DYNC1LI1

Summary

DYNC1LI1 (dynein cytoplasmic 1 light intermediate chain 1, HGNC:18745) is a protein-coding gene on chromosome 3p22.3, encoding Cytoplasmic dynein 1 light intermediate chain 1 (Q9Y6G9). Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function.

The protein encoded by this gene belongs to light intermediate subunit family, whose members are components of the multiprotein cytoplasmic dynein complex, which is involved in intracellular trafficking and chromosome segregation during mitosis. The protein plays a role in moving the spindle assembly checkpoint (SAC) from kinetochores to spindle poles. The protein may also mediate binding to other cargo molecules to facilitate intracellular vesicle trafficking.

Source: NCBI Gene 51143 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 83 total
• Druggable target: yes
• MANE Select transcript: NM_016141

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18745
Approved symbol	DYNC1LI1
Name	dynein cytoplasmic 1 light intermediate chain 1
Location	3p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144635
Ensembl biotype	protein_coding
OMIM	615890
Entrez	51143

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 4 retained_intron

ENST00000273130, ENST00000413350, ENST00000424991, ENST00000432458, ENST00000472985, ENST00000474077, ENST00000475193, ENST00000481915, ENST00000891298, ENST00000891299, ENST00000891300, ENST00000918076, ENST00000954369, ENST00000954370

RefSeq mRNA: 2 — MANE Select: NM_016141 NM_001329135, NM_016141

CCDS: CCDS2654, CCDS87058

Canonical transcript exons

ENST00000273130 — 13 exons

Exon	Start	End
ENSE00000966235	32525974	32526908
ENSE00001134515	32570625	32570858
ENSE00003462499	32541037	32541206
ENSE00003490847	32537011	32537104
ENSE00003507477	32530461	32530520
ENSE00003511101	32544876	32545106
ENSE00003546144	32545849	32545965
ENSE00003546484	32530284	32530328
ENSE00003565423	32570346	32570419
ENSE00003614590	32528446	32528601
ENSE00003634937	32534511	32534646
ENSE00003662188	32532986	32533097
ENSE00003691994	32529540	32529660

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 95.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.1034 / max 444.9620, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41599	47.7688	1825
41600	0.3345	133

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.52	gold quality
monocyte	CL:0000576	95.08	gold quality
heart right ventricle	UBERON:0002080	94.73	gold quality
mononuclear cell	CL:0000842	94.65	gold quality
ganglionic eminence	UBERON:0004023	94.39	gold quality
leukocyte	CL:0000738	94.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.52	gold quality
pons	UBERON:0000988	93.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.08	gold quality
gastrocnemius	UBERON:0001388	93.03	gold quality
ventricular zone	UBERON:0003053	92.87	gold quality
embryo	UBERON:0000922	92.81	gold quality
biceps brachii	UBERON:0001507	92.76	gold quality
muscle of leg	UBERON:0001383	92.74	gold quality
skin of abdomen	UBERON:0001416	92.60	gold quality
dorsal root ganglion	UBERON:0000044	92.45	gold quality
skin of leg	UBERON:0001511	92.41	gold quality
cardiac ventricle	UBERON:0002082	92.36	gold quality
heart left ventricle	UBERON:0002084	92.36	gold quality
substantia nigra pars compacta	UBERON:0001965	92.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.35	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.30	gold quality
skeletal muscle organ	UBERON:0014892	92.27	gold quality
muscle organ	UBERON:0001630	92.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.25	gold quality
zone of skin	UBERON:0000014	92.22	gold quality
deltoid	UBERON:0001476	92.18	silver quality
myocardium	UBERON:0002349	91.92	gold quality
heart	UBERON:0000948	91.74	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	365.56
E-GEOD-134144	yes	27.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting DYNC1LI1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-135A-5P	99.36	71.85	1601

Literature-anchored findings (GeneRIF, showing 11)

• Dynein light intermediate chain 1 is required for progress through the spindle assembly checkpoint (PMID:19229290)
• Rab11a, FIP3 and DLIC-1 form a ternary complex and DLIC-1 colocalises with endogenous FIP3 and Rab11a in A431 cells. (PMID:20026645)
• using a variety of complementary approaches, our results indicate a novel specific role for the LICs in dynein recruitment to components of the late endocytic pathway. (PMID:21169557)
• although dynein lacking light intermediate chains (LICs) drives microtubule gliding at normal rates, the LICs are required for the formation and maintenance of a bipolar spindle. (PMID:25422374)
• This work reveals the structural details of Hook3’s interaction with dynein and offers insight into how cargo adaptors form processive dynein-dynactin motor complexes. (PMID:27482052)
• the DYNC1I1 deficiency, a neuron-specific dynein intermediate chain, causes neuronal atrophy in primary hippocampal neurons. (PMID:27510948)
• conserved mechanism of effector interaction with dynein-dynactin necessary for processive motility (PMID:29515126)
• High DLIC1 expression is associated with colon cancer (PMID:30657258)
• Association between aberrant dynein cytoplasmic 1 light intermediate chain 1 expression levels, mucins and chemosensitivity in colorectal cancer. (PMID:32319648)
• Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes. (PMID:32513296)
• Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions. (PMID:34709360)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dync1li1	ENSDARG00000098317
mus_musculus	Dync1li1	ENSMUSG00000032435
rattus_norvegicus	Dync1li1	ENSRNOG00000010434
drosophila_melanogaster	Dlic	FBGN0030276
caenorhabditis_elegans		WBGENE00001007

Paralogs (1): DYNC1LI2 (ENSG00000135720)

Protein

Protein identifiers

Cytoplasmic dynein 1 light intermediate chain 1 — Q9Y6G9 (reviewed: Q9Y6G9)

Alternative names: Dynein light chain A, Dynein light intermediate chain 1, cytosolic

All UniProt accessions (4): Q9Y6G9, C9JGM7, C9JLW1, E9PHI6

UniProt curated annotations — full annotation on UniProt →

Function. Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes. Probably involved in the microtubule-dependent transport of pericentrin. Is required for progress through the spindle assembly checkpoint. The phosphorylated form appears to be involved in the selective removal of MAD1L1 and MAD1L2 but not BUB1B from kinetochores. Forms a functional Rab11/RAB11FIP3/dynein complex onto endosomal membrane that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC).

Subunit / interactions. Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Self-associates. Interacts with DYNC1H1; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H1. Interacts with PCNT. Forms a complex with RAB11FIP3 and RAB11A1; the interaction between DYNC1LI1 and RAB11FIP3 is direct and induces DYNC1LI1 localization onto endosomal membrane; the complex regulates endocytic trafficking. Interacts with RUFY3. (Microbial infection) Interacts with human adenovirus 5 hexon protein; this interaction probably allows virus intracellular transport.

Subcellular location. Cytoplasm. Chromosome. Centromere. Kinetochore. Cytoskeleton. Spindle pole. Recycling endosome membrane.

Post-translational modifications. Phosphorylated during mitosis but not in interphase.

Similarity. Belongs to the dynein light intermediate chain family.

RefSeq proteins (2): NP_001316064, NP_057225* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008467	Dynein1_light_intermed_chain	Family
IPR022780	Dynein_light_int_chain	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF05783

UniProt features (33 total): modified residue 15, sequence conflict 5, compositionally biased region 5, region of interest 3, sequence variant 2, chain 1, helix 1, binding site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6B9H	X-RAY DIFFRACTION	1.5
6PSE	X-RAY DIFFRACTION	2.4
6PSD	X-RAY DIFFRACTION	2.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6G9-F1	60.63	0.00

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): 74–81

Post-translational modifications (15): 207, 213, 398, 405, 408, 412, 419, 421, 427, 487, 510, 512, 513, 515, 516

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2132295	MHC class II antigen presentation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6798695	Neutrophil degranulation
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-68877	Mitotic Prometaphase
R-HSA-9609690	HCMV Early Events
R-HSA-9646399	Aggrephagy
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 231 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, REACTOME_INNATE_IMMUNE_SYSTEM, WWTAAGGC_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CHROMOSOME_SEPARATION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (6): microtubule cytoskeleton organization (GO:0000226), microtubule-based movement (GO:0007018), cell division (GO:0051301), regulation of vesicle-mediated transport (GO:0060627), obsolete early endosome to recycling endosome transport (GO:0061502), positive regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090267)

GO Molecular Function (8): RNA binding (GO:0003723), ATP binding (GO:0005524), GDP binding (GO:0019003), protein-macromolecule adaptor activity (GO:0030674), dynein heavy chain binding (GO:0045504), molecular adaptor activity (GO:0060090), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (18): kinetochore (GO:0000776), spindle pole (GO:0000922), centrosome (GO:0005813), cytosol (GO:0005829), cytoplasmic dynein complex (GO:0005868), microtubule (GO:0005874), plasma membrane (GO:0005886), membrane (GO:0016020), endocytic vesicle membrane (GO:0030666), secretory granule membrane (GO:0030667), recycling endosome membrane (GO:0055038), ficolin-1-rich granule membrane (GO:0101003), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), endosome (GO:0005768), cytoskeleton (GO:0005856), dynein complex (GO:0030286)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Adaptive Immune System	1
Mitotic Anaphase	1
Cellular responses to stress	1
RHO GTPase Effectors	1
Innate Immune System	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
M Phase	1
HCMV Infection	1
Selective autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	3
microtubule-based process	2
protein binding	2
binding	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
cytoskeleton organization	1
cellular process	1
vesicle-mediated transport	1
regulation of cellular process	1
regulation of transport	1
mitotic spindle assembly checkpoint signaling	1
positive regulation of cell cycle process	1
positive regulation of spindle checkpoint	1
regulation of mitotic cell cycle spindle assembly checkpoint	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
guanyl ribonucleotide binding	1
anion binding	1
molecular adaptor activity	1
molecular_function	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
spindle	1
centriole	1
microtubule organizing center	1
cytoplasm	1
dynein complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
endocytic vesicle	1
secretory granule	1
endosome membrane	1
recycling endosome	1

Protein interactions and networks

STRING

1798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNC1LI1	PCNT	O95613	922
DYNC1LI1	DYNC1H1	Q14204	922
DYNC1LI1	IKBKG	Q9Y6K9	805
DYNC1LI1	BICD2	Q8TD16	789
DYNC1LI1	DYNLRB1	Q9NP97	783
DYNC1LI1	HOOK1	Q9UJC3	762
DYNC1LI1	DYNLL1	P63167	759
DYNC1LI1	RAB11FIP3	O75154	755
DYNC1LI1	DYNC1I1	O14576	740
DYNC1LI1	DYNC1LI2	O43237	732
DYNC1LI1	HOOK3	Q86VS8	716
DYNC1LI1	DYNC1I2	Q13409	697
DYNC1LI1	DCTN6	O00399	685
DYNC1LI1	DYNLT1	P63172	681
DYNC1LI1	RAB4A	P20338	652

IntAct

132 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DCTN2	DCTN3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.680
REL	DYNC1LI1	psi-mi:“MI:0915”(physical association)	0.670
DYNC1LI1	REL	psi-mi:“MI:0915”(physical association)	0.670
DYNLT1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
PGAM2	DYNC1LI1	psi-mi:“MI:0915”(physical association)	0.560
DYNC1H1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.530
DYNC1LI1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
DYNC1LI1	DYNC1I2	psi-mi:“MI:0914”(association)	0.530
GLMN	MGST3	psi-mi:“MI:0914”(association)	0.530
PAFAH1B1	DYNLT3	psi-mi:“MI:0914”(association)	0.510
vpr	AGPS	psi-mi:“MI:0914”(association)	0.460
vpr	ANKRD17	psi-mi:“MI:0914”(association)	0.460

BioGRID (351): DYNC1LI1 (Two-hybrid), DYNC1LI1 (Affinity Capture-MS), DYNC1H1 (Co-fractionation), DYNC1LI1 (Co-fractionation), DYNC1LI1 (Co-fractionation), DYNC1LI1 (Co-fractionation), DYNC1LI1 (Co-fractionation), DYNLT1 (Co-fractionation), XRCC6 (Co-fractionation), DYNC1LI1 (Affinity Capture-MS), DYNC1LI1 (Proximity Label-MS), DYNC1LI1 (Proximity Label-MS), DYNC1LI1 (Proximity Label-MS), DYNC1LI1 (Affinity Capture-MS), DYNC1LI1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMV4, A0JNI5, A2VDN6, A4IFB1, A4IGK4, B1H1X4, B4KLY7, O60271, P49140, Q02225, Q0V989, Q12872, Q13435, Q15459, Q17FR9, Q1LZD9, Q3UJB0, Q3UQU0, Q3USH5, Q4V872, Q4VGL6, Q58A65, Q5HZB6, Q5R539, Q5RHQ8, Q5SFM8, Q5T8P6, Q5TUF1, Q60436, Q61909, Q66I22, Q6DDU9, Q6INH5, Q6NUC6, Q6NZN0, Q7KW14, Q7PQ25, Q8CFC7, Q8CID0, Q8K4Z5

Diamond homologs: O43237, Q4R5P6, Q54CI8, Q5RE09, Q62698, Q6PDL0, Q8R1Q8, Q90828, Q9QXU8, Q9Y6G9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	DYNC1LI1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 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
COPI-independent Golgi-to-ER retrograde traffic	12	24.0×	1e-11
Aggrephagy	10	23.9×	4e-10
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	11	20.5×	2e-10
Loss of Nlp from mitotic centrosomes	13	19.8×	1e-11
Loss of proteins required for interphase microtubule organization from the centrosome	13	19.8×	1e-11
AURKA Activation by TPX2	13	19.0×	1e-11
Recruitment of mitotic centrosome proteins and complexes	13	17.0×	4e-11
RHO GTPases activate IQGAPs	5	16.6×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	7	15.3×	2e-04
microtubule-based movement	5	11.9×	6e-03
microtubule cytoskeleton organization	8	7.8×	2e-03
intracellular protein localization	8	6.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1879 predictions. Top by Δscore:

Variant	Effect	Δscore
3:32526904:CTGGC:C	acceptor_gain	1.0000
3:32526905:TGGC:T	acceptor_gain	1.0000
3:32526906:GGC:G	acceptor_gain	1.0000
3:32526907:GC:G	acceptor_gain	1.0000
3:32526908:CC:C	acceptor_gain	1.0000
3:32526908:CCTA:C	acceptor_loss	1.0000
3:32526909:C:CC	acceptor_gain	1.0000
3:32526909:CTAC:C	acceptor_loss	1.0000
3:32526912:CAT:C	acceptor_gain	1.0000
3:32526913:A:C	acceptor_gain	1.0000
3:32526914:T:C	acceptor_gain	1.0000
3:32526914:T:TC	acceptor_gain	1.0000
3:32528440:GCATA:G	donor_loss	1.0000
3:32528441:CATA:C	donor_loss	1.0000
3:32528443:TA:T	donor_loss	1.0000
3:32528444:A:AT	donor_loss	1.0000
3:32528445:CCTGA:C	donor_gain	1.0000
3:32528480:TCC:T	donor_gain	1.0000
3:32528597:TCCAG:T	acceptor_gain	1.0000
3:32528598:CCAG:C	acceptor_gain	1.0000
3:32528598:CCAGC:C	acceptor_gain	1.0000
3:32528599:CAG:C	acceptor_gain	1.0000
3:32528599:CAGC:C	acceptor_gain	1.0000
3:32528600:AG:A	acceptor_gain	1.0000
3:32528600:AGC:A	acceptor_loss	1.0000
3:32528602:C:CC	acceptor_gain	1.0000
3:32528604:A:AC	acceptor_gain	1.0000
3:32528604:A:C	acceptor_gain	1.0000
3:32528612:A:AC	acceptor_gain	1.0000
3:32528612:A:C	acceptor_gain	1.0000

AlphaMissense

3389 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:32528553:A:G	L452S	1.000
3:32528556:A:C	L451W	1.000
3:32528556:A:G	L451S	1.000
3:32528564:G:C	F448L	1.000
3:32528564:G:T	F448L	1.000
3:32528565:A:C	F448C	1.000
3:32528565:A:G	F448S	1.000
3:32528566:A:G	F448L	1.000
3:32528567:G:C	F447L	1.000
3:32528567:G:T	F447L	1.000
3:32528568:A:C	F447C	1.000
3:32528568:A:G	F447S	1.000
3:32528569:A:G	F447L	1.000
3:32528577:A:T	L444Q	1.000
3:32570408:A:G	L53P	1.000
3:32570408:A:T	L53H	1.000
3:32570419:C:A	W49C	1.000
3:32570419:C:G	W49C	1.000
3:32528553:A:C	L452W	0.999
3:32528558:A:C	S450R	0.999
3:32528558:A:T	S450R	0.999
3:32528560:T:G	S450R	0.999
3:32528566:A:C	F448V	0.999
3:32528566:A:T	F448I	0.999
3:32528569:A:C	F447V	0.999
3:32528575:C:G	A445P	0.999
3:32528577:A:C	L444R	0.999
3:32528577:A:G	L444P	0.999
3:32530474:A:G	L376P	0.999
3:32533084:C:G	D328H	0.999

dbSNP variants (sampled 300 via entrez): RS1000017978 (3:32548822 T>C), RS1000050945 (3:32561158 A>C), RS1000084994 (3:32549739 T>A), RS1000113294 (3:32567347 C>T), RS1000235963 (3:32564847 A>C), RS1000266018 (3:32532494 T>C), RS1000339860 (3:32561444 C>G,T), RS1000438924 (3:32530796 T>G), RS1000448381 (3:32525745 T>A), RS1000460403 (3:32530987 C>G), RS1000511615 (3:32525719 T>G), RS1000535037 (3:32545517 G>A,C), RS1000687614 (3:32550976 G>A,T), RS1000754006 (3:32557131 A>G), RS1000772263 (3:32532281 C>G)

Disease associations

OMIM: gene MIM:615890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008017_5	Bitter taste perception (6-n-propylthiouracil) in obesity with metabolic syndrome	3.000000e-06
GCST010396_136	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06
GCST011347_19	Low density lipoprotein cholesterol levels	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066283 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.61	Kd	24.35	nM	CHEMBL3752910
7.61	ED50	24.35	nM	CHEMBL3752910
6.05	Kd	896.9	nM	CHEMBL5653589
6.05	ED50	896.9	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148272: Binding affinity to human DYNC1LI1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0244	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148272: Binding affinity to human DYNC1LI1 incubated for 45 mins by Kinobead based pull down assay	kd	0.8969	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment, increases expression	6
bisphenol A	affects expression, decreases expression, affects cotreatment, increases expression	3
sodium arsenite	increases reaction, affects cotreatment, increases abundance, increases expression, affects binding	3
trichostatin A	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Cyclosporine	increases expression	2
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
entinostat	decreases expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651314	Binding	Binding affinity to human DYNC1LI1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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