DYNLL1

Summary

DYNLL1 (dynein light chain LC8-type 1, HGNC:15476) is a protein-coding gene on chromosome 12q24.31, encoding Dynein light chain 1, cytoplasmic (P63167). Component of dynein, a family of motor proteins essential for movement along microtubules. It is a selective cancer dependency (DepMap: 56.6% of cell lines).

Cytoplasmic dyneins are large enzyme complexes with a molecular mass of about 1,200 kD. They contain two force-producing heads formed primarily from dynein heavy chains, and stalks linking the heads to a basal domain, which contains a varying number of accessory intermediate chains. The complex is involved in intracellular transport and motility. The protein described in this record is a light chain and exists as part of this complex but also physically interacts with and inhibits the activity of neuronal nitric oxide synthase. Binding of this protein destabilizes the neuronal nitric oxide synthase dimer, a conformation necessary for activity, and it may regulate numerous biologic processes through its effects on nitric oxide synthase activity. Alternate transcriptional splice variants have been characterized.

Source: NCBI Gene 8655 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 3 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 56.6% of screened cell lines
• MANE Select transcript: NM_003746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15476
Approved symbol	DYNLL1
Name	dynein light chain LC8-type 1
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	hdlc1, DLC1, PIN, LC8, DLC8
Ensembl gene	ENSG00000088986
Ensembl biotype	protein_coding
OMIM	601562
Entrez	8655

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 28 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000242577, ENST00000392508, ENST00000392509, ENST00000548214, ENST00000548342, ENST00000549649, ENST00000549989, ENST00000550178, ENST00000550845, ENST00000552316, ENST00000552870, ENST00000866841, ENST00000866842, ENST00000866843, ENST00000866844, ENST00000866845, ENST00000866846, ENST00000866847, ENST00000866848, ENST00000933719, ENST00000933720, ENST00000933721, ENST00000933722, ENST00000933723, ENST00000933724, ENST00000957679, ENST00000957680, ENST00000957681, ENST00000957682

RefSeq mRNA: 3 — MANE Select: NM_003746 NM_001037494, NM_001037495, NM_003746

CCDS: CCDS9200

Canonical transcript exons

ENST00000242577 — 3 exons

Exon	Start	End
ENSE00001642434	120496416	120496553
ENSE00002349129	120498073	120498493
ENSE00002403763	120496113	120496216

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 403.6204 / max 2459.7373, expressed in 1828 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128351	372.2771	1828
128350	26.9596	1811
128348	4.2050	1575
128353	0.1585	53
128349	0.0202	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	99.83	gold quality
frontal pole	UBERON:0002795	99.80	gold quality
gingival epithelium	UBERON:0001949	99.79	gold quality
cingulate cortex	UBERON:0003027	99.79	gold quality
anterior cingulate cortex	UBERON:0009835	99.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.78	gold quality
gingiva	UBERON:0001828	99.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.74	gold quality
bronchial epithelial cell	CL:0002328	99.73	gold quality
right testis	UBERON:0004534	99.73	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.73	gold quality
right frontal lobe	UBERON:0002810	99.72	gold quality
frontal cortex	UBERON:0001870	99.71	gold quality
neocortex	UBERON:0001950	99.70	gold quality
left testis	UBERON:0004533	99.70	gold quality
epithelium of bronchus	UBERON:0002031	99.69	gold quality
middle frontal gyrus	UBERON:0002702	99.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.68	gold quality
amygdala	UBERON:0001876	99.68	gold quality
cortical plate	UBERON:0005343	99.67	gold quality
cerebral cortex	UBERON:0000956	99.66	gold quality
hypothalamus	UBERON:0001898	99.66	gold quality
olfactory bulb	UBERON:0002264	99.66	gold quality
nucleus accumbens	UBERON:0001882	99.64	gold quality
Ammon’s horn	UBERON:0001954	99.64	gold quality
bronchus	UBERON:0002185	99.64	gold quality
caudate nucleus	UBERON:0001873	99.63	gold quality
right uterine tube	UBERON:0001302	99.62	gold quality
telencephalon	UBERON:0001893	99.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.62	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	5701.27
E-HCAD-15	yes	4482.29
E-CURD-114	yes	3543.66
E-MTAB-6505	yes	2972.81
E-MTAB-7037	yes	1704.89
E-HCAD-1	yes	234.61
E-HCAD-4	yes	143.98
E-GEOD-134144	yes	39.03
E-CURD-88	yes	26.53
E-GEOD-135922	yes	19.59
E-MTAB-6701	yes	17.23
E-MTAB-9221	yes	15.27
E-GEOD-130148	yes	14.92
E-CURD-46	yes	12.82
E-MTAB-10553	yes	6.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting DYNLL1, 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-432-3P	100.00	67.86	705
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-6776-3P	98.38	66.34	655
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-4774-5P	95.92	68.27	827
HSA-MIR-874-3P	95.02	65.66	806

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 56.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• the regulation of DLC1 by p21-activated kinase 1 is a novel mechanism by which a signaling kinase might influence macropinocytosis (PMID:15504720)
• LC8 binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation (PMID:15611139)
• PAX6 interacts with HOMER3, DNCL1, and TRIM11. Three C-terminal PAX6 mutations, previously identified in patients with eye malformations, all reduced or abolished the interactions. (PMID:16098226)
• the DLC1-KIBRA interaction is essential for ER transactivation in breast cancer cells (PMID:16684779)
• PIN not only inhibits nitric oxide but also .O(2)(-) production from nitric oxide synthase 1 (PMID:16781079)
• dynein light chain 1 represents a novel anchoring protein for RasGRP3 that may regulate subcellular localization of the exchange factor (PMID:17012239)
• we established for the first time expression of PIN/LC8 in human mast cells (PMID:17169380)
• findings reveal a previously unrecognized regulatory mechanism of DLC1 in which the Ser(88) phosphorylation acts as a molecular switch for the transition of DLC1 from dimer to monomer (PMID:18084006)
• LC8 binds IkappaBalpha in a redox-dependent manner and thereby prevents its phosphorylation by IKK. TRP14 contributes to this inhibitory activity by maintaining LC8 in a reduced state. (PMID:18579519)
• pH dependent unfolding characteristics of DLC8 dimer: Residue level details from NMR. (PMID:18692162)
• The data indicated the presence of intermediates along the equilibrium unfolding transition; the hydrogen exchange data suggested that the DLC8 molecule has differential stability in its various segments. (PMID:18767155)
• Hierarchy in guanidine unfolding of DYNLL1 dimer is reported. (PMID:19032974)
• LC8 facilitates nuclear import of Pak1 and this function is indispensable during vertebrate development (PMID:19557173)
• Data identify GRINL1A as a membrane-associated DYNLL1 binding partner and suggest that additional DYNLL1-binding partners are present near this glutamate channel homolog. (PMID:20412299)
• Data suggest that MTOC-directed movement of lytic granules in NK cells is independent of actin and microtubule reorganization, dependent on dynein motor function, occurs before MTOC polarization, and does not require a commitment to cytotoxicity. (PMID:20444980)
• Data provide the first trafficking regulatory role for Crmp2 in non-neuronal cells and support a model in which Crmp2 is an important endocytic regulatory protein that links MICAL-L1.EHD1-based vesicular transport to dynein motors. (PMID:20801876)
• the thermodynamic and kinetic fine-tuning of binding of various ligands to DYNLL could have physiological relevance in its interaction network. (PMID:20889982)
• effect of glycosylation on protein folding thermodynamics and kinetics (PMID:20936810)
• Data demonstrate the direct interaction between DYNLL1 and peptides derived from ASFV p54 and gephyrin interacting sequences. (PMID:21094642)
• DYNLL/LC8 protein controls signal transduction through the Nek9/Nek6 signaling module by regulating Nek6 binding to Nek9. (PMID:21454704)
• results significantly widen the scope of the human interactome around DYNLL and will certainly shed more light on the biological functions and organizing role of DYNLL in the human and other eukaryotic interactomes (PMID:21533121)
• The study uses thermodynamics and dynamics measurements of LC8 complexes to group LC8 binding partners in two categories: those whose binding is enthalpically driven and those that are entropically favored. (PMID:21621319)
• these results imply a potential cellular interference between DYNLL1 and ATMIN functions. (PMID:21971545)
• The ASCIZ-DYNLL1 feedback loop represents a novel mechanism for auto-regulation of gene expression, where the gene product directly inhibits the transcriptional activator while bound at its own promoter. (PMID:22167198)
• Cytosolic mfGbeta is recruited to dynein by Nudel and transported to the centrosome for rapid sequestration and degradation. (PMID:22430153)
• Study found the secretion of calu-1/2-EGFP required microtubule integrity, and that calu-1/2-EGFP-containing vesicles were transported by the motor proteins Kif5b and cytoplasmic dynein. (PMID:22514732)
• DYNLL1 interacted with a spindle-microtubule-associated adaptor formed by CHICA and HMMR via TQT motifs in CHICA. (PMID:22965910)
• appropriate levels of ternary complex components are critical for dynein-dependent spindle positioning in HeLa cells and C. elegans embryos (PMID:23027904)
• Overexpressed human LC8 inhibits mouse osteoclast differentiation by regulating NF-kappaB & MAPK pathways and suppressing RANKL signaling. (PMID:23293355)
• Structural analysis of LC8 with both Nek9 peptides, together with different biophysical experiments, explains the observed diminished binding affinity of Nek9 to LC8 upon phosphorylation on Ser(944) within the Nek9 sequence (PMID:23482567)
• Dynein forms distinct complexes requiring specific recruiters and activators to promote orderly progression through mitosis. (PMID:23589491)
• The dynein light intermediate chain has a Ras-like fold with insertions that distinguish it from Ras and other previously described G proteins. (PMID:25272277)
• Overall, this study demonstrates the novel interaction between HIV-1 integrase and cellular DYNLL1 proteins and suggests the requirement of this virus-cell interaction for proper uncoating and efficient reverse transcription of HIV-1. (PMID:25568209)
• Authors demonstrate that the interaction between ebola virus VP35 and dynein LC8 is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. (PMID:25741013)
• DLC1 binding motif in L is involved in cytoskeleton localization and reorganization, primary transcription regulation by DLC1, and regulation of cellular DLC1 gene expression. (PMID:26157129)
• Studies indicate that dynein light chain LC8 has been termed an intrinsically disordered proteins (IDPs) dimerization ‘hub’ protein. (PMID:26226419)
• NMR-derived secondary chemical shifts and relaxation properties show that the Chica LC8 binding domain is essentially disordered with a dynamically restricted segment in one linker between motifs. (PMID:26652654)
• DLC1 binding to nNOS-calmodulin complex does not affect the electron transport from the reductase to the oxygenase domain. (PMID:26923072)
• High PIN expression is associated with Dilated Hearts. (PMID:27481317)
• An expanded list of LC8 binding partners revealed the evolutionary plasticity of binding partners despite the highly conserved binding interface. In addition, it also highlighted a novel, conserved function of LC8 in the upstream regulation of the Hippo signaling pathway. (PMID:29240760)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dynll1	ENSDARG00000058454
mus_musculus	Dynll1	ENSMUSG00000009013
rattus_norvegicus	Dynll1	ENSRNOG00000083010
drosophila_melanogaster	ctp	FBGN0011760
drosophila_melanogaster	Cdlc2	FBGN0026141
caenorhabditis_elegans		WBGENE00001005

Paralogs (1): DYNLL2 (ENSG00000264364)

Protein

Protein identifiers

Dynein light chain 1, cytoplasmic — P63167 (reviewed: P63167)

Alternative names: 8 kDa dynein light chain, Dynein light chain LC8-type 1, Protein inhibitor of neuronal nitric oxide synthase

All UniProt accessions (5): P63167, F8VRV5, F8VXI7, F8VXL2, Q6FGH9

UniProt curated annotations — full annotation on UniProt →

Function. Component of dynein, a family of motor proteins essential for movement along microtubules. Required for structural and functional integrity of cilia. 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 changing or maintaining the spatial distribution of cytoskeletal structures. In addition to its role in cytoskeleton and transport, acts as a protein-protein adapter, which inhibits and/or sequesters target proteins. Involved in the response to DNA damage by acting as a key regulator of DNA end resection: when phosphorylated at Ser-88, recruited to DNA double-strand breaks (DSBs) by TP53BP1 and acts by disrupting MRE11 dimerization, thereby inhibiting DNA end resection. In a subset of DSBs, DYNLL1 remains unphosphorylated and promotes the recruitment of the Shieldin complex. Binds and inhibits the catalytic activity of neuronal nitric oxide synthase/NOS1. Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1. Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity.

Subunit / interactions. Homodimer. Monomer; the monomeric form is incapable of binding to target proteins. 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. Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains. The ODAs interact with DNAAF9; this interaction inactivates the dyneins. Interacts with TXNDC17. Interacts with WWC1 and ESR1. The WWC1-DYNLL1 interaction is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin. Interacts with BCL2L11 isoform 1 and isoform 2. Interacts with BCL2; the interaction is greatly enhanced in the nucleus and in mitochondria upon induction of apoptosis. Interacts with PAK1; the interaction requires dimeric DYNLL1. Interacts with MYZAP. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with ATMIN; this interaction inhibits ATMIN transcriptional activity and hence may play a role in a feedback loop whereby DYNLL1 inhibits transactivation of its own promoter by ATMIN. Interacts with NEK9 (not phosphorylated at ‘Ser-944’). Interacts with BICD2. Interacts with BCAS1. Interacts with Basson/BSN. Interacts with HDAC6. Interacts with TPPP. Interacts with AMBRA1 (via TQT motifs); tethering AMBRA1 to the cytoskeleton. Interacts with FAM83D/CHICA (via C-terminus). Interacts with HMMR, SPAG5/Astrin and KNSTRN/Kinastrin. Interacts with TLK2. Interacts with NOS1. Interacts with WWC1, WWC2 and WWC3. Interacts with MRE11; inhibiting MRE11 homodimerization and activity. (Microbial infection) Interacts with human spumaretrovirus Gag protein; this interaction is critical for intracellular microtubule-dependent viral genome transport toward the centrosome. (Microbial infection) Interacts with ebolavirus protein VP35; this interaction stabilizes VP35 N-terminal oligomerization domain and enhances viral RNA synthesis.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Chromosome. Nucleus. Mitochondrion.

Tissue specificity. Ubiquitous. Expressed in testis.

Post-translational modifications. Phosphorylation at Ser-88 promotes recruitment to DNA double-strand breaks (DSBs) by TP53BP1 and ability to inhibit MRE11. Phosphorylation at Ser-88 appears to control the dimer-monomer transition. According to PubMed:15193260, it is phosphorylated at Ser-88 by PAK1, however, according to PubMed:18650427, the DYNLL1 dimer is not accessible for PAK1 and the phosphorylation could not be demonstrated in vitro.

Induction. Up-regulated by ATMIN, PAK1 and estrogen.

Similarity. Belongs to the dynein light chain family.

RefSeq proteins (3): NP_001032583, NP_001032584, NP_003737* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001372	Dynein_light_chain_typ-1/2	Family
IPR019763	Dynein_light_1/2_CS	Conserved_site
IPR037177	DLC_sf	Homologous_superfamily

Pfam: PF01221

UniProt features (16 total): strand 6, mutagenesis site 3, helix 2, modified residue 2, chain 1, region of interest 1, cross-link 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
9NZ7	X-RAY DIFFRACTION	1.41
6GZL	X-RAY DIFFRACTION	1.95
6GZJ	X-RAY DIFFRACTION	1.98
3ZKE	X-RAY DIFFRACTION	2.2
7D35	X-RAY DIFFRACTION	2.4
1CMI	X-RAY DIFFRACTION	2.5
3ZKF	X-RAY DIFFRACTION	2.6
9BLY	ELECTRON MICROSCOPY	3.5
6SC2	ELECTRON MICROSCOPY	3.9
8RGG	ELECTRON MICROSCOPY	4
9E28	ELECTRON MICROSCOPY	4.4
6RLB	ELECTRON MICROSCOPY	4.5
9E12	ELECTRON MICROSCOPY	4.5
9E13	ELECTRON MICROSCOPY	4.5
9E14	ELECTRON MICROSCOPY	5
9YNH	ELECTRON MICROSCOPY	5.5
9E23	ELECTRON MICROSCOPY	6.2
8PR1	ELECTRON MICROSCOPY	8.2
9YNE	ELECTRON MICROSCOPY	8.46
8PR0	ELECTRON MICROSCOPY	9.4
8PTK	ELECTRON MICROSCOPY	10

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63167-F1	95.45	0.94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 36, 88, 43

Mutagenesis-validated functional residues (3):

Position	Phenotype
67	abolishes interaction with pak1.
88	abolishes growth factor-mediated phosphorylation. increases bcl2l11 protein level and promotes apoptosis.
88	abolishes homodimerization. abolishes interaction with bcl2l11 isoform 1 and isoform 2.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-111446	Activation of BIM and translocation to mitochondria
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-1632852	Macroautophagy
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-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5620924	Intraflagellar transport
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-8854518	AURKA Activation by TPX2
R-HSA-9609690	HCMV Early Events
R-HSA-9646399	Aggrephagy
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 960 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_CHROMOSOME_ORGANIZATION, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, HONMA_DOCETAXEL_RESISTANCE, WALLACE_PROSTATE_CANCER_RACE_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PHOSPHORYLATION

GO Biological Process (13): apoptotic process (GO:0006915), DNA damage response (GO:0006974), spermatid development (GO:0007286), substantia nigra development (GO:0021762), positive regulation of intracellular transport (GO:0032388), intraciliary retrograde transport (GO:0035721), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), negative regulation of phosphorylation (GO:0042326), motile cilium assembly (GO:0044458), negative regulation of nitric oxide biosynthetic process (GO:0045019), negative regulation of DNA strand resection involved in replication fork processing (GO:0110027), microtubule-based process (GO:0007017), DNA strand resection involved in replication fork processing (GO:0110025)

GO Molecular Function (10): enzyme inhibitor activity (GO:0004857), enzyme binding (GO:0019899), nitric-oxide synthase inhibitor activity (GO:0036487), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), dynein intermediate chain binding (GO:0045505), scaffold protein binding (GO:0097110), protein binding (GO:0005515), nitric-oxide synthase regulator activity (GO:0030235), deoxyribonuclease inhibitor activity (GO:0060703)

GO Cellular Component (24): kinetochore (GO:0000776), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), centrosome (GO:0005813), cytosol (GO:0005829), cytoskeleton (GO:0005856), cytoplasmic dynein complex (GO:0005868), microtubule (GO:0005874), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), site of double-strand break (GO:0035861), tertiary granule membrane (GO:0070821), mitotic spindle (GO:0072686), ciliary tip (GO:0097542), ficolin-1-rich granule membrane (GO:0101003), axon cytoplasm (GO:1904115), chromosome (GO:0005694), microtubule associated complex (GO:0005875), COP9 signalosome (GO:0008180), microtubule cytoskeleton (GO:0015630), secretory granule (GO:0030141), dynein complex (GO:0030286)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Mitotic Prometaphase	2
G2/M Transition	2
Centrosome maturation	2
Assembly of the 9+0 primary cilium	2
Activation of BH3-only proteins	1
Amplification of signal from the kinetochores	1
Autophagy	1
Adaptive Immune System	1
Mitotic Anaphase	1
Cellular responses to stress	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
RHO GTPase Effectors	1
Innate Immune System	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
cellular anatomical structure	4
intracellular membraneless organelle	3
enzyme regulator activity	2
nitric-oxide synthase activity	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
microtubule cytoskeleton	2
secretory granule membrane	2
tertiary granule	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
germ cell development	1
spermatid differentiation	1
midbrain development	1
neural nucleus development	1
regulation of intracellular transport	1
intracellular transport	1
positive regulation of cellular process	1
positive regulation of transport	1
intraciliary transport	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
phosphorylation	1
regulation of phosphorylation	1
negative regulation of phosphate metabolic process	1
cilium assembly	1
nitric oxide biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
DNA strand resection involved in replication fork processing	1
regulation of DNA strand resection involved in replication fork processing	1
negative regulation of DNA-templated DNA replication	1
cellular process	1
DNA metabolic process	1
replication fork processing	1

Protein interactions and networks

STRING

3252 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNLL1	BCL2L11	O43521	965
DYNLL1	DYNC2H1	Q8NCM8	937
DYNLL1	NDE1	Q9NXR1	931
DYNLL1	DYNC1H1	Q14204	899
DYNLL1	DYNLT1	P63172	887
DYNLL1	TP53BP1	Q12888	838
DYNLL1	DYNLRB1	Q9NP97	820
DYNLL1	DYNC2I2	Q96EX3	820
DYNLL1	DYNC1I2	Q13409	808
DYNLL1	WWC1	Q8IX03	801
DYNLL1	DYNC1I1	O14576	794
DYNLL1	ATMIN	O43313	793
DYNLL1	OCA2	Q04671	791
DYNLL1	DYNLT3	P51808	791
DYNLL1	POTEF	A5A3E0	779

IntAct

440 interactions, top by confidence:

A	B	Type	Score
NEK9	DYNLL1	psi-mi:“MI:0915”(physical association)	0.900
PRKCZ	PRKCI	psi-mi:“MI:0914”(association)	0.890
OFD1	DYNLL1	psi-mi:“MI:0914”(association)	0.890
DYNLL1	KANK2	psi-mi:“MI:0915”(physical association)	0.870
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL1	IHO1	psi-mi:“MI:0915”(physical association)	0.720
IHO1	DYNLL1	psi-mi:“MI:0915”(physical association)	0.720
DYNC2I1	DYNLL1	psi-mi:“MI:0915”(physical association)	0.700
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.680
DYNLT1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.640
DYNC2I2	DYNLL1	psi-mi:“MI:0914”(association)	0.640
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
RACK1	DYNLL1	psi-mi:“MI:0915”(physical association)	0.630
RACK1	DYNLL1	psi-mi:“MI:0407”(direct interaction)	0.630
DYNLL1	RACK1	psi-mi:“MI:0915”(physical association)	0.630
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
DYNLL1	IQUB	psi-mi:“MI:0915”(physical association)	0.560
DYNLL1	AMOTL2	psi-mi:“MI:0915”(physical association)	0.560
IQUB	DYNLL1	psi-mi:“MI:0915”(physical association)	0.560
FAM83D	HMMR	psi-mi:“MI:0914”(association)	0.560
DYNLL1	OTUD6A	psi-mi:“MI:0915”(physical association)	0.560
LRFN4	RIMOC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (849): DYNLL1 (Two-hybrid), AMBRA1 (Affinity Capture-Western), DYNLL1 (Affinity Capture-Western), DYNLL1 (Affinity Capture-Western), KANK2 (Two-hybrid), AMOTL2 (Two-hybrid), IQUB (Two-hybrid), CCDC36 (Two-hybrid), DYNLL1 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q7I7R4, A7YW45, O02414, O14744, O77210, O94111, O96860, P22953, P25840, P26639, P27322, P48612, P61273, P61285, P63167, P63168, P63169, P63170, Q02647, Q03389, Q16WA6, Q21557, Q22799, Q24117, Q39580, Q3MHR3, Q3ZBV8, Q4R5M3, Q58DV0, Q5R698, Q5RCE3, Q5U567, Q5XHY5, Q5XIP1, Q5ZK01, Q6BZF8, Q6CWX4, Q6FUJ0, Q6NUA1, Q759T0

