DYNLT1

Summary

DYNLT1 (dynein light chain Tctex-type 1, HGNC:11697) is a protein-coding gene on chromosome 6q25.3, encoding Dynein light chain Tctex-type 1 (P63172). Component of dynein, a family of motor proteins essential for movement along microtubules.

This gene encodes a component of the motor complex, cytoplasmic dynein, which transports cellular cargo along microtubules in the cell. The encoded protein regulates the length of primary cilia which are sensory organelles found on the surface of cells. The protein encoded by this gene interacts with viral proteins, like the minor capsid protein L2 of human papillomavirus, and is required for dynein-mediated delivery of the viral nucleic acid to the host nucleus. This protein interacts with oncogenic nucleoporins to disrupt gene regulation and cause leukemic transformation. Pseudogenes of this gene are present on chromosomes 4 and 17. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 6993 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 29 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006519

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11697
Approved symbol	DYNLT1
Name	dynein light chain Tctex-type 1
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	Tctex-1, TCTEX1
Ensembl gene	ENSG00000146425
Ensembl biotype	protein_coding
OMIM	601554
Entrez	6993

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 2 protein_coding

ENST00000367085, ENST00000367088, ENST00000367089, ENST00000883048

RefSeq mRNA: 3 — MANE Select: NM_006519 NM_001291602, NM_001291603, NM_006519

CCDS: CCDS5257

Canonical transcript exons

ENST00000367089 — 5 exons

Exon	Start	End
ENSE00000975793	158637771	158637894
ENSE00000975794	158637128	158637205
ENSE00001028533	158641319	158641360
ENSE00001443457	158636474	158636897
ENSE00001443458	158644682	158644743

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.0739 / max 421.0361, expressed in 1812 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76389	32.8548	1811
76388	0.2191	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.71	gold quality
epithelium of bronchus	UBERON:0002031	99.64	gold quality
bronchus	UBERON:0002185	99.60	gold quality
epithelium of nasopharynx	UBERON:0001951	99.59	gold quality
palpebral conjunctiva	UBERON:0001812	99.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.15	gold quality
nasal cavity epithelium	UBERON:0005384	99.14	gold quality
adult organism	UBERON:0007023	99.12	gold quality
oral cavity	UBERON:0000167	98.99	gold quality
nasal cavity mucosa	UBERON:0001826	98.98	gold quality
ganglionic eminence	UBERON:0004023	98.90	gold quality
islet of Langerhans	UBERON:0000006	98.88	gold quality
jejunal mucosa	UBERON:0000399	98.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.84	gold quality
monocyte	CL:0000576	98.83	gold quality
mononuclear cell	CL:0000842	98.80	gold quality
right uterine tube	UBERON:0001302	98.78	gold quality
parotid gland	UBERON:0001831	98.78	gold quality
leukocyte	CL:0000738	98.70	gold quality
cauda epididymis	UBERON:0004360	98.65	gold quality
right testis	UBERON:0004534	98.64	gold quality
smooth muscle tissue	UBERON:0001135	98.63	gold quality
seminal vesicle	UBERON:0000998	98.59	gold quality
left testis	UBERON:0004533	98.58	gold quality
endometrium	UBERON:0001295	98.53	gold quality
popliteal artery	UBERON:0002250	98.53	gold quality
tibial artery	UBERON:0007610	98.53	gold quality
lower esophagus	UBERON:0013473	98.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.49	gold quality
ventricular zone	UBERON:0003053	98.48	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	11.37
E-CURD-114	yes	10.86
E-MTAB-5061	yes	5.89
E-MTAB-6524	no	491.10
E-MTAB-7606	no	310.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting DYNLT1, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-548L	99.06	70.90	2560

Literature-anchored findings (GeneRIF, showing 29)

• Association with Tctex-1 and, hence, with the dynein motor complex may offer an explanation for how poliovirus hijacks the cellular transport machinery to retrogradely ascend along the axon to the neuronal cell body. (PMID:11751937)
• We now report that Tctex-1, a light chain of the motor complex dynein, interacts with the cytoplasmic domain of BMPR-II and demonstrate that Tctex-1 is phosphorylated by BMPR-II, a function disrupted by PPH disease causing mutations within exon 12 (PMID:14583445)
• Results suggest that the dynein complex disassembles to release cargo due to the specific phosphorylation of Tctex-1 at the S82 residue and that this process is critical for the apical delivery of membrane cargoes. (PMID:16956385)
• Tctex-1, a light chain of the molecular motor dynein, is involved in the intracellular targeting of Mason-Pfizer monkey virus (M-PMV) polyproteins to the cytoplasmic assembly site (PMID:18647839)
• The N-terminal half of pUL35, in particular residues 30-43, was identified as a common region for the binding of DYNLT1 and DYNLT3. (PMID:20668116)
• These data show that both DYNLT1 and DYNLT3 interact with L2 of human papillomavirus 16 during virus infection. (PMID:21166973)
• Targeted disruption of Tctex-1 by RNA interference significantly impairs bone resorption capacity and mislocalizes Rab3D vesicles in osteoclasts. (PMID:21262767)
• Data show that Tctex-1 phosphorylated at Thr 94 is recruited to ciliary transition zones before S-phase entry and has a pivotal role in both ciliary disassembly and cell cycle progression. (PMID:21394082)
• A role for Tctex-1 (DYNLT1) in controlling primary cilium length (PMID:21700358)
• These data show that Tctex-1 may play a role in late stages of viral replication through its interaction with the flavivirus membrane protein. (PMID:21767858)
• A link between REIC/Dkk- 3 and Tctex-1 may therefore be of significance for understanding the molecular functions of the proteins in ER stress signaling and the intracellular dynein motor dynamics, respectively. (PMID:21835165)
• Dynlt1 modulates orexin signaling by regulating OX1R (PMID:22028875)
• there are two possible mechanisms triggered by MAP4: stabilization of MT networks; DYNLT1 modulation, which is connected with VDAC1, and inhibition of hypoxia-induced mitochondrial permeabilization (PMID:22164227)
• DYNLT1 interacts with nucleoporins and plays a role in the dysregulation of gene expression and induction of hematopoietic cell proliferation by the leukemogenic nucleoporin fusion, NUP98-HOXA9 (PMID:23840580)
• Data suggest that DYNLT1 phosphorylation at serine S82 is involved in microtubule and mitochondria regulation, and their interaction and cooperation contribute to the cellular hypoxic tolerance. (PMID:24170091)
• Reveal a dynein independent role of Tctex-1 at the kinetochore to enhance the stability of kinetochore-microtubule attachment. (PMID:25928583)
• DYNLT1 is enriched at focal concentrations of CT850 on the chlamydial inclusion membrane that are known to interact with dynein and microtubules. (PMID:25944661)
• Data suggest that both microtubule-associated DYNLT (dynein light chain Tctex-type 1) and cytoplasmic DYNLT (dynein 1 intermediate chain 2 DYNC1LI2) are equally able to bind to small GTPases Rab3D (Rab3d GTPase) and RagA (Ras-related GTP binding A). (PMID:26227614)
• Study reports a defect in the expression of DYNLT1 in the germ cells of infertile human males and implicates DYNLT1 in spermatogonial cell division and differentiation. (PMID:26432663)
• The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications. (PMID:26792716)
• activin receptor IIB as a novel DYNLT1 ligand and suggest that DYNLT1 functions as a molecular dimerization engine bringing together two receptor monomers in the cytoplasmic side of the membrane. (PMID:27502274)
• results support a model in which phospho(T94)Tctex-1-regulated actin polymerization and periciliary endocytosis play an active role in orchestrating the initial phase of ciliary resorption (PMID:28607034)
• Tctex1 overexpression promoted autophagy lysosome fusion and effectively degraded alpha-synuclein with increased cell activity (PMID:28970129)
• siRNA silencing of Tctex1 suppressed cellular viability and promoted cell apoptosis. Protein and mRNA expression of Tctex1 and dynein decreased after Tctex1 knockdown, whereas alpha-synuclein, LC3-II, and LAMP2 increased. Consistently, fluorescence intensity of Tctex1 was weaker in siRNA-Tctex1-transfected cells, and that of alpha-synuclein, LC3-II, and LAMP2 was increased. (PMID:29406369)
• Desmosomal cadherin association with Tctex-1 and cortactin-Arp2/3 drives perijunctional actin polymerization to promote keratinocyte delamination. (PMID:29535305)
• expression of Tctex-1 T94E did not influence KIM-1-mediated efferocytosis (PMID:29693725)
• MAP4 and Tctex-1 play important roles in regulating the migration of epidermal cells under hypoxia. (PMID:30091292)
• Beclin1 mRNA and protein were significantly increased in spermatozoa from infertile patients of different etiologies in comparison to healthy controls. However, DYNLT1 mRNA expression was significantly decreased in infertile groups than controls. Mature spermatozoa extracted from all studied subjects showed increased DYNLT1 mRNA and decreased Beclin1 mRNA and protein expression compared with the whole sample. (PMID:31382319)
• DYNLT1 gene expression is downregulated in whole blood of patients at different Huntington’s disease stages. (PMID:32995988)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	dynlt1b	ENSDARG00000045909
danio_rerio	dynlt1a	ENSDARG00000094627
mus_musculus	Dynlt1c	ENSMUSG00000000579
mus_musculus	Dynlt1a	ENSMUSG00000092074
mus_musculus	Dynlt1f	ENSMUSG00000095677
mus_musculus	Dynlt1b	ENSMUSG00000096255
rattus_norvegicus	Dynlt1	ENSRNOG00000018207
drosophila_melanogaster	Dlc90F	FBGN0024432

Paralogs (5): DYNLT5 (ENSG00000152760), DYNLT3 (ENSG00000165169), DYNLT2 (ENSG00000184786), DYNLT4 (ENSG00000188396), DYNLT2B (ENSG00000213123)

Protein

Protein identifiers

Dynein light chain Tctex-type 1 — P63172 (reviewed: P63172)

Alternative names: Protein CW-1, T-complex testis-specific protein 1 homolog

All UniProt accessions (1): P63172

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. Binds to transport cargos and is involved in apical cargo transport such as rhodopsin-bearing vesicles in polarized epithelia. Plays a role in neuronal morphogenesis; the function is independent of cytoplasmic dynein and seems to be coupled to regulation of the actin cytoskeleton by enhancing Rac1 activity. The function in neurogenesis may be regulated by association with a G-protein beta-gamma dimer. May function as a receptor-independent activator of heterotrimeric G-protein signaling; the activation appears to be independent of a nucleotide exchange. Plays a role in regulating neurogenesis; inhibits the genesis of neurons from precursor cells during cortical development presumably by antagonizing ARHGEF2. Involved in the regulation of mitotic spindle orientation. Unrelated to the role in retrograde microtubule-associated movement may play a role in the dimerization of cytoplasmic proteins/domains such as for ACVR2B. Binds to the cytoplasmic domain of ACVR2B and, in vitro, inhibits ACVR2B signaling. (Microbial infection) Is involved in intracellular targeting of D-type retrovirus gag polyproteins to the cytoplasmic assembly site.

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. DYNLT1 and DYNLT3 compete for association with dynein IC (DYNC1I1 or DYNC1I2). Self-associates. 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 DYNC1I1 and DYNC1I2. Interacts with RHO. Interacts with DOC2A, DOC2B and SCN10A. Interacts with PVR. Interacts with SVIL isoform 2. Interacts with BMPR2. Interacts with GNB1; the interaction occurs in presence of guanine nucleotide-binding protein G(T) subunit gamma; the interaction diminishes the association of DYNLT1 with dynein IC (DYNC1I1 or DYNC1I2). Interacts with GNB2, GNB3 and GNB5; the interactions occur in presence of guanine nucleotide-binding protein G(T) subunit gamma. Interacts with ACVR2B and ARHGEF2. Interacts with DNAI4. Interacts with CFAP61. (Microbial infection) Interacts with human papillomavirus 16 L2 protein; this interaction is essential for virus intracellular transport during entry. (Microbial infection) Interacts with Mason-Pfizer monkey virus protein Gag.

Subcellular location. Golgi apparatus. Cytoplasm. Cytoskeleton. Spindle.

Tissue specificity. Expressed in heart, placenta, skeletal muscle kidney, pancreas, spleen, prostate, testis, ovary, ileum and colon. Expressed in lung endothelial and smooth muscle cells (at protein level).

Post-translational modifications. Phosphorylated by BMPR2; the phosphorylation is abolished by BMPR2 mutations in exon 12 which lead to truncated forms of BMPR2 and which are linked to primary pulmonary hypertension (PPH1) [MIM:178600]. The phosphorylation status is proposed to regulate the association with the cytoplasmic dynein complex and may have role in cytoplasmic dynein cargo release.

Similarity. Belongs to the dynein light chain Tctex-type family.

RefSeq proteins (3): NP_001278531, NP_001278532, NP_006510* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005334	Tctex-1-like	Family
IPR038586	Tctex-1-like_sf	Homologous_superfamily

Pfam: PF03645

UniProt features (14 total): strand 4, helix 4, turn 3, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
8RGI	X-RAY DIFFRACTION	2.02
9BLY	ELECTRON MICROSCOPY	3.5
8J07	ELECTRON MICROSCOPY	4.1
9E28	ELECTRON MICROSCOPY	4.4
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
5JPW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63172-F1	95.06	0.91

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 (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 387 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOCC_SECRETORY_GRANULE, GOBP_SPINDLE_LOCALIZATION, GOBP_REGULATION_BY_VIRUS_OF_VIRAL_PROTEIN_LEVELS_IN_HOST_CELL, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (11): establishment of mitotic spindle orientation (GO:0000132), microtubule-based movement (GO:0007018), nervous system development (GO:0007399), regulation of G protein-coupled receptor signaling pathway (GO:0008277), intracellular transport of viral protein in host cell (GO:0019060), positive regulation of intracellular transport (GO:0032388), symbiont entry into host cell (GO:0046718), negative regulation of neurogenesis (GO:0050768), cell division (GO:0051301), microtubule-dependent intracellular transport of viral material towards nucleus (GO:0075521), transport of viral material towards nucleus (GO:0075606)

GO Molecular Function (3): identical protein binding (GO:0042802), dynein intermediate chain binding (GO:0045505), protein binding (GO:0005515)

GO Cellular Component (13): extracellular region (GO:0005576), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), spindle (GO:0005819), cytoplasmic dynein complex (GO:0005868), cytoplasmic microtubule (GO:0005881), secretory granule lumen (GO:0034774), host cell (GO:0043657), secretory vesicle (GO:0099503), ficolin-1-rich granule lumen (GO:1904813), cytoskeleton (GO:0005856), microtubule (GO:0005874), dynein complex (GO:0030286)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cellular anatomical structure	2
cytoplasm	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
microtubule-based process	1
system development	1
G protein-coupled receptor signaling pathway	1
regulation of signal transduction	1
symbiont intracellular protein transport in host	1
regulation by virus of viral protein levels in host cell	1
regulation of intracellular transport	1
intracellular transport	1
positive regulation of cellular process	1
positive regulation of transport	1
viral life cycle	1
symbiont entry into host	1
negative regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
negative regulation of nervous system development	1
cellular process	1
microtubule-dependent intracellular transport of viral material	1
transport of viral material towards nucleus	1
intracellular transport of virus	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
dynein complex	1
microtubule	1
secretory granule	1
cytoplasmic vesicle lumen	1
host cellular component	1
cytoplasmic vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

1893 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNLT1	BMPR2	Q13873	935
DYNLT1	DYNLT4	Q5JR98	917
DYNLT1	DYNLL1	P63167	887
DYNLT1	RHO	P08100	820
DYNLT1	PVR	P15151	813
DYNLT1	ARHGEF2	Q92974	799
DYNLT1	DYNC2I1	Q8WVS4	775
DYNLT1	DYNLL2	Q96FJ2	769
DYNLT1	DRC5	Q5JU00	761
DYNLT1	VDAC1	P21796	757
DYNLT1	SPART	Q8N0X7	753
DYNLT1	DYNLRB1	Q9NP97	741
DYNLT1	DYNLRB2	Q8TF09	731
DYNLT1	HLA-C	P04222	719
DYNLT1	DYNC1LI2	O43237	710

IntAct

167 interactions, top by confidence:

A	B	Type	Score
DYNLT1	DYNLT2B	psi-mi:“MI:0915”(physical association)	0.790
DYNLT2B	DYNLT1	psi-mi:“MI:0914”(association)	0.790
DYNLT3	DYNLT1	psi-mi:“MI:0915”(physical association)	0.730
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.680
DYNLT1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
MARK1	DYNLT1	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	HSPB7	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	PITX2	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	MARK1	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	OLFM3	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	LNX1	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	DYNLT1	psi-mi:“MI:0915”(physical association)	0.560
ACTN1	DYNLT1	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	DYNC1I2	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	NHSL2	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	RRAGA	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	KLK15	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	ACOX2	psi-mi:“MI:0915”(physical association)	0.560
PTH2R	DYNLT1	psi-mi:“MI:0915”(physical association)	0.560
	DYNLT1	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	AARSD1	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (318): DYNC1H1 (Co-fractionation), DYNLT1 (Co-fractionation), DYNLT1 (Co-fractionation), DYNLT1 (Co-fractionation), LMNA (Co-fractionation), LMNB2 (Co-fractionation), NPEPPS (Co-fractionation), SUMO3 (Co-fractionation), DYNLT1 (Two-hybrid), DYNLT1 (Reconstituted Complex), DYNLT1 (Proximity Label-MS), AAK1 (Proximity Label-MS), ADD3 (Proximity Label-MS), ARFGAP3 (Proximity Label-MS), ARFIP1 (Proximity Label-MS)

ESM2 similar proteins: B0BN93, B4F6Y3, B5G0G8, F1QGH9, F6P3G4, O54956, O88653, P56282, P63171, P63172, P84169, Q17QQ1, Q2TBL9, Q3SX43, Q3T102, Q4R5H6, Q4SSF5, Q503S6, Q5E964, Q5FVD6, Q5R3Z6, Q5R8I6, Q5R9J9, Q5RES2, Q5U204, Q5ZIP2, Q63486, Q63ZJ2, Q69BT7, Q6DF40, Q6PC62, Q6Y228, Q6Z844, Q7L523, Q7T0T2, Q7T0V2, Q80X95, Q8IWZ6, Q8K0F1, Q8K2G4

Diamond homologs: F1QMY1, P51807, P51808, P56387, P63171, P63172, Q54PG1, Q5NVF5, Q6XXL8, Q8SPS9, Q94524, Q9Z336, Q8WW35, Q9CQ66, A2VDD2, P11985, Q3B8D7, Q32P71, Q5JR98, Q66IC8, Q8N7M0, Q9D5I4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DYNLT1	“down-regulates activity”	ARHGEF2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 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
Aggrephagy	12	46.5×	1e-15
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	14	42.3×	3e-17
COPI-independent Golgi-to-ER retrograde traffic	12	38.9×	8e-15
Intraflagellar transport	11	34.4×	5e-13
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	13	23.7×	3e-13
EML4 and NUDC in mitotic spindle formation	16	23.2×	9e-16
Resolution of Sister Chromatid Cohesion	16	21.6×	1e-15
Loss of Nlp from mitotic centrosomes	8	19.8×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary retrograde transport	5	66.9×	1e-06
microtubule-based movement	9	31.7×	3e-09
microtubule cytoskeleton organization	12	17.3×	3e-09
cell division	10	5.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58157	GRCh38/hg38 6q25.3(chr6:157827805-159726548)x3	Pathogenic

SpliceAI

901 predictions. Top by Δscore:

Variant	Effect	Δscore
6:158637204:CACT:C	acceptor_gain	1.0000
6:158637207:T:TC	acceptor_gain	1.0000
6:158637766:ATTAC:A	donor_loss	1.0000
6:158637767:TTA:T	donor_loss	1.0000
6:158637768:TA:T	donor_loss	1.0000
6:158637825:C:CT	donor_gain	1.0000
6:158637826:T:TT	donor_gain	1.0000
6:158641316:TA:T	donor_loss	1.0000
6:158641318:C:CA	donor_loss	1.0000
6:158641318:CCT:C	donor_gain	1.0000
6:158641356:GCAGT:G	acceptor_gain	1.0000
6:158641357:CAGT:C	acceptor_gain	1.0000
6:158641357:CAGTC:C	acceptor_gain	1.0000
6:158641358:AGTC:A	acceptor_loss	1.0000
6:158641361:C:CC	acceptor_gain	1.0000
6:158641361:CT:C	acceptor_loss	1.0000
6:158641362:T:A	acceptor_loss	1.0000
6:158644683:T:TA	donor_gain	1.0000
6:158636894:CTCC:C	acceptor_gain	0.9900
6:158636896:CC:C	acceptor_gain	0.9900
6:158636897:CC:C	acceptor_gain	0.9900
6:158636898:C:CC	acceptor_gain	0.9900
6:158637204:CA:C	acceptor_gain	0.9900
6:158637206:C:CC	acceptor_gain	0.9900
6:158637207:T:C	acceptor_gain	0.9900
6:158637769:A:AC	donor_gain	0.9900
6:158637770:C:CC	donor_gain	0.9900
6:158637891:TAGC:T	acceptor_gain	0.9900
6:158637894:CCTAG:C	acceptor_loss	0.9900
6:158637895:C:CC	acceptor_gain	0.9900

AlphaMissense

751 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:158636840:C:T	G110E	1.000
6:158636857:G:C	C104W	1.000
6:158637131:C:G	D90H	1.000
6:158637146:A:G	W85R	1.000
6:158637146:A:T	W85R	1.000
6:158637198:A:C	C67W	1.000
6:158637803:A:G	L54P	1.000
6:158637840:A:G	W42R	1.000
6:158637840:A:T	W42R	1.000
6:158636837:A:G	L111P	0.999
6:158636841:C:G	G110R	0.999
6:158636841:C:T	G110R	0.999
6:158636842:G:C	F109L	0.999
6:158636842:G:T	F109L	0.999
6:158636844:A:G	F109L	0.999
6:158636852:A:T	V106D	0.999
6:158636859:A:G	C104R	0.999
6:158636878:C:A	W97C	0.999
6:158636878:C:G	W97C	0.999
6:158636880:A:G	W97R	0.999
6:158636880:A:T	W97R	0.999
6:158637130:T:A	D90V	0.999
6:158637131:C:A	D90Y	0.999
6:158637144:C:A	W85C	0.999
6:158637144:C:G	W85C	0.999
6:158637155:A:G	S82P	0.999
6:158637160:G:T	A80E	0.999
6:158637161:C:G	A80P	0.999
6:158637172:C:T	G76E	0.999
6:158637173:C:G	G76R	0.999

dbSNP variants (sampled 300 via entrez): RS1000160813 (6:158638695 C>G,T), RS1000349597 (6:158640287 C>A,T), RS1000377034 (6:158644326 C>A,T), RS1000420457 (6:158646254 C>T), RS1000497962 (6:158637409 A>G), RS1000572952 (6:158637138 G>C), RS1000743572 (6:158644488 C>T), RS1001112582 (6:158643003 G>A), RS1001364723 (6:158644941 C>A,G), RS1001418417 (6:158644765 C>G,T), RS1001553790 (6:158643963 G>T), RS1001599775 (6:158639229 T>C), RS1001757633 (6:158638915 A>G), RS1001854801 (6:158642869 A>G), RS1001914868 (6:158644251 A>C)

Disease associations

OMIM: gene MIM:601554 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4742281 (PROTEIN-PROTEIN INTERACTION)

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
bisphenol A	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	decreases expression, affects expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Benzophenoneidum	increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Phenolsulfonphthalein	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, 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
CHEMBL4713749	Binding	Protac activity at CRBN/DYNLT1 in human BxPC-3 cells assessed as DYNLT1 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Clinical trials (associated diseases)

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