DDX18

Summary

DDX18 (DEAD-box helicase 18, HGNC:2741) is a protein-coding gene on chromosome 2q14.1, encoding ATP-dependent RNA helicase DDX18 (Q9NVP1). ATP-dependent RNA helicase that plays a role in the regulation of R-loop homeostasis in both endogenous R-loop-prone regions and at sites of DNA damage. It is a common-essential gene (DepMap: required in 99.8% 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, and it is activated by Myc protein.

Source: NCBI Gene 8886 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 121 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_006773

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2741
Approved symbol	DDX18
Name	DEAD-box helicase 18
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	MrDb, Has1
Ensembl gene	ENSG00000088205
Ensembl biotype	protein_coding
OMIM	606355
Entrez	8886

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000263239, ENST00000415038, ENST00000461443, ENST00000474694, ENST00000476149, ENST00000489933, ENST00000898166, ENST00000898167, ENST00000898168, ENST00000898169, ENST00000898170, ENST00000898171, ENST00000898172, ENST00000898173, ENST00000921664, ENST00000921665, ENST00000921666, ENST00000921667, ENST00000921668, ENST00000921669

RefSeq mRNA: 1 — MANE Select: NM_006773 NM_006773

CCDS: CCDS2120

Canonical transcript exons

ENST00000263239 — 14 exons

Exon	Start	End
ENSE00000417581	117828949	117829005
ENSE00000774518	117824569	117824708
ENSE00000774532	117826269	117826382
ENSE00000774534	117829289	117829466
ENSE00000857030	117814691	117814862
ENSE00001947621	117830582	117832377
ENSE00003479988	117819649	117819792
ENSE00003495344	117821161	117821296
ENSE00003553380	117821650	117821750
ENSE00003572182	117821862	117822061
ENSE00003580221	117822147	117822261
ENSE00003584167	117825447	117825599
ENSE00003611292	117817444	117817728
ENSE00003647595	117824940	117825101

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.1546 / max 1679.3729, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22223	74.9004	1815
22226	1.2542	131

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.86	gold quality
lower lobe of lung	UBERON:0008949	96.58	gold quality
cauda epididymis	UBERON:0004360	96.28	gold quality
calcaneal tendon	UBERON:0003701	95.97	gold quality
trabecular bone tissue	UBERON:0002483	95.82	gold quality
pylorus	UBERON:0001166	95.75	gold quality
oral cavity	UBERON:0000167	95.68	gold quality
cardia of stomach	UBERON:0001162	95.50	gold quality
mammalian vulva	UBERON:0000997	95.42	gold quality
mucosa of urinary bladder	UBERON:0001259	95.41	gold quality
caput epididymis	UBERON:0004358	95.31	gold quality
corpus epididymis	UBERON:0004359	95.12	gold quality
pericardium	UBERON:0002407	95.07	gold quality
nipple	UBERON:0002030	94.97	gold quality
superficial temporal artery	UBERON:0001614	94.93	gold quality
vena cava	UBERON:0004087	94.92	gold quality
caecum	UBERON:0001153	94.88	gold quality
cranial nerve II	UBERON:0000941	94.82	gold quality
tonsil	UBERON:0002372	94.79	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.77	gold quality
mammary duct	UBERON:0001765	94.71	gold quality
medial globus pallidus	UBERON:0002477	94.55	gold quality
vermiform appendix	UBERON:0001154	94.52	gold quality
epithelium of mammary gland	UBERON:0003244	94.46	gold quality
tendon	UBERON:0000043	94.44	gold quality
lymph node	UBERON:0000029	94.42	gold quality
tendon of biceps brachii	UBERON:0008188	94.32	gold quality
globus pallidus	UBERON:0001875	94.28	gold quality
skin of hip	UBERON:0001554	94.25	gold quality
rectum	UBERON:0001052	94.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	4.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

71 targeting DDX18, 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-4713-3P	100.00	65.92	505
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6883-5P	99.69	68.05	3785

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• findings suggest that MrDb is important for cell proliferation and that its inhibition could prevent tumor cell proliferation. (PMID:18351129)
• We identified 4 nonsynonymous sequence variants of DDX18 in acute myeloid leukemia patient samples (PMID:21653321)
• Data show that odulation of RNA helicase DDX18 directly affects growth of tamoxifen-resistant cells, suggesting that it may be a critical downstream effector of the estrogen receptors (ERs) and high mobility group box 2 (HMGB2) complex. (PMID:25284587)
• DNA 6mA demethylase ALKBH1 regulates DDX18 expression to promote proliferation of human head and neck squamous cell carcinoma. (PMID:36976498)
• DDX18 Facilitates the Tumorigenesis of Lung Adenocarcinoma by Promoting Cell Cycle Progression through the Upregulation of CDK4. (PMID:38732173)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddx18	ENSDARG00000030789
mus_musculus	Ddx18	ENSMUSG00000001674
rattus_norvegicus	Ddx18	ENSRNOG00000025430
drosophila_melanogaster	pit	FBGN0266581
caenorhabditis_elegans	B0511.6	WBGENE00015232

Paralogs (38): DDX20 (ENSG00000064703), DDX3Y (ENSG00000067048), DDX1 (ENSG00000079785), DDX43 (ENSG00000080007), 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

ATP-dependent RNA helicase DDX18 — Q9NVP1 (reviewed: Q9NVP1)

Alternative names: DEAD box protein 18, Myc-regulated DEAD box protein

All UniProt accessions (2): Q9NVP1, H7C452

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent RNA helicase that plays a role in the regulation of R-loop homeostasis in both endogenous R-loop-prone regions and at sites of DNA damage. At endogenous loci such as actively transcribed genes, may act as a helicase to resolve the formation of R-loop during transcription and prevent the interference of R-loop with DNA-replication machinery. Also participates in the removal of DNA-lesion-associated R-loop. Plays an essential role for establishing pluripotency during embryogenesis and for pluripotency maintenance in embryonic stem cells. Mechanistically, prevents the polycomb repressive complex 2 (PRC2) from accessing rDNA loci and protects the active chromatin status in nucleolus.

Subunit / interactions. Interacts with NOL8; the interaction is RNA-dependent. Interacts with PRC2 complex components EZH2, SUZ2 and JARID2; these interactions prevent deposition of the repressive H3K27me3 mark onto rDNA in pluripotent cells.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Similarity. Belongs to the DEAD box helicase family. DDX18/HAS1 subfamily.

RefSeq proteins (1): NP_006764* (*=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
IPR025313	SPB4-like_CTE	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR044773	DDX18/Has1_DEADc	Domain

Pfam: PF00270, PF00271, PF13959

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (35 total): helix 11, strand 6, sequence variant 3, compositionally biased region 3, domain 2, mutagenesis site 2, sequence conflict 2, short sequence motif 2, chain 1, turn 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FKW	ELECTRON MICROSCOPY	2.5
8FKX	ELECTRON MICROSCOPY	2.59
8FKY	ELECTRON MICROSCOPY	2.67
8FKQ	ELECTRON MICROSCOPY	2.76
3LY5	X-RAY DIFFRACTION	2.8
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82
8FKP	ELECTRON MICROSCOPY	2.85
8FKS	ELECTRON MICROSCOPY	2.88
8FKR	ELECTRON MICROSCOPY	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NVP1-F1	73.34	0.38

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): 223–230

Mutagenesis-validated functional residues (2):

Position	Phenotype
518	decreased poly(adp-ribose) (par) polymers-binding ability; when associated with a-523.
523	decreased poly(adp-ribose) (par) polymers-binding ability; when associated with a-518.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 408 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, ATF_B, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RIBOSOME_BIOGENESIS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, TSENG_IRS1_TARGETS_UP, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CELLULAR_RESPONSE_TO_LIPID, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, CAIRO_PML_TARGETS_BOUND_BY_MYC_UP, GOBP_REGULATION_OF_FIBROBLAST_MIGRATION

GO Biological Process (2): maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000463), cellular response to estradiol stimulus (GO:0071392)

GO Molecular Function (9): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), 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 (4): chromosome (GO:0005694), nucleolus (GO:0005730), membrane (GO:0016020), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
binding	2
intracellular membraneless organelle	2
maturation of LSU-rRNA	1
response to estradiol	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	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
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

4344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX18	DHX8	Q14562	747
DDX18	NIFK	Q9BYG3	741
DDX18	DHX15	O43143	696
DDX18	BRIX1	Q8TDN6	661
DDX18	DKC1	O60832	658
DDX18	RSL1D1	O76021	654
DDX18	EIF4E	P06730	628
DDX18	BMS1	Q14692	615
DDX18	DHX37	Q8IY37	575
DDX18	MAX	P25912	546
DDX18	CPSF3	Q9UKF6	537
DDX18	NOL6	Q9H6R4	525
DDX18	METAP2	P50579	516
DDX18	RBM41	Q96IZ5	496
DDX18	MAK16	Q9BXY0	489

IntAct

211 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
RPL28	MAGEB2	psi-mi:“MI:0914”(association)	0.560
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
H1-4	RRP8	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ESR1		psi-mi:“MI:0914”(association)	0.460
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
RPL29	DDX18	psi-mi:“MI:0915”(physical association)	0.400
GNL3	DDX18	psi-mi:“MI:0915”(physical association)	0.400
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
NP	HNRNPAB	psi-mi:“MI:0914”(association)	0.350
NP	HNRNPCL1	psi-mi:“MI:0914”(association)	0.350
NP	NKRF	psi-mi:“MI:0914”(association)	0.350
NP	KPNA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (414): DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), DDX18 (Affinity Capture-MS), ABCF2 (Co-fractionation), BCCIP (Co-fractionation), BRIX1 (Co-fractionation)

ESM2 similar proteins: A1CIQ5, A1CW14, A2Q9T6, A3LNR6, A4R8B5, A5DID7, A5DLF4, A5E2Z9, A5E3K3, A6ZPU3, A7ESL8, P0CQ84, P0CQ85, P20448, Q09916, Q0CZS8, Q0DBS1, Q0UMB9, Q0UR48, Q1EA54, Q2GMX1, Q2UUN6, Q4IAS1, Q4IEK8, Q4P6N0, Q4WM60, Q4WQM4, Q5AF95, Q5AK59, Q5BBY1, Q6BH93, Q6BXG0, Q6C7D2, Q6CGD1, Q6CRF4, Q74Z73, Q755A5, Q75C76, Q761Z9, Q7S2N9

Diamond homologs: A1CB55, A1CIQ5, A1CR32, A1CTZ2, A1CW14, A1DE84, A1DNF9, A2Q9T6, A2QS00, A2RA55, A2RB17, A3LNR6, A3LWH3, A4QX49, A4R8B5, A4RGD1, A4RGU2, A5DAR2, A5DID7, A5DQF1, A5E2Z9, A6QRQ7, A6RSH5, A6ZZY8, A7F8V8, A7TNT1, O60173, P0CQ82, P0CQ83, P0CQ84, P0CQ85, P0CQ94, P0CQ95, P0CR00, P0CR01, P36120, Q03532, Q09916, Q0CF43, Q0CMM5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 225 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
Peptide chain elongation	23	19.1×	2e-21
Viral mRNA Translation	23	19.1×	2e-21
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	23	18.9×	2e-21
Selenocysteine synthesis	23	18.1×	4e-21
Eukaryotic Translation Termination	23	18.1×	4e-21
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	23	17.7×	6e-21
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	23	17.7×	6e-21
Formation of a pool of free 40S subunits	24	17.6×	2e-21

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	25	23.3×	2e-24
ribosomal large subunit biogenesis	8	17.8×	3e-06
ribosomal small subunit biogenesis	12	13.7×	2e-08
translation	26	13.4×	3e-19
rRNA processing	15	10.7×	5e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	6
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

2469 predictions. Top by Δscore:

Variant	Effect	Δscore
2:117814861:GG:G	donor_gain	1.0000
2:117814862:GG:G	donor_gain	1.0000
2:117817442:A:AG	acceptor_gain	1.0000
2:117817442:AG:A	acceptor_gain	1.0000
2:117817442:AGG:A	acceptor_gain	1.0000
2:117817443:G:GG	acceptor_gain	1.0000
2:117817443:GG:G	acceptor_gain	1.0000
2:117817443:GGG:G	acceptor_gain	1.0000
2:117817443:GGGGC:G	acceptor_gain	1.0000
2:117817727:TGGT:T	donor_loss	1.0000
2:117817728:GGTA:G	donor_loss	1.0000
2:117817729:G:A	donor_loss	1.0000
2:117817730:T:G	donor_loss	1.0000
2:117819639:A:AG	acceptor_gain	1.0000
2:117819640:A:AG	acceptor_gain	1.0000
2:117819641:A:AG	acceptor_gain	1.0000
2:117819642:A:AG	acceptor_gain	1.0000
2:117819646:A:G	acceptor_gain	1.0000
2:117819794:T:C	donor_loss	1.0000
2:117819804:G:GT	donor_gain	1.0000
2:117821155:GTTTA:G	acceptor_loss	1.0000
2:117821156:TTTAG:T	acceptor_loss	1.0000
2:117821157:TTAG:T	acceptor_loss	1.0000
2:117821159:A:AG	acceptor_gain	1.0000
2:117821160:G:GG	acceptor_gain	1.0000
2:117821160:GGA:G	acceptor_gain	1.0000
2:117821294:CAG:C	donor_loss	1.0000
2:117821295:AG:A	donor_loss	1.0000
2:117821296:GGT:G	donor_loss	1.0000
2:117821297:G:GC	donor_loss	1.0000

AlphaMissense

4416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:117821658:T:C	L220P	1.000
2:117821661:C:A	A221E	1.000
2:117821663:G:C	A222P	1.000
2:117821666:G:C	A223P	1.000
2:117821667:C:A	A223E	1.000
2:117821675:G:C	G226R	1.000
2:117821676:G:A	G226D	1.000
2:117821681:G:C	G228R	1.000
2:117821681:G:T	G228C	1.000
2:117821682:G:A	G228D	1.000
2:117821682:G:T	G228V	1.000
2:117821684:A:C	K229Q	1.000
2:117821685:A:T	K229I	1.000
2:117821686:A:C	K229N	1.000
2:117821686:A:T	K229N	1.000
2:117821688:C:T	T230I	1.000
2:117821694:C:A	A232D	1.000
2:117821862:G:A	G251E	1.000
2:117821862:G:T	G251V	1.000
2:117821886:C:A	P259H	1.000
2:117821891:A:G	R261G	1.000
2:117821892:G:C	R261T	1.000
2:117821892:G:T	R261I	1.000
2:117821893:A:C	R261S	1.000
2:117821893:A:T	R261S	1.000
2:117821894:G:A	E262K	1.000
2:117821895:A:T	E262V	1.000
2:117821896:A:C	E262D	1.000
2:117821896:A:T	E262D	1.000
2:117821898:T:A	L263Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000195747 (2:117814966 C>A,G,T), RS1000632763 (2:117814725 G>A,C,T), RS1000878206 (2:117831647 C>T), RS1001248303 (2:117831399 C>T), RS1001570832 (2:117819899 T>C), RS1001625477 (2:117815003 C>G,T), RS1001702996 (2:117814645 G>A,C), RS1001982780 (2:117827903 C>T), RS1002085484 (2:117825656 T>A,G), RS1002133898 (2:117814452 G>A,C,T), RS1002519954 (2:117825912 T>A), RS1002669865 (2:117822715 G>A), RS1003195068 (2:117818712 G>T), RS1003248070 (2:117818929 T>A), RS1003402057 (2:117813148 T>C)

Disease associations

OMIM: gene MIM:606355 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002826_8	Urate levels (BMI interaction)	6.000000e-06
GCST003123_6	Severe influenza A (H1N1) infection	2.000000e-19
GCST003427_151	Alzheimer disease and age of onset	4.000000e-07
GCST003783_2	Multiple system atrophy (pathologically confirmed)	6.000000e-06
GCST007327_62	Smoking status (ever vs never smokers)	4.000000e-08
GCST008596_1	Opioid overdose severity score	5.000000e-08
GCST008596_4	Opioid overdose severity score	9.000000e-06
GCST008829_4	Neuritic plaque	6.000000e-07
GCST009379_25	Type 2 diabetes	4.000000e-08
GCST009391_1187	Metabolite levels	3.000000e-06
GCST009615_5	Triglyceride levels x loop diuretics use interaction	4.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:1001488	influenza A (H1N1)
EFO:0004847	age at onset
EFO:0004318	smoking behavior
EFO:0010140	opioid overdose severity measurement
EFO:0006798	neuritic plaque measurement
EFO:0021575	adipic acid measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5060 (SINGLE PROTEIN)

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

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
7.78	Kd	16.43	nM	CHEMBL5653589
7.78	ED50	16.43	nM	CHEMBL5653589
7.61	Kd	24.37	nM	CHEMBL3752910
7.61	ED50	24.37	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	2148217: Binding affinity to human DDX18 incubated for 45 mins by Kinobead based pull down assay	kd	0.0164	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148217: Binding affinity to human DDX18 incubated for 45 mins by Kinobead based pull down assay	kd	0.0244	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, increases reaction	3
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	increases expression	1
nivalenol	increases expression	1
beta-methylcholine	affects expression	1
tamibarotene	affects 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
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Aspirin	decreases expression	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Cannabidiol	increases expression	1
Cisplatin	affects cotreatment, decreases expression	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
CHEMBL5651259	Binding	Binding affinity to human DDX18 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

Clinical trials (associated diseases)

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