KIF3B

Summary

KIF3B (kinesin family member 3B, HGNC:6320) is a protein-coding gene on chromosome 20q11.21, encoding Kinesin-like protein KIF3B (O15066). Microtubule-based molecular motor that transport intracellular cargos, such as vesicles, organelles and protein complexes.

The protein encoded by this gene acts as a heterodimer with kinesin family member 3A to aid in chromosome movement during mitosis and meiosis. The encoded protein is a plus end-directed microtubule motor and can interact with the SMC3 subunit of the cohesin complex. In addition, the encoded protein may be involved in the intracellular movement of membranous organelles. This protein and kinesin family member 3A form the kinesin II subfamily of the kinesin superfamily.

Source: NCBI Gene 9371 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 89 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 92 total — 2 pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes
• MANE Select transcript: NM_004798

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6320
Approved symbol	KIF3B
Name	kinesin family member 3B
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0359, FLA8, KLP-11
Ensembl gene	ENSG00000101350
Ensembl biotype	protein_coding
OMIM	603754
Entrez	9371

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000375712, ENST00000929131, ENST00000929132

RefSeq mRNA: 1 — MANE Select: NM_004798 NM_004798

CCDS: CCDS13200

Canonical transcript exons

ENST00000375712 — 9 exons

Exon	Start	End
ENSE00000661193	32316218	32316319
ENSE00000661194	32316527	32316649
ENSE00000661195	32316756	32316874
ENSE00000661196	32326771	32326884
ENSE00000661197	32327556	32327661
ENSE00000661198	32330141	32330319
ENSE00001180424	32277651	32277765
ENSE00001468136	32309713	32311181
ENSE00001922694	32331223	32335011

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 96.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9001 / max 301.4259, expressed in 1773 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184032	12.2711	1769
184033	0.6291	340

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	96.18	gold quality
cortical plate	UBERON:0005343	95.82	gold quality
islet of Langerhans	UBERON:0000006	95.79	gold quality
sperm	CL:0000019	95.74	gold quality
male germ cell	CL:0000015	94.27	gold quality
bronchial epithelial cell	CL:0002328	93.81	gold quality
renal medulla	UBERON:0000362	93.70	gold quality
jejunal mucosa	UBERON:0000399	93.23	gold quality
secondary oocyte	CL:0000655	93.00	gold quality
epithelium of bronchus	UBERON:0002031	92.98	gold quality
bronchus	UBERON:0002185	92.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.78	gold quality
parietal lobe	UBERON:0001872	92.60	gold quality
superior frontal gyrus	UBERON:0002661	92.51	gold quality
cerebellar vermis	UBERON:0004720	92.28	gold quality
entorhinal cortex	UBERON:0002728	92.20	gold quality
postcentral gyrus	UBERON:0002581	92.16	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.13	gold quality
epithelium of nasopharynx	UBERON:0001951	91.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.96	gold quality
occipital lobe	UBERON:0002021	91.65	gold quality
ventral tegmental area	UBERON:0002691	91.52	gold quality
parietal pleura	UBERON:0002400	91.28	gold quality
primary visual cortex	UBERON:0002436	91.25	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.12	gold quality
prefrontal cortex	UBERON:0000451	91.05	gold quality
ileal mucosa	UBERON:0000331	91.01	gold quality
lateral globus pallidus	UBERON:0002476	90.95	gold quality
frontal cortex	UBERON:0001870	90.71	gold quality
temporal lobe	UBERON:0001871	90.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.50
E-GEOD-83139	no	2.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

238 targeting KIF3B, 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-4262	100.00	73.26	3931
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 19)

• both motor domains of KIF3A/B coordinate for processive motility and move at different speeds (PMID:15345558)
• Interaction of KIF3A/3B with KAP3 may be important for the proper progression of mitosis. (PMID:16298999)
• kinesin-2 is a linker between polycystin-2(PC2) and fibrocystin and mediates the regulation of PC2 channel function by fibrocystin (PMID:17008358)
• Rip11/FIP5-kinesin-II complex plays a key role in the routing of internalized receptors through the perinuclear recycling endosomes. (PMID:18957512)
• Data indicate that p0071 and Ect2 are transported via distinct motors and identify a novel pathway implicating KIF3 in the regulation of actin organization during cytokinesis (PMID:19339549)
• Interaction with KIF3B alters CLC-5 cell surface expression, chloride current, and alters albumin endocytosis. Interaction with KIF3B facilitates microtubular transport and endocytosis of CLC-5-containing vesicles away from cell surface. (PMID:19940036)
• KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney alpha-intercalated cells. (PMID:21871436)
• Results suggest that KIF3B expression was upregulated in HCC tumor tissues and proliferating HCC cells, and an increasd KIF3B expression was associated with poor overall survival. (PMID:24368420)
• These data suggest that GLI interactions with KIF3A-KIF3B-KAP3 complexes are essential for proper GLI transcriptional activity. (PMID:25588831)
• High KIF3B expression is associated with seminoma. (PMID:28161539)
• The rate of transport is set by an equilibrium between a faster state, where only kinesin family member 17 protein (KIF17) motors move the train, and a slower state, where at least one kinesin family member 3A/B protein (KIF3AB) motor on the train remains active in transport. (PMID:28761002)
• miR-127-3p was downregulated in oral squamous cell carcinoma (OSCC) tissues and was associated with malignant clinicopathological features and poor prognosis. KIF3B was confirmed to be a direct target of miR-127-3p. Upregulation of KIF3B observed in OSCC promoted tumorigenesis. miR-127-3p targeted KIF3B to inhibit the development of OSCC by suppressing cell proliferation, migration and invasion. (PMID:30720171)
• High KIF3B expression is associated with Pancreatic Cancer. (PMID:31157987)
• Kif3b mutation reduces NMDAR subunit NR2A trafficking and causes schizophrenia. (PMID:31746486)
• LEF-AS1 participates in occurrence of colorectal cancer through adsorbing miR-505 and promoting KIF3B expression. (PMID:31773695)
• Identification of kinesin family member 3B (KIF3B) as a molecular target for gastric cancer. (PMID:32237034)
• Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy. (PMID:32386558)
• Circular RNA circ_0032462 Enhances Osteosarcoma Cell Progression by Promoting KIF3B Expression. (PMID:33153390)
• KIF3B gene silent variant leading to sperm morphology and motility defects and male infertilitydagger. (PMID:34918036)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif3b	ENSDARG00000101120
mus_musculus	Kif3b	ENSMUSG00000027475
rattus_norvegicus	Kif3b	ENSRNOG00000010361
drosophila_melanogaster	Klp68D	FBGN0004381
caenorhabditis_elegans		WBGENE00002222

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF22 (ENSG00000079616), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF20A (ENSG00000112984), KIF21B (ENSG00000116852), KIF17 (ENSG00000117245), KIF14 (ENSG00000118193), KIF18A (ENSG00000121621), KIF25 (ENSG00000125337), KIF1C (ENSG00000129250), KIF1A (ENSG00000130294), KIF3A (ENSG00000131437), KIF12 (ENSG00000136883), KIF13A (ENSG00000137177), KIF23 (ENSG00000137807), KIF11 (ENSG00000138160), CENPE (ENSG00000138778), KIF21A (ENSG00000139116), KIFC3 (ENSG00000140859), KIF2B (ENSG00000141200), KIF2C (ENSG00000142945), KIF5A (ENSG00000155980), KIF26B (ENSG00000162849), KIF15 (ENSG00000163808), KIF6 (ENSG00000164627), KIF27 (ENSG00000165115), KIF7 (ENSG00000166813), KIFC2 (ENSG00000167702), KIF5C (ENSG00000168280), KIF5B (ENSG00000170759), KIF18B (ENSG00000186185), KIF24 (ENSG00000186638), KIF19 (ENSG00000196169), KIF13B (ENSG00000197892), KIF4B (ENSG00000226650)

Protein

Protein identifiers

Kinesin-like protein KIF3B — O15066 (reviewed: O15066)

Alternative names: HH0048, Microtubule plus end-directed kinesin motor 3B

All UniProt accessions (1): O15066

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-based molecular motor that transport intracellular cargos, such as vesicles, organelles and protein complexes. Uses ATP hydrolysis to generate force to bind and move along the microtubule. Plays a role in cilia formation. Involved in photoreceptor integrity and opsin trafficking in rod photoreceptors. Transports vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit GRIN2A into neuronal dendrites.

Subunit / interactions. Heterodimer of KIF3A and KIF3B. KIF3A/KIF3B heterodimer interacts with KIFAP3 forming a heterotrimeric (KIF3A/KIF3B/KIFAP3) complex. Interacts directly with IFT20. Interacts with the SMC3 subunit of the cohesin complex. Interacts with FLCN.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Cilium. Dendritic spine.

Disease relevance. Retinitis pigmentosa 89 (RP89) [MIM:618955] A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP89 is an autosomal dominant form associated with features of ciliopathy, including postaxial polydactyly, and renal and hepatic disease. The gene represented in this entry may be involved in disease pathogenesis.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O15066-1	1	yes
O15066-2	2

RefSeq proteins (1): NP_004789* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027640	Kinesin-like_fam	Family
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00225

UniProt features (54 total): helix 15, strand 14, turn 5, compositionally biased region 4, region of interest 3, chain 2, modified residue 2, splice variant 2, sequence variant 2, initiator methionine 1, binding site 1, mutagenesis site 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3B6U	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15066-F1	76.87	0.28

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): 96–103

Post-translational modifications (2): 1, 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
435	does not affect protein stability nor cilia length.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-2132295	MHC class II antigen presentation
R-HSA-5620924	Intraflagellar transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-199991	Membrane Trafficking
R-HSA-5617833	Cilium Assembly
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: 350 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_CHROMOSOME_ORGANIZATION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_KINESIN_COMPLEX, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOMF_GTPASE_BINDING, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_MITOTIC_SPINDLE_ASSEMBLY, GOBP_VESICLE_CYTOSKELETAL_TRAFFICKING, GOBP_ORGANELLE_FISSION

GO Biological Process (15): microtubule-based movement (GO:0007018), mitotic spindle organization (GO:0007052), mitotic centrosome separation (GO:0007100), determination of left/right symmetry (GO:0007368), anterograde axonal transport (GO:0008089), vesicle-mediated transport (GO:0016192), protein-containing complex localization (GO:0031503), positive regulation of cytokinesis (GO:0032467), opsin transport (GO:0036372), intraciliary transport (GO:0042073), cilium assembly (GO:0060271), plus-end-directed vesicle transport along microtubule (GO:0072383), mitotic spindle assembly (GO:0090307), anterograde dendritic transport of neurotransmitter receptor complex (GO:0098971), axo-dendritic transport (GO:0008088)

GO Molecular Function (9): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), plus-end-directed microtubule motor activity (GO:0008574), ATP hydrolysis activity (GO:0016887), small GTPase binding (GO:0031267), intraciliary transport particle B binding (GO:0120170), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (24): cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), kinesin complex (GO:0005871), plus-end kinesin complex (GO:0005873), microtubule (GO:0005874), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), kinesin II complex (GO:0016939), dendrite (GO:0030425), midbody (GO:0030496), dendrite cytoplasm (GO:0032839), dendritic spine (GO:0043197), extracellular exosome (GO:0070062), ciliary tip (GO:0097542), glutamatergic synapse (GO:0098978), axon cytoplasm (GO:1904115), cytoskeleton (GO:0005856), spindle microtubule (GO:0005876), axon (GO:0030424), cell projection (GO:0042995), synapse (GO:0045202), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Membrane Trafficking	2
Adaptive Immune System	1
Assembly of the 9+0 primary cilium	1
Golgi-to-ER retrograde transport	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Vesicle-mediated transport	1
Organelle biogenesis and maintenance	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	5
mitotic nuclear division	2
cilium	2
transport along microtubule	2
cilium organization	2
neuron projection	2
ATP-dependent activity	2
kinesin complex	2
dendrite	2
neuron projection cytoplasm	2
microtubule-based process	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
centrosome separation	1
mitotic cell cycle process	1
determination of bilateral symmetry	1
left/right pattern formation	1
axonal transport	1
axon cytoplasm	1
transport	1
cellular process	1
macromolecule localization	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
protein transport	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
vesicle transport along microtubule	1
plus-end-directed organelle transport along microtubule	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1

Protein interactions and networks

STRING

1354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF3B	KIFAP3	Q92845	998
KIF3B	KIF3A	Q9Y496	984
KIF3B	IFT88	Q13099	863
KIF3B	IFT20	Q8IY31	809
KIF3B	TRIM60	Q495X7	777
KIF3B	IFT46	Q9NQC8	761
KIF3B	ASXL1	Q8IXJ9	752
KIF3B	POFUT1	Q9H488	748
KIF3B	PLAGL2	Q9UPG8	743
KIF3B	RIMBP3	Q9UFD9	743
KIF3B	IFT52	Q9Y366	736
KIF3B	PKP4	Q99569	724
KIF3B	ASXL2	Q76L83	701
KIF3B	IFT56	A0AVF1	688
KIF3B	IFT57	Q9NWB7	686

IntAct

56 interactions, top by confidence:

A	B	Type	Score
KIFAP3	KIF3B	psi-mi:“MI:0914”(association)	0.900
KIF3B	KIFAP3	psi-mi:“MI:0914”(association)	0.900
KIFAP3	KIF3B	psi-mi:“MI:0915”(physical association)	0.900
KIF3A	KIF3B	psi-mi:“MI:0914”(association)	0.840
KIF3A	KIF3C	psi-mi:“MI:0914”(association)	0.730
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
CLCN5	KIF3B	psi-mi:“MI:0915”(physical association)	0.600
KIF3B	CLCN5	psi-mi:“MI:0403”(colocalization)	0.600
ARHGEF10	KIF3B	psi-mi:“MI:0915”(physical association)	0.540
KIF3B	ARHGEF10	psi-mi:“MI:0914”(association)	0.540
KIF3B	ARHGEF10	psi-mi:“MI:0915”(physical association)	0.540
KIFBP	KIF3C	psi-mi:“MI:0914”(association)	0.530
KIF3B	PSMC5	psi-mi:“MI:0914”(association)	0.510
KIF3B	LMO2	psi-mi:“MI:0915”(physical association)	0.370
KIF3B	LMO4	psi-mi:“MI:0915”(physical association)	0.370
Hax1	DERL1	psi-mi:“MI:0914”(association)	0.350
Magoh	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
Homer1	KIF3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): KIF3B (Affinity Capture-RNA), KIF3B (Affinity Capture-RNA), KIF3B (Affinity Capture-MS), KIF3B (Reconstituted Complex), KIF3B (Affinity Capture-Western), KIF3B (Affinity Capture-MS), KIF3B (Affinity Capture-MS), KIF3B (Affinity Capture-MS), KIF3B (Affinity Capture-MS), KIF3B (Affinity Capture-MS), KIF3B (Affinity Capture-MS), KIF3B (Affinity Capture-MS), KIF3B (Affinity Capture-MS), KIF3B (Affinity Capture-MS), KIF3B (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

2 interactions.

A	Effect	B	Mechanism
KIF3B	up-regulates	“Plus-end directed sliding movement”
KIF3B	up-regulates	“Minus-end directed microtubule movement”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	71
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
973171	NM_004798.4(KIF3B):c.748G>C (p.Glu250Gln)	Pathogenic
973172	NM_004798.4(KIF3B):c.1568T>C (p.Leu523Pro)	Pathogenic

SpliceAI

1476 predictions. Top by Δscore:

Variant	Effect	Δscore
20:32277763:CAGGT:C	donor_loss	1.0000
20:32277764:AGG:A	donor_loss	1.0000
20:32277766:GT:G	donor_loss	1.0000
20:32316317:CAG:C	donor_loss	1.0000
20:32316319:GGTA:G	donor_loss	1.0000
20:32316320:G:GC	donor_loss	1.0000
20:32316521:GCTCA:G	acceptor_loss	1.0000
20:32316523:TCA:T	acceptor_loss	1.0000
20:32316524:CA:C	acceptor_loss	1.0000
20:32316526:GAAAC:G	acceptor_gain	1.0000
20:32316647:AAGG:A	donor_loss	1.0000
20:32316650:GT:G	donor_loss	1.0000
20:32316651:T:G	donor_loss	1.0000
20:32316754:A:AC	acceptor_loss	1.0000
20:32316754:A:AG	acceptor_gain	1.0000
20:32316755:G:GA	acceptor_gain	1.0000
20:32316755:GCT:G	acceptor_gain	1.0000
20:32316755:GCTC:G	acceptor_gain	1.0000
20:32316860:G:GT	donor_gain	1.0000
20:32316870:CTCAA:C	donor_gain	1.0000
20:32316871:TCAA:T	donor_gain	1.0000
20:32316872:CAA:C	donor_gain	1.0000
20:32316873:AA:A	donor_gain	1.0000
20:32316874:AGT:A	donor_loss	1.0000
20:32316875:G:GG	donor_gain	1.0000
20:32316875:GT:G	donor_loss	1.0000
20:32326770:GGC:G	acceptor_gain	1.0000
20:32326770:GGCAT:G	acceptor_gain	1.0000
20:32326880:CTGGA:C	donor_gain	1.0000
20:32326881:TGGA:T	donor_gain	1.0000

AlphaMissense

4922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:32310058:C:A	A94D	1.000
20:32310063:G:A	G96R	1.000
20:32310063:G:C	G96R	1.000
20:32310064:G:A	G96E	1.000
20:32310064:G:T	G96V	1.000
20:32310070:C:T	T98I	1.000
20:32310078:G:A	G101R	1.000
20:32310078:G:C	G101R	1.000
20:32310079:G:A	G101E	1.000
20:32310079:G:T	G101V	1.000
20:32310081:A:C	K102Q	1.000
20:32310082:A:T	K102I	1.000
20:32310083:A:C	K102N	1.000
20:32310083:A:T	K102N	1.000
20:32310085:C:T	T103I	1.000
20:32310099:G:A	G108R	1.000
20:32310099:G:C	G108R	1.000
20:32310127:G:A	G117E	1.000
20:32310193:T:C	L139P	1.000
20:32310196:T:A	V140D	1.000
20:32310237:G:C	D154H	1.000
20:32310241:T:G	L155W	1.000
20:32310366:G:A	G197R	1.000
20:32310366:G:C	G197R	1.000
20:32310366:G:T	G197W	1.000
20:32310367:G:A	G197E	1.000
20:32310367:G:T	G197V	1.000
20:32310378:C:A	R201S	1.000
20:32310379:G:C	R201P	1.000
20:32310411:A:C	S212R	1.000

dbSNP variants (sampled 300 via entrez): RS1000111811 (20:32328939 G>A), RS1000133284 (20:32279755 T>C), RS1000201323 (20:32279162 A>G), RS1000213510 (20:32325223 C>A,G), RS1000318471 (20:32321585 G>A), RS1000353805 (20:32332215 T>C), RS1000362712 (20:32285279 G>A), RS1000390326 (20:32306116 C>T), RS1000482885 (20:32279340 G>C), RS1000538663 (20:32277530 C>T), RS1000582547 (20:32323443 A>C), RS1000680993 (20:32330558 G>A), RS1000757294 (20:32323606 T>C), RS1000761435 (20:32305658 C>G), RS1000768978 (20:32277215 C>T)

Disease associations

OMIM: gene MIM:603754 | disease phenotypes: MIM:618955

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 89	Strong	Autosomal dominant
ciliopathy	Moderate	Autosomal dominant

Mondo (5): optic atrophy (MONDO:0003608), retinitis pigmentosa 89 (MONDO:0030071), inherited retinal dystrophy (MONDO:0019118), oligospermia (MONDO:0001913), ciliopathy (MONDO:0005308)

Orphanet (1): OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

15 total (17 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000510	Rod-cone dystrophy
HP:0000662	Nyctalopia
HP:0001133	Constriction of peripheral visual field
HP:0001395	Hepatic fibrosis
HP:0001413	Micronodular cirrhosis
HP:0001433	Hepatosplenomegaly
HP:0001647	Bicuspid aortic valve
HP:0002040	Esophageal varix
HP:0011463	Childhood onset
HP:0025158	Hyperautofluorescent retinal lesion
HP:0030329	Retinal thinning on OCT
HP:0030473	Abnormal light-adapted flicker electroretinogram
HP:0033149	Intrahepatic bile duct dilatation
HP:0100259	Postaxial polydactyly
HP:0000556	Retinal dystrophy
HP:0000798	Oligozoospermia

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004131_132	Inflammatory bowel disease	6.000000e-06
GCST004147_6	Chronic obstructive pulmonary disease	7.000000e-06
GCST004608_142	Granulocyte percentage of myeloid white cells	4.000000e-15
GCST004609_157	Monocyte percentage of white cells	3.000000e-22
GCST007335_32	Age at first sexual intercourse	4.000000e-08
GCST007611_4	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	4.000000e-08
GCST90000047_239	Age at first sexual intercourse	2.000000e-09
GCST90002393_332	Monocyte count	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0009749	age at first sexual intercourse measurement
EFO:0005091	monocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009845	Oligospermia	C12.100.500.430.508; C12.100.750.700.508; C12.200.294.430.508
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6109 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Benzo(a)pyrene	decreases methylation, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
bisphenol F	increases methylation	1
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases 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	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Methyl Methanesulfonate	increases expression	1
Poly I-C	increases expression, affects cotreatment	1
Uranium	affects expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1035571	Binding	Inhibition of Kif3B	Substituted benzimidazoles: A novel chemotype for small molecule hKSP inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT05320536	PHASE4	UNKNOWN	A Clinical Study of Gulingji Capsule in the Treatment of Idiopathic Oligospermia, Asthenia, and Teratozoospermia
NCT06260007	PHASE4	RECRUITING	Efficacy and Safety Study of Products Based on Tribulus Terrestris, L. in Men With Oligospermia
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00440180	PHASE3	TERMINATED	Aromatase Inhibitors in the Treatment of Male Infertility
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01409837	PHASE2	COMPLETED	The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count
NCT02234206	PHASE2	COMPLETED	A Clinical Trial to Study the Safety and Efficacy of Chandrakanthi Choornam in Patients With Low Sperm Count
NCT07481370	PHASE2	ENROLLING_BY_INVITATION	Isotretinoin vs hCG for Male Infertility Due to Low or Absent Sperm
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT05158114	PHASE1	WITHDRAWN	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Testicular Injury and Oligospermia
NCT00068224	Not specified	COMPLETED	Clinical and Molecular Investigations Into Ciliopathies
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	PHASE1/PHASE2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	PHASE1/PHASE2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph
NCT06390579	Not specified	COMPLETED	Building Research With Artificial Intelligence in Neuro-Ophthalmology
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer