DDX39A

Summary

DDX39A (DExD-box helicase 39A, HGNC:17821) is a protein-coding gene on chromosome 19p13.12, encoding ATP-dependent RNA helicase DDX39A (O00148). Helicase that plays an essential role in mRNA export and is involved in multiple steps in RNA metabolism including alternative splicing.

This gene encodes a member of the DEAD box protein family. These proteins are characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD) and 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 the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene is thought to play a role in the prognosis of patients with gastrointestinal stromal tumors. A pseudogene of this gene is present on chromosome 13. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 10212 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 51 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_005804

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17821
Approved symbol	DDX39A
Name	DExD-box helicase 39A
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	DDXL, BAT1L, URH49
Ensembl gene	ENSG00000123136
Ensembl biotype	protein_coding
OMIM	619906
Entrez	10212

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 17 protein_coding, 9 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000242776, ENST00000324340, ENST00000454233, ENST00000586558, ENST00000586993, ENST00000587730, ENST00000588542, ENST00000588692, ENST00000589318, ENST00000589675, ENST00000590239, ENST00000590260, ENST00000590315, ENST00000590556, ENST00000590696, ENST00000591275, ENST00000592391, ENST00000592632, ENST00000592927, ENST00000593008, ENST00000593026, ENST00000898538, ENST00000898539, ENST00000898540, ENST00000926035, ENST00000926036, ENST00000926037, ENST00000926038, ENST00000926039, ENST00000950771

RefSeq mRNA: 1 — MANE Select: NM_005804 NM_005804

CCDS: CCDS12308

Canonical transcript exons

ENST00000242776 — 11 exons

Exon	Start	End
ENSE00002881659	14419270	14419341
ENSE00002941012	14408798	14408952
ENSE00003498299	14410989	14411172
ENSE00003516439	14409742	14409873
ENSE00003540297	14409037	14409184
ENSE00003564750	14412551	14412678
ENSE00003607722	14411506	14411598
ENSE00003608809	14413013	14413224
ENSE00003654903	14409536	14409645
ENSE00003665124	14409303	14409447
ENSE00003790102	14410216	14410334

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.8419 / max 321.8767, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179640	28.3501	1811
179639	12.8203	1736
179641	5.3072	1312
179638	0.3643	152

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.15	gold quality
right testis	UBERON:0004534	99.13	gold quality
adult organism	UBERON:0007023	98.67	gold quality
granulocyte	CL:0000094	98.28	gold quality
testis	UBERON:0000473	97.39	gold quality
ventricular zone	UBERON:0003053	97.30	gold quality
spleen	UBERON:0002106	97.18	gold quality
lymph node	UBERON:0000029	96.36	gold quality
mucosa of transverse colon	UBERON:0004991	96.25	gold quality
vermiform appendix	UBERON:0001154	96.09	gold quality
ganglionic eminence	UBERON:0004023	96.02	gold quality
lower esophagus mucosa	UBERON:0035834	95.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.78	gold quality
upper lobe of left lung	UBERON:0008952	95.78	gold quality
skin of abdomen	UBERON:0001416	95.69	gold quality
monocyte	CL:0000576	95.60	gold quality
mononuclear cell	CL:0000842	95.52	gold quality
upper lobe of lung	UBERON:0008948	95.48	gold quality
leukocyte	CL:0000738	95.46	gold quality
omental fat pad	UBERON:0010414	95.20	gold quality
peritoneum	UBERON:0002358	95.16	gold quality
left uterine tube	UBERON:0001303	95.12	gold quality
skin of leg	UBERON:0001511	95.11	gold quality
metanephros cortex	UBERON:0010533	95.10	gold quality
transverse colon	UBERON:0001157	95.04	gold quality
body of stomach	UBERON:0001161	95.04	gold quality
endocervix	UBERON:0000458	94.95	gold quality
body of uterus	UBERON:0009853	94.88	gold quality
esophagus mucosa	UBERON:0002469	94.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.81	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	24.14
E-HCAD-13	yes	22.20
E-HCAD-1	yes	18.68
E-GEOD-99795	no	395.31
E-MTAB-7381	no	331.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 24)

• Regulation of URH49 mRNA expression and comparison with the related UAP56 RNA helicase. (PMID:15047853)
• Reducing the expression of UAP56 and URH49 resulted in a reduction in reporter gene expression as well as cell death within 72 h suggest that both helicases have essential but largely overlapping functions in the processing and export of mammalian mRNAs. (PMID:16949217)
• CIP29 physically and functionally associates with DDX39, suggesting their cooperation in the RNA metabolism. (PMID:17196963)
• DDX39 is a novel RNA helicase capable of promoting cancer cell growth (PMID:17548965)
• Data show that the two closely related RNA helicases UAP56 and URH49 have evolved to form distinct mRNA export machineries, which regulate mitosis at different steps. (PMID:20573985)
• Using a UL69 viral mutant that is unable to bind UAP56 and URH49, the authors demonstrated that UL69’s interaction with UAP56 or URH49 does not contribute to the growth phenotype associated with the UL69 deletion mutant. (PMID:20610707)
• Requirement of DDX39 DEAD box RNA helicase for genome integrity and telomere protection (PMID:21388492)
• UAP56 and URH49 exhibit an intrinsic CRM1-independent nucleocytoplasmic shuttling (PMID:21799930)
• Mx proteins exert their antiviral activity against IAV by interfering with the function of the RNA helicases UAP56 and URH49 (PMID:21859714)
• -dependent RNA helicase DDX39 has a role in poor prognosis of patients with gastrointestinal stromal tumor (PMID:22119546)
• Results suggest that DDX39 is a suppressor of invasion and loss of its function predicts disease progression in bladder cancers. (PMID:22494014)
• The protein levels of DDX39 were found to be higher in malignant pleural mesothelioma cell lines compared to normal pleural mesothelial cells. (PMID:23749908)
• DDX39A is a potential biomarker for unfavorable neuroblastoma (PMID:26469522)
• DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation (PMID:28025139)
• DDX39 regulates hepatocellular carcinoma progression by activating Wnt/beta-catenin pathway. (PMID:29867138)
• UAP56- and URH49-dependent mRNA export pathways are integrated into NXF1 through the remodeling of each complex formation by ATP loading. (PMID:31917363)
• SUMOylation of DDX39A Alters Binding and Export of Antiviral Transcripts to Control Innate Immunity. (PMID:32393512)
• The Mammalian Ecdysoneless Protein Interacts with RNA Helicase DDX39A To Regulate Nuclear mRNA Export. (PMID:33941617)
• DDX39 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with clear cell renal cell carcinoma. (PMID:34421357)
• Structural differences between the closely related RNA helicases, UAP56 and URH49, fashion distinct functional apo-complexes. (PMID:38225262)
• Terminal regions of UAP56 and URH49 are required for their distinct complex formation functioning to an essential role in mRNA processing and export. (PMID:38377942)
• Parsing the roles of DExD-box proteins DDX39A and DDX39B in alternative RNA splicing. (PMID:38801080)
• Intron Retention of DDX39A Driven by SNRPD2 is a Crucial Splicing Axis for Oncogenic MYC/Spliceosome Program in Hepatocellular Carcinoma. (PMID:39018261)
• Novel role for Ddx39 in differentiation and telomere length regulation of embryonic stem cells. (PMID:39107495)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddx39aa	ENSDARG00000006225
danio_rerio	ddx39ab	ENSDARG00000015111
mus_musculus	Ddx39a	ENSMUSG00000005481
rattus_norvegicus	Ddx39a	ENSRNOG00000004373
drosophila_melanogaster	Hel25E	FBGN0014189
caenorhabditis_elegans		WBGENE00001840

Paralogs (38): DDX20 (ENSG00000064703), 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), 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

ATP-dependent RNA helicase DDX39A — O00148 (reviewed: O00148)

Alternative names: DEAD box protein 39, Nuclear RNA helicase URH49

All UniProt accessions (8): A0A0D9SEM9, K7EIL8, K7EL56, K7EN69, K7ENP6, K7EPJ3, K7EQN7, O00148

UniProt curated annotations — full annotation on UniProt →

Function. Helicase that plays an essential role in mRNA export and is involved in multiple steps in RNA metabolism including alternative splicing. Regulates nuclear mRNA export to the cytoplasm through association with ECD. Also involved in spliceosomal uridine-rich small nuclear RNA (U snRNA) export by stimulating the RNA binding of adapter PHAX. Plays a role in the negative regulation of type I IFN production by increasing the nuclear retention of antiviral transcripts and thus reducing their protein expression. Independently of the interferon pathway, plays an antiviral role against alphaviruses by binding to a 5’ conserved sequence element in the viral genomic RNA.

Subunit / interactions. Binds ALYREF/THOC4 and DDX39B/BAT1. Interacts with the apo-AREX complex component SARNP. Interacts with MX1. Interacts with MCM3AP isoform GANP. Interacts with ECD. Interacts with PHAX; this interaction stimulates PHAX RNA binding activity. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL69.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Detected in testis, and at lower levels in brain, kidney, lung, thymus, spleen and salivary gland.

Post-translational modifications. SUMOylated by RANBP2; SUMOylation modification affects its ability to bind RNA.

Induction. Up-regulated in proliferating cells. Present at low levels in quiescent cells.

Miscellaneous. Probably devoid of RNA helicase activity. Probably devoid of RNA helicase activity.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O00148-1	1, L	yes
O00148-2	2, S
O00148-3	3, SS

RefSeq proteins (1): NP_005795* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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), 1 shown:

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

UniProt features (32 total): cross-link 6, sequence conflict 6, modified residue 5, splice variant 4, domain 2, short sequence motif 2, initiator methionine 1, chain 1, sequence variant 1, mutagenesis site 1, region of interest 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8IJU	X-RAY DIFFRACTION	1.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00148-F1	85.50	0.67

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): 88–95

Post-translational modifications (11): 35, 37, 171, 426, 31, 35, 154, 162, 240, 255, 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
223	exhibits a switch in complex formation from the apo-arex complex to the apo-trex complex.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination

MSigDB gene sets: 233 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, MORF_HDAC2, MODULE_16, GOBP_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, PUJANA_CHEK2_PCC_NETWORK, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, GOBP_NUCLEAR_TRANSPORT, MORF_RAF1, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (9): mRNA splicing, via spliceosome (GO:0000398), RNA export from nucleus (GO:0006405), mRNA export from nucleus (GO:0006406), negative regulation of innate immune response (GO:0045824), negative regulation of RNA export from nucleus (GO:0046832), toll-like receptor signaling pathway (GO:0002224), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (11): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), mRNA binding (GO:0003729), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), membrane (GO:0016020), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Transport of Mature Transcript to Cytoplasm	1
Processing of Capped Intron-Containing Pre-mRNA	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA export from nucleus	2
pattern recognition receptor signaling pathway	2
RNA processing	2
ATP-dependent activity	2
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
RNA transport	1
nuclear export	1
gene expression	1
mRNA transport	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
negative regulation of nucleobase-containing compound transport	1
negative regulation of nucleocytoplasmic transport	1
regulation of RNA export from nucleus	1
positive regulation of cytokine production	1
intracellular receptor signaling pathway	1
mRNA metabolic 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 binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

5836 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX39A	SARNP	P82979	977
DDX39A	ALYREF	Q86V81	832
DDX39A	FYTTD1	Q96QD9	763
DDX39A	FUS	P35637	751
DDX39A	U2AF2	P26368	714
DDX39A	CHTOP	Q9Y3Y2	670
DDX39A	THOC7	Q6I9Y2	640
DDX39A	NXF1	Q9UBU9	639
DDX39A	RAE1	P78406	638
DDX39A	NCBP2	P52298	625
DDX39A	THOC2	Q8NI27	625
DDX39A	NCBP1	Q09161	613
DDX39A	SUPT6H	Q7KZ85	611
DDX39A	THOC6	Q86W42	581
DDX39A	FLT3LG	P49771	571

IntAct

159 interactions, top by confidence:

A	B	Type	Score
DDX39A	DDX39B	psi-mi:“MI:0915”(physical association)	0.770
DDX39A	DDX39B	psi-mi:“MI:0914”(association)	0.770
SARNP	DDX39A	psi-mi:“MI:0915”(physical association)	0.740
DDX39A	SARNP	psi-mi:“MI:0915”(physical association)	0.740
SARNP	DDX39A	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DDX39A	DDX39A	psi-mi:“MI:0915”(physical association)	0.670
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
	DDX39A	psi-mi:“MI:0915”(physical association)	0.560
DDX39A	SAT1	psi-mi:“MI:0915”(physical association)	0.560
DDX39A		psi-mi:“MI:0915”(physical association)	0.560
SAT1	DDX39A	psi-mi:“MI:0915”(physical association)	0.560
DDX39A	RNF4	psi-mi:“MI:0915”(physical association)	0.560
DDX39A	CHTOP	psi-mi:“MI:0915”(physical association)	0.560
DDX39A	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
DDX39A	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
DDX39A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
DDX39A	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1239): DDX39A (Two-hybrid), DDX39A (Two-hybrid), SARNP (Two-hybrid), DDX39A (Affinity Capture-MS), DDX39A (Affinity Capture-MS), DDX39A (Affinity Capture-MS), CELSR1 (Affinity Capture-MS), FAT3 (Affinity Capture-MS), FAT4 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), WDR19 (Affinity Capture-MS), FREM2 (Affinity Capture-MS), MCM3AP (Affinity Capture-MS), PCDH7 (Affinity Capture-MS)

ESM2 similar proteins: A1CMQ7, A1DL85, A2R0B5, A3LST5, A4RBS3, A5DDN0, A5E3W5, A6R603, A6ZXP4, A7EIX7, A7TJT7, A7TLA0, O00148, O13792, P0CQ96, P0CQ97, P54823, P60024, Q07478, Q0CGJ9, Q0JM17, Q0TXZ2, Q13838, Q18212, Q1DI07, Q27268, Q29024, Q29S22, Q2H4D0, Q2U6P7, Q3T147, Q4WCW2, Q56XG6, Q5ASK8, Q5JK84, Q5RE47, Q5TM17, Q5U216, Q5WR10, Q5ZHZ0

Diamond homologs: A1C595, A1CJT5, A1CMQ7, A1D071, A1D7N3, A1DL85, A2QEN5, A2R0B5, A3GFI4, A3GFV3, A3LST5, A4QU31, A4QVP2, A4RBS3, A5AAE5, A5DB98, A5DDN0, A5DE68, A5DVM3, A5E3W5, A6QSQ0, A6R603, A6RJ45, A6ZQJ1, A6ZXP4, A7EGL7, A7EIX7, A7EM88, A7TJT7, A7TK55, A7TLA0, O00148, O02494, O13792, P0CQ70, P0CQ71, P0CQ96, P0CQ97, P10081, P10630

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Transport of Mature Transcript to Cytoplasm	6	25.4×	9e-06
mRNA 3’-end processing	11	24.1×	2e-10
RNA Polymerase II Transcription Termination	8	19.5×	8e-07
Transport of Mature mRNA derived from an Intron-Containing Transcript	10	16.9×	6e-08
Processing of Capped Intron-Containing Pre-mRNA	15	13.7×	1e-10
mRNA Splicing	8	9.8×	1e-04
mRNA Splicing - Major Pathway	14	8.5×	1e-07
DNA Repair	7	7.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	11	28.5×	1e-10
vascular endothelial growth factor receptor signaling pathway	6	25.3×	2e-05
positive regulation of telomere maintenance	5	22.4×	4e-04
anatomical structure morphogenesis	10	12.2×	2e-06
mRNA splicing, via spliceosome	12	9.6×	2e-06
RNA splicing	12	9.3×	2e-06
mRNA processing	12	8.3×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	34
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
191100	NM_005804.4(DDX39A):c.677T>A (p.Phe226Tyr)	Likely pathogenic

SpliceAI

1300 predictions. Top by Δscore:

Variant	Effect	Δscore
19:14408950:CGA:C	acceptor_gain	1.0000
19:14408953:C:CC	acceptor_gain	1.0000
19:14409033:TTACT:T	donor_loss	1.0000
19:14409034:TA:T	donor_loss	1.0000
19:14409035:A:AC	donor_gain	1.0000
19:14409035:ACT:A	donor_loss	1.0000
19:14409036:C:CT	donor_gain	1.0000
19:14409036:CT:C	donor_gain	1.0000
19:14409036:CTG:C	donor_gain	1.0000
19:14409036:CTGT:C	donor_gain	1.0000
19:14409036:CTGTA:C	donor_gain	1.0000
19:14409180:GCCAC:G	acceptor_gain	1.0000
19:14409181:CCAC:C	acceptor_gain	1.0000
19:14409181:CCACC:C	acceptor_gain	1.0000
19:14409182:CAC:C	acceptor_gain	1.0000
19:14409182:CACC:C	acceptor_gain	1.0000
19:14409183:AC:A	acceptor_gain	1.0000
19:14409184:CC:C	acceptor_gain	1.0000
19:14409185:C:CC	acceptor_gain	1.0000
19:14409185:CT:C	acceptor_loss	1.0000
19:14409188:C:CT	acceptor_gain	1.0000
19:14409298:CTCAC:C	donor_loss	1.0000
19:14409299:TCACC:T	donor_loss	1.0000
19:14409300:CA:C	donor_loss	1.0000
19:14409301:A:AC	donor_gain	1.0000
19:14409301:AC:A	donor_gain	1.0000
19:14409301:ACC:A	donor_gain	1.0000
19:14409302:C:CC	donor_gain	1.0000
19:14409302:CC:C	donor_gain	1.0000
19:14409302:CCC:C	donor_gain	1.0000

AlphaMissense

2853 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:14409164:A:C	F380L	1.000
19:14409164:A:T	F380L	1.000
19:14409166:A:G	F380L	1.000
19:14412605:C:A	K94N	0.999
19:14412605:C:G	K94N	0.999
19:14412606:T:A	K94M	0.999
19:14412607:T:G	K94Q	0.999
19:14412609:C:T	G93D	0.999
19:14412610:C:G	G93R	0.999
19:14412615:C:T	G91E	0.999
19:14412616:C:A	G91W	0.999
19:14412629:G:C	C86W	0.999
19:14412630:C:T	C86Y	0.999
19:14412631:A:G	C86R	0.999
19:14412639:T:A	D83V	0.999
19:14412655:C:G	A78P	0.999
19:14412665:G:C	C74W	0.999
19:14412674:C:A	Q71H	0.999
19:14412674:C:G	Q71H	0.999
19:14413021:G:T	P67H	0.999
19:14413083:G:C	F46L	0.999
19:14413083:G:T	F46L	0.999
19:14413085:A:G	F46L	0.999
19:14409086:A:C	F406L	0.998
19:14409086:A:T	F406L	0.998
19:14409088:A:G	F406L	0.998
19:14409150:A:G	L385P	0.998
19:14409304:C:G	R373P	0.998
19:14409613:G:C	C299W	0.998
19:14410267:G:C	S227R	0.998

dbSNP variants (sampled 300 via entrez): RS1000048124 (19:14408622 G>A,T), RS1000183340 (19:14419929 G>A), RS1000244471 (19:14418488 C>T), RS1000411332 (19:14419659 C>G,T), RS1000816480 (19:14413333 T>A,C), RS1001317673 (19:14419592 G>A,T), RS1001427569 (19:14413670 C>A), RS1001499294 (19:14410086 G>A), RS1001533104 (19:14419375 G>A), RS1001569122 (19:14413741 C>T), RS1001588772 (19:14413497 C>T), RS1001800118 (19:14413439 T>A,C,G), RS1002123210 (19:14419032 T>A), RS1002266758 (19:14409660 G>T), RS1002321497 (19:14420992 G>A)

Disease associations

OMIM: gene MIM:619906 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST90002385_500	High light scatter reticulocyte count	5.000000e-16
GCST90002386_69	High light scatter reticulocyte percentage of red cells	3.000000e-15
GCST90002387_46	Immature fraction of reticulocytes	5.000000e-13
GCST90002390_530	Mean corpuscular hemoglobin	5.000000e-12
GCST90002392_69	Mean corpuscular volume	2.000000e-20
GCST90002405_537	Reticulocyte count	2.000000e-11
GCST90002406_491	Reticulocyte fraction of red cells	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105795 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	3
Caffeine	affects phosphorylation, decreases expression	2
Nickel	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	increases expression, affects expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
epigallocatechin gallate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
seocalcitol	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
bromovanin	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Dasatinib	decreases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	increases expression, increases abundance	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4044788	Binding	Inhibition of DDX39A (unknown origin) expressed in Escherichia coli BL21(Rosetta 2) preincubated for 10 mins followed by ATP addition measured after 60 mins by malachite green dye-based assay	ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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