KIF17

Summary

KIF17 (kinesin family member 17, HGNC:19167) is a protein-coding gene on chromosome 1p36.12, encoding Kinesin-like protein KIF17 (Q9P2E2). Together with RAB23 and IFT57, it is required for the localization of specific G protein-coupled receptors, such as dopamime receptor DRD1, to primary cilia.

Predicted to enable ATP hydrolysis activity; microtubule binding activity; and plus-end-directed microtubule motor activity. Predicted to be involved in anterograde dendritic transport of neurotransmitter receptor complex and cell projection organization. Predicted to act upstream of or within microtubule-based process; protein-containing complex localization; and vesicle-mediated transport. Predicted to be located in cytosol. Predicted to be part of kinesin complex. Predicted to be active in several cellular components, including cilium; microtubule cytoskeleton; and postsynapse.

Source: NCBI Gene 57576 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microphthalmia, isolated, with coloboma (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 227 total — 1 pathogenic
• MANE Select transcript: NM_001122819

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19167
Approved symbol	KIF17
Name	kinesin family member 17
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1405, KIF3X, KIF17B, OSM-3, KLP-2
Ensembl gene	ENSG00000117245
Ensembl biotype	protein_coding
OMIM	605037
Entrez	57576

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding_CDS_not_defined, 5 protein_coding

ENST00000247986, ENST00000375044, ENST00000400463, ENST00000462858, ENST00000463389, ENST00000477167, ENST00000490034, ENST00000493818, ENST00000498225, ENST00000939125, ENST00000939126

RefSeq mRNA: 3 — MANE Select: NM_001122819 NM_001122819, NM_001287212, NM_020816

CCDS: CCDS213, CCDS44079, CCDS72722

Canonical transcript exons

ENST00000400463 — 15 exons

Exon	Start	End
ENSE00000756272	20687388	20687944
ENSE00000756295	20698379	20698488
ENSE00001281615	20704447	20704899
ENSE00001361633	20709639	20709828
ENSE00001361634	20713454	20713555
ENSE00001891922	20717476	20718007
ENSE00003462146	20684809	20685020
ENSE00003471522	20666214	20666331
ENSE00003476161	20671938	20672196
ENSE00003522161	20715493	20715639
ENSE00003583865	20670421	20670488
ENSE00003631001	20682653	20682884
ENSE00003641975	20664014	20664762
ENSE00003649528	20690188	20690335
ENSE00003668142	20686046	20686126

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 90.93.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7394 / max 49.7362, expressed in 338 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10776	0.7578	149
10771	0.3628	98
10774	0.1955	109
10775	0.1832	82
10778	0.0574	17
10779	0.0522	26
10777	0.0403	10
10772	0.0395	21
10770	0.0372	18
10773	0.0136	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	90.93	gold quality
right testis	UBERON:0004534	90.82	gold quality
right adrenal gland cortex	UBERON:0035827	88.41	gold quality
left adrenal gland	UBERON:0001234	88.13	gold quality
right adrenal gland	UBERON:0001233	88.03	gold quality
spleen	UBERON:0002106	87.95	gold quality
testis	UBERON:0000473	87.63	gold quality
left adrenal gland cortex	UBERON:0035825	87.57	gold quality
adrenal cortex	UBERON:0001235	85.86	gold quality
adrenal gland	UBERON:0002369	85.39	gold quality
right frontal lobe	UBERON:0002810	85.20	gold quality
prefrontal cortex	UBERON:0000451	85.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.65	gold quality
apex of heart	UBERON:0002098	83.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.44	gold quality
right uterine tube	UBERON:0001302	82.12	gold quality
cingulate cortex	UBERON:0003027	81.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.56	gold quality
anterior cingulate cortex	UBERON:0009835	81.35	gold quality
frontal cortex	UBERON:0001870	81.30	gold quality
neocortex	UBERON:0001950	80.24	gold quality
adrenal tissue	UBERON:0018303	80.07	gold quality
nucleus accumbens	UBERON:0001882	79.23	gold quality
right lung	UBERON:0002167	78.90	gold quality
caudate nucleus	UBERON:0001873	78.54	gold quality
cerebral cortex	UBERON:0000956	77.82	gold quality
putamen	UBERON:0001874	77.09	gold quality
telencephalon	UBERON:0001893	76.94	gold quality
amygdala	UBERON:0001876	76.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFE2L2, NRF1

miRNA regulators (miRDB)

27 targeting KIF17, 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-12118	100.00	65.88	1270
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Literature-anchored findings (GeneRIF, showing 12)

• KIF17b serves as a molecular motor component of a TB-RBP-mouse ribonucleoprotein complex transporting a group of specific CREM-regulated mRNAs. (PMID:14673085)
• The intense placental expression of KIFC1 in syncytiotrophoblast and KIF17 in vascular endothelium suggests that both proteins might be important in a cargo-transport system. KIFC1 and KIF17 expression are increased of both in preeclamptia and diabetes. (PMID:19679349)
• Data show that the homodimeric kinesin-2 motor KIF17 is kept in an inactive state in the absence of cargo, and define two molecular mechanisms that contribute to autoinhibition of KIF17. (PMID:20530208)
• This study suggested that disruption of KIF17, although rare, could result in a schizophrenia phenotype and emphasize the possible involvement of rare de novo mutations in this disorder. (PMID:20646681)
• Depletion of KIF17 from cells growing in three-dimensional matrices results in aberrant epithelial cysts that fail to generate a single central lumen and to polarize apical markers. (PMID:20696710)
• although EB1 and KIF17-Tail may coordinate KIF17 catalytic activity, our data reveal a novel and direct role for KIF17 in regulating MT dynamics. (PMID:24072717)
• Expression of KIF17 in schizophrenic postmortem brains was significantly lower than controls. Both genotypic distribution and allelic frequency of rs2296225 polymorphism were significantly different between the chronic schizophrenia subjects and controls. (PMID:26421900)
• KIF17 can modify RhoA-GTPase signaling to influence junctional actin and the stability of the apical junctional complex of epithelial cells. (PMID:26759174)
• The first evidence of an interaction between septins and a nonmitotic kinesin is provided and it is suggested that SEPT9 modulates the interactions of KIF17 with membrane cargo. (PMID:26823018)
• In mammalian cells, KIF17 is dispensable for ciliogenesis and IFT-B trafficking but requires IFT-B, as well as its NLS, for its ciliary entry across the permeability barrier located at the ciliary base. (PMID:28077622)
• 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)
• Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum. (PMID:33922911)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif17	ENSDARG00000055238
mus_musculus	Kif17	ENSMUSG00000028758
rattus_norvegicus	Kif17	ENSRNOG00000014970
drosophila_melanogaster	Kif3C	FBGN0039925
caenorhabditis_elegans		WBGENE00003884

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF22 (ENSG00000079616), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF3B (ENSG00000101350), KIF20A (ENSG00000112984), KIF21B (ENSG00000116852), 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 KIF17 — Q9P2E2 (reviewed: Q9P2E2)

Alternative names: KIF3-related motor protein

All UniProt accessions (2): Q9P2E2, A0A0A0MRS8

UniProt curated annotations — full annotation on UniProt →

Function. Together with RAB23 and IFT57, it is required for the localization of specific G protein-coupled receptors, such as dopamime receptor DRD1, to primary cilia. In association with the Apba1-containing complex (LIN-10-LIN-2-LIN-7 complex), transports vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules.

Subunit / interactions. Homodimer. Interacts with APBA1 (via PDZ domain); the interaction is direct and is required for association of KIF17 with the cargo that is to be transported. Interacts with IFT B complex components IFT52 and IFT57. Interacts with IFT70B. Interacts with PIWIL1. Interacts with TBATA. Interacts with RAB23.

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

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P2E2-1	1, KIF17b	yes
Q9P2E2-3	2

RefSeq proteins (3): NP_001116291, NP_001274141, NP_065867 (=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 (21 total): sequence variant 6, region of interest 4, sequence conflict 2, coiled-coil region 2, compositionally biased region 2, chain 1, domain 1, binding site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2E2-F1	64.81	0.22

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): 91–98

Mutagenesis-validated functional residues (1):

Position	Phenotype
234	reduced localization of drd1 to primary cilia.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-442755	Activation of NMDA receptors and postsynaptic events
R-HSA-5617833	Cilium Assembly

MSigDB gene sets: 149 (showing top): GOBP_AXO_DENDRITIC_TRANSPORT, GOCC_KINESIN_COMPLEX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_MICROTUBULE_ORGANIZING_CENTER, CREB_Q4, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, MORF_BMPR2, SAKAI_TUMOR_INFILTRATING_MONOCYTES_UP, AFFAR_YY1_TARGETS_UP, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, ETF_Q6, GOCC_CYTOPLASMIC_REGION

GO Biological Process (7): protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), cell projection organization (GO:0030030), protein-containing complex localization (GO:0031503), anterograde dendritic transport of neurotransmitter receptor complex (GO:0098971), microtubule-based process (GO:0007017), microtubule-based movement (GO:0007018)

GO Molecular Function (6): 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)

GO Cellular Component (19): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), cilium (GO:0005929), axoneme (GO:0005930), photoreceptor connecting cilium (GO:0032391), dendrite cytoplasm (GO:0032839), ciliary basal body (GO:0036064), neuron projection (GO:0043005), postsynapse (GO:0098794), periciliary membrane compartment (GO:1990075), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630), dendrite (GO:0030425), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1
Activation of NMDA receptors and postsynaptic events	1
Transmission across Chemical Synapses	1
Neuronal System	1
Neurotransmitter receptors and postsynaptic signal transmission	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
transport	2
cellular process	2
ATP-dependent activity	2
photoreceptor cell cilium	2
microtubule cytoskeleton	2
plasma membrane bounded cell projection	2
cytoskeleton	2
intracellular protein localization	1
establishment of protein localization	1
cellular component organization	1
macromolecule localization	1
receptor localization to synapse	1
anterograde dendritic transport	1
microtubule-based process	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
intracellular anatomical structure	1
cytoplasm	1
microtubule associated complex	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
microtubule	1
ciliary plasm	1
ciliary transition zone	1
dendrite	1
neuron projection cytoplasm	1
microtubule organizing center	1
cilium	1
synapse	1
plasma membrane region	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF17	APBA1	Q02410	956
KIF17	GRIN2B	Q13224	955
KIF17	LIN7A	O14910	846
KIF17	CASK	O14936	846
KIF17	TNPO1	Q92973	822
KIF17	SEPTIN9	Q9UHD8	822
KIF17	CREM	Q03060	791
KIF17	IFT88	Q13099	770
KIF17	IFT46	Q9NQC8	757
KIF17	PIWIL1	Q96J94	742
KIF17	IFT56	A0AVF1	740
KIF17	FHL5	Q5TD97	704
KIF17	KIFAP3	Q92845	698
KIF17	IFT52	Q9Y366	679
KIF17	APBA2	Q99767	647

IntAct

136 interactions, top by confidence:

A	B	Type	Score
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
KIF17	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
DLG2	KIF17	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI3	KIF17	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	RAPGEF6	psi-mi:“MI:0407”(direct interaction)	0.440
LIN7B	KIF17	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	HTRA2	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	KIF17	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
KIF17	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (7): KIF17 (Affinity Capture-MS), KIF17 (Affinity Capture-MS), KIF17 (Affinity Capture-MS), KIF17 (Two-hybrid), KIF17 (Two-hybrid), KIF17 (Two-hybrid), KIF17 (Two-hybrid)

ESM2 similar proteins: A3KMI0, A3KQS4, A5PF44, A6QP16, A8E7C5, B1H2Q2, F4HZF0, O15226, O96838, P34550, Q09874, Q29FC1, Q2KI23, Q2KJ22, Q3SWY8, Q3T9Z9, Q3V0G7, Q4R4A2, Q5BJQ2, Q5R7G8, Q5U2S3, Q5VVW2, Q5XHY7, Q61502, Q6NZC7, Q6P158, Q6P5D3, Q6PDI6, Q6PGC1, Q75E61, Q76LS9, Q7M760, Q7TSI3, Q7XI08, Q7Z478, Q8C437, Q8GY87, Q8H106, Q8N5J2, Q8NBR6

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

1 interactions.

A	Effect	B	Mechanism
KIF17	up-regulates	“Plus-end directed sliding movement”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Ras activation upon Ca2+ influx through NMDA receptor	5	50.1×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	47.7×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	47.7×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	44.5×	1e-12
Dopamine Neurotransmitter Release Cycle	5	43.5×	2e-06
Long-term potentiation	5	41.7×	3e-06
Neurexins and neuroligins	11	38.0×	7e-13
Protein-protein interactions at synapses	7	32.6×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	70.9×	4e-14
protein localization to synapse	6	56.0×	1e-07
receptor clustering	7	53.3×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	42.3×	4e-08
protein-containing complex assembly	9	12.5×	3e-06
cell-cell adhesion	10	12.4×	7e-07
chemical synaptic transmission	7	6.6×	3e-03
protein transport	8	4.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	180
Likely benign	19
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3242274	GRCh37/hg19 1p36.32-36.12(chr1:4436802-22782007)x2	Pathogenic

SpliceAI

2853 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20666210:TCACT:T	donor_loss	1.0000
1:20666211:CACT:C	donor_loss	1.0000
1:20666212:A:AC	donor_gain	1.0000
1:20666212:A:T	donor_loss	1.0000
1:20666213:C:CA	donor_loss	1.0000
1:20666213:C:CC	donor_gain	1.0000
1:20666213:CT:C	donor_gain	1.0000
1:20666213:CTG:C	donor_gain	1.0000
1:20666213:CTGA:C	donor_gain	1.0000
1:20666213:CTGAG:C	donor_gain	1.0000
1:20666223:T:TA	donor_gain	1.0000
1:20667666:A:C	acceptor_gain	1.0000
1:20667695:A:T	acceptor_gain	1.0000
1:20670489:CTG:C	acceptor_gain	1.0000
1:20671937:CCTA:C	donor_gain	1.0000
1:20671940:A:AC	donor_gain	1.0000
1:20671941:C:CT	donor_gain	1.0000
1:20671980:T:TA	donor_gain	1.0000
1:20672015:CG:C	donor_gain	1.0000
1:20672192:CGAAG:C	acceptor_gain	1.0000
1:20672193:GAAG:G	acceptor_gain	1.0000
1:20672194:AAG:A	acceptor_gain	1.0000
1:20672195:AG:A	acceptor_gain	1.0000
1:20672197:C:CC	acceptor_gain	1.0000
1:20682647:CCTCA:C	donor_loss	1.0000
1:20682649:TCACC:T	donor_loss	1.0000
1:20682650:CACC:C	donor_loss	1.0000
1:20682651:A:C	donor_loss	1.0000
1:20682651:ACCTT:A	donor_gain	1.0000
1:20682652:C:G	donor_loss	1.0000

AlphaMissense

6713 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:20704848:A:G	L241P	1.000
1:20704575:G:T	A332D	0.999
1:20704584:G:T	A329D	0.999
1:20704593:A:G	L326P	0.999
1:20704637:G:C	C311W	0.999
1:20704641:G:T	A310D	0.999
1:20704650:A:G	L307P	0.999
1:20704770:A:G	L267P	0.999
1:20704770:A:T	L267H	0.999
1:20704776:A:G	L265P	0.999
1:20704778:G:C	N264K	0.999
1:20704778:G:T	N264K	0.999
1:20704838:G:C	S244R	0.999
1:20704838:G:T	S244R	0.999
1:20704840:T:G	S244R	0.999
1:20704843:C:G	G243R	0.999
1:20704848:A:T	L241Q	0.999
1:20715581:T:A	K97M	0.999
1:20715599:C:A	G91V	0.999
1:20715599:C:T	G91D	0.999
1:20715600:C:G	G91R	0.999
1:20672165:A:G	L832P	0.998
1:20704578:C:G	R331P	0.998
1:20704585:C:G	A329P	0.998
1:20704590:C:G	R327P	0.998
1:20704647:A:C	M308R	0.998
1:20704647:A:T	M308K	0.998
1:20704683:A:G	L296P	0.998
1:20704749:A:T	I274N	0.998
1:20704758:C:T	G271D	0.998

dbSNP variants (sampled 300 via entrez): RS1000014120 (1:20702703 A>G), RS1000046022 (1:20665798 C>G,T), RS1000130630 (1:20717062 G>A,C), RS1000180022 (1:20689278 A>G), RS1000270889 (1:20688270 G>A,C,T), RS1000317688 (1:20713842 G>A,C), RS1000352698 (1:20678880 C>T), RS1000423408 (1:20663383 T>G), RS1000457130 (1:20684100 G>A), RS1000464525 (1:20679951 T>C,G), RS1000492454 (1:20662908 A>G), RS1000646534 (1:20715086 C>T), RS1000663803 (1:20695282 G>C), RS1000770161 (1:20672941 G>T), RS1000879740 (1:20697596 C>A,G,T)

Disease associations

OMIM: gene MIM:605037 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
microphthalmia, isolated, with coloboma	Limited	Autosomal recessive
schizophrenia	No Known Disease Relationship	Unknown

Mondo (2): schizophrenia (MONDO:0005090), microphthalmia, isolated, with coloboma (MONDO:0000170)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010121_1	Ceramide levels (C24:0)	2.000000e-07
GCST010916_1	Proportion of activated microglia (inferior temporal cortex)	6.000000e-06
GCST011773_22	Type 1 diabetes (age at diagnosis)	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004918	age at diagnosis

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537463	Microphthalmia associated with colobomatous cyst (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
bufotalin	increases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenate	increases abundance, increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
tebuconazole	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Amiodarone	increases expression	1
Arsenic	increases abundance, increases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety