DCTN6

Summary

DCTN6 (dynactin subunit 6, HGNC:16964) is a protein-coding gene on chromosome 8p12, encoding Dynactin subunit 6 (O00399). Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. It is a common-essential gene (DepMap: required in 97.7% of cancer cell lines).

The protein encoded by this gene contains an RGD (Arg-Gly-Asp) motif in the N-terminal region, which confers adhesive properties to macromolecular proteins like fibronectin. It shares a high degree of sequence similarity with the mouse homolog, which has been suggested to play a role in mitochondrial biogenesis. The exact biological function of this gene is not known.

Source: NCBI Gene 10671 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 31 total
• Cancer dependency (DepMap): dependent in 97.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_006571

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16964
Approved symbol	DCTN6
Name	dynactin subunit 6
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	WS-3, p27
Ensembl gene	ENSG00000104671
Ensembl biotype	protein_coding
OMIM	612963
Entrez	10671

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000221114, ENST00000519830, ENST00000520829, ENST00000522141, ENST00000522540, ENST00000523666, ENST00000882954, ENST00000882955, ENST00000882956

RefSeq mRNA: 1 — MANE Select: NM_006571 NM_006571

CCDS: CCDS6076

Canonical transcript exons

ENST00000221114 — 7 exons

Exon	Start	End
ENSE00002095991	30183075	30183639
ENSE00003500202	30180488	30180630
ENSE00003531027	30177126	30177214
ENSE00003564634	30175085	30175190
ENSE00003572086	30156369	30156406
ENSE00003578822	30179408	30179455
ENSE00003675511	30164111	30164175

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 97.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.2031 / max 904.2777, expressed in 1810 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88290	40.1690	1807
88289	5.8745	1692
88288	0.1070	38
88287	0.0526	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
myocardium	UBERON:0002349	97.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.12	gold quality
heart right ventricle	UBERON:0002080	97.11	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.07	gold quality
vena cava	UBERON:0004087	97.00	gold quality
spinal cord	UBERON:0002240	96.93	gold quality
subthalamic nucleus	UBERON:0001906	96.89	gold quality
medial globus pallidus	UBERON:0002477	96.87	gold quality
pons	UBERON:0000988	96.77	gold quality
globus pallidus	UBERON:0001875	96.76	gold quality
substantia nigra pars compacta	UBERON:0001965	96.71	gold quality
ganglionic eminence	UBERON:0004023	96.68	gold quality
left ventricle myocardium	UBERON:0006566	96.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.65	gold quality
substantia nigra	UBERON:0002038	96.64	gold quality
postcentral gyrus	UBERON:0002581	96.56	gold quality
adrenal tissue	UBERON:0018303	96.53	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.50	gold quality
midbrain	UBERON:0001891	96.46	gold quality
hypothalamus	UBERON:0001898	96.37	gold quality
lateral globus pallidus	UBERON:0002476	96.33	gold quality
calcaneal tendon	UBERON:0003701	96.30	gold quality
islet of Langerhans	UBERON:0000006	96.23	gold quality
amygdala	UBERON:0001876	96.20	gold quality
corpus callosum	UBERON:0002336	96.19	gold quality
type B pancreatic cell	CL:0000169	96.07	gold quality
cortical plate	UBERON:0005343	96.00	gold quality
nucleus accumbens	UBERON:0001882	95.97	gold quality
orbitofrontal cortex	UBERON:0004167	95.95	gold quality
caudate nucleus	UBERON:0001873	95.91	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	1322.79
E-CURD-10	no	312.66
E-CURD-112	no	2.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1

miRNA regulators (miRDB)

52 targeting DCTN6, 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-548C-3P	99.99	74.01	7587
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-4677-3P	99.49	67.91	1246

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• Dynactin helps target Polo-like kinase 1 to kinetochores via its left-handed beta-helical p27 subunit. (PMID:23455152)
• Study on the Prognostic Values of Dynactin Genes in Low-Grade Glioma. (PMID:33896271)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dctn6	ENSMUSG00000031516
rattus_norvegicus	Dctn6	ENSRNOG00000013254
drosophila_melanogaster	DCTN6-p27	FBGN0086446
caenorhabditis_elegans	dnc-6	WBGENE00021827

Protein

Protein identifiers

Dynactin subunit 6 — O00399 (reviewed: O00399)

Alternative names: Dynactin subunit p27, Protein WS-3

All UniProt accessions (5): E5RFU3, E5RGW9, E5RIK5, E5RK00, O00399

UniProt curated annotations — full annotation on UniProt →

Function. Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.

Subunit / interactions. Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. Within the complex DCTN6 forms a heterodimer with DCTN5. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin. Interacts with PLK1. Interacts with N4BP2L1.

Subcellular location. Cytoplasm. Cytoskeleton. Chromosome. Centromere. Kinetochore.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylation at Thr-186 by CDK1 during mitotic prometaphase creates a binding site for PLK1 that facilitates its recruitment to kinetochores.

Similarity. Belongs to the dynactin subunits 5/6 family. Dynactin subunit 6 subfamily.

RefSeq proteins (1): NP_006562* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011004	Trimer_LpxA-like_sf	Homologous_superfamily
IPR027777	DCTN6	Family

UniProt features (13 total): strand 11, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3TV0	X-RAY DIFFRACTION	2.15
9B85	ELECTRON MICROSCOPY	3.47
9B7J	ELECTRON MICROSCOPY	3.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00399-F1	70.40	0.06

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): 186

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic

MSigDB gene sets: 178 (showing top): FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, REACTOME_MEMBRANE_TRAFFICKING, GOCC_MICROTUBULE_ORGANIZING_CENTER, ZHAN_V2_LATE_DIFFERENTIATION_GENES, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, GOCC_CENTROSOME, GOBP_MITOTIC_CELL_CYCLE, SCHLOSSER_SERUM_RESPONSE_DN, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, chr8p12, WONG_MITOCHONDRIA_GENE_MODULE, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, GOCC_CHROMOSOMAL_REGION

GO Biological Process (1): mitotic spindle organization (GO:0007052)

GO Molecular Function (1): dynein complex binding (GO:0070840)

GO Cellular Component (9): kinetochore (GO:0000776), centrosome (GO:0005813), cytosol (GO:0005829), dynactin complex (GO:0005869), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Adaptive Immune System	1
Cellular responses to stress	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
intracellular membraneless organelle	3
cellular anatomical structure	2
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
protein-containing complex binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
centriole	1
microtubule organizing center	1
cytoplasm	1
microtubule associated complex	1
actin cytoskeleton	1
chromosomal region	1
intracellular anatomical structure	1
cytoskeleton	1

Protein interactions and networks

STRING

1150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCTN6	DCTN4	Q9UJW0	955
DCTN6	DCTN5	Q9BTE1	953
DCTN6	DYNC1H1	Q14204	918
DCTN6	ACTR10	Q9NZ32	905
DCTN6	DCTN3	O75935	859
DCTN6	DCTN1	Q14203	812
DCTN6	ACTR3C	Q9C0K3	803
DCTN6	ACTR3B	Q9P1U1	791
DCTN6	TPPP	O94811	768
DCTN6	RBPMS	Q93062	767
DCTN6	DCTN2	Q13561	759
DCTN6	DYNC1LI2	O43237	756
DCTN6	DYNC1LI1	Q9Y6G9	685
DCTN6	DYNLRB1	Q9NP97	654
DCTN6	ACTR1A	P42024	646

IntAct

101 interactions, top by confidence:

A	B	Type	Score
MED22	MED19	psi-mi:“MI:0914”(association)	0.790
DCTN1	DCTN6	psi-mi:“MI:0914”(association)	0.780
DCTN2	DCTN6	psi-mi:“MI:0914”(association)	0.730
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
MIS18A	DCTN6	psi-mi:“MI:0914”(association)	0.640
DCTN5	DCTN6	psi-mi:“MI:0914”(association)	0.640
MAPK8IP3	RCCD1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
Dctn2	DCTN6	psi-mi:“MI:0914”(association)	0.560
INAVA	DCTN6	psi-mi:“MI:0914”(association)	0.530
UQCRH	DCTN6	psi-mi:“MI:0914”(association)	0.530
GPS2	DCTN6	psi-mi:“MI:0914”(association)	0.530
RPS19BP1	DCTN6	psi-mi:“MI:0914”(association)	0.530
SPMIP6	DCTN6	psi-mi:“MI:0914”(association)	0.530
BMERB1	DCTN6	psi-mi:“MI:0914”(association)	0.530
MAPK8IP3	DCTN6	psi-mi:“MI:0914”(association)	0.530
ORC6	DCTN6	psi-mi:“MI:0914”(association)	0.530
DEFB127	DCTN6	psi-mi:“MI:0914”(association)	0.530
DCTN6	ZBTB43	psi-mi:“MI:0914”(association)	0.530

BioGRID (129): DCTN6 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), DCTN5 (Co-fractionation), DCTN6 (Co-fractionation), DCTN6 (Co-fractionation), DCTN6 (Two-hybrid), DCTN6 (Proximity Label-MS), DCTN6 (Affinity Capture-MS)

ESM2 similar proteins: A0A286ZK88, A1L1L6, A7MB28, A8WGF4, B8BJ39, D0G6S1, O00399, O54956, P11029, P11497, Q13085, Q148G7, Q28007, Q28943, Q28DR7, Q2HJF8, Q2RAK2, Q4R4U1, Q502J7, Q5FVD6, Q5R559, Q5R5F8, Q5R7D8, Q5R8Q7, Q5SWU9, Q5ZIT8, Q5ZM73, Q6AYR2, Q6NVC5, Q6NWV3, Q6P1X5, Q6PC62, Q7TPD1, Q7TSL3, Q86XK2, Q8BG51, Q8BH44, Q8C176, Q8CHR6, Q8IWZ6

Diamond homologs: A7SGU3, A8WWC0, D0G6S1, O00399, Q148G7, Q28DR7, Q502J7, Q54FM4, Q5R7D8, Q9N3F1, Q9WUB4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK1	“up-regulates activity”	DCTN6	phosphorylation
DCTN6	“up-regulates activity”	PLK1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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	6	29.7×	6e-06
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	27.6×	6e-06
Loss of Nlp from mitotic centrosomes	5	18.9×	3e-04
Loss of proteins required for interphase microtubule organization from the centrosome	5	18.9×	3e-04
AURKA Activation by TPX2	5	18.1×	3e-04
MHC class II antigen presentation	8	17.0×	5e-06
Recruitment of mitotic centrosome proteins and complexes	5	16.2×	4e-04
COPI-mediated anterograde transport	6	15.7×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1000 predictions. Top by Δscore:

Variant	Effect	Δscore
8:30156403:AGAGG:A	donor_loss	1.0000
8:30156404:GAG:G	donor_gain	1.0000
8:30156404:GAGG:G	donor_loss	1.0000
8:30156407:GTGG:G	donor_loss	1.0000
8:30156408:T:A	donor_loss	1.0000
8:30164109:A:AG	acceptor_gain	1.0000
8:30164110:G:GA	acceptor_gain	1.0000
8:30164110:GT:G	acceptor_gain	1.0000
8:30164172:ATCGG:A	donor_loss	1.0000
8:30164174:CGGT:C	donor_loss	1.0000
8:30164175:GGTAA:G	donor_loss	1.0000
8:30164176:G:GG	donor_gain	1.0000
8:30164176:G:T	donor_loss	1.0000
8:30164177:T:A	donor_loss	1.0000
8:30175189:GC:G	donor_gain	1.0000
8:30175191:G:GG	donor_gain	1.0000
8:30177124:A:AG	acceptor_gain	1.0000
8:30177125:G:GA	acceptor_gain	1.0000
8:30177125:GT:G	acceptor_gain	1.0000
8:30177125:GTT:G	acceptor_gain	1.0000
8:30177125:GTTA:G	acceptor_gain	1.0000
8:30177125:GTTAC:G	acceptor_gain	1.0000
8:30177199:TTTG:T	donor_gain	1.0000
8:30177202:G:GT	donor_gain	1.0000
8:30180484:GCA:G	acceptor_loss	1.0000
8:30180486:A:AG	acceptor_gain	1.0000
8:30180487:G:GT	acceptor_gain	1.0000
8:30180487:GC:G	acceptor_gain	1.0000
8:30180487:GCA:G	acceptor_gain	1.0000
8:30180487:GCAT:G	acceptor_gain	1.0000

AlphaMissense

1251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:30164137:T:A	V17E	1.000
8:30164139:T:C	C18R	1.000
8:30164140:G:A	C18Y	1.000
8:30164141:T:G	C18W	1.000
8:30164160:G:A	G25R	1.000
8:30164160:G:C	G25R	1.000
8:30164161:G:A	G25E	1.000
8:30164173:T:A	I29N	1.000
8:30175094:C:A	T33K	1.000
8:30175097:T:A	V34E	1.000
8:30175102:C:G	H36D	1.000
8:30175103:A:G	H36R	1.000
8:30175105:C:T	P37S	1.000
8:30175106:C:A	P37H	1.000
8:30175118:T:A	I41N	1.000
8:30175139:T:A	I48K	1.000
8:30175139:T:G	I48R	1.000
8:30175145:T:A	I50N	1.000
8:30175158:C:A	N54K	1.000
8:30175158:C:G	N54K	1.000
8:30175160:T:C	L55P	1.000
8:30175163:T:A	I56K	1.000
8:30175166:A:T	E57V	1.000
8:30175169:A:T	E58V	1.000
8:30177195:T:A	N88K	1.000
8:30177195:T:G	N88K	1.000
8:30179439:T:A	N105K	1.000
8:30179439:T:G	N105K	1.000
8:30180523:T:C	C123R	1.000
8:30180525:C:G	C123W	1.000

dbSNP variants (sampled 300 via entrez): RS1000093106 (8:30176369 A>C), RS1000156469 (8:30157293 A>G), RS1000165544 (8:30179168 A>G), RS1000193317 (8:30177008 C>T), RS1000388650 (8:30172819 A>G), RS1000443187 (8:30157581 G>T), RS1000467716 (8:30181122 T>G), RS1000491355 (8:30165679 T>A,C), RS1000498751 (8:30180724 G>A,T), RS1000529144 (8:30175553 T>G), RS1000819764 (8:30169901 G>A,T), RS1000824904 (8:30167223 T>A), RS1000880807 (8:30167568 G>T), RS1000938963 (8:30161113 C>G), RS1001082223 (8:30182238 T>A)

Disease associations

OMIM: gene MIM:612963 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003985_22	Breast size	1.000000e-06
GCST90011900_205	Serum alkaline phosphatase levels	5.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
Particulate Matter	increases abundance, increases expression, affects expression, increases reaction	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
trichostatin A	affects expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	affects expression, increases reaction	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Rotenone	increases expression	1
Testosterone	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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