DDX42

Summary

DDX42 (DEAD-box helicase 42, HGNC:18676) is a protein-coding gene on chromosome 17q23.3, encoding ATP-dependent RNA helicase DDX42 (Q86XP3). ATP-dependent RNA helicase that binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures. It is a common-essential gene (DepMap: required in 98.7% of cancer cell lines).

This gene encodes a member of the Asp-Glu-Ala-Asp (DEAD) box protein family. Members of this protein family are putative RNA helicases, and 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. Members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Two transcript variants encoding the same protein have been identified for this gene.

Source: NCBI Gene 11325 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 120 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_203499

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18676
Approved symbol	DDX42
Name	DEAD-box helicase 42
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	RNAHP, RHELP, SF3b125, SF3B8
Ensembl gene	ENSG00000198231
Ensembl biotype	protein_coding
OMIM	613369
Entrez	11325

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 18 protein_coding, 9 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000359353, ENST00000389924, ENST00000577940, ENST00000577978, ENST00000578137, ENST00000578593, ENST00000578681, ENST00000579511, ENST00000579539, ENST00000580108, ENST00000581135, ENST00000581477, ENST00000581767, ENST00000582985, ENST00000583590, ENST00000584010, ENST00000584261, ENST00000584951, ENST00000878522, ENST00000878523, ENST00000878524, ENST00000878525, ENST00000878526, ENST00000878527, ENST00000878528, ENST00000927681, ENST00000927682, ENST00000927683, ENST00000927684, ENST00000927685, ENST00000960536

RefSeq mRNA: 2 — MANE Select: NM_203499 NM_007372, NM_203499

CCDS: CCDS32704

Canonical transcript exons

ENST00000389924 — 18 exons

Exon	Start	End
ENSE00003496120	63815563	63815673
ENSE00003502403	63810513	63810560
ENSE00003522787	63809560	63809659
ENSE00003557275	63811076	63811173
ENSE00003585313	63805071	63805175
ENSE00003617601	63816868	63816966
ENSE00003623946	63807724	63807900
ENSE00003645966	63792412	63792562
ENSE00003659844	63811932	63812208
ENSE00003672140	63808820	63808948
ENSE00003674808	63806535	63806654
ENSE00003691014	63813228	63813454
ENSE00003846367	63774170	63774376
ENSE00003889389	63798038	63798099
ENSE00003890079	63817694	63819317
ENSE00003893082	63800468	63800617
ENSE00003894032	63787034	63787270
ENSE00003894682	63799589	63799625

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.9931 / max 244.0114, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162224	31.7995	1815
162223	0.1936	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.31	gold quality
right uterine tube	UBERON:0001302	98.08	gold quality
mucosa of stomach	UBERON:0001199	97.93	gold quality
left ovary	UBERON:0002119	97.81	gold quality
right ovary	UBERON:0002118	97.75	gold quality
colonic epithelium	UBERON:0000397	97.74	gold quality
calcaneal tendon	UBERON:0003701	97.66	gold quality
endocervix	UBERON:0000458	97.50	gold quality
sural nerve	UBERON:0015488	97.50	gold quality
minor salivary gland	UBERON:0001830	97.43	gold quality
tibial nerve	UBERON:0001323	97.39	gold quality
gall bladder	UBERON:0002110	97.39	gold quality
body of uterus	UBERON:0009853	97.39	gold quality
ovary	UBERON:0000992	97.38	gold quality
rectum	UBERON:0001052	97.28	gold quality
left uterine tube	UBERON:0001303	97.22	gold quality
skin of leg	UBERON:0001511	97.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.17	gold quality
skin of abdomen	UBERON:0001416	97.14	gold quality
lower esophagus	UBERON:0013473	97.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.12	gold quality
adenohypophysis	UBERON:0002196	97.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.11	gold quality
ectocervix	UBERON:0012249	97.03	gold quality
body of stomach	UBERON:0001161	97.00	gold quality
right coronary artery	UBERON:0001625	96.97	gold quality
saliva-secreting gland	UBERON:0001044	96.95	gold quality
right lung	UBERON:0002167	96.86	gold quality
popliteal artery	UBERON:0002250	96.83	gold quality
tibial artery	UBERON:0007610	96.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting DDX42, 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-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4719	99.73	72.10	3329

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• characterization of protein associated with the human 17S U2 snRNP and one of its stable subunits, SF3b; may facilitate the assembly of the 17S U2 snRNP (PMID:12234937)
• Ddx42p represents the first example of a human DEAD box protein possessing RNA helicase, protein displacement and RNA annealing activities. (PMID:16397294)
• expression of N-terminal DDX42 is able to overcome Japanese encephalitis virus-induced antagonism of IFN responses and so may be important for Japanese encephalitis virus pathogenesis (PMID:18588927)
• Cancer-associated mutations in SF3B1 disrupt the interaction between SF3B1 and DDX42. (PMID:35652295)
• The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses. (PMID:36161446)
• Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly. (PMID:36797247)
• [The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses]. (PMID:37094262)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddx42	ENSDARG00000037928
mus_musculus	Ddx42	ENSMUSG00000020705
rattus_norvegicus	Ddx42	ENSRNOG00000009474
drosophila_melanogaster	CG6418	FBGN0036104
caenorhabditis_elegans		WBGENE00008119

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), 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), DDX39B (ENSG00000198563), DDX47 (ENSG00000213782), DDX3X (ENSG00000215301), DDX52 (ENSG00000278053)

Protein

Protein identifiers

ATP-dependent RNA helicase DDX42 — Q86XP3 (reviewed: Q86XP3)

Alternative names: DEAD box protein 42, RNA helicase-like protein, RNA helicase-related protein, SF3b DEAD box protein, Splicing factor 3B-associated 125 kDa protein

All UniProt accessions (5): Q86XP3, J3KRE3, J3KRV0, J3KTK9, J3QRI2

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent RNA helicase that binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures. Unwinding is promoted in the presence of single-strand binding proteins. Also mediates RNA duplex formation thereby displacing the single-strand RNA binding protein. ATP and ADP modulate its activity: ATP binding and hydrolysis by DDX42 triggers RNA strand separation, whereas the ADP-bound form of the protein triggers annealing of complementary RNA strands. Required for assembly of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs: DDX42 associates transiently with the SF3B subcomplex of the 17S U2 SnRNP complex and is released after fulfilling its role in the assembly of 17S U2 SnRNP. Involved in the survival of cells by interacting with TP53BP2 and thereby counteracting the apoptosis-stimulating activity of TP53BP2. Relocalizes TP53BP2 to the cytoplasm.

Subunit / interactions. Transient component of the SF3B subcomplex of the 17S U2 SnRNP complex. Interacts (via the C-terminus) with TP53BP2; the interaction is not inhibited by TP53BP2 ubiquitination and is independent of p53/TP53.

Subcellular location. Cytoplasm. Nucleus Nucleus. Cajal body. Nucleus speckle.

Tissue specificity. Expressed in several cell lines (at protein level). Expressed in liver, lung, tonsil, thymus, muscle and pancreatic islets.

Similarity. Belongs to the DEAD box helicase family. DDX42 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86XP3-1	1	yes
Q86XP3-2	2

RefSeq proteins (2): NP_031398, NP_987095* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00270, PF00271

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (71 total): helix 28, strand 14, modified residue 9, compositionally biased region 6, region of interest 4, domain 2, short sequence motif 2, chain 1, binding site 1, cross-link 1, splice variant 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8DPE	X-RAY DIFFRACTION	1.53
7EVN	ELECTRON MICROSCOPY	2.6
8HK1	ELECTRON MICROSCOPY	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XP3-F1	66.98	0.33

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): 297–304

Post-translational modifications (10): 5, 12, 58, 96, 104, 109, 111, 185, 754, 899

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9943411	CHD1 and CHD2 subfamily

MSigDB gene sets: 167 (showing top): BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, SENESE_HDAC1_TARGETS_UP, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_NUCLEAR_SPECK, GOCC_CAJAL_BODY, GOCC_NUCLEAR_BODY

GO Biological Process (3): intracellular protein localization (GO:0008104), regulation of apoptotic process (GO:0042981), U2-type prespliceosome assembly (GO:1903241)

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 (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), Cajal body (GO:0015030), membrane (GO:0016020), nuclear speck (GO:0016607), U2-type prespliceosome (GO:0071004)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
mRNA Splicing	2
mRNA 3’-end processing	1
Dengue Virus Infection	1
CHD chromatin remodelers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ATP-dependent activity	2
binding	2
nuclear ribonucleoprotein granule	2
macromolecule localization	1
apoptotic process	1
regulation of programmed cell death	1
spliceosomal complex assembly	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
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
prespliceosome	1

Protein interactions and networks

STRING

3171 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX42	TP53BP2	Q13625	897
DDX42	AGO2	Q9UKV8	644
DDX42	DHX15	O43143	612
DDX42	SF3B2	Q13435	554
DDX42	PRPF6	O94906	535
DDX42	BCAS2	O75934	517
DDX42	ANK2	Q01484	516
DDX42	ANK3	Q12955	512
DDX42	ANK1	P16157	511
DDX42	PRPF31	Q8WWY3	508
DDX42	DDX20	Q9UHI6	508
DDX42	DDX3X	O00571	501
DDX42	TNRC6A	Q8NDV7	481
DDX42	GPN2	Q9H9Y4	475
DDX42	DHX8	Q14562	468

IntAct

122 interactions, top by confidence:

A	B	Type	Score
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
LRIF1	SMCHD1	psi-mi:“MI:0914”(association)	0.680
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
DNAJC8	SF3B1	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SF3B4	DDX42	psi-mi:“MI:0915”(physical association)	0.640
SF3B4	SF3B1	psi-mi:“MI:0914”(association)	0.610
DDX42	SF3A2	psi-mi:“MI:0915”(physical association)	0.560
DDX42	SNRPC	psi-mi:“MI:0915”(physical association)	0.550
DDX42	SF3A1	psi-mi:“MI:0915”(physical association)	0.550
DHX15	DDX42	psi-mi:“MI:0915”(physical association)	0.550
MAGEA10	POTEF	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SF3A3	SF3B1	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
	DDX42	psi-mi:“MI:0407”(direct interaction)	0.440
DDX42	ACSL3	psi-mi:“MI:0915”(physical association)	0.400
DDX42	TMX1	psi-mi:“MI:0915”(physical association)	0.400
DDX42	DNAJB11	psi-mi:“MI:0915”(physical association)	0.400
CDX1	DDX42	psi-mi:“MI:0915”(physical association)	0.400
Sf3a1	U2SURP	psi-mi:“MI:0915”(physical association)	0.400
U2SURP	DDX42	psi-mi:“MI:0915”(physical association)	0.370
PRPF19	DDX42	psi-mi:“MI:0915”(physical association)	0.370
Kifc5b	KPNA3	psi-mi:“MI:0914”(association)	0.350
Itgb1	SSR3	psi-mi:“MI:0914”(association)	0.350
Bap1	RNF40	psi-mi:“MI:0914”(association)	0.350
Kif13b	TCF3	psi-mi:“MI:0914”(association)	0.350
Aff1	UVRAG	psi-mi:“MI:0914”(association)	0.350
SF1	U2SURP	psi-mi:“MI:0914”(association)	0.350

BioGRID (280): DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-RNA), DDX42 (Affinity Capture-RNA), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS), DDX42 (Affinity Capture-MS)

ESM2 similar proteins: A1CHL3, A1CNV8, A1CQA9, A1CX72, A1D1R8, A1D373, A2QIL2, A2QQA8, A4QYM6, A4RN46, A5DDF4, A6RJA2, A6RUH2, A6RW79, A7EGG4, A7ENE0, A7F4L5, P0C2N7, P0C2N8, P0CQ88, P0CQ89, P0CQ98, P0CQ99, Q0CLX0, Q0CZN5, Q0D1K3, Q0J7Y8, Q0U6X2, Q0V1Z7, Q1DHB2, Q1DMX8, Q1E2B2, Q2HAD8, Q2U2J6, Q2UH00, Q2UQI6, Q4I830, Q4IP34, Q4PFD9, Q4WPE9

Diamond homologs: A1C6C4, A1CQA9, A1D373, A1DGZ7, A2QC74, A2QQA8, A3LQ55, A3LQW7, A4QSS5, A4RN46, A5A6J2, A5DL80, A5DS77, A5E058, A6RGE3, A6RW79, A6SFW7, A6ZRX0, A7E449, A7ENE0, A7TTT5, G0SFM2, O22907, P0CQ76, P0CQ77, P17844, P19109, P24782, P24783, P46942, Q0D1K3, Q0DB53, Q0J7Y8, Q10MH8, Q1DHB2, Q1DP69, Q26696, Q2H720, Q2HAD8, Q2R1M8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 150 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of non-coding RNA	6	36.2×	6e-07
mRNA Splicing	29	30.3×	5e-34
mRNA Splicing - Minor Pathway	13	27.7×	4e-14
mRNA Polyadenylation	33	27.6×	3e-37
Processing of Capped Intron-Containing Pre-mRNA	32	25.0×	1e-34
mRNA Splicing - Major Pathway	44	22.9×	6e-47
CHD1 and CHD2 subfamily	21	21.8×	6e-21
RNA Polymerase II Transcription Termination	8	16.7×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	16	79.3×	2e-25
RNA splicing, via transesterification reactions	8	39.6×	3e-09
mRNA cis splicing, via spliceosome	5	39.3×	1e-05
spliceosomal complex assembly	8	38.2×	3e-09
spliceosomal snRNP assembly	8	36.9×	4e-09
negative regulation of mRNA splicing, via spliceosome	5	30.4×	4e-05
mRNA splicing, via spliceosome	37	26.9×	2e-40
RNA splicing	21	14.7×	2e-16

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2646 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63785967:G:GT	donor_gain	1.0000
17:63787196:A:T	donor_gain	1.0000
17:63787266:AATGC:A	donor_gain	1.0000
17:63787267:ATGC:A	donor_gain	1.0000
17:63787269:GC:G	donor_gain	1.0000
17:63787271:G:GG	donor_gain	1.0000
17:63792409:CA:C	acceptor_loss	1.0000
17:63792410:A:AG	acceptor_gain	1.0000
17:63792411:G:GG	acceptor_gain	1.0000
17:63792411:GC:G	acceptor_gain	1.0000
17:63792411:GCT:G	acceptor_gain	1.0000
17:63792411:GCTA:G	acceptor_gain	1.0000
17:63792562:GGC:G	donor_loss	1.0000
17:63792563:G:T	donor_loss	1.0000
17:63792567:G:GG	donor_gain	1.0000
17:63798100:G:GG	donor_gain	1.0000
17:63799626:G:GG	donor_gain	1.0000
17:63800292:T:TA	acceptor_gain	1.0000
17:63800463:T:A	acceptor_gain	1.0000
17:63800464:GCA:G	acceptor_loss	1.0000
17:63800466:A:AG	acceptor_gain	1.0000
17:63800466:A:T	acceptor_loss	1.0000
17:63800466:AG:A	acceptor_gain	1.0000
17:63800467:G:GG	acceptor_gain	1.0000
17:63800467:GG:G	acceptor_gain	1.0000
17:63800467:GGA:G	acceptor_gain	1.0000
17:63800467:GGAA:G	acceptor_gain	1.0000
17:63800614:AGAGG:A	donor_loss	1.0000
17:63800615:GAG:G	donor_gain	1.0000
17:63800615:GAGG:G	donor_loss	1.0000

AlphaMissense

6241 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63792537:T:C	L116S	1.000
17:63792545:T:C	F119L	1.000
17:63792546:T:C	F119S	1.000
17:63792546:T:G	F119C	1.000
17:63792547:C:A	F119L	1.000
17:63792547:C:G	F119L	1.000
17:63792549:T:C	M120T	1.000
17:63792550:G:A	M120I	1.000
17:63792550:G:C	M120I	1.000
17:63792550:G:T	M120I	1.000
17:63792551:G:C	A121P	1.000
17:63799597:G:C	R148P	1.000
17:63799602:G:C	D150H	1.000
17:63800474:T:G	Y160D	1.000
17:63800481:G:C	R162P	1.000
17:63800555:G:A	G187R	1.000
17:63800555:G:C	G187R	1.000
17:63800595:T:A	L200H	1.000
17:63805153:T:C	L235P	1.000
17:63806541:G:C	G245R	1.000
17:63806542:G:A	G245D	1.000
17:63806571:T:C	F255L	1.000
17:63806572:T:C	F255S	1.000
17:63806572:T:G	F255C	1.000
17:63806573:T:A	F255L	1.000
17:63806573:T:G	F255L	1.000
17:63806611:T:A	I268N	1.000
17:63806614:G:C	R269P	1.000
17:63806635:C:A	P276H	1.000
17:63806635:C:G	P276R	1.000

dbSNP variants (sampled 300 via entrez): RS1000066153 (17:63790186 T>C,G), RS1000096647 (17:63789931 A>G), RS1000097118 (17:63806207 A>G), RS1000170405 (17:63806555 T>C), RS1000279054 (17:63801003 T>C), RS1000304089 (17:63778997 A>G), RS1000427658 (17:63802015 A>C,G), RS1000515461 (17:63788614 T>C), RS1000616592 (17:63808003 A>G), RS1000737896 (17:63782990 T>A), RS1000830397 (17:63817458 A>G), RS1000843281 (17:63779389 G>A,C,T), RS1000853832 (17:63819374 G>A), RS1000874279 (17:63779112 A>T), RS1000878023 (17:63773486 G>C,T)

Disease associations

OMIM: gene MIM:613369 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002783_163	Body mass index	1.000000e-06
GCST002783_217	Body mass index	1.000000e-07
GCST004067_107	Hip circumference adjusted for BMI	2.000000e-13
GCST004067_145	Hip circumference adjusted for BMI	8.000000e-10
GCST004067_39	Hip circumference adjusted for BMI	1.000000e-06
GCST90002384_423	Hemoglobin	5.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008039	BMI-adjusted hip circumference
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105782 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.70	Kd	2	nM	CHEMBL3991935

PubChem BioAssay actives

1 with measured affinity, of 198 total; 1 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
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one;hydrochloride	1424976: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
FR900359	increases phosphorylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases abundance, increases expression	1
coumarin	affects phosphorylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
K 7174	increases expression	1
pyrimidifen	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
CC-8490	increases expression	1
bisphenol S	increases expression	1
PP242	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991689	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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