DCTN4

Summary

DCTN4 (dynactin subunit 4, HGNC:15518) is a protein-coding gene on chromosome 5q33.1, encoding Dynactin subunit 4 (Q9UJW0). Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. It is a selective cancer dependency (DepMap: 89.4% of cell lines).

Located in centrosome.

Source: NCBI Gene 51164 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystic fibrosis (Supportive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 85 total
• Phenotypes (HPO): 35
• Cancer dependency (DepMap): dependent in 89.4% of screened cell lines
• MANE Select transcript: NM_016221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15518
Approved symbol	DCTN4
Name	dynactin subunit 4
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	Dyn4, p62
Ensembl gene	ENSG00000132912
Ensembl biotype	protein_coding
OMIM	614758
Entrez	51164

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000424236, ENST00000446090, ENST00000447998, ENST00000517421, ENST00000518015, ENST00000518909, ENST00000519313, ENST00000519552, ENST00000520195, ENST00000521093, ENST00000521448, ENST00000521533, ENST00000521728, ENST00000522625, ENST00000627368, ENST00000873419, ENST00000873421, ENST00000957095

RefSeq mRNA: 3 — MANE Select: NM_016221 NM_001135643, NM_001135644, NM_016221

CCDS: CCDS4310, CCDS47310, CCDS47311

Canonical transcript exons

ENST00000447998 — 13 exons

Exon	Start	End
ENSE00001592269	150715565	150715662
ENSE00001822665	150758859	150759017
ENSE00001855401	150708440	150711362
ENSE00003481944	150756417	150756487
ENSE00003485379	150742114	150742157
ENSE00003503172	150731044	150731156
ENSE00003546545	150722907	150722980
ENSE00003594504	150719716	150719770
ENSE00003602781	150718276	150718383
ENSE00003631456	150730631	150730740
ENSE00003675391	150731416	150731489
ENSE00003682834	150753479	150753657
ENSE00003756970	150733368	150733475

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.3558 / max 361.1099, expressed in 1819 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64260	46.4684	1819
64259	0.3663	189
64258	0.1929	68
64257	0.1325	70
64255	0.0821	49
64256	0.0820	36
64261	0.0315	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	97.45	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.18	gold quality
pigmented layer of retina	UBERON:0001782	97.15	gold quality
cauda epididymis	UBERON:0004360	97.01	gold quality
adult organism	UBERON:0007023	96.98	gold quality
corpus epididymis	UBERON:0004359	96.82	gold quality
mammary duct	UBERON:0001765	96.72	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.71	gold quality
substantia nigra pars compacta	UBERON:0001965	96.68	gold quality
caput epididymis	UBERON:0004358	96.67	gold quality
seminal vesicle	UBERON:0000998	96.48	gold quality
secondary oocyte	CL:0000655	96.47	gold quality
parotid gland	UBERON:0001831	96.40	gold quality
germinal epithelium of ovary	UBERON:0001304	96.37	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.34	gold quality
ganglionic eminence	UBERON:0004023	96.28	gold quality
endothelial cell	CL:0000115	96.26	gold quality
parietal pleura	UBERON:0002400	96.24	gold quality
postcentral gyrus	UBERON:0002581	96.20	gold quality
adrenal tissue	UBERON:0018303	96.19	gold quality
lateral globus pallidus	UBERON:0002476	96.16	gold quality
cortical plate	UBERON:0005343	96.04	gold quality
entorhinal cortex	UBERON:0002728	96.03	gold quality
dorsal root ganglion	UBERON:0000044	95.95	gold quality
oocyte	CL:0000023	95.93	gold quality
subthalamic nucleus	UBERON:0001906	95.87	gold quality
parietal lobe	UBERON:0001872	95.68	gold quality
amniotic fluid	UBERON:0000173	95.67	gold quality
ventricular zone	UBERON:0003053	95.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6

miRNA regulators (miRDB)

149 targeting DCTN4, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• ATP7B interaction with p62 is a key component of the copper-induced trafficking pathway that delivers ATP7B to subapical vesicles of hepatocytes for the removal of excess copper into bile (PMID:16554302)
• used an extreme phenotype study to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis (PMID:22772370)
• Findings provide evidence that DCTN4 missense variants, especially p.Tyr263Cys, may be involved in the pathogenesis of chronic Pseudomonas aeruginosa infection in male with cystic fi brosis. (PMID:25763772)
• Study on the Prognostic Values of Dynactin Genes in Low-Grade Glioma. (PMID:33896271)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dctn4	ENSDARG00000023988
mus_musculus	Dctn4	ENSMUSG00000024603
rattus_norvegicus	Dctn4	ENSRNOG00000019298
drosophila_melanogaster	DCTN4-p62	FBGN0033206
caenorhabditis_elegans		WBGENE00016124

Protein

Protein identifiers

Dynactin subunit 4 — Q9UJW0 (reviewed: Q9UJW0)

Alternative names: Dynactin subunit p62

All UniProt accessions (6): A0A0S2Z5D4, E5RGG1, E5RI97, E5RK21, Q9UJW0, H9KVE0

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. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin. Interacts with ATP7B, but not ATP7A, in a copper-dependent manner. Interacts with ANK2; this interaction is required for localization at costameres. Interacts with N4BP2L1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Stress fiber. Cell cortex. Myofibril. Sarcomere.

Similarity. Belongs to the dynactin subunit 4 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UJW0-1	1	yes
Q9UJW0-2	2
Q9UJW0-3	3

RefSeq proteins (3): NP_001129115, NP_001129116, NP_057305* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008603	DCTN4	Family

Pfam: PF05502

UniProt features (25 total): mutagenesis site 12, sequence variant 4, modified residue 3, splice variant 2, initiator methionine 1, chain 1, coiled-coil region 1, cross-link 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9B85	ELECTRON MICROSCOPY	3.47
9B7J	ELECTRON MICROSCOPY	3.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJW0-F1	84.78	0.65

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 (4): 2, 196, 407, 215

Mutagenesis-validated functional residues (12):

Position	Phenotype
30	loss of atp7b-binding; when associated with s-33; s-51; s-54; s-70, s-73; s-76; s-79; s-111; s-114; s-277 and s-280.
33	loss of atp7b-binding; when associated with s-30; s-51; s-54; s-70, s-73; s-76; s-79; s-111; s-114; s-277 and s-280.
51	loss of atp7b-binding; when associated with s-30; s-33; s-54; s-70, s-73; s-76; s-79; s-111; s-114; s-277 and s-280.
54	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-70, s-73; s-76; s-79; s-111; s-114; s-277 and s-280.
70	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-54, s-73; s-76; s-79; s-111; s-114; s-277 and s-280.
73	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-54, s-70; s-76; s-79; s-111; s-114; s-277 and s-280.
76	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-54, s-70; s-73; s-79; s-111; s-114; s-277 and s-280.
79	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-54, s-70; s-73; s-76; s-111; s-114; s-277 and s-280.
111	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-54, s-70; s-73; s-76; s-79; s-114; s-277 and s-280.
114	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-54, s-70; s-73; s-76; s-79; s-111; s-277 and s-280.
277	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-54, s-70; s-73; s-76; s-79; s-111; s-114 and s-280.
280	loss of atp7b-binding; when associated with s-30; s-33; s-51; s-54, s-70; s-73; s-76; s-79; s-111; s-114 and s-277.

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: 324 (showing top): AGGAAGC_MIR5163P, GCM_GSPT1, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, REACTOME_MEMBRANE_TRAFFICKING, GGGTGGRR_PAX4_03, GOCC_MICROTUBULE_ORGANIZING_CENTER, AGGCACT_MIR5153P, VERNELL_RETINOBLASTOMA_PATHWAY_DN, MARTINEZ_RB1_TARGETS_DN, USF_01, GOCC_CENTROSOME, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, KEGG_HUNTINGTONS_DISEASE

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (13): kinetochore (GO:0000776), spindle pole (GO:0000922), stress fiber (GO:0001725), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cytoplasmic dynein complex (GO:0005868), dynactin complex (GO:0005869), focal adhesion (GO:0005925), cell cortex (GO:0005938), sarcomere (GO:0030017), cytoskeleton (GO:0005856)

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
cellular anatomical structure	4
intracellular membraneless organelle	2
cytoplasm	2
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
spindle	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
dynein complex	1
microtubule associated complex	1
actin cytoskeleton	1
cell-substrate junction	1
cell periphery	1
myofibril	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCTN4	DCTN5	Q9BTE1	964
DCTN4	DCTN6	O00399	955
DCTN4	ACTR10	Q9NZ32	941
DCTN4	DCTN2	Q13561	929
DCTN4	ACTR3C	Q9C0K3	864
DCTN4	DCTN1	Q14203	810
DCTN4	TPPP	O94811	806
DCTN4	ACTR3B	Q9P1U1	767
DCTN4	ANK2	Q01484	699
DCTN4	ACTR1A	P42024	685
DCTN4	DCTN3	O75935	669
DCTN4	ACTR1B	P42025	649
DCTN4	CAPZA2	P47755	619
DCTN4	CAPZA1	P52907	608
DCTN4	TMOD4	Q9NZQ9	558

IntAct

126 interactions, top by confidence:

A	B	Type	Score
MED22	MED19	psi-mi:“MI:0914”(association)	0.790
ACTR1A	DCTN2	psi-mi:“MI:0914”(association)	0.790
DCTN4	GOLGA2	psi-mi:“MI:0915”(physical association)	0.780
GOLGA2	DCTN4	psi-mi:“MI:0915”(physical association)	0.780
DCTN1	DCTN6	psi-mi:“MI:0914”(association)	0.780
DCTN2	DCTN6	psi-mi:“MI:0914”(association)	0.730
DCTN2	DCTN3	psi-mi:“MI:0914”(association)	0.730
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DCTN1	DCTN3	psi-mi:“MI:0914”(association)	0.710
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.680
DCTN4	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
MTUS2	DCTN4	psi-mi:“MI:0915”(physical association)	0.670
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
DCTN5	DCTN6	psi-mi:“MI:0914”(association)	0.640
MIS18A	DCTN6	psi-mi:“MI:0914”(association)	0.640

BioGRID (236): DCTN4 (Two-hybrid), DCTN4 (Two-hybrid), DCTN4 (Two-hybrid), DCTN4 (Two-hybrid), DCTN4 (Affinity Capture-MS), DCTN4 (Affinity Capture-MS), DCTN4 (Affinity Capture-MS), DCTN4 (Affinity Capture-MS), DCTN4 (Affinity Capture-MS), DCTN4 (Affinity Capture-MS), ACTR1A (Co-fractionation), ACTR1B (Co-fractionation), CAPZA1 (Co-fractionation), CAPZA2 (Co-fractionation), CAPZB (Co-fractionation)

ESM2 similar proteins: A0A4X1TB62, A4VCH4, G3V7Q0, O14795, O35841, O43237, O70585, P23116, P48553, Q0P5J8, Q14152, Q15542, Q1JU68, Q3TLI0, Q3UHE1, Q4R5P6, Q5R660, Q5R7S4, Q5R7U7, Q5RE09, Q5RE70, Q5VSL9, Q5XI83, Q658Y4, Q68E01, Q6IQ26, Q6PAL8, Q6PDL0, Q6TEP1, Q6WKZ8, Q7SYD9, Q7TPD0, Q8BIK4, Q8BWQ6, Q8C079, Q8C092, Q8C9H6, Q8CBY8, Q8IWV8, Q8K400

Diamond homologs: A0A4X1TB62, Q5R7U7, Q8CBY8, Q9QUR2, Q9UJW0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ANK2	“up-regulates quantity”	DCTN4	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 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	17	51.2×	6e-23
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	17	47.7×	1e-22
Aggrephagy	10	36.0×	1e-11
COPI-mediated anterograde transport	19	30.2×	1e-21
Sensory processing of sound	6	26.8×	1e-06
RHO GTPases activate IQGAPs	5	25.1×	2e-05
MHC class II antigen presentation	19	24.6×	7e-20
Loss of Nlp from mitotic centrosomes	10	23.0×	6e-10

GO biological processes:

GO term	Partners	Fold	FDR
barbed-end actin filament capping	5	49.5×	3e-05
mitotic spindle organization	5	16.8×	2e-03
microtubule cytoskeleton organization	6	9.0×	6e-03
endocytosis	7	8.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2140 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150711358:TAATG:T	acceptor_gain	1.0000
5:150711360:ATG:A	acceptor_gain	1.0000
5:150711361:TG:T	acceptor_gain	1.0000
5:150711363:C:CC	acceptor_gain	1.0000
5:150711365:A:C	acceptor_gain	1.0000
5:150715558:CACT:C	donor_loss	1.0000
5:150715561:TCACT:T	donor_loss	1.0000
5:150715562:CACT:C	donor_loss	1.0000
5:150715563:A:AC	donor_gain	1.0000
5:150715564:C:CT	donor_gain	1.0000
5:150715564:C:G	donor_loss	1.0000
5:150715564:CT:C	donor_gain	1.0000
5:150715574:T:TA	donor_gain	1.0000
5:150719766:AATTG:A	acceptor_gain	1.0000
5:150719767:ATTG:A	acceptor_gain	1.0000
5:150719768:TTG:T	acceptor_gain	1.0000
5:150719769:TG:T	acceptor_gain	1.0000
5:150719769:TGCTG:T	acceptor_loss	1.0000
5:150719770:GCTG:G	acceptor_loss	1.0000
5:150719771:C:A	acceptor_loss	1.0000
5:150719771:C:CC	acceptor_gain	1.0000
5:150719772:T:G	acceptor_loss	1.0000
5:150719773:G:C	acceptor_gain	1.0000
5:150719773:G:GC	acceptor_gain	1.0000
5:150719776:C:CT	acceptor_gain	1.0000
5:150719777:A:C	acceptor_gain	1.0000
5:150722899:ATACT:A	donor_loss	1.0000
5:150722900:TACTT:T	donor_loss	1.0000
5:150722901:ACTTA:A	donor_loss	1.0000
5:150722902:CTTAC:C	donor_loss	1.0000

AlphaMissense

3012 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150722910:G:T	A302D	1.000
5:150722922:A:C	I298S	1.000
5:150722922:A:G	I298T	1.000
5:150722924:T:A	K297N	1.000
5:150722924:T:G	K297N	1.000
5:150722925:T:A	K297I	1.000
5:150722926:T:C	K297E	1.000
5:150722927:G:C	F296L	1.000
5:150722927:G:T	F296L	1.000
5:150722929:A:G	F296L	1.000
5:150722930:T:A	K295N	1.000
5:150722930:T:G	K295N	1.000
5:150722932:T:C	K295E	1.000
5:150722938:A:G	S293P	1.000
5:150722953:C:T	E288K	1.000
5:150722957:C:A	K286N	1.000
5:150722957:C:G	K286N	1.000
5:150722958:T:A	K286M	1.000
5:150722959:T:C	K286E	1.000
5:150722959:T:G	K286Q	1.000
5:150722964:A:C	L284W	1.000
5:150722964:A:G	L284S	1.000
5:150722966:A:C	N283K	1.000
5:150722966:A:T	N283K	1.000
5:150722970:T:G	H282P	1.000
5:150722971:G:C	H282D	1.000
5:150722975:A:C	C280W	1.000
5:150722976:C:A	C280F	1.000
5:150722976:C:G	C280S	1.000
5:150722976:C:T	C280Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000094028 (5:150730157 T>C), RS1000094136 (5:150719344 G>C), RS1000180638 (5:150747022 T>C,G), RS1000287471 (5:150758307 T>C,G), RS1000293874 (5:150753420 TG>T), RS1000396672 (5:150731644 G>A,C), RS1000406704 (5:150742227 C>G), RS1000422357 (5:150747226 T>C), RS1000443226 (5:150719976 C>T), RS1000444639 (5:150730461 G>A), RS1000623756 (5:150752151 C>G), RS1000693168 (5:150740911 AG>A,AGG), RS1000796503 (5:150708859 G>C), RS1000806357 (5:150746290 G>A), RS1000808401 (5:150753398 G>A)

Disease associations

OMIM: gene MIM:614758 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cystic fibrosis	Supportive	Autosomal recessive

Mondo (1): cystic fibrosis (MONDO:0009061)

Orphanet (0):

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001508	Failure to thrive
HP:0001738	Exocrine pancreatic insufficiency
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002035	Rectal prolapse
HP:0002099	Asthma
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002570	Steatorrhea
HP:0002724	Recurrent Aspergillus infections
HP:0002726	Recurrent Staphylococcus aureus infections
HP:0002783	Recurrent lower respiratory tract infections
HP:0002842	Recurrent Burkholderia cepacia infections
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003251	Male infertility
HP:0004401	Meconium ileus
HP:0005376	Recurrent Haemophilus influenzae infections
HP:0006536	Airway obstruction
HP:0012236	Elevated sweat chloride

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19
GCST004744_71	Lung adenocarcinoma	8.000000e-08
GCST005758_8	Dimensional psychopathology (Arousal)	5.000000e-07
GCST005855_1	Cholangiocarcinoma in primary sclerosing cholangitis	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009099	arousal domain measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases expression	3
cobaltous chloride	increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
decabromobiphenyl ether	increases expression	1
benzo(e)pyrene	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Dronabinol	decreases expression	1
Thiram	increases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis