (GO:1904115), cytoskeleton (GO:0005856), membrane (GO:0016020), transport vesicle membrane (GO:0030658), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuron projection (GO:0043005)

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
cellular anatomical structure	4
axon	2
vesicle transport along microtubule	2
dense core granule cytoskeletal transport	2
ATP-dependent activity	2
catalytic activity	2
neuron projection	2
cytoplasm	2
axonal transport	1
axon cytoplasm	1
transport	1
cellular process	1
regulation of developmental process	1
dendritic spine development	1
regulation of neuron projection development	1
regulation of anatomical structure morphogenesis	1
dendritic spine morphogenesis	1
regulation of postsynapse organization	1
vesicle cytoskeletal trafficking	1
dense core granule transport	1
anterograde axonal transport	1
retrograde axonal transport	1
microtubule-based process	1
microtubule-based movement	1
cytoskeleton-dependent intracellular transport	1
microtubule-based transport	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
protein binding	1
cation binding	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

Protein interactions and networks

STRING

2598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF1A	PPFIA1	Q13136	817
KIF1A	RAB3A	P20336	761
KIF1A	ARL5B	Q96KC2	759
KIF1A	MADD	Q8WXG6	742
KIF1A	SYP	P08247	725
KIF1A	PPFIA3	O75145	716
KIF1A	VAMP1	P23763	713
KIF1A	PTPN21	Q16825	707
KIF1A	TUBB2A	Q13885	704
KIF1A	KLC2	Q9H0B6	694
KIF1A	PAFAH1B3	Q15102	688
KIF1A	KLC3	Q6P597	667
KIF1A	NDE1	Q9NXR1	647
KIF1A	SYT4	Q9H2B2	627
KIF1A	KLC1	Q07866	612

IntAct

115 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
KIF1A	KIF1A	psi-mi:“MI:0407”(direct interaction)	0.740
KIF1B	YWHAZ	psi-mi:“MI:0914”(association)	0.740
KIF1A	KIF1A	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
IMP3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.670
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
KIF1A	CTSD	psi-mi:“MI:0915”(physical association)	0.560
GRN	KIF1A	psi-mi:“MI:0915”(physical association)	0.560
KIF1A	TTR	psi-mi:“MI:0915”(physical association)	0.560
KIF1A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
KIF1A	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
KIF1A	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (120): KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS), KIF5B (Co-fractionation), MAPK8IP3 (Co-fractionation), KIF1A (Affinity Capture-MS), KIF1A (Proximity Label-MS), KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS), KIF1A (Affinity Capture-MS)

ESM2 similar proteins: A0JN40, A8BB91, A8BKD1, B1AVY7, B9F2Y7, F1M4A4, F1M5N7, F1QN54, F4K0J3, G5EGS3, O14782, O15066, O35066, O55165, O60333, O75037, O88658, P28741, P33173, P33176, P34540, P35978, P46867, P46871, P46872, P46873, Q10E64, Q12756, Q29DY1, Q2PQA9, Q4R628, Q5JKW1, Q5R4H3, Q5R706, Q60575, Q61768, Q61771, Q6YUL8, Q7Z4S6, Q86Z98

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
KIF1A	up-regulates	“Plus-end directed sliding movement”
CALM1	“up-regulates activity”	KIF1A	binding
CALM2	“up-regulates activity”	KIF1A	binding
CALM3	“up-regulates activity”	KIF1A	binding
TANC2	“up-regulates activity”	KIF1A	binding
Liprin-alpha	“up-regulates activity”	KIF1A	binding
KIF1A	up-regulates	Dense-core_vesicle_exocytosis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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
Defective CFTR causes cystic fibrosis	6	16.9×	7e-04
Hh mutants are degraded by ERAD	5	15.6×	2e-03
Negative regulation of NOTCH4 signaling	5	15.2×	2e-03
Hedgehog ligand biogenesis	5	13.6×	2e-03
Asymmetric localization of PCP proteins	5	13.1×	2e-03
Proteasome assembly	5	13.1×	2e-03
Regulation of RAS by GAPs	5	12.4×	2e-03
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	5	12.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
ubiquitin-dependent protein catabolic process	10	7.3×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

3466 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	83
Likely pathogenic	97
Uncertain significance	1256
Likely benign	1404
Benign	176

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1004912	NM_001244008.2(KIF1A):c.934A>C (p.Thr312Pro)	Pathogenic
1058331	NM_001244008.2(KIF1A):c.467A>T (p.Asp156Val)	Pathogenic
1076894	NC_000002.11:g.(?_241656771)_241759735del	Pathogenic
1320162	NM_001244008.2(KIF1A):c.3073del (p.Glu1025fs)	Pathogenic
1323148	NM_001244008.2(KIF1A):c.4869-2A>C	Pathogenic
1349128	NM_001244008.2(KIF1A):c.173C>G (p.Ser58Trp)	Pathogenic
1395436	NM_001244008.2(KIF1A):c.785_798+1del	Pathogenic
1413300	NM_001244008.2(KIF1A):c.361C>T (p.Gln121Ter)	Pathogenic
1439490	NM_001244008.2(KIF1A):c.4529del (p.Pro1510fs)	Pathogenic
1451452	NM_001244008.2(KIF1A):c.2389G>T (p.Glu797Ter)	Pathogenic
1451736	NM_001244008.2(KIF1A):c.864+1del	Pathogenic
1452132	NM_001244008.2(KIF1A):c.1031C>T (p.Thr344Met)	Pathogenic
1454352	NM_001244008.2(KIF1A):c.919C>T (p.Arg307Ter)	Pathogenic
1456633	NM_001244008.2(KIF1A):c.2270_2271del (p.Gln757fs)	Pathogenic
1459290	NM_001244008.2(KIF1A):c.4624del (p.Leu1542fs)	Pathogenic
1460332	NC_000002.11:g.(?241676460)(241686758_?)del	Pathogenic
162057	NM_001244008.2(KIF1A):c.643A>C (p.Ser215Arg)	Pathogenic
162059	NM_001244008.2(KIF1A):c.757G>A (p.Glu253Lys)	Pathogenic
1685908	NM_001244008.2(KIF1A):c.653A>G (p.His218Arg)	Pathogenic
1709861	NM_001244008.2(KIF1A):c.798+1G>C	Pathogenic
1711083	NM_001244008.2(KIF1A):c.812_817del (p.Ile271_Asn272del)	Pathogenic
1801064	NM_001244008.2(KIF1A):c.835G>C (p.Gly279Arg)	Pathogenic
1937691	NM_001244008.2(KIF1A):c.5014C>T (p.Arg1672Ter)	Pathogenic
1962714	NM_001244008.2(KIF1A):c.4700_4701del (p.Glu1567fs)	Pathogenic
2031536	NM_001244008.2(KIF1A):c.200dup (p.Tyr67Ter)	Pathogenic
2098196	NM_001244008.2(KIF1A):c.751G>A (p.Gly251Arg)	Pathogenic
2105634	NM_001244008.2(KIF1A):c.3074_3075dup (p.Cys1027fs)	Pathogenic
2127421	NM_001244008.2(KIF1A):c.2451del (p.Leu818fs)	Pathogenic
2134284	NM_001244008.2(KIF1A):c.1693dup (p.Thr565fs)	Pathogenic
224157	NM_001244008.2(KIF1A):c.265T>G (p.Tyr89Asp)	Pathogenic

SpliceAI

9186 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240718045:CCTA:C	donor_loss	1.0000
2:240718047:TA:T	donor_loss	1.0000
2:240718048:A:AC	donor_gain	1.0000
2:240718048:A:AT	donor_loss	1.0000
2:240718049:C:CC	donor_gain	1.0000
2:240718049:CCGTA:C	donor_loss	1.0000
2:240718085:CAG:C	donor_gain	1.0000
2:240718101:T:TA	donor_gain	1.0000
2:240718164:GGTGT:G	acceptor_gain	1.0000
2:240718165:GTGT:G	acceptor_gain	1.0000
2:240718166:TGT:T	acceptor_gain	1.0000
2:240718167:GT:G	acceptor_gain	1.0000
2:240718168:TCTGC:T	acceptor_loss	1.0000
2:240718169:C:CA	acceptor_loss	1.0000
2:240718169:C:CC	acceptor_gain	1.0000
2:240718170:T:C	acceptor_loss	1.0000
2:240719001:CGCA:C	donor_loss	1.0000
2:240719002:GCAC:G	donor_loss	1.0000
2:240719004:ACCT:A	donor_loss	1.0000
2:240719005:C:CG	donor_loss	1.0000
2:240719030:A:AC	donor_gain	1.0000
2:240719031:C:CC	donor_gain	1.0000
2:240719031:CTGTA:C	donor_gain	1.0000
2:240719195:CGGG:C	acceptor_gain	1.0000
2:240719770:ACACC:A	donor_loss	1.0000
2:240719772:ACCT:A	donor_loss	1.0000
2:240719773:C:A	donor_loss	1.0000
2:240719773:CCTGA:C	donor_gain	1.0000
2:240721802:CCCA:C	donor_loss	1.0000
2:240721803:CCAC:C	donor_loss	1.0000

AlphaMissense

11741 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240718053:A:T	I1676K	1.000
2:240718086:A:G	L1665P	1.000
2:240718090:A:G	W1664R	1.000
2:240718090:A:T	W1664R	1.000
2:240718155:A:G	F1642S	1.000
2:240723482:C:A	W1364C	1.000
2:240723482:C:G	W1364C	1.000
2:240723484:A:G	W1364R	1.000
2:240723484:A:T	W1364R	1.000
2:240723505:C:G	G1357R	1.000
2:240726915:A:G	W1244R	1.000
2:240726915:A:T	W1244R	1.000
2:240743990:C:T	G1078D	1.000
2:240745434:A:T	V1052D	1.000
2:240745490:G:C	F1033L	1.000
2:240745490:G:T	F1033L	1.000
2:240745491:A:G	F1033S	1.000
2:240745492:A:G	F1033L	1.000
2:240745740:G:C	F1023L	1.000
2:240745740:G:T	F1023L	1.000
2:240745741:A:G	F1023S	1.000
2:240745742:A:G	F1023L	1.000
2:240745749:G:C	F1020L	1.000
2:240745749:G:T	F1020L	1.000
2:240745751:A:G	F1020L	1.000
2:240745789:A:G	L1007P	1.000
2:240745792:A:T	V1006D	1.000
2:240745804:A:G	F1002S	1.000
2:240747270:G:T	A909D	1.000
2:240750443:A:T	V887D	1.000

dbSNP variants (sampled 300 via entrez): RS1000009387 (2:240761104 G>A,T), RS1000041763 (2:240739981 G>A,T), RS1000073004 (2:240739649 G>A), RS1000116607 (2:240754552 T>C), RS1000123422 (2:240779897 C>A), RS1000139461 (2:240814986 A>C), RS1000170482 (2:240736417 C>T), RS1000173114 (2:240791897 A>C), RS1000175256 (2:240779701 C>A), RS1000182558 (2:240744615 C>G,T), RS1000196454 (2:240775936 A>G), RS1000222795 (2:240736565 C>A,T), RS1000228318 (2:240811414 T>C), RS1000277195 (2:240749585 G>A), RS1000306287 (2:240806130 A>C)

Disease associations

OMIM: gene MIM:601255 | disease phenotypes: MIM:614213, MIM:614255, MIM:201300, MIM:108600, MIM:303350, MIM:620607, MIM:610357, MIM:260565, MIM:145290, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
neuropathy, hereditary sensory, type 2C	Definitive	Autosomal recessive
intellectual disability, autosomal dominant 9	Definitive	Autosomal dominant
syndromic intellectual disability	Definitive	Autosomal dominant
hereditary spastic paraplegia 30	Strong	Autosomal dominant
spastic paraplegia 30A, autosomal dominant	Strong	Autosomal dominant
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant
PEHO syndrome	Supportive	Autosomal dominant
hereditary sensory and autonomic neuropathy type 2	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (18): hereditary spastic paraplegia 30 (MONDO:0012476), neuropathy, hereditary sensory, type 2C (MONDO:0013634), intellectual disability, autosomal dominant 9 (MONDO:0013656), neuropathy, hereditary sensory and autonomic, type 2A (MONDO:0024309), spastic ataxia (MONDO:0017845), hereditary spastic paraplegia (MONDO:0019064), KIF1A related neurological disorder (MONDO:0700055), spastic paraplegia 30B, autosomal recessive (MONDO:0971149), spastic paraplegia 30A, autosomal dominant (MONDO:0700307), syndromic intellectual disability (MONDO:0000508), PEHO syndrome (MONDO:0009841), intellectual disability (MONDO:0001071), hereditary ataxia (MONDO:0100309), Charcot-Marie-Tooth disease type 2 (MONDO:0018993), hyperreflexia (MONDO:0007774)

Orphanet (13): Autosomal spastic paraplegia type 30 (Orphanet:101010), NESCAV syndrome (Orphanet:662367), Hereditary sensory and autonomic neuropathy type 2 (Orphanet:970), Spastic ataxia (Orphanet:316226), Hereditary spastic paraplegia (Orphanet:685), Rare genetic syndromic intellectual disability (Orphanet:183763), PEHO syndrome (Orphanet:2836), PEHO-like syndrome (Orphanet:99807), Hereditary ataxia (Orphanet:183518), Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746), Autosomal dominant non-syndromic intellectual disability (Orphanet:178469), Craniosynostosis (Orphanet:1531), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

100 total (30 of 100 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000224	Hypogeusia
HP:0000252	Microcephaly
HP:0000570	Abnormal saccadic eye movements
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0000762	Decreased nerve conduction velocity
HP:0000970	Anhidrosis
HP:0000975	Hyperhidrosis
HP:0001069	Episodic hyperhidrosis
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001310	Dysmetria
HP:0001324	Muscle weakness
HP:0001344	Absent speech
HP:0001347	Hyperreflexia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008839_196	Height	5.000000e-10
GCST009276_3	Response to placebo treatment in childhood asthma (FVC change)	6.000000e-06
GCST012227_980	Hip circumference adjusted for BMI	3.000000e-08
GCST90020028_709	Hip circumference adjusted for BMI	2.000000e-08
GCST90020028_723	Hip circumference adjusted for BMI	7.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008344	response to placebo
EFO:0010339	FVC change measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (8)

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
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D012021	Reflex, Abnormal	C10.597.704; C23.888.592.717; E01.370.376.550.650.655; E01.370.600.550.650.655; G11.561.731.587
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
C531684	Hereditary spinal ataxia (supp.)
C536317	PEHO syndrome (supp.)
C564815	Spastic Ataxia (supp.)
C563677	Spastic Paraplegia 30, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3308914 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
propionaldehyde	increases expression	2
bisphenol A	decreases methylation, increases expression	2
butyraldehyde	increases expression	2
pentanal	increases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
terbufos	increases methylation	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
mercuric bromide	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Troglitazone	increases expression	1
Vorinostat	decreases expression	1
Dactinomycin	increases expression	1
Daunorubicin	affects response to substance	1
Diethylnitrosamine	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1226591	Binding	Inhibition of Kif1A at 10 uM by puruvate kinsase-lactate dehydrogenase detection system	ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism. — Nat Chem Biol

Cellosaurus cell lines

8 cell lines: 7 induced pluripotent stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2TN	GM27933	Induced pluripotent stem cell	Female
CVCL_A2TP	GM27934	Induced pluripotent stem cell	Male
CVCL_A2TQ	GM27935	Induced pluripotent stem cell	Male
CVCL_A2TR	GM27936	Induced pluripotent stem cell	Male
CVCL_A5MP	GM27937	Induced pluripotent stem cell	Female
CVCL_D2ZN	GM28967	Induced pluripotent stem cell	Female
CVCL_JF42	GM25994	Finite cell line	Female
CVCL_YT38	SDUBMSi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
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
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
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
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
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04297891	Not specified	UNKNOWN	Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia