DDX20

Summary

DDX20 (DEAD-box helicase 20, HGNC:2743) is a protein-coding gene on chromosome 1p13.2, encoding Probable ATP-dependent RNA helicase DDX20 (Q9UHI6). The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. It is a common-essential gene (DepMap: required in 96.4% of cancer cell lines).

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs.

Source: NCBI Gene 11218 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 81 total
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 96.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_007204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2743
Approved symbol	DDX20
Name	DEAD-box helicase 20
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	DP103, GEMIN3
Ensembl gene	ENSG00000064703
Ensembl biotype	protein_coding
OMIM	606168
Entrez	11218

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 12 retained_intron, 5 protein_coding, 5 nonsense_mediated_decay

ENST00000369702, ENST00000475700, ENST00000524894, ENST00000533164, ENST00000534200, ENST00000679381, ENST00000679498, ENST00000679576, ENST00000679724, ENST00000679774, ENST00000680038, ENST00000680317, ENST00000680383, ENST00000680415, ENST00000680518, ENST00000680627, ENST00000680936, ENST00000680983, ENST00000681529, ENST00000681559, ENST00000681747, ENST00000937510

RefSeq mRNA: 1 — MANE Select: NM_007204 NM_007204

CCDS: CCDS842

Canonical transcript exons

ENST00000369702 — 11 exons

Exon	Start	End
ENSE00000783731	111756646	111756740
ENSE00000783732	111759400	111759568
ENSE00001142728	111765737	111768000
ENSE00001450683	111755901	111756225
ENSE00003529832	111762906	111763007
ENSE00003530441	111760987	111761125
ENSE00003608070	111762255	111762337
ENSE00003654711	111762677	111762782
ENSE00003670557	111760706	111760848
ENSE00003682768	111761226	111761284
ENSE00003686144	111760474	111760588

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.2001 / max 173.2166, expressed in 1801 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4657	15.4863	1792
4656	3.0675	1397
4658	0.3643	161
4652	0.1534	15
4651	0.0649	19
4654	0.0395	5
4655	0.0243	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.66	gold quality
left testis	UBERON:0004533	95.10	gold quality
right testis	UBERON:0004534	94.93	gold quality
testis	UBERON:0000473	93.76	gold quality
adult organism	UBERON:0007023	93.28	gold quality
tibialis anterior	UBERON:0001385	91.30	gold quality
secondary oocyte	CL:0000655	89.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.75	gold quality
epithelial cell of pancreas	CL:0000083	86.43	gold quality
ileal mucosa	UBERON:0000331	86.25	gold quality
deltoid	UBERON:0001476	86.01	silver quality
calcaneal tendon	UBERON:0003701	84.95	gold quality
epithelium of nasopharynx	UBERON:0001951	83.57	gold quality
cauda epididymis	UBERON:0004360	83.47	gold quality
adrenal tissue	UBERON:0018303	82.78	gold quality
gastrocnemius	UBERON:0001388	82.52	gold quality
caput epididymis	UBERON:0004358	82.51	gold quality
upper arm skin	UBERON:0004263	82.26	gold quality
muscle of leg	UBERON:0001383	82.20	gold quality
bronchial epithelial cell	CL:0002328	82.11	gold quality
lower lobe of lung	UBERON:0008949	81.97	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.69	gold quality
stromal cell of endometrium	CL:0002255	81.66	gold quality
kidney epithelium	UBERON:0004819	81.60	silver quality
bronchus	UBERON:0002185	81.34	gold quality
ganglionic eminence	UBERON:0004023	81.28	gold quality
islet of Langerhans	UBERON:0000006	81.14	gold quality
cortical plate	UBERON:0005343	80.94	gold quality
biceps brachii	UBERON:0001507	80.93	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	383.50
E-ANND-3	no	4.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR2, ETV3, NR5A1

miRNA regulators (miRDB)

50 targeting DDX20, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-2392	99.43	67.50	708

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• Gemin3 and Gemin4 function in Sm core assembly and correlate the activity of this pathway with Spinal Muscular Atrophy. (PMID:16301532)
• Data show that the two motor neuropathy-associated mutant HspB8 forms have abnormally increased binding to Ddx20. (PMID:20157854)
• utilised a targeted screen to identify mRNA associated with SMN, Gemin2 and Gemin3 in the cytoplasm of a human neuroblastoma cell line, SHSY5Y (PMID:20620147)
• NANOS1-PUMILIO2 complex, together with GEMIN3 and small noncoding RNAs, possibly regulate mRNA translation within the chromatoid body of the human germ cells. (PMID:21800163)
• Gemin3 binds with p53, forming a complex, and plays an anti-apoptotic role by repressing the p53 expression in Saos-2 cells. (PMID:22335944)
• While DDX20 normally suppresses NF-kappaB activity by regulating NF-kappaB-suppressing miRNA-140 function, this suppressive effect was lost in DDX20-deficient cells. (PMID:22445758)
• Impairment of miRNA-140 function due to a deficiency of DDX20, a miRNA machinery component, could lead to hepatocarcinogenesis (PMID:22898998)
• DP103 defines metastatic potential of human breast cancers. (PMID:25083991)
• In stage-adjusted analysis, the nominal associations of DDX20-rs197412, PTGS2-rs5275, and HSPA5-rs391957 with DFS were detected. However, after FDR correction none of these polymorphisms remained significantly associated with the survival outcomes (PMID:26064972)
• The findings show that DDX20 may promote the progression of prostate cancer through the NF-kappaB pathway. (PMID:27121695)
• Our data has shown that GEMIN3 gene (rs197388) polymorphisms might be associated with a risk of POAG development in the Polish population. This is the first report evaluating the polymorphic variants of miRNA processing genes, RAN and GEMIN3, with a changed risk of glaucoma. (PMID:29095070)
• Death-associated protein kinase 1 suppresses hepatocellular carcinoma cell migration and invasion by upregulation of DEAD-box helicase 20. (PMID:32449268)
• Human bone mesenchymal stem cells-derived exosomal miRNA-361-5p alleviates osteoarthritis by downregulating DDX20 and inactivating the NF-kappaB signaling pathway. (PMID:34052737)
• The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma. (PMID:34290392)
• Genetic Variation in DEAD-Box Helicase 20 as a Putative Marker of Recurrence in Propensity-Matched Colon Cancer Patients. (PMID:36011315)
• A Macrophage Differentiation-Mediated Gene: DDX20 as a Molecular Biomarker Encompassing the Tumor Microenvironment, Disease Staging, and Prognoses in Hepatocellular Carcinoma. (PMID:36246406)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddx20	ENSDARG00000061204
mus_musculus	Ddx20	ENSMUSG00000027905
rattus_norvegicus	Ddx20	ENSRNOG00000015274
drosophila_melanogaster	Gem3	FBGN0011802
caenorhabditis_elegans		WBGENE00020284

Paralogs (38): DDX3Y (ENSG00000067048), DDX1 (ENSG00000079785), DDX43 (ENSG00000080007), DDX18 (ENSG00000088205), DDX24 (ENSG00000089737), DDX17 (ENSG00000100201), DDX49 (ENSG00000105671), DDX50 (ENSG00000107625), DDX5 (ENSG00000108654), DDX25 (ENSG00000109832), DDX6 (ENSG00000110367), DDX55 (ENSG00000111364), DDX59 (ENSG00000118197), DDX54 (ENSG00000123064), DDX39A (ENSG00000123136), DDX27 (ENSG00000124228), DDX31 (ENSG00000125485), DDX56 (ENSG00000136271), EIF4A3 (ENSG00000141543), DDX46 (ENSG00000145833), DDX4 (ENSG00000152670), EIF4A2 (ENSG00000156976), DDX19B (ENSG00000157349), EIF4A1 (ENSG00000161960), DDX21 (ENSG00000165732), DDX19A (ENSG00000168872), TDRD12 (ENSG00000173809), DDX23 (ENSG00000174243), DDX10 (ENSG00000178105), DDX28 (ENSG00000182810), DDX41 (ENSG00000183258), DDX53 (ENSG00000184735), DDX51 (ENSG00000185163), DDX42 (ENSG00000198231), DDX39B (ENSG00000198563), DDX47 (ENSG00000213782), DDX3X (ENSG00000215301), DDX52 (ENSG00000278053)

Protein

Protein identifiers

Probable ATP-dependent RNA helicase DDX20 — Q9UHI6 (reviewed: Q9UHI6)

Alternative names: Component of gems 3, DEAD box protein 20, DEAD box protein DP 103, Gemin-3

All UniProt accessions (7): Q9UHI6, A0A7P0T8G7, A0A7P0T9T8, A0A7P0TB94, A0A7P0TBA6, A0A7P0Z4I9, A0A7P0Z4K8

UniProt curated annotations — full annotation on UniProt →

Function. The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs).

Subunit / interactions. Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG. Interacts with SMN1; the interaction is direct. Interacts with GEMIN4; the interaction is direct. Interacts with GEMIN5. Interacts with SNUPN; the interaction is direct. Interacts with PPP4R2. Interacts with FOXL2. Interacts with EBV EBNA2 and EBNA3C. Interacts with NANOS1 and PUM2.

Subcellular location. Cytoplasm. Nucleus. Gem.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the DEAD box helicase family. DDX20 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UHI6-1	1	yes
Q9UHI6-2	2

RefSeq proteins (1): NP_009135* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000629	RNA-helicase_DEAD-box_CS	Conserved_site
IPR001650	Helicase_C-like	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014014	RNA_helicase_DEAD_Q_motif	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00270, PF00271

Catalyzed reactions (Rhea), 2 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
• a ribonucleoside 5’-triphosphate + H2O = a ribonucleoside 5’-diphosphate + phosphate + H(+) (RHEA:23680)

UniProt features (68 total): modified residue 19, helix 11, strand 7, compositionally biased region 6, sequence conflict 6, region of interest 4, binding site 3, sequence variant 3, domain 2, splice variant 2, turn 2, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2OXC	X-RAY DIFFRACTION	1.3
3B7G	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHI6-F1	61.40	0.30

Functional residue map

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

Ligand- & substrate-binding residues (3): 84; 89; 109–114

Post-translational modifications (19): 48, 187, 268, 269, 500, 505, 532, 552, 560, 652, 654, 656, 672, 677, 678, 688, 703, 705, 714

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-191859	snRNP Assembly
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery

MSigDB gene sets: 132 (showing top): GOBP_OOGENESIS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, WANG_LMO4_TARGETS_DN, GOBP_STEROID_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GARY_CD5_TARGETS_DN, GOBP_LIPID_METABOLIC_PROCESS, BIOCARTA_ETS_PATHWAY, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_FEMALE_GAMETE_GENERATION

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), spliceosomal tri-snRNP complex assembly (GO:0000244), spliceosomal snRNP assembly (GO:0000387), RNA processing (GO:0006396), negative regulation of cell population proliferation (GO:0008285), positive regulation of apoptotic process (GO:0043065), oogenesis (GO:0048477), regulation of steroid biosynthetic process (GO:0050810), mRNA processing (GO:0006397), RNA splicing (GO:0008380), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (15): DNA binding (GO:0003677), RNA helicase activity (GO:0003724), mRNA binding (GO:0003729), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein domain specific binding (GO:0019904), protein-macromolecule adaptor activity (GO:0030674), histone deacetylase binding (GO:0042826), DNA-binding transcription factor binding (GO:0140297), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787), ribonucleoside triphosphate phosphatase activity (GO:0017111)

GO Cellular Component (13): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), membrane (GO:0016020), nuclear body (GO:0016604), SMN complex (GO:0032797), SMN-Sm protein complex (GO:0034719), RNA polymerase II transcription repressor complex (GO:0090571), Gemini of Cajal bodies (GO:0097504), transcription repressor complex (GO:0017053), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of non-coding RNA	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA processing	2
ATP-dependent activity	2
protein binding	2
binding	2
cytoplasm	2
intracellular membraneless organelle	2
Sm-like protein family complex	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
spliceosomal snRNP assembly	1
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
germ cell development	1
female gamete generation	1
steroid biosynthetic process	1
regulation of steroid metabolic process	1
regulation of lipid biosynthetic process	1
mRNA metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
RNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1

Protein interactions and networks

STRING

3429 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX20	GEMIN2	O14893	999
DDX20	GEMIN4	P57678	999
DDX20	AGO2	Q9UKV8	998
DDX20	GEMIN5	Q8TEQ6	998
DDX20	GEMIN6	Q8WXD5	994
DDX20	GEMIN7	Q9H840	943
DDX20	AGO1	Q9UL18	927
DDX20	STRAP	Q9Y3F4	879
DDX20	FOXL2	P58012	853
DDX20	TP53	P04637	832
DDX20	GEMIN8	Q9NWZ8	815
DDX20	DICER1	Q9UPY3	795
DDX20	SMN1	Q16637	782
DDX20	NR5A1	Q13285	745
DDX20	FMR1	Q06787	723

IntAct

236 interactions, top by confidence:

A	B	Type	Score
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
GEMIN4	DDX20	psi-mi:“MI:0915”(physical association)	0.910
DDX20	SMN1	psi-mi:“MI:0915”(physical association)	0.910
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
SMN1	SNRPB	psi-mi:“MI:0914”(association)	0.850
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCKIPSD	GEMIN2	psi-mi:“MI:0914”(association)	0.640
SNRNP70	GEMIN2	psi-mi:“MI:0914”(association)	0.640
SMN1	PRMT5	psi-mi:“MI:0914”(association)	0.600
DDX20	A2M	psi-mi:“MI:0915”(physical association)	0.560
DDX20	DNM2	psi-mi:“MI:0915”(physical association)	0.560
DDX20	TOR1A	psi-mi:“MI:0915”(physical association)	0.560
DDX20		psi-mi:“MI:0915”(physical association)	0.560
DDX20	MECP2	psi-mi:“MI:0915”(physical association)	0.560
DDX20	GDAP1	psi-mi:“MI:0915”(physical association)	0.560
HTT	DDX20	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (386): DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-Western), DDX20 (Affinity Capture-MS), DDX20 (Reconstituted Complex), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX20 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HTT5, A0A2R6W1B1, A2XC52, A6QR44, B9F4I8, F4I9G2, F4JSE7, O88566, O94763, P35922, P53349, P55265, Q06787, Q13233, Q1EQW7, Q2R2B1, Q3UDK1, Q3ULM0, Q53NI2, Q5E9N5, Q5EAH9, Q5QLS7, Q62925, Q63505, Q651A1, Q6PHZ5, Q7T3U0, Q7TN31, Q80Z10, Q80ZW0, Q86UB2, Q8CBX9, Q8CDG3, Q8CF97, Q8CFE5, Q8H8C6, Q8IPH9, Q8IVF5, Q8K284, Q8N9B5

Diamond homologs: A1CJ18, A1CJT5, A1D071, A1D7N3, A1D8G1, A2QEN5, A2QY39, A4QU31, A4QVP2, A4RBS3, A5A6N4, A5DIP0, A5DVM3, A6QSQ0, A6R3R5, A6RJ45, A6ZQJ1, A6ZXG9, A7EGL7, A7EIX7, A7TGU7, A7TK55, O00148, O02494, O13792, P0C218, P0CQ70, P0CQ71, P0CQ96, P0CQ97, P10081, P10630, P26196, P27639, P29562, P39517, P47943, P54823, P54824, P60024

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
DDX20	up-regulates	FOXL2	binding
ETV3	“down-regulates quantity by repression”	DDX20	“transcriptional regulation”
DDX20	“form complex”	“SMN complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
Metabolism of non-coding RNA	9	39.6×	5e-11
snRNP Assembly	17	25.0×	4e-17
SARS-CoV-2 modulates host translation machinery	13	20.2×	1e-11
RNA Polymerase II Transcription Termination	9	13.7×	8e-07
mRNA Splicing - Minor Pathway	8	12.4×	1e-05
mRNA Splicing	16	12.2×	4e-11
mRNA Polyadenylation	16	9.8×	5e-10
Processing of Capped Intron-Containing Pre-mRNA	17	9.7×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	16	53.1×	7e-22
spliceosomal complex assembly	7	24.1×	3e-06
U2-type prespliceosome assembly	6	21.4×	6e-05
mRNA splicing, via spliceosome	21	11.0×	2e-13
RNA splicing	15	7.6×	6e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1443 predictions. Top by Δscore:

Variant	Effect	Δscore
1:111756223:TCGG:T	donor_loss	1.0000
1:111756226:G:C	donor_loss	1.0000
1:111756226:G:GG	donor_gain	1.0000
1:111756227:T:A	donor_loss	1.0000
1:111756642:GCA:G	acceptor_loss	1.0000
1:111756643:CA:C	acceptor_loss	1.0000
1:111756644:A:AG	acceptor_gain	1.0000
1:111756644:A:AT	acceptor_loss	1.0000
1:111756645:G:GG	acceptor_gain	1.0000
1:111756737:CCAGG:C	donor_loss	1.0000
1:111756739:AGGTG:A	donor_loss	1.0000
1:111756741:GT:G	donor_loss	1.0000
1:111756742:T:A	donor_loss	1.0000
1:111759394:TTTTA:T	acceptor_loss	1.0000
1:111759395:TTTA:T	acceptor_loss	1.0000
1:111759396:TTA:T	acceptor_loss	1.0000
1:111759397:TA:T	acceptor_loss	1.0000
1:111759398:A:AG	acceptor_gain	1.0000
1:111759398:A:T	acceptor_loss	1.0000
1:111759399:G:GA	acceptor_gain	1.0000
1:111760468:A:AG	acceptor_gain	1.0000
1:111760469:A:G	acceptor_gain	1.0000
1:111760472:A:AG	acceptor_gain	1.0000
1:111760473:G:GT	acceptor_gain	1.0000
1:111760473:GGCA:G	acceptor_gain	1.0000
1:111760584:ATAAA:A	donor_gain	1.0000
1:111760585:TAAA:T	donor_gain	1.0000
1:111760586:AAA:A	donor_gain	1.0000
1:111760587:AA:A	donor_gain	1.0000
1:111760588:AG:A	donor_loss	1.0000

AlphaMissense

5422 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:111756655:T:A	V104D	1.000
1:111759413:C:A	A137D	1.000
1:111759431:C:A	A143D	1.000
1:111759554:C:A	A184D	1.000
1:111759557:T:A	V185D	1.000
1:111759559:G:A	G186R	1.000
1:111759559:G:C	G186R	1.000
1:111759560:G:A	G186E	1.000
1:111760489:T:C	L194P	1.000
1:111760537:T:C	L210P	1.000
1:111760543:A:T	E212V	1.000
1:111760555:T:C	L216P	1.000
1:111761104:T:A	V314D	1.000
1:111762759:G:C	R396P	1.000
1:111756198:G:C	A92P	0.999
1:111756210:G:A	G96R	0.999
1:111756210:G:C	G96R	0.999
1:111756210:G:T	G96W	0.999
1:111756211:G:A	G96E	0.999
1:111756646:A:T	D101V	0.999
1:111756660:G:C	A106P	0.999
1:111756675:G:T	G111W	0.999
1:111756676:G:A	G111E	0.999
1:111756676:G:T	G111V	0.999
1:111756678:A:C	K112Q	0.999
1:111756679:A:T	K112I	0.999
1:111756703:C:A	A120D	0.999
1:111759422:G:T	R140I	0.999
1:111759423:A:C	R140S	0.999
1:111759423:A:T	R140S	0.999

dbSNP variants (sampled 300 via entrez): RS1000037753 (1:111757224 G>A), RS1000067426 (1:111763916 T>C), RS1000220277 (1:111761290 T>C), RS1000536865 (1:111767116 C>A), RS1000616736 (1:111758936 T>A,C), RS1001620808 (1:111766251 T>C), RS1001660937 (1:111754235 C>T), RS1001784317 (1:111759986 A>G), RS1002051324 (1:111760001 G>A,T), RS1002114180 (1:111758703 C>T), RS1002283616 (1:111755386 G>T), RS1002425323 (1:111754878 T>G), RS1002655987 (1:111755333 T>C), RS1002695124 (1:111760250 G>A), RS1003457038 (1:111758086 G>A)

Disease associations

OMIM: gene MIM:606168 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (1): Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0007354	Amyotrophic lateral sclerosis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008129_5	Body mass index	8.000000e-13
GCST009391_1348	Metabolite levels	5.000000e-07
GCST009391_593	Metabolite levels	8.000000e-06
GCST009936_7	Venous thromboembolism	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010363	lysophosphatidylcholine 20:4 measurement
EFO:0010501	indole-3-propionate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067394 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs197388	DDX20, INKA2		0.00	0

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.63	Kd	23.6	nM	CHEMBL5653589
7.54	ED50	28.52	nM	CHEMBL5653589
6.29	Kd	509.8	nM	CHEMBL3752910
6.21	ED50	616	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148219: Binding affinity to human DDX20 incubated for 45 mins by Kinobead based pull down assay	kd	0.0236	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148219: Binding affinity to human DDX20 incubated for 45 mins by Kinobead based pull down assay	kd	0.5098	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases activity	3
Valproic Acid	affects expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	increases methylation	1
coumarin	affects phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
cylindrospermopsin	increases 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, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Caffeine	affects phosphorylation	1
Catechin	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	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
CHEMBL5651261	Binding	Binding affinity to human DDX20 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW17	K562 eGFP-DDX20	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS