DSTN

gene
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Also known as ADFACTDP

Summary

DSTN (destrin, actin depolymerizing factor, HGNC:15750) is a protein-coding gene on chromosome 20p12.1, encoding Destrin (P60981). Actin-depolymerizing protein. It is a selective cancer dependency (DepMap: 10.2% of cell lines).

The product of this gene belongs to the actin-binding proteins ADF family. This family of proteins is responsible for enhancing the turnover rate of actin in vivo. This gene encodes the actin depolymerizing protein that severs actin filaments (F-actin) and binds to actin monomers (G-actin). Two transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 11034 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 17 total
  • Druggable target: yes
  • Cancer dependency (DepMap): dependent in 10.2% of screened cell lines
  • MANE Select transcript: NM_006870

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:15750
Approved symbolDSTN
Namedestrin, actin depolymerizing factor
Location20p12.1
Locus typegene with protein product
StatusApproved
AliasesADF, ACTDP
Ensembl geneENSG00000125868
Ensembl biotypeprotein_coding
OMIM609114
Entrez11034

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000246069, ENST00000449141, ENST00000474024, ENST00000888381, ENST00000925115, ENST00000925116, ENST00000955166

RefSeq mRNA: 2 — MANE Select: NM_006870 NM_001011546, NM_006870

CCDS: CCDS13127, CCDS46580

Canonical transcript exons

ENST00000246069 — 4 exons

ExonStartEnd
ENSE000017102021757007517570211
ENSE000034590311760703717609919
ENSE000034937061760073817601045
ENSE000037025891760455517604631

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 287.5698 / max 2127.3404, expressed in 1825 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
183652273.77081825
1836539.41441631
1836493.12811071
1836510.5376244
1836500.3805198
1836480.3385203

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
blood vessel layerUBERON:000479799.97gold quality
saphenous veinUBERON:000731899.97gold quality
urethraUBERON:000005799.95gold quality
popliteal arteryUBERON:000225099.93gold quality
tibial arteryUBERON:000761099.93gold quality
right coronary arteryUBERON:000162599.92gold quality
arteryUBERON:000163799.92gold quality
aortaUBERON:000094799.91gold quality
descending thoracic aortaUBERON:000234599.90gold quality
vena cavaUBERON:000408799.90gold quality
ascending aortaUBERON:000149699.88gold quality
thoracic aortaUBERON:000151599.88gold quality
superficial temporal arteryUBERON:000161499.87gold quality
cauda epididymisUBERON:000436099.86gold quality
lower esophagus muscularis layerUBERON:003583399.85gold quality
seminal vesicleUBERON:000099899.84gold quality
coronary arteryUBERON:000162199.84gold quality
lower esophagusUBERON:001347399.84gold quality
left coronary arteryUBERON:000162699.83gold quality
esophagogastric junction muscularis propriaUBERON:003584199.81gold quality
bronchial epithelial cellCL:000232899.80gold quality
mucosa of stomachUBERON:000119999.80gold quality
lower lobe of lungUBERON:000894999.80gold quality
ponsUBERON:000098899.79gold quality
adult organismUBERON:000702399.79gold quality
smooth muscle tissueUBERON:000113599.77gold quality
cardia of stomachUBERON:000116299.77gold quality
muscle layer of sigmoid colonUBERON:003580599.76gold quality
penisUBERON:000098999.74gold quality
pylorusUBERON:000116699.73gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 25.

ExperimentMarker?Max mean expression
E-CURD-126yes6642.58
E-HCAD-36yes5332.53
E-MTAB-10287yes5048.57
E-MTAB-10885yes4601.43
E-MTAB-8410yes4509.24
E-MTAB-8322yes4158.30
E-HCAD-13yes3075.68
E-MTAB-8381yes2944.65
E-MTAB-8142yes2721.45
E-MTAB-9906yes2218.02
E-HCAD-1yes211.24
E-GEOD-134144yes34.79
E-GEOD-137537yes31.31
E-MTAB-6678yes28.74
E-CURD-46yes28.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF331

miRNA regulators (miRDB)

71 targeting DSTN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4668-3P100.0068.742635
HSA-MIR-656-3P100.0072.152788
HSA-MIR-186-5P99.9970.833707
HSA-MIR-1250-3P99.9670.044038
HSA-MIR-1236-3P99.9468.041695
HSA-MIR-335-3P99.9373.364958
HSA-MIR-314399.9371.963104
HSA-MIR-10527-5P99.9172.283754
HSA-MIR-4753-3P99.9071.033786
HSA-MIR-95-5P99.8972.173973
HSA-MIR-7162-3P99.8968.161682
HSA-MIR-153-5P99.8973.866317
HSA-MIR-5582-3P99.8672.484221
HSA-MIR-607999.8468.541170
HSA-MIR-6875-3P99.8270.262983
HSA-MIR-313399.8170.923506
HSA-MIR-4760-5P99.8069.881619
HSA-MIR-44899.7972.372103
HSA-MIR-548AJ-5P99.7871.123085
HSA-MIR-548F-5P99.7871.023093
HSA-MIR-548G-5P99.7871.123085
HSA-MIR-548X-5P99.7871.123085
HSA-MIR-3680-3P99.7572.513095
HSA-MIR-6885-3P99.7570.363187
HSA-MIR-46699.6770.852863
HSA-MIR-4804-3P99.6567.78866
HSA-MIR-806199.6369.441411
HSA-MIR-885-5P99.5968.59879
HSA-MIR-427699.5667.662514
HSA-MIR-451B99.5568.281380

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

  • differences in actin binding by human ADF and cofilin (PMID:11812157)
  • Important sequence differences between actin-depolymerizing factor/cofilin were correlated with unique structural determinants in the F-actin-binding site to account for differences in biochemical activities of the two proteins. (PMID:14627701)
  • downregulated following UV exposure in epidermis (PMID:15816841)
  • In the absence of any crystal structures of ADF or cofilin in complex with actin, these studies provide further information about the binding sites on F-actin for these important actin regulatory proteins. (PMID:17196218)
  • destrin is a significant regulator of various processes important for invasive phenotype of human colon cancer Isreco1 cells whereas cofilin-1 may be involved in only a subset of them (PMID:17583572)
  • The results of this study suggested that temporally regulated ADF/cofilin activities function in postsynaptic modifications of receptor number and spine size during synaptic plasticity. (PMID:20835250)
  • Changes in the expression of cytoskeletal regulatory proteins such as LIMK and cofilin may play a role in weakening thoracic aortic medial tissue, as a precondition to thoracic aortic dissection. (PMID:20873970)
  • The ADF/cofilin1-dependent severing of actin filaments exposes and promotes the activation of SPCA1, which pumps Ca(2+) into the lumen of the TGN for the sorting of the class of secretory cargo that binds Ca(2+). (PMID:21571222)
  • Destrin is upregulated in nerve-invasive pancreatic cancer cells and its expression might be related to perineural invasiveness (PMID:22898637)
  • analysis of human Cof1, Cof2, and ADF effects on actin filament severing and turnover (PMID:26996939)
  • Destrin Contributes to Lung Adenocarcinoma Progression by Activating Wnt/beta-Catenin Signaling Pathway. (PMID:32878967)
  • Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes. (PMID:34120636)
  • ADF and cofilin-1 collaborate to promote cortical actin flow and the leader bleb-based migration of confined cells. (PMID:34169836)
  • The actin depolymerizing factor destrin serves as a negative feedback inhibitor of smooth muscle cell differentiation. (PMID:34559579)
  • DSTN Hypomethylation Promotes Radiotherapy Resistance of Rectal Cancer by Activating the Wnt/beta-Catenin Signaling Pathway. (PMID:37019366)

Cross-species orthologs

7 orthologs

OrganismSymbolGene ID
mus_musculusDstnENSMUSG00000015932
rattus_norvegicusDstnENSRNOG00000005924
rattus_norvegicusENSRNOG00000073635
drosophila_melanogastertsrFBGN0011726
drosophila_melanogasterCG6873FBGN0030951
caenorhabditis_elegansWBGENE00006794
caenorhabditis_elegansWBGENE00302980

Paralogs (2): CFL2 (ENSG00000165410), CFL1 (ENSG00000172757)

Protein

Protein identifiers

DestrinP60981 (reviewed: P60981)

Alternative names: Actin-depolymerizing factor

All UniProt accessions (3): P60981, F6RFD5, V9HWA6

UniProt curated annotations — full annotation on UniProt →

Function. Actin-depolymerizing protein. Severs actin filaments (F-actin) and binds to actin monomers (G-actin). Acts in a pH-independent manner.

Tissue specificity. Widely distributed in various tissues.

Post-translational modifications. ISGylated.

Similarity. Belongs to the actin-binding proteins ADF family.

Isoforms (2)

UniProt IDNamesCanonical?
P60981-11yes
P60981-22

RefSeq proteins (2): NP_001011546, NP_006861* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR002108ADF-HDomain
IPR017904ADF/CofilinFamily
IPR029006ADF-H/Gelsolin-like_dom_sfHomologous_superfamily

Pfam: PF00241

UniProt features (9 total): modified residue 3, initiator methionine 1, chain 1, domain 1, short sequence motif 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P60981-F187.030.28

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): 2, 3, 19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 267 (showing top): FREAC2_01, GRUETZMANN_PANCREATIC_CANCER_DN, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, HSIAO_HOUSEKEEPING_GENES, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOLDRATH_ANTIGEN_RESPONSE, SRF_Q5_01, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN, SRF_C, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP

GO Biological Process (6): actin polymerization or depolymerization (GO:0008154), actin filament depolymerization (GO:0030042), actin filament fragmentation (GO:0030043), positive regulation of actin filament depolymerization (GO:0030836), cell motility (GO:0048870), actin filament severing (GO:0051014)

GO Molecular Function (3): actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), actin cytoskeleton (GO:0015629), cortical actin cytoskeleton (GO:0030864), extracellular exosome (GO:0070062), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
synapse3
actin filament depolymerization2
actin filament organization1
actin polymerization or depolymerization1
protein depolymerization1
regulation of actin filament depolymerization1
positive regulation of cytoskeleton organization1
positive regulation of protein depolymerization1
positive regulation of supramolecular fiber organization1
cellular process1
actin filament-based process1
actin binding1
protein-containing complex binding1
cytoskeletal protein binding1
binding1
intracellular anatomical structure1
cytoskeleton1
actin cytoskeleton1
cortical cytoskeleton1
extracellular vesicle1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

105 interactions, top by confidence:

ABTypeScore
DSTNACTBpsi-mi:“MI:0915”(physical association)0.900
ACTBDSTNpsi-mi:“MI:0915”(physical association)0.900
AKR7A3AKR7A2psi-mi:“MI:0914”(association)0.890
DSTNACTG1psi-mi:“MI:0915”(physical association)0.790
ACTG1DSTNpsi-mi:“MI:0915”(physical association)0.790
CFTRDSTNpsi-mi:“MI:0915”(physical association)0.740
TAX1BP1DSTNpsi-mi:“MI:0915”(physical association)0.720
DSTNTAX1BP1psi-mi:“MI:0915”(physical association)0.720
CFTRESYT2psi-mi:“MI:0914”(association)0.710
CFL1CAP2psi-mi:“MI:0914”(association)0.640
CFTRHAX1psi-mi:“MI:0914”(association)0.610
DSTNPS1TP5BP1psi-mi:“MI:0915”(physical association)0.560

BioGRID (244): DSTN (Two-hybrid), DSTN (Two-hybrid), DSTN (Two-hybrid), DSTN (Two-hybrid), DSTN (Affinity Capture-MS), DSTN (Two-hybrid), DSTN (Two-hybrid), ABAT (Co-fractionation), ALDH4A1 (Co-fractionation), DSTN (Co-fractionation), DSTN (Co-fractionation), DSTN (Co-fractionation), DSTN (Co-fractionation), DSTN (Co-fractionation), DSTN (Co-fractionation)

ESM2 similar proteins: O60234, O88600, O95757, P10668, P18359, P18760, P21566, P23514, P23528, P34932, P45591, P45592, P45593, P45594, P45695, P48722, P54577, P60981, P60982, P60983, P60984, Q03048, Q148F1, Q2TFN9, Q4I963, Q4KM49, Q4R5C0, Q56JZ9, Q5E9D5, Q5E9F7, Q5G6V9, Q5R6P6, Q5R8T5, Q5RDM4, Q5U4Y2, Q5XHH8, Q5ZJ08, Q61316, Q63228, Q6B7M7

Diamond homologs: C4LVG4, O49606, P0CM06, P0CM07, P0DJ26, P0DJ27, P10668, P18359, P18760, P23528, P30174, P30175, P37167, P45592, P45594, P46251, P60981, P60982, P78929, P86293, Q03048, Q0D744, Q0DLA3, Q17A58, Q2QLT8, Q337A5, Q39250, Q39251, Q41764, Q43694, Q4I963, Q4P6E9, Q4R5C0, Q54R65, Q570Y6, Q5E9D5, Q5E9F7, Q5I082, Q5ZM35, Q640W2

SIGNOR signaling

1 interactions.

AEffectBMechanism
TESK2“down-regulates activity”DSTNphosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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:

PathwayPartnersFoldFDR
Signaling by VEGF522.0×1e-03
Regulation of actin dynamics for phagocytic cup formation518.4×1e-03
Leishmania infection516.3×1e-03
Parasitic Infection Pathways516.3×1e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane515.4×1e-03
VEGFA-VEGFR2 Pathway513.9×1e-03
MAPK family signaling cascades510.3×3e-03
Diseases of signal transduction by growth factor receptors and second messengers78.0×1e-03

GO biological processes:

GO termPartnersFoldFDR
Ras protein signal transduction515.3×3e-03
transforming growth factor beta receptor signaling pathway614.2×2e-03
axonogenesis512.0×6e-03
positive regulation of cell migration87.4×3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance12
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1007 predictions. Top by Δscore:

VariantEffectΔscore
20:17601043:GTG:Gdonor_gain1.0000
20:17601045:GGTA:Gdonor_loss1.0000
20:17601046:GT:Gdonor_loss1.0000
20:17570208:GATG:Gdonor_gain0.9900
20:17570209:ATGG:Adonor_loss0.9900
20:17570210:TG:Tdonor_gain0.9900
20:17570210:TGGT:Tdonor_loss0.9900
20:17570211:GG:Gdonor_gain0.9900
20:17570212:G:GGdonor_gain0.9900
20:17570212:G:Tdonor_loss0.9900
20:17570213:TGA:Tdonor_loss0.9900
20:17570214:GAG:Gdonor_loss0.9900
20:17590477:ATGGG:Aacceptor_gain0.9900
20:17600733:CATA:Cacceptor_loss0.9900
20:17600735:TAGGC:Tacceptor_loss0.9900
20:17600736:A:AGacceptor_gain0.9900
20:17600736:A:Gacceptor_loss0.9900
20:17600737:G:GGacceptor_gain0.9900
20:17600737:G:GTacceptor_loss0.9900
20:17601023:G:GTdonor_gain0.9900
20:17601046:G:GGdonor_gain0.9900
20:17601047:T:Gdonor_loss0.9900
20:17601048:AA:Adonor_loss0.9900
20:17604552:TAGG:Tacceptor_loss0.9900
20:17604553:A:AGacceptor_gain0.9900
20:17604554:G:GAacceptor_loss0.9900
20:17604554:G:GGacceptor_gain0.9900
20:17604542:T:Gacceptor_gain0.9800
20:17604553:AG:Aacceptor_gain0.9800
20:17604554:GG:Gacceptor_gain0.9800

AlphaMissense

1096 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
20:17600744:G:AG4R1.000
20:17600744:G:CG4R1.000
20:17600745:G:AG4E1.000
20:17600978:T:CY82H1.000
20:17600999:T:CF89L1.000
20:17601001:T:AF89L1.000
20:17601001:T:GF89L1.000
20:17601044:T:AW104R1.000
20:17601044:T:CW104R1.000
20:17604585:A:CK114N1.000
20:17604585:A:TK114N1.000
20:17604587:T:AM115K1.000
20:17604587:T:CM115T1.000
20:17604587:T:GM115R1.000
20:17604602:C:TS120F1.000
20:17600745:G:TG4V0.999
20:17600777:T:CF15L0.999
20:17600779:T:AF15L0.999
20:17600779:T:GF15L0.999
20:17600791:A:CK19N0.999
20:17600791:A:TK19N0.999
20:17600830:A:CR32S0.999
20:17600830:A:TR32S0.999
20:17600836:G:CK34N0.999
20:17600836:G:TK34N0.999
20:17600841:T:AV36D0.999
20:17600847:T:CF38S0.999
20:17600874:T:AI47N0.999
20:17600874:T:CI47T0.999
20:17600874:T:GI47S0.999

dbSNP variants (sampled 300 via entrez): RS1000011717 (20:17605741 A>G), RS1000110313 (20:17579970 T>A), RS1000141934 (20:17589147 C>A,T), RS1000269101 (20:17586238 C>G), RS1000420569 (20:17593186 G>C), RS1000497831 (20:17609931 CTG>C), RS1000523595 (20:17600153 T>C), RS1000611030 (20:17573407 G>A,T), RS1000700560 (20:17606623 G>A), RS1000808552 (20:17585933 G>A), RS1000809018 (20:17568960 G>A), RS1000815338 (20:17606415 G>A), RS1000825712 (20:17579389 A>G), RS1000943079 (20:17568686 C>A,G,T), RS1001112318 (20:17581392 G>A)

Disease associations

OMIM: gene MIM:609114 | 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):

StudyTraitp-value
GCST001872_12Presence of antiphospholipid antibodies6.000000e-06
GCST005196_242Coronary artery disease1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725005 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
5.76Kd1744nMCHEMBL5653589
5.76ED501744nMCHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148266: Binding affinity to human DSTN incubated for 45 mins by Kinobead based pull down assaykd1.7440uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, decreases expression4
sodium arsenitedecreases expression, affects cotreatment3
Smokeincreases expression, decreases expression2
Tetrachlorodibenzodioxinincreases expression2
aristolochic acid Idecreases expression1
FR900359increases phosphorylation1
TAK-243increases sumoylation1
methylmercuric chloridedecreases expression1
triphenyl phosphateaffects expression1
bisphenol Aincreases expression1
lead acetateaffects cotreatment, decreases expression1
sodium arsenatedecreases expression1
pyrogallol 1,3-dimethyl etherdecreases expression, increases expression, affects cotreatment, affects localization1
kojic acidincreases expression1
arseniteincreases reaction, affects binding1
nickel sulfatedecreases expression1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamineincreases expression1
perfluorooctane sulfonic aciddecreases expression1
CGP 52608affects binding, increases reaction1
chloropicrinincreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
nutlin 3affects cotreatment, increases secretion1
ICG 001decreases expression1
bromovanindecreases expression1
dorsomorphinaffects cotreatment, increases expression1
bisphenol Sincreases expression1
jinfukangdecreases expression1
bisphenol AFincreases expression1
Resveratrolaffects expression1
Sunitinibincreases expression1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5651308BindingBinding affinity to human DSTN incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.