DDX17

Summary

DDX17 (DEAD-box helicase 17, HGNC:2740) is a protein-coding gene on chromosome 22q13.1, encoding Probable ATP-dependent RNA helicase DDX17 (Q92841). As an RNA helicase, unwinds RNA and alters RNA structures through ATP binding and hydrolysis.

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 splicesosome 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 is an ATPase activated by a variety of RNA species, but not by dsDNA. This protein, and that encoded by DDX5 gene, are more closely related to each other than to any other member of the DEAD box family. This gene can encode multiple isoforms due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) start codon.

Source: NCBI Gene 10521 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 39 total — 3 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2740
Approved symbol	DDX17
Name	DEAD-box helicase 17
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	P72
Ensembl gene	ENSG00000100201
Ensembl biotype	protein_coding
OMIM	608469
Entrez	10521

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 protein_coding, 1 nonsense_mediated_decay

ENST00000216019, ENST00000396821, ENST00000403230, ENST00000431312, ENST00000432525, ENST00000467279, ENST00000475004, ENST00000477112, ENST00000479734, ENST00000497196

RefSeq mRNA: 2 — MANE Select: NM_006386 NM_001098504, NM_006386

CCDS: CCDS33646, CCDS46706

Canonical transcript exons

ENST00000403230 — 13 exons

Exon	Start	End
ENSE00000654335	38487879	38488115
ENSE00000880295	38505951	38506311
ENSE00001561956	38483438	38486440
ENSE00003470372	38494021	38494131
ENSE00003514079	38494630	38494802
ENSE00003542271	38498440	38498573
ENSE00003563080	38493710	38493771
ENSE00003569469	38501130	38501280
ENSE00003599537	38494886	38495046
ENSE00003603561	38492056	38492115
ENSE00003627468	38495796	38495937
ENSE00003656279	38498085	38498150
ENSE00003690878	38499400	38499499

Expression profiles

Bgee: expression breadth ubiquitous, 306 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 260.5476 / max 9280.8802, expressed in 1827 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194191	144.9011	1827
194192	49.3058	1819
194163	23.4010	1755
194165	22.8131	1744
194166	11.3320	1691
194162	6.0875	1489
194161	1.0889	601
194187	0.7866	390
194164	0.7729	382
194194	0.0537	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.85	gold quality
middle temporal gyrus	UBERON:0002771	99.85	gold quality
endothelial cell	CL:0000115	99.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.79	gold quality
germinal epithelium of ovary	UBERON:0001304	99.76	gold quality
pleura	UBERON:0000977	99.73	gold quality
parietal pleura	UBERON:0002400	99.73	gold quality
visceral pleura	UBERON:0002401	99.73	gold quality
choroid plexus epithelium	UBERON:0003911	99.72	gold quality
right uterine tube	UBERON:0001302	99.71	gold quality
bronchial epithelial cell	CL:0002328	99.65	gold quality
corpus callosum	UBERON:0002336	99.65	gold quality
upper leg skin	UBERON:0004262	99.64	gold quality
renal medulla	UBERON:0000362	99.63	gold quality
superficial temporal artery	UBERON:0001614	99.63	gold quality
parotid gland	UBERON:0001831	99.63	gold quality
caput epididymis	UBERON:0004358	99.63	gold quality
trabecular bone tissue	UBERON:0002483	99.62	gold quality
corpus epididymis	UBERON:0004359	99.62	gold quality
seminal vesicle	UBERON:0000998	99.61	gold quality
cardia of stomach	UBERON:0001162	99.61	gold quality
pituitary gland	UBERON:0000007	99.60	gold quality
skin of hip	UBERON:0001554	99.59	gold quality
right lobe of thyroid gland	UBERON:0001119	99.58	gold quality
ventricular zone	UBERON:0003053	99.57	gold quality
left lobe of thyroid gland	UBERON:0001120	99.56	gold quality
pylorus	UBERON:0001166	99.56	gold quality
thyroid gland	UBERON:0002046	99.55	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.55	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	22.58
E-GEOD-125970	yes	6.45
E-CURD-120	no	824.67
E-MTAB-6524	no	293.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ESR1, NFAT5, TP53

Literature-anchored findings (GeneRIF, showing 40)

• Alternate protein isoforms arise through the use of a non-AUG (CUG) and a downstream in-frame AUG translation initiation codons. (PMID:11675387)
• Results show that the abundant DEAD-box RNA helicase p72, but not its close relative p68, affects the splicing of alternative exons containing AC-rich exon enhancer elements. (PMID:12138182)
• has a role in pre-mRNA splicing, in particular, at the early stages of the splicing reaction involving U1snRNP (PMID:12193588)
• p72 is an important transcriptional regulator, functioning as a co-activator and/or co-repressor depending on the context of the promoter & the transcriptional complex. AA 1-474 of p72 can repress transcription as well as the full-length protein. (PMID:15298701)
• p72 RNA helicase may not only be involved in the p53-Mdm2 regulatory loop, but also profoundly impact on the transcriptome through various CBP/p300 and P/CAF interacting proteins. (PMID:17226766)
• p68/p72 may contribute to colon cancer formation by directly up-regulating proto-oncogenes and indirectly by down-regulating the growth suppressor p21(WAF1/CIP1). (PMID:17699760)
• The DEAD-box proteins p68(Ddx5) and p72(Ddx17) were used as models for this coexpression frequency analysis as there are defined functions for these proteins in splicing and transcription. (PMID:18005418)
• p72 is required for the optimal activity of zinc-finger antiviral protein (PMID:18334637)
• putative AR co-factor, DDX17, is known to be a co-factor for estrogen receptor alpha (ERalpha), but has never been associated (PMID:19059367)
• A crucial role for p72 in ERalpha co-activation and oestrogen-dependent cell growth. (PMID:19718048)
• Short-term exercise resulted in a significant increase of mRNA expression of genes encoding proteins involved in the formation of precatalytic splisosome: DDX17. (PMID:19902070)
• Pleiotropic effects of p300-mediated acetylation on p68 and p72 RNA helicase. (PMID:20663877)
• Data indicate that transcriptional coregulator ddx5/ddx17 RNA helicases can simultaneously regulate the transcriptional activity and alternative splicing of NFAT5 transcription factor. (PMID:22266867)
• RNA helicases Ddx17 and Ddx5 contribute to tumor-cell invasiveness by regulating alternative splicing of several DNA- and chromatin-binding factors, including the macroH2A1 histone. (PMID:23022728)
• DDX17 promotes the production of HIV-1 infectious particles by modulating HIV-1 RNA metabolism. (PMID:23769241)
• Downregulation of DDX5 and DDX17 protein expression during myogenesis and epithelial-to-mesenchymal transdifferentiation contributes to the switching of splicing programs during these processes. (PMID:24910439)
• Depletion of DDX17 but not the related helicase DDX5 increased Rift Valley fever virus replication in human cells. (PMID:25126784)
• Systematic Determination of Human Cyclin Dependent Kinase (CDK)-9 Interactome Identifies Novel Functions in RNA Splicing Mediated by the DDX5 and DDX17 RNA Helicases (PMID:26209609)
• DDX17 is a Sox2-binding protein in estrogen receptor-positive breast cancer; in reporter responsive (RR) cells but not reporter unresponsive (RU) cells, DDX17 enhances the tumorigenic and stem-like features of Sox2 by promoting its binding to its target genes (PMID:26569340)
• Mutant p53 protein (Mutp53) binds and sequesters RNA helicases p72/82 from microprocessor causing an attenuation of microRNAs (miRNAs) maturation. (PMID:26996669)
• Overexpression of p72 decreased Beclin1 expression partially by increasing miR-34-5p and miR-5195-3p expression in glioma cells. (PMID:27301285)
• The miRNA biogenesis factors, DDX17 and KHSRP, regulate the protein level of Ago2 in human cells. (PMID:27478153)
• DDX17 contributes to acquired gefitinib resistance through exportin/importin-dependent cytoplasmic shuttling and activation of beta-catenin in non-small lung cancer cells. (PMID:28259822)
• This study demonstrated that the association of DDX17delG in the treatment-resistant ophthalmoplegic subphenotype of myasthenia gravis. (PMID:28673556)
• Data indicate a central role for DEAD-box helicase 17 (DDX17) in the pathway involving transcription factor REST (REST) and miRNAs that allows neuronal gene repression. (PMID:29931089)
• The results of qRT-PCR for circDDX17 in 60 paired CRC tissues showed that circDDX17 was significantly down-regulated in CRC tissues and associated with unfavorable clinicopathological parameters. In vitro experiments showed that silencing of circDDX17 promoted CRC cell proliferation, migration, invasion, and inhibited apoptosis. (PMID:30591054)
• Hypoxia-induced polyubiquitination of DDX17 controls its dissociation from the pri-miRNA-Drosha-DCGR8 complex to reduce anti-stemness miRNA biogenesis and association with YAP and p300 to enhance transcription of stemness-related genes (PMID:30877109)
• DDX17 promotes hepatocellular carcinoma progression via inhibiting Klf4 transcriptional activity. (PMID:31653828)
• Upregulation of DEAD box helicase 5 and 17 are correlated with the progression and poor prognosis in gliomas. (PMID:32008867)
• Differential roles of two DDX17 isoforms in the formation of membraneless organelles. (PMID:32065632)
• CircDDX17 reduces 5-fluorouracil resistance and hinders tumorigenesis in colorectal cancer by regulating miR-31-5p/KANK1 axis. (PMID:32141542)
• The Significance of Circular RNA DDX17 in Prostate Cancer. (PMID:32904557)
• DDX17 is involved in DNA damage repair and modifies FUS toxicity in an RGG-domain dependent manner. (PMID:34061233)
• RNA Helicase DDX17 Inhibits Hepatitis B Virus Replication by Blocking Viral Pregenomic RNA Encapsidation. (PMID:34287051)
• DDX17-regulated alternative splicing that produced an oncogenic isoform of PXN-AS1 to promote HCC metastasis. (PMID:34626132)
• DDX17 modulates the expression and alternative splicing of genes involved in apoptosis and proliferation in lung adenocarcinoma cells. (PMID:36164607)
• DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci. (PMID:36200807)
• MTDH-stabilized DDX17 promotes tumor initiation and progression through interacting with YB1 to induce EGFR transcription in Hepatocellular Carcinoma. (PMID:36385375)
• DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells. (PMID:36453994)
• DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer. (PMID:36593242)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddx17	ENSDARG00000010873
mus_musculus	Ddx17	ENSMUSG00000055065
rattus_norvegicus	Ddx17	ENSRNOG00000051170
drosophila_melanogaster	CG10077	FBGN0035720
caenorhabditis_elegans		WBGENE00010260

Paralogs (38): DDX20 (ENSG00000064703), DDX3Y (ENSG00000067048), DDX1 (ENSG00000079785), DDX43 (ENSG00000080007), DDX18 (ENSG00000088205), DDX24 (ENSG00000089737), 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 DDX17 — Q92841 (reviewed: Q92841)

Alternative names: DEAD box protein 17, DEAD box protein p72, DEAD box protein p82, RNA-dependent helicase p72

All UniProt accessions (4): Q92841, A0A0U1RQJ0, A0A1X7SBZ2, A0A5H1ZRQ2

UniProt curated annotations — full annotation on UniProt →

Function. As an RNA helicase, unwinds RNA and alters RNA structures through ATP binding and hydrolysis. Involved in multiple cellular processes, including pre-mRNA splicing, alternative splicing, ribosomal RNA processing and miRNA processing, as well as transcription regulation. Regulates the alternative splicing of exons exhibiting specific features. For instance, promotes the inclusion of AC-rich alternative exons in CD44 transcripts. This function requires the RNA helicase activity. Affects NFAT5 and histone macro-H2A.1/MACROH2A1 alternative splicing in a CDK9-dependent manner. In NFAT5, promotes the introduction of alternative exon 4, which contains 2 stop codons and may target NFAT5 exon 4-containing transcripts to nonsense-mediated mRNA decay, leading to the down-regulation of NFAT5 protein. Affects splicing of mediators of steroid hormone signaling pathway, including kinases that phosphorylates ESR1, such as CDK2, MAPK1 and GSK3B, and transcriptional regulators, such as CREBBP, MED1, NCOR1 and NCOR2. By affecting GSK3B splicing, participates in ESR1 and AR stabilization. In myoblasts and epithelial cells, cooperates with HNRNPH1 to control the splicing of specific subsets of exons. In addition to binding mature mRNAs, also interacts with certain pri-microRNAs, including MIR663/miR-663a, MIR99B/miR-99b, and MIR6087/miR-6087. Binds pri-microRNAs on the 3’ segment flanking the stem loop via the 5’-[ACG]CAUC[ACU]-3’ consensus sequence. Required for the production of subsets of microRNAs, including MIR21 and MIR125B1. May be involved not only in microRNA primary transcript processing, but also stabilization. Participates in MYC down-regulation at high cell density through the production of MYC-targeting microRNAs. Along with DDX5, may be involved in the processing of the 32S intermediate into the mature 28S ribosomal RNA. Promoter-specific transcription regulator, functioning as a coactivator or corepressor depending on the context of the promoter and the transcriptional complex in which it exists. Enhances NFAT5 transcriptional activity. Synergizes with TP53 in the activation of the MDM2 promoter; this activity requires acetylation on lysine residues. May also coactivate MDM2 transcription through a TP53-independent pathway. Coactivates MMP7 transcription. Along with CTNNB1, coactivates MYC, JUN, FOSL1 and cyclin D1/CCND1 transcription. Alone or in combination with DDX5 and/or SRA1 non-coding RNA, plays a critical role in promoting the assembly of proteins required for the formation of the transcription initiation complex and chromatin remodeling leading to coactivation of MYOD1-dependent transcription. This helicase-independent activity is required for skeletal muscle cells to properly differentiate into myotubes. During epithelial-to-mesenchymal transition, coregulates SMAD-dependent transcriptional activity, directly controlling key effectors of differentiation, including miRNAs which in turn directly repress its expression. Plays a role in estrogen and testosterone signaling pathway at several levels. Mediates the use of alternative promoters in estrogen-responsive genes and regulates transcription and splicing of a large number of steroid hormone target genes. Contrary to splicing regulation activity, transcriptional coregulation of the estrogen receptor ESR1 is helicase-independent. Plays a role in innate immunity. Specifically restricts bunyavirus infection, including Rift Valley fever virus (RVFV) or La Crosse virus (LACV), but not vesicular stomatitis virus (VSV), in an interferon- and DROSHA-independent manner. Binds to RVFV RNA, likely via structured viral RNA elements. Promotes mRNA degradation mediated by the antiviral zinc-finger protein ZC3HAV1, in an ATPase-dependent manner.

Subunit / interactions. Interacts with DDX5 in an RNA-independent manner. Interacts with CDK9 transcription elongation complex under basal conditions. Following cell stimulation with poly(I:C), a synthetic double-stranded RNA mimicking viral infection, the interaction with CDK9 is decreased. Interacts with ESR1 in an estrogen-independent manner. Interacts with HNRNPH1; this interaction is important for the regulation of alternative splicing on G-quadruplex structures. At high, but not low, cell density, interacts with DROSHA and DGCR8, the core components of the microprocessor complex involved in the maturation of primary microRNAs (pri-miRNAs) into pre-miRNAs. The interaction with DGCR8 is reduced during mitosis. At low, but not high, cell density, interacts with YAP1 and with its paralog, WWTR1/TAZ. Interactions with DROSHA and YAP1 are mutually exclusive. In vitro, the pre-miRNA processing activity of the DDX17-containing microprocessor complex is weaker than that of the DROSHA/DGCR8 microprocessor complex devoid of DDX17. Interacts with UPF3B. Interacts with NFAT5; this interaction leads to DDX17 recruitment to LNC2 and S100A4 promoters and NFAT5-mediated DDX17-enhanced transactivation. Interacts with HDAC1, HDAC2 and HDAC3; this interaction with HDAC1 and HDAC3, but not HDAC2, depends upon DDX17 acetylation. Interacts with ZC3HAV1 (via N-terminal domain) in an RNA-independent manner. Interacts with EXOSC3/RRP40 and EXOSC5/RRP46; this interaction may be indirect and mediated by ZC3HAV1-binding. Interacts with EP300; this interaction leads to acetylation at lysine residues. Interacts with CREBBP/CBP and KAT2B/P/CAF. Directly interacts with CTNNB1. Interacts with MYOD1. Interacts with TP53. Interacts with DCP1A in an RNA-independent manner. Interacts with DCP2 in an RNA-dependent manner. Interacts with DHX36; this interaction occurs in a RNA-dependent manner. Interacts with ERCC6.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed. Low expression, if any, in normal colonic epithelial cells (at protein level). Levels tend to increase during colon cancer progression, from very low in benign hyperplastic polyps to very high in tubular and villous adenomas.

Post-translational modifications. Sumoylation significantly increases stability. It also promotes interaction specifically with HDAC1 (but not HDAC2, nor HDAC3) and strongly stimulates ESR1 and TP53 coactivation. Acetylation at lysine residues stabilizes the protein, stimulates interaction with HDAC1 and HDAC3, but not HDAC2, and represses ESR1 and TP53 coactivation activity.

Miscellaneous. Starts at an alternative CUG codon. Produced by alternative initiation at Met-80 of isoform 1. Produced by alternative splicing of isoform 2. Produced by alternative splicing of isoform 2.

Similarity. Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q92841-4	1, p82	yes
Q92841-1	2, p72
Q92841-2	3
Q92841-3	4

RefSeq proteins (2): NP_001091974, NP_006377* (*=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
IPR046330	DDX17_ATP-bd-dom	Domain

Pfam: PF00270, PF00271

Enzyme classification (BRENDA):

• EC 3.6.4.13 — RNA helicase (BRENDA: 3 organisms, 3 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (85 total): helix 24, strand 18, mutagenesis site 10, compositionally biased region 7, modified residue 6, region of interest 5, cross-link 4, splice variant 3, domain 2, turn 2, short sequence motif 2, chain 1, binding site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6UV3	X-RAY DIFFRACTION	1.6
6UV4	X-RAY DIFFRACTION	1.7
6UV2	X-RAY DIFFRACTION	1.89
6UV1	X-RAY DIFFRACTION	2.31
6UV0	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92841-F1	72.88	0.48

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 (1): 215–222

Post-translational modifications (10): 64, 108, 109, 121, 523, 684, 129, 129, 129, 528

Mutagenesis-validated functional residues (10):

Position	Phenotype
108–109	no effect on hdac1-, hdac2- nor hdac3-binding, small decrease in esr1 coactivation, decreased tp53 coactivation. complet
121	no effect on hdac1-, hdac2- nor hdac3-binding, decreased esr1 coactivation, strongly decreased tp53 coactivation. comple
129	impaired sumoylation and decreased stability. impairs interaction with hdac1, but not with hdac2, nor hdac3. no effect o
221	no effect on transcription activation, when assayed in luciferase reporter gene assays using mdm2 or fos promoters, eith
221	loss of helicase activity. loss of splicing regulation in the estrogen signaling pathway. reduced cd44 alternative splic
222	decreased cd44 alternative splicing.
325	loss of helicase activity. no effect on esr1 coactivation.
328	small decrease in cd44 alternative splicing.
355	small decrease in cd44 alternative splicing.
356	small decrease in cd44 alternative splicing.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3899300	SUMOylation of transcription cofactors

MSigDB gene sets: 401 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, E2F_Q4, MODULE_52, GCM_MAP4K4, E2F_Q4_01, GOBP_RIBOSOME_BIOGENESIS, YAATNRNNNYNATT_UNKNOWN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, IIZUKA_LIVER_CANCER_EARLY_RECURRENCE, PAX4_01, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CELL_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, LFA1_Q6, TTTGTAG_MIR520D, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME

GO Biological Process (17): alternative mRNA splicing, via spliceosome (GO:0000380), regulation of alternative mRNA splicing, via spliceosome (GO:0000381), epithelial to mesenchymal transition (GO:0001837), immune system process (GO:0002376), regulation of transcription by RNA polymerase II (GO:0006357), rRNA processing (GO:0006364), RNA processing (GO:0006396), miRNA metabolic process (GO:0010586), estrogen receptor signaling pathway (GO:0030520), androgen receptor signaling pathway (GO:0030521), regulatory ncRNA-mediated gene silencing (GO:0031047), myoblast differentiation (GO:0045445), positive regulation of transcription by RNA polymerase II (GO:0045944), defense response to virus (GO:0051607), regulation of skeletal muscle cell differentiation (GO:2001014), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (12): transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), RNA helicase activity (GO:0003724), mRNA binding (GO:0003729), ATP binding (GO:0005524), ATP-dependent activity, acting on RNA (GO:0008186), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), nuclear speck (GO:0016607), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA processing	3
ATP-dependent activity	3
transcription by RNA polymerase II	2
nuclear receptor-mediated steroid hormone signaling pathway	2
positive regulation of DNA-templated transcription	2
binding	2
nuclear lumen	2
mRNA splicing, via spliceosome	1
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
mesenchymal cell differentiation	1
biological_process	1
regulation of DNA-templated transcription	1
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
negative regulation of gene expression	1
cell differentiation	1
muscle structure development	1
regulation of transcription by RNA polymerase II	1
defense response	1
response to virus	1
skeletal muscle cell differentiation	1
regulation of cell differentiation	1
mRNA metabolic process	1
transcription coregulator activity	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
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

4313 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX17	DROSHA	Q9NRR4	995
DDX17	DGCR8	Q8WYQ5	992
DDX17	ESR1	P03372	979
DDX17	TP53	P04637	955
DDX17	DDX5	P17844	949
DDX17	AKAP4	Q5JQC9	899
DDX17	MYOD1	P15172	887
DDX17	HNRNPM	P52272	860
DDX17	HDAC1	Q13547	820
DDX17	ZNF398	Q8TD17	807
DDX17	KAT2B	Q92831	790
DDX17	SRA1	Q9HD15	790
DDX17	DDX3X	O00571	783
DDX17	DHX9	Q08211	724
DDX17	DHX36	Q9H2U1	708

IntAct

288 interactions, top by confidence:

A	B	Type	Score
XRCC5	PARP1	psi-mi:“MI:0915”(physical association)	0.880
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
DDX17	BYSL	psi-mi:“MI:0915”(physical association)	0.720
BYSL	DDX17	psi-mi:“MI:0915”(physical association)	0.720
RBM10	DDX17	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
Zc3hav1	DDX17	psi-mi:“MI:0915”(physical association)	0.700
Zc3hav1	DDX17	psi-mi:“MI:0407”(direct interaction)	0.700
DROSHA	TP53	psi-mi:“MI:0914”(association)	0.680
PTK6	DDX17	psi-mi:“MI:0915”(physical association)	0.670
DDX6	DDX17	psi-mi:“MI:0915”(physical association)	0.670
LNX1	DDX17	psi-mi:“MI:0915”(physical association)	0.670
EXOSC3	Zc3hav1	psi-mi:“MI:0914”(association)	0.620
DDX17	GRB2	psi-mi:“MI:0915”(physical association)	0.560
RBM15	DDX17	psi-mi:“MI:0915”(physical association)	0.560
GRB2	DDX17	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (647): DDX17 (Two-hybrid), DDX17 (Two-hybrid), RBM15 (Two-hybrid), DDX17 (Biochemical Activity), EP300 (Affinity Capture-Western), ESR1 (Affinity Capture-Western), DDX17 (Affinity Capture-Western), DDX17 (Affinity Capture-Western), DDX17 (Affinity Capture-Western), DDX17 (Affinity Capture-MS), DDX17 (Affinity Capture-MS), DDX17 (Affinity Capture-MS), DDX17 (Affinity Capture-MS), DDX17 (Reconstituted Complex), DDX17 (Reconstituted Complex)

ESM2 similar proteins: A0A1D6GDY8, A0A1D6LAB7, A1CHL3, A1CX72, A6RJA2, A7EGG4, O22907, P0CQ88, P0CQ89, P16381, P19109, P46942, Q0CLX0, Q0D8N0, Q0DM51, Q0ILZ4, Q0INC5, Q1DMX8, Q2HEB0, Q39189, Q3B8Q1, Q3MSQ8, Q41382, Q4I7F9, Q4WPE9, Q5BCU6, Q5N7W4, Q5VQL1, Q5W5U4, Q61496, Q62095, Q64060, Q650T9, Q6CCZ1, Q6GVM6, Q6H601, Q6H6R9, Q750Q4, Q7ZY47, Q8H136

Diamond homologs: A1C5V3, A1C6C4, A1DG51, A1DGZ7, A2QC74, A2QFL3, A3LQ01, A3LQW7, A3LRW2, A4QSS5, A5A6J2, A5DAC8, A5DL80, A5DS77, A5DZE6, A5E1W4, A6QXC1, A6RGE3, A6SCT6, A6SFW7, A6ZP47, A6ZRX0, A6ZUA1, A6ZWD3, A7E449, A7EYW0, A7TJ36, A7TKR8, G0SFM2, O22907, P06634, P0CQ78, P0CQ79, P17844, P19109, P20447, P24782, P24783, P24784, P46942

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
DDX17	“form complex”	“RNA helicases DDX5/DDX17”	binding
YAP/TAZ	“down-regulates activity”	DDX17	binding
DDX17	“up-regulates activity”	“Microprocessor complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 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
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	5	24.2×	1e-04
Processing of Capped Intron-Containing Pre-mRNA	20	12.5×	6e-14
mRNA Polyadenylation	16	10.7×	3e-10
mRNA 3’-end processing	7	10.5×	4e-04
RNA Polymerase II Transcription Termination	6	10.1×	2e-03
mRNA Splicing - Major Pathway	22	9.2×	7e-13
mRNA Splicing	10	8.4×	4e-05
Regulation of PLK1 Activity at G2/M Transition	8	7.8×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	28.9×	1e-05
mitophagy	7	14.0×	1e-04
regulation of alternative mRNA splicing, via spliceosome	8	12.3×	6e-05
intrinsic apoptotic signaling pathway	5	11.3×	6e-03
autophagosome maturation	5	11.0×	6e-03
negative regulation of translation	8	9.9×	2e-04
mRNA splicing, via spliceosome	16	9.2×	3e-08
autophagosome assembly	6	8.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	16
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3378013	NM_006386.5(DDX17):c.738+1G>A	Pathogenic
3378053	NM_006386.5(DDX17):c.416del (p.Pro139fs)	Pathogenic
441653	GRCh37/hg19 22q11.1-13.33(chr22:16888900-51197838)x3	Pathogenic
3378067	NM_006386.5(DDX17):c.1567A>G (p.Thr523Ala)	Likely pathogenic
4531849	NM_006386.5(DDX17):c.1133A>G (p.Asn378Ser)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4757 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38487920:A:G	L548P	1.000
22:38487920:A:T	L548Q	1.000
22:38487937:C:A	Q542H	1.000
22:38487937:C:G	Q542H	1.000
22:38487938:T:G	Q542P	1.000
22:38487944:G:T	A540D	1.000
22:38487945:C:G	A540P	1.000
22:38487953:A:G	L537P	1.000
22:38487965:A:G	L533P	1.000
22:38487965:A:T	L533H	1.000
22:38487998:A:G	F522S	1.000
22:38488001:A:G	F521S	1.000
22:38488008:A:C	Y519D	1.000
22:38488010:G:T	A518D	1.000
22:38488011:C:G	A518P	1.000
22:38488016:C:A	G516V	1.000
22:38488016:C:T	G516D	1.000
22:38488017:C:A	G516C	1.000
22:38488017:C:G	G516R	1.000
22:38488017:C:T	G516S	1.000
22:38488031:C:G	R511P	1.000
22:38488031:C:T	R511H	1.000
22:38488032:G:A	R511C	1.000
22:38488032:G:T	R511S	1.000
22:38488034:G:A	A510V	1.000
22:38488034:G:T	A510D	1.000
22:38488037:G:A	T509I	1.000
22:38488040:C:G	R508P	1.000
22:38488041:G:C	R508G	1.000
22:38488043:C:A	G507V	1.000

dbSNP variants (sampled 300 via entrez): RS1000072115 (22:38501663 T>C), RS1000411664 (22:38483710 C>T), RS1000427810 (22:38489668 C>A), RS1000502419 (22:38495594 T>TGTACA), RS1000507383 (22:38501484 T>C), RS1000643673 (22:38484247 G>A,C,T), RS1000777747 (22:38489978 G>C), RS1000836461 (22:38506505 G>A), RS1000950495 (22:38500802 A>G), RS1001134616 (22:38505485 A>G), RS1001139253 (22:38507984 C>T), RS1001150283 (22:38484793 C>T), RS1001166728 (22:38491369 T>C), RS1001267237 (22:38490058 C>T), RS1001360862 (22:38496392 G>A,C)

Disease associations

OMIM: gene MIM:608469 | disease phenotypes: MIM:620450

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (2): intellectual developmental disorder, autosomal dominant 73 (MONDO:0957536), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003818_40	Resting heart rate	5.000000e-16
GCST005312_48	Menopause (age at onset)	2.000000e-13
GCST007561_72	Sleep duration	4.000000e-08
GCST012229_172	Hip index	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105760 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 5 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.90	Kd	126.2	nM	CHEMBL3752910
6.90	ED50	126.2	nM	CHEMBL3752910
5.16	Kd	6991	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 15 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148216: Binding affinity to human DDX17 incubated for 45 mins by Kinobead based pull down assay	kd	0.1262	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179145: Binding affinity against DDX17 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	6.9910	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression, affects expression	4
Benzo(a)pyrene	decreases expression	4
sodium arsenite	decreases expression	2
methacrylaldehyde	decreases expression, increases oxidation, increases expression, increases abundance, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	2
bisphenol S	decreases expression, affects cotreatment	2
Vorinostat	decreases expression	2
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, increases expression	2
Cisplatin	decreases expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases expression, increases abundance	2
Tretinoin	decreases expression, increases acetylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
bisphenol A	affects cotreatment, decreases expression	1
deoxynivalenol	increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4044789	Binding	Inhibition of DDX17 (unknown origin) expressed in Escherichia coli BL21(DE3) preincubated for 10 mins followed by ATP addition measured after 120 mins by malachite green dye-based assay	ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1AR	Abcam HEK293 DDX17 KO	Transformed cell line	Female
CVCL_E1VG	HAP1 DDX17 (-) 2	Cancer cell line	Male
CVCL_F1NU	HyCyte GES-1 KO-hDDX17	Transformed cell line	Sex unspecified
CVCL_XN20	HAP1 DDX17 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice