DDX43

Summary

DDX43 (DEAD-box helicase 43, HGNC:18677) is a protein-coding gene on chromosome 6q13, encoding Probable ATP-dependent RNA helicase DDX43 (Q9NXZ2). In precision oncology, DDX43 Overexpression is associated with resistance to Trametinib + Mirdametinib + Selumetinib in Uveal Melanoma (CIViC Level D).

The protein encoded by this gene is an ATP-dependent RNA helicase in the DEAD-box family and displays tumor-specific expression.

Source: NCBI Gene 55510 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 95 total
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_018665

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18677
Approved symbol	DDX43
Name	DEAD-box helicase 43
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	HAGE, DKFZp434H2114, CT13
Ensembl gene	ENSG00000080007
Ensembl biotype	protein_coding
OMIM	606286
Entrez	55510

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000370336, ENST00000464221, ENST00000479773, ENST00000901441, ENST00000942801

RefSeq mRNA: 1 — MANE Select: NM_018665 NM_018665

CCDS: CCDS4977

Canonical transcript exons

ENST00000370336 — 17 exons

Exon	Start	End
ENSE00000810481	73404690	73404771
ENSE00000810500	73413970	73414079
ENSE00000810501	73414548	73414686
ENSE00000810504	73415497	73415584
ENSE00000810505	73416113	73416251
ENSE00000918559	73397689	73397744
ENSE00000918560	73400234	73400363
ENSE00000918561	73401859	73401990
ENSE00001452417	73417187	73417566
ENSE00001452453	73394828	73395155
ENSE00003487044	73405679	73405835
ENSE00003489933	73407505	73407615
ENSE00003491705	73412205	73412292
ENSE00003516381	73407960	73408101
ENSE00003521399	73409248	73409348
ENSE00003634796	73413658	73413785
ENSE00003640417	73406364	73406482

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 97.60.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2785 / max 277.4988, expressed in 571 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68574	0.7772	355
68573	0.7462	241
68575	0.7153	319
68572	0.0398	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.60	gold quality
secondary oocyte	CL:0000655	96.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.22	gold quality
sperm	CL:0000019	86.96	gold quality
right testis	UBERON:0004534	86.81	gold quality
left testis	UBERON:0004533	86.00	gold quality
testis	UBERON:0000473	85.91	gold quality
male germ cell	CL:0000015	85.84	gold quality
calcaneal tendon	UBERON:0003701	73.18	gold quality
granulocyte	CL:0000094	71.41	gold quality
mucosa of stomach	UBERON:0001199	71.01	gold quality
mucosa of transverse colon	UBERON:0004991	68.84	gold quality
right coronary artery	UBERON:0001625	67.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.83	gold quality
lower esophagus	UBERON:0013473	66.81	gold quality
placenta	UBERON:0001987	66.72	gold quality
thoracic aorta	UBERON:0001515	66.66	gold quality
right lung	UBERON:0002167	66.64	gold quality
ascending aorta	UBERON:0001496	66.42	gold quality
aorta	UBERON:0000947	66.24	gold quality
popliteal artery	UBERON:0002250	66.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	66.15	gold quality
tibial artery	UBERON:0007610	66.14	gold quality
descending thoracic aorta	UBERON:0002345	64.74	gold quality
right lobe of thyroid gland	UBERON:0001119	64.39	gold quality
gall bladder	UBERON:0002110	64.32	gold quality
left ovary	UBERON:0002119	64.24	gold quality
tibial nerve	UBERON:0001323	63.80	gold quality
body of pancreas	UBERON:0001150	63.61	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	87.75
E-ANND-3	no	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting DDX43, 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-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 16)

• HAGE is a cancer/testis antigen with potential for melanoma immunotherapy (PMID:17487488)
• HAGE protein expression was confirmed in 75% (12/16) of carcinomas as compared to normal tissues (PMID:20058853)
• HAGE cDNA expression is relevant to specific subtypes of acute myeloid leukemiaand to the progression of chronic myeloid leukemia. (PMID:22040965)
• the helicase HAGE is required for ABCB5+ MMIC-dependent tumor growth through promoting RAS protein expression (PMID:22393060)
• DDX43 promoter in frequently hypomethylated in myelodysplastic syndrome and is associated with favourable outcome. (PMID:22563673)
• data suggest that hypomethylation of the DDX43 promoter may be an early and frequent molecular event in the development of CML in Chinese patients (PMID:23495895)
• Suggest that the helicase HAGE has a key role in the resistance of ABCB5+ malignant melanoma stem cells to IFNalpha treatment by promoting SOCS1 expression. (PMID:24525737)
• DDX43 gene is activated by promoter hypomethylation and DDX43 hypomethylation may be a favorable prognostic factor in acute myeloid leukemia. (PMID:24656837)
• DDX43 induces RAS protein expression and signaling, mediating a novel mechanism of MEK inhibitor resistance. (PMID:24899684)
• HAGE expression is a potential prognostic marker and a predictor of response to anthracycline treatment in triple negative breast cancer. (PMID:26240276)
• results demonstrate that DDX43 is a dual helicase and the KH domain is required for its full unwinding activity. (PMID:28468824)
• DDX43 is highly expressed in lung adenocarcinoma, and the expression level is related to the stage and metastasis of lung adenocarcinoma. (PMID:29044003)
• DDX43 provides critical support to the progression of chronic myeloid leukemia (CML) by enhancing cell survival, colony formation, and inhibiting cell apoptosis, thereby implicating DDX43 as a potential therapeutic target in CML. (PMID:29449695)
• DDX43 prefers single-strand DNA or RNA with length longer than 12nt and much prefers guanosine than the other three nucleotides. Achievement of the full binding affinity of protein to substrate needs the existence of all domains, and they must be connected. The absence of either of them or the disjunction can result in a decreased binding affinity to substrates, approximately reduced 10-fold. (PMID:31623828)
• DDX43 mRNA expression and protein levels in relation to clinicopathological profile of breast cancer. (PMID:37200388)
• Effect of DNMT3A R882H Hot Spot Mutations on DDX43 Promoter Methylation in Acute Myeloid Leukemia. (PMID:38807916)

Cross-species orthologs

0 orthologs

Paralogs (38): DDX20 (ENSG00000064703), DDX3Y (ENSG00000067048), DDX1 (ENSG00000079785), 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 DDX43 — Q9NXZ2 (reviewed: Q9NXZ2)

Alternative names: Cancer/testis antigen 13, DEAD box protein 43, DEAD box protein HAGE, Helical antigen

All UniProt accessions (1): Q9NXZ2

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in testis. Expressed in many tumors of various histological types at a level that is 100-fold higher than the level observed in normal tissues except testis.

Similarity. Belongs to the DEAD box helicase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NXZ2-1	1	yes
Q9NXZ2-2	2

RefSeq proteins (1): NP_061135* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000629	RNA-helicase_DEAD-box_CS	Conserved_site
IPR001650	Helicase_C-like	Domain
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	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
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF00013, PF00270, PF00271

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (17 total): domain 3, compositionally biased region 3, splice variant 2, sequence variant 2, region of interest 2, short sequence motif 2, chain 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXZ2-F1	80.28	0.45

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): 286–293

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): ROZANOV_MMP14_TARGETS_UP, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOMF_MRNA_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ATP_HYDROLYSIS_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_ISOMERASE_ACTIVITY, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, NFE2L2.V2, GOMF_ATP_DEPENDENT_ACTIVITY_ACTING_ON_RNA, MIR3658, MIR6844, MIR3682_5P, MIR6890_3P

GO Biological Process (0):

GO Molecular Function (10): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), mRNA binding (GO:0003729), ATP binding (GO:0005524), 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 (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
binding	2
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
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1

Protein interactions and networks

STRING

2011 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX43	MAGEA1	P43355	878
DDX43	SAGE1	Q9NXZ1	869
DDX43	GAGE4	P0DSO3	681
DDX43	MAGEA2B	P43356	538
DDX43	PASD1	Q8IV76	511
DDX43	CAGE1	Q8TC20	476
DDX43	DPPA5	A6NC42	446
DDX43	CTAGE1	Q96RT6	435
DDX43	PRAME	P78395	420
DDX43	CCNDBP1	O95273	397
DDX43	CT45A1	Q5HYN5	392
DDX43	MAGEA12	P43365	373
DDX43	CTAG1A	P78358	370
DDX43	NXF2B	Q9GZY0	362
DDX43	TDRD12	Q587J7	356

IntAct

15 interactions, top by confidence:

A	B	Type	Score
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
DDX43	DDX53	psi-mi:“MI:0915”(physical association)	0.590
	DDX43	psi-mi:“MI:0915”(physical association)	0.560
DDX43		psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	DDX43	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	DDX43	psi-mi:“MI:0915”(physical association)	0.560
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
DDX43	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
DDX43	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): KRTAP10-3 (Two-hybrid), DDX43 (Co-fractionation), DDX43 (Co-fractionation), DDX43 (Co-fractionation), DDX43 (Co-fractionation), HNRNPH1 (Co-fractionation), HNRNPH3 (Co-fractionation), DDX43 (Reconstituted Complex), DDX43 (Synthetic Lethality), DDX53 (Affinity Capture-MS), DDX43 (Two-hybrid), DDX43 (Affinity Capture-MS), DDX43 (Affinity Capture-MS), KRTAP10-8 (Two-hybrid), CYSRT1 (Two-hybrid)

ESM2 similar proteins: A2VD92, A5D7C1, A5DIX5, A5E1N2, A6ZU15, O16102, O74393, P23394, P45818, P54823, Q07886, Q09775, Q0DBS1, Q0IHV9, Q0IIK5, Q10202, Q19614, Q4R7L5, Q55CP6, Q5NVJ8, Q5T1V6, Q5XH91, Q641Y8, Q6AZV7, Q6C024, Q6CDS6, Q6CKI1, Q6FM43, Q7FGZ2, Q84T03, Q86TM3, Q8GXD6, Q90WU3, Q91VN6, Q91VR5, Q92499, Q9C551, Q9DBN9, Q9DF35, Q9FLB0

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

0 interactions.

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2226 predictions. Top by Δscore:

Variant	Effect	Δscore
6:73397745:G:GG	donor_gain	1.0000
6:73400225:T:TA	acceptor_gain	1.0000
6:73400228:A:AG	acceptor_gain	1.0000
6:73400229:C:G	acceptor_gain	1.0000
6:73400229:CCTA:C	acceptor_loss	1.0000
6:73400230:CTA:C	acceptor_loss	1.0000
6:73400231:TAG:T	acceptor_loss	1.0000
6:73400232:A:AG	acceptor_gain	1.0000
6:73400232:A:AT	acceptor_loss	1.0000
6:73400233:G:GG	acceptor_gain	1.0000
6:73400233:GA:G	acceptor_gain	1.0000
6:73400233:GAT:G	acceptor_gain	1.0000
6:73400233:GATA:G	acceptor_gain	1.0000
6:73400233:GATAA:G	acceptor_gain	1.0000
6:73400359:AATTG:A	donor_gain	1.0000
6:73400360:ATTG:A	donor_gain	1.0000
6:73400360:ATTGG:A	donor_loss	1.0000
6:73400361:TTG:T	donor_gain	1.0000
6:73400361:TTGGT:T	donor_loss	1.0000
6:73400362:TG:T	donor_gain	1.0000
6:73400362:TGG:T	donor_loss	1.0000
6:73400363:GG:G	donor_gain	1.0000
6:73400363:GGTA:G	donor_loss	1.0000
6:73400364:G:GG	donor_gain	1.0000
6:73400364:GT:G	donor_loss	1.0000
6:73400365:T:A	donor_loss	1.0000
6:73401857:A:AG	acceptor_gain	1.0000
6:73401858:G:GG	acceptor_gain	1.0000
6:73401957:G:GT	donor_gain	1.0000
6:73401958:A:T	donor_gain	1.0000

AlphaMissense

4264 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:73414662:G:C	R574P	0.998
6:73413766:T:C	F493L	0.997
6:73413768:C:A	F493L	0.997
6:73413768:C:G	F493L	0.997
6:73414050:G:C	R526P	0.996
6:73414563:T:C	L541P	0.996
6:73408034:C:A	A371E	0.995
6:73414617:T:A	V559D	0.994
6:73414568:G:C	A543P	0.993
6:73414569:C:A	A543E	0.993
6:73414671:G:C	R577P	0.993
6:73408033:G:C	A371P	0.992
6:73409284:T:C	F406L	0.992
6:73409286:T:A	F406L	0.992
6:73409286:T:G	F406L	0.992
6:73414624:T:A	N561K	0.991
6:73414624:T:G	N561K	0.991
6:73414670:C:A	R577S	0.991
6:73413764:T:A	V492D	0.990
6:73414681:A:C	R580S	0.990
6:73414681:A:T	R580S	0.990
6:73415505:G:A	G585D	0.989
6:73406373:T:A	W273R	0.988
6:73406373:T:C	W273R	0.988
6:73408058:T:C	L379P	0.988
6:73414023:T:C	L517P	0.985
6:73406412:G:C	A286P	0.984
6:73414680:G:C	R580T	0.984
6:73415517:C:A	T589K	0.984
6:73413770:T:A	V494D	0.983

dbSNP variants (sampled 300 via entrez): RS1000156678 (6:73394213 A>G), RS1000161828 (6:73406260 G>C,T), RS1000193229 (6:73403441 G>A), RS1000245719 (6:73403115 A>G), RS1000530045 (6:73394958 G>A,T), RS1000544176 (6:73401657 C>T), RS1000577880 (6:73401599 G>A), RS1000760284 (6:73395184 G>A,C,T), RS1000794375 (6:73415304 T>A), RS1000816509 (6:73395183 G>A,C), RS1000846567 (6:73415102 C>T), RS1000940923 (6:73414331 A>G), RS1001023763 (6:73409125 C>G,T), RS1001477844 (6:73408817 A>G), RS1001542870 (6:73403051 T>C)

Disease associations

OMIM: gene MIM:606286 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008925_16	Lysophosphatidylcholine levels	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010224	lysophosphatidylcholine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
DDX43 Overexpression	Trametinib + Mirdametinib + Selumetinib	Uveal Melanoma	Resistance	CIViC D	EID1135

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases methylation, decreases expression	2
Valproic Acid	increases methylation, increases expression	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	increases expression	1
sodium arsenite	increases expression	1
ICG 001	increases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Progesterone	decreases expression	1
Ribonucleotides	affects binding	1
tert-Butylhydroperoxide	increases expression	1

Clinical trials (associated diseases)

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