Diamond homologs: A4F4L4, O02414, O94111, O96015, O96860, P61273, P61285, P63167, P63168, P63169, P63170, Q02647, Q22799, Q24117, Q32KN5, Q39580, Q3MHR3, Q6BZF8, Q6CWX4, Q6FUJ0, Q759T0, Q78P75, Q86A88, Q94758, Q96FJ2, Q9D0M5, Q9DCM4, Q9UR05, Q21557, Q39579, Q94748

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PAK1	down-regulates	DYNLL1	phosphorylation
DYNLL1	down-regulates	AMBRA1	binding
DYNLL1	“down-regulates activity”	RHOA	“gtpase-activating protein”
CDK5	“up-regulates activity”	DYNLL1	phosphorylation
PRKD1	“down-regulates activity”	DYNLL1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	12.8×	1e-03
COPI-independent Golgi-to-ER retrograde traffic	5	11.4×	4e-03
EML4 and NUDC in mitotic spindle formation	11	11.2×	2e-06
Intraflagellar transport	5	11.0×	5e-03
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	7	9.0×	1e-03
Mitotic Prometaphase	11	8.4×	2e-05
Resolution of Sister Chromatid Cohesion	8	7.6×	1e-03
RHO GTPases Activate Formins	8	6.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

6248 predictions. Top by Δscore:

Variant	Effect	Δscore
12:120496411:ACTAG:A	acceptor_loss	1.0000
12:120496414:AGGT:A	acceptor_loss	1.0000
12:120496415:G:GT	acceptor_loss	1.0000
12:120496550:GAAG:G	donor_gain	1.0000
12:120496553:GGTG:G	donor_loss	1.0000
12:120496554:G:GG	donor_gain	1.0000
12:120496554:GTG:G	donor_loss	1.0000
8:13085927:GGCCC:G	acceptor_gain	1.0000
8:13085928:GCCC:G	acceptor_gain	1.0000
8:13085929:CCC:C	acceptor_gain	1.0000
8:13085929:CCCC:C	acceptor_gain	1.0000
8:13085930:CC:C	acceptor_gain	1.0000
8:13085930:CCC:C	acceptor_gain	1.0000
8:13085931:CC:C	acceptor_gain	1.0000
8:13085932:C:CA	acceptor_loss	1.0000
8:13085932:C:CC	acceptor_gain	1.0000
8:13085937:A:T	acceptor_gain	1.0000
8:13088484:CAC:C	donor_loss	1.0000
8:13088485:A:AC	donor_gain	1.0000
8:13088486:C:A	donor_loss	1.0000
8:13088486:C:CC	donor_gain	1.0000
8:13088539:A:AC	donor_gain	1.0000
8:13088540:C:CC	donor_gain	1.0000
8:13088703:ACCT:A	acceptor_loss	1.0000
8:13090246:CCTTA:C	donor_loss	1.0000
8:13090247:CTTAC:C	donor_loss	1.0000
8:13090250:A:AC	donor_gain	1.0000
8:13090250:ACC:A	donor_loss	1.0000
8:13090251:C:CA	donor_loss	1.0000
8:13090251:C:CC	donor_gain	1.0000

AlphaMissense

598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:120496495:C:A	A25D	1.000
12:120496537:C:A	A39E	1.000
12:120496550:G:C	K43N	1.000
12:120496550:G:T	K43N	1.000
12:120498100:T:A	W54R	1.000
12:120498100:T:C	W54R	1.000
12:120498102:G:C	W54C	1.000
12:120498102:G:T	W54C	1.000
12:120498106:T:C	C56R	1.000
12:120498107:G:A	C56Y	1.000
12:120498108:C:G	C56W	1.000
12:120498115:G:A	G59R	1.000
12:120498115:G:C	G59R	1.000
12:120498115:G:T	G59W	1.000
12:120498116:G:A	G59E	1.000
12:120498116:G:T	G59V	1.000
12:120498124:T:C	F62L	1.000
12:120498126:C:A	F62L	1.000
12:120498126:C:G	F62L	1.000
12:120498142:C:G	H68D	1.000
12:120498191:T:C	L84P	1.000
12:120498196:T:A	F86I	1.000
12:120498196:T:C	F86L	1.000
12:120498198:C:A	F86L	1.000
12:120498198:C:G	F86L	1.000
12:120496448:A:C	K9N	0.999
12:120496448:A:T	K9N	0.999
12:120496494:G:C	A25P	0.999
12:120496539:G:C	A40P	0.999
12:120496548:A:G	K43E	0.999

dbSNP variants (sampled 300 via entrez): RS1000168021 (12:120473566 A>C), RS1000172043 (12:120471504 A>G), RS1000204532 (12:120471138 T>A,C,G), RS1000217439 (12:120482131 C>A), RS1000386945 (12:120477953 A>C), RS1000548363 (12:120474908 C>A), RS1000565244 (12:120485522 G>A), RS1000575353 (12:120485181 T>C), RS1000612770 (12:120481980 T>C), RS1000718376 (12:120497873 C>T), RS1000978449 (12:120497642 T>G), RS1001003708 (12:120474642 A>G), RS1001055406 (12:120469239 G>A,T), RS1001109060 (12:120469056 A>G), RS1001173260 (12:120492365 C>T)

Disease associations

OMIM: gene MIM:601562 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST004401_6	Reading disability or specific language impairment (pleiotropy)	4.000000e-06
GCST004402_1	Reading disability or specific language impairment adjusted for intelligence quotient (pleiotropy)	1.000000e-06
GCST004611_191	High light scatter reticulocyte count	5.000000e-78
GCST004612_125	High light scatter reticulocyte percentage of red cells	2.000000e-83
GCST004612_126	High light scatter reticulocyte percentage of red cells	2.000000e-79
GCST004619_210	Reticulocyte fraction of red cells	9.000000e-68
GCST004622_122	Reticulocyte count	4.000000e-66
GCST004628_53	Immature fraction of reticulocytes	6.000000e-60
GCST90002385_5	High light scatter reticulocyte count	6.000000e-18
GCST90002386_338	High light scatter reticulocyte percentage of red cells	2.000000e-19
GCST90002387_128	Immature fraction of reticulocytes	6.000000e-12
GCST90002390_73	Mean corpuscular hemoglobin	1.000000e-26
GCST90002392_393	Mean corpuscular volume	2.000000e-37
GCST90002396_537	Mean reticulocyte volume	4.000000e-33
GCST90002397_218	Mean spheric corpuscular volume	2.000000e-52
GCST90002405_244	Reticulocyte count	3.000000e-12
GCST90002406_349	Reticulocyte fraction of red cells	8.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725118 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.11	Kd	7.748	nM	CHEMBL3752910
7.81	ED50	15.47	nM	CHEMBL3752910
6.29	IC50	510	nM	MOLIBRESIB
5.59	Kd	2584	nM	CHEMBL5653589
5.29	ED50	5158	nM	CHEMBL5653589

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 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	2148274: Binding affinity to human DYNLL1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0077	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178905: Inhibition of DYNLL1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.5100	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148274: Binding affinity to human DYNLL1 incubated for 45 mins by Kinobead based pull down assay	kd	2.5839	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases methylation	3
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Leflunomide	decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
tetrabromobisphenol A	decreases expression	1
sulindac sulfide	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression, increases expression	1
GW 7604	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
abrine	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651316	Binding	Binding affinity to human DYNLL1 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1QH	Abcam HeLa DYNLL1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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