DHX58

Summary

DHX58 (DExH-box helicase 58, HGNC:29517) is a protein-coding gene on chromosome 17q21.2, encoding ATP-dependent RNA helicase DHX58 (Q96C10). Acts as a regulator of RIGI and IFIH1/MDA5 mediated antiviral signaling.

Enables several functions, including ATP hydrolysis activity; RNA binding activity; and zinc ion binding activity. Involved in negative regulation of type I interferon production and regulation of innate immune response. Predicted to be active in cytoplasm.

Source: NCBI Gene 79132 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_024119

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29517
Approved symbol	DHX58
Name	DExH-box helicase 58
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	LGP2, D11LGP2
Ensembl gene	ENSG00000108771
Ensembl biotype	protein_coding
OMIM	608588
Entrez	79132

Gene structure

Transcript identifiers

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

ENST00000251642, ENST00000413196, ENST00000430773, ENST00000586522, ENST00000589979, ENST00000590637, ENST00000591220, ENST00000592024, ENST00000900696, ENST00000900697, ENST00000900698, ENST00000900699, ENST00000900700, ENST00000900701, ENST00000900702, ENST00000900703, ENST00000954404, ENST00000954405, ENST00000954406, ENST00000954407

RefSeq mRNA: 1 — MANE Select: NM_024119 NM_024119

CCDS: CCDS11416

Canonical transcript exons

ENST00000251642 — 14 exons

Exon	Start	End
ENSE00002341651	42112113	42112205
ENSE00002366439	42111725	42111893
ENSE00002965810	42112605	42112714
ENSE00003484944	42101411	42101946
ENSE00003493338	42102216	42102312
ENSE00003519716	42111296	42111497
ENSE00003521573	42105018	42105167
ENSE00003544527	42110723	42110913
ENSE00003550414	42109270	42109386
ENSE00003575514	42105736	42105989
ENSE00003603587	42107982	42108108
ENSE00003641316	42104766	42104927
ENSE00003671497	42103608	42103798
ENSE00003678720	42107604	42107795

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 93.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.2934 / max 622.4082, expressed in 1380 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166095	5.5224	1354
166092	1.8065	205
166091	0.3128	73
166089	0.2850	79
166090	0.1575	64
166093	0.0859	27
166088	0.0725	38
166094	0.0508	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.30	gold quality
right lobe of liver	UBERON:0001114	91.82	gold quality
right uterine tube	UBERON:0001302	91.41	gold quality
right adrenal gland	UBERON:0001233	90.00	gold quality
right adrenal gland cortex	UBERON:0035827	89.48	gold quality
left adrenal gland cortex	UBERON:0035825	89.22	gold quality
left adrenal gland	UBERON:0001234	89.05	gold quality
apex of heart	UBERON:0002098	88.87	gold quality
monocyte	CL:0000576	88.40	gold quality
mononuclear cell	CL:0000842	88.05	gold quality
left ovary	UBERON:0002119	88.01	gold quality
leukocyte	CL:0000738	87.98	gold quality
tibial nerve	UBERON:0001323	87.88	gold quality
right ovary	UBERON:0002118	87.67	gold quality
right testis	UBERON:0004534	87.50	gold quality
left testis	UBERON:0004533	87.49	gold quality
spleen	UBERON:0002106	87.30	gold quality
metanephros cortex	UBERON:0010533	87.05	gold quality
right lung	UBERON:0002167	86.39	gold quality
adrenal cortex	UBERON:0001235	86.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.34	gold quality
upper lobe of left lung	UBERON:0008952	86.28	gold quality
ectocervix	UBERON:0012249	86.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.22	gold quality
gall bladder	UBERON:0002110	86.05	gold quality
adrenal gland	UBERON:0002369	85.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.78	gold quality
body of stomach	UBERON:0001161	85.59	gold quality
adenohypophysis	UBERON:0002196	85.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	107.23
E-ANND-3	no	2.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting DHX58, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4313	97.18	63.15	420
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-2114-3P	95.45	66.11	579
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-3677-5P	93.16	64.62	393
HSA-MIR-210-3P	92.54	65.16	165

Literature-anchored findings (GeneRIF, showing 40)

• Cloning and expression of the mouse Lpg2 mRNA, and comparison of the ORF to that of human LPG2 mRNA. (PMID:11735219)
• Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. (PMID:16116171)
• LGP2 competes with the kinase IKKi for a common interaction site on IPS-1, as an element of negative-feedback regulation of intracellular antiviral signaling. (PMID:17020950)
• LGP2 can be coexpressed with RIG-I to inhibit activation of the NF-kappaB reporter expression and that LGP2 protein produced in insect cells can bind both single- and double-stranded RNA (dsRNA), with higher affinity and cooperativity for dsRNA. (PMID:18411269)
• The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA. (PMID:19278996)
• The V protein interaction was found to disrupt ATP hydrolysis mediated by both MDA5 and LGP2. (PMID:19403670)
• Data sugget that DeltaPsi(m) and MAVS are coupled at the same stage in the RLR antiviral signaling pathway. (PMID:21285412)
• LGP2 functions as an inhibitor of the innate immune response triggered by Rabeis virus infection (PMID:21525357)
• the present study shows the presence of RIG-1,MDA-5, and LGP-2 in the human upper airways, most prominently inthe epithelium. (PMID:22185736)
• Paramyxovirus 5 V proteins interact with the RNA Helicase LGP2 to inhibit RIG-I-dependent interferon beta induction. (PMID:22301134)
• LGP2, a host protein induced during influenza A virus infection, downregulates the host antiviral IFN response (PMID:22837208)
• results demonstrate previously unrecognized properties of LGP2 ATP hydrolysis and RNA interaction and provide a mechanistic basis for a positive regulatory role for LGP2 in antiviral signaling (PMID:23184951)
• Data show that LGP2 is able to synergize with melanoma differentiation associated gene-5 (mda-5) to render cells to induction by poly(I:C), but did not enhance retinoic acid-inducible gene-I (RIG-I) to induce type I interferon in response to poly(I:C). (PMID:23671710)
• L region antisense RNA of EMCV is a key determinant of innate immunity to the virus and represents an RNA that activates LGP2 associated MDA5 in virally-infected cells. (PMID:24550253)
• Experiments with paramyxovirus V protein-insensitive proteins revealed that the primary outcome of LGP2 interference is suppression of its ability to synergize with MDA5. (PMID:24829334)
• LGP2 increases the initial rate of MDA5-RNA interaction and regulates MDA5 filament assembly. (PMID:25127512)
• LGP2 did not reveal significant single-SNP associations with multiple sclerosis risk. (PMID:25288302)
• This review briefly summarizes the RLR system, and focuses on the relationship between LGP2 and MDA5, describing in detail how these two proteins work together to detect foreign RNA and generate a fully functional antiviral response. (PMID:25794939)
• essential role in activating interferon signaling against hepatitis C virus (HCV) infection by promoting MDA5 recognition of HCV pathogen-associated molecular patterns (PMID:28090671)
• Data support a new model where an LGP2-MDA5 oligomer shuttles NS3 to the mitochondria to block antiviral signaling (PMID:28483922)
• Results indicate that pumilio RNA binding family member 1 (PUM1) is a negative regulator of RNA helicase LGP2 (LGP2), a master regulator of innate immunity genes expressed in a cascade fashion. (PMID:28760986)
• study documents that recombinant measles virus produce defective interfering genomes that have high immunostimulatory properties via their binding to RIG-I and LGP2 proteins, both of which are cytosolic nonself RNA sensors of innate immunity. (PMID:28768856)
• genetic loss of LGP2 uncovers dsRNA-mediated RNAi albeit less strongly than complete loss of the IFN system (PMID:29351913)
• These findings provide a unique mechanism for LGP2 negative regulation through TRAF suppression and extend the potential impact of LGP2 negative regulation beyond the IFN antiviral response. (PMID:29661858)
• LGP2 represses specific miRNA activities by interacting with TRBP, resulting in selective regulation of target genes. This novel function of LGP2 is to modulate RNA silencing, indicating the crosstalk between RNA silencing and RLR signaling in mammalian cells. (PMID:29939295)
• Study demonstrated a tumor suppressor role of LGP2 in neuroblastoma (NB). LGP2 was effective in promoting poly (I:C)-induced NB suppression and cytoplasmic LGP2 can serve as an independent favorable prognostic factor in NB patients. (PMID:30179292)
• DHX58 expression positively correlate with osteogenic process. DHX58 overexpression enhances osteogenesis via the Wnt/beta-Catenin pathway. (PMID:30795861)
• LGP2 binds to PACT to regulate RIG-I- and MDA5-mediated antiviral responses. (PMID:31575732)
• characterize the involvement of PACT in the synergy between LGP2 and MDA5 (PMID:31575732)
• Our findings may shed light on the mechanism of apoptosis, induced by the TRBP-bound miRNAs through the interaction of TRBP with LGP2, as an antiviral defense system in mammalian cells. (PMID:31799626)
• Spatiotemporal dynamics of innate immune signaling via RIG-I-like receptors. (PMID:32571931)
• RIG-I-Like Receptor LGP2 Is Required for Tumor Control by Radiotherapy. (PMID:33087322)
• RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency. (PMID:35156720)
• Function conservation and disparities of zebrafish and human LGP2 genes in fish and mammalian cells responsive to poly(I:C). (PMID:36059486)
• Effect of variants in LGP2 on MDA5-mediated activation of interferon response and suppression of hepatitis D virus replication. (PMID:36152765)
• K63-linked polyubiquitination of LGP2 by Riplet regulates RIG-I-dependent innate immune response. (PMID:36515138)
• Genetic variants of IFIH1 and DHX58 affect the chronicity of hepatitis C in the Chinese Han population. (PMID:36743960)
• The RNA-Binding Proteins OAS1, ZFP36L2, and DHX58 Are Involved in the Regulation of CD44 mRNA Splicing in Colorectal Cancer Cells. (PMID:37336810)
• Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2. (PMID:38015453)
• Contrasting functions of ATP hydrolysis by MDA5 and LGP2 in viral RNA sensing. (PMID:38309507)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhx58	ENSDARG00000089463
mus_musculus	Dhx58	ENSMUSG00000017830
rattus_norvegicus	Dhx58	ENSRNOG00000018247
caenorhabditis_elegans	drh-3	WBGENE00008400

Paralogs (2): RIGI (ENSG00000107201), IFIH1 (ENSG00000115267)

Protein

Protein identifiers

ATP-dependent RNA helicase DHX58 — Q96C10 (reviewed: Q96C10)

Alternative names: ATP-dependent helicase LGP2, Protein D11Lgp2 homolog, RIG-I-like receptor 3, RIG-I-like receptor LGP2

All UniProt accessions (6): Q96C10, A0AA51U9C6, C9JE76, C9JG98, K7EMZ5, K7EPP0

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a regulator of RIGI and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to RIGI and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on RIG-I signaling may involve the following mechanisms: competition with RIGI for binding to the viral RNA, binding to RIGI and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3 (IRF3). Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by RIGI and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses and coronavirus SARS-CoV-2, and also to the bacterial pathogen Listeria monocytogenes. Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5’-triphosphorylated RNA, although it can recognize RNA lacking a 5’-triphosphate.

Subunit / interactions. Monomer in the absence of dsRNA. Homodimer in the presence of dsRNA. Interacts with RIGI (via CARD domain), MAVS/IPS1 and DDX60. Found in a complex with RIGI and IFIH1/MDA5. Interacts with ANKRD17. Directly interacts with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5 conjugates. (Microbial infection) Interacts (via helicase C-terminal domain) with non-structural protein V of paramyxoviruses including human parainfluenza 2 virus, human parainfluenza 5 virus, measles virus, mumps virus, hendra virus and nipah virus.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in testis, nerve and spleen. Also expressed in the brain.

Domain organisation. The RLR CTR domain is capable of inhibiting dimerization and signaling of RIGI and also facilitates binding of dsRNA.

Induction. By interferon (IFN), virus infection, or intracellular dsRNA.

Similarity. Belongs to the helicase family. RLR subfamily.

RefSeq proteins (1): NP_077024* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
IPR006935	Helicase/UvrB_N	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR021673	RLR_CTR	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR038557	RLR_C_sf	Homologous_superfamily
IPR041204	RIG-I-like_C	Domain
IPR051363	RLR_Helicase	Family

Pfam: PF00271, PF04851, PF11648, PF18119

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (49 total): strand 13, mutagenesis site 8, helix 7, binding site 5, sequence variant 5, domain 3, turn 3, chain 1, sequence conflict 1, region of interest 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3EQT	X-RAY DIFFRACTION	2
2W4R	X-RAY DIFFRACTION	2.6
9LOV	ELECTRON MICROSCOPY	3.07
9LOU	ELECTRON MICROSCOPY	3.36
2RQA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96C10-F1	91.15	0.72

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 (5): 612; 615; 24–31; 556; 559

Mutagenesis-validated functional residues (8):

Position	Phenotype
30	loss of dsrna-induced atpase activity. no effect on ds-rna binding. no effect on cytoplasmic pattern recognition recepto
131–134	loss of dsrna-induced atpase activity.
167–169	loss of dsrna-induced atpase activity. loss of ds-rna binding. no effect on cytoplasmic pattern recognition receptor sig
373–376	loss of dsrna-induced atpase activity. no effect on cytoplasmic pattern recognition receptor signaling pathway in respon
438–442	loss of dsrna-induced atpase activity. no effect on cytoplasmic pattern recognition receptor signaling pathway in respon
467–471	loss of dsrna-induced atpase activity. no effect on cytoplasmic pattern recognition receptor signaling pathway in respon
634	abolishes rna binding.
651	abolishes rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta

MSigDB gene sets: 327 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_CYTOKINE_PRODUCTION, HASEGAWA_TUMORIGENESIS_BY_RET_C634R

GO Biological Process (15): cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), response to virus (GO:0009615), response to bacterium (GO:0009617), negative regulation of type I interferon production (GO:0032480), positive regulation of type I interferon production (GO:0032481), negative regulation of MDA-5 signaling pathway (GO:0039534), negative regulation of RIG-I signaling pathway (GO:0039536), regulation of innate immune response (GO:0045088), negative regulation of innate immune response (GO:0045824), antiviral innate immune response (GO:0140374), positive regulation of MDA-5 signaling pathway (GO:1900245), positive regulation of RIG-I signaling pathway (GO:1900246), immune system process (GO:0002376), innate immune response (GO:0045087), defense response to virus (GO:0051607)

GO Molecular Function (14): DNA binding (GO:0003677), RNA helicase activity (GO:0003724), double-stranded RNA binding (GO:0003725), single-stranded RNA binding (GO:0003727), ATP binding (GO:0005524), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
innate immune response	3
positive regulation of cytokine production	2
response to other organism	2
regulation of type I interferon production	2
type I interferon production	2
MDA-5 signaling pathway	2
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	2
regulation of MDA-5 signaling pathway	2
RIG-I signaling pathway	2
regulation of RIG-I signaling pathway	2
positive regulation of pattern recognition receptor signaling pathway	2
positive regulation of intracellular signal transduction	2
nucleic acid binding	2
RNA binding	2
ATP-dependent activity	2
binding	2
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
negative regulation of cytokine production	1
regulation of response to biotic stimulus	1
regulation of defense response	1
regulation of response to external stimulus	1
regulation of immune response	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of innate immune response	1
negative regulation of immune response	1
defense response to virus	1
positive regulation of immune effector process	1
biological_process	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	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

Protein interactions and networks

STRING

2262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHX58	MAVS	Q7Z434	998
DHX58	IFIH1	Q9BYX4	975
DHX58	IRF3	Q14653	889
DHX58	RIGI	O95786	876
DHX58	IFNB1	P01574	851
DHX58	TRIM25	Q14258	833
DHX58	TBK1	Q9UHD2	825
DHX58	ISG15	P05161	796
DHX58	IFNA13	P01562	792
DHX58	DDX60	Q8IY21	792
DHX58	TRAF3	Q13114	785
DHX58	TLR3	O15455	781
DHX58	RNF125	Q96EQ8	760
DHX58	IRF7	Q92985	735
DHX58	TANK	Q92844	731
DHX58	TRAF6	Q9Y4K3	731

IntAct

24 interactions, top by confidence:

A	B	Type	Score
DHX58	NKRF	psi-mi:“MI:0914”(association)	0.500
DHX58	NKRF	psi-mi:“MI:0915”(physical association)	0.500
DHX58	DHX30	psi-mi:“MI:0915”(physical association)	0.500
DHX58	EIF2AK2	psi-mi:“MI:0915”(physical association)	0.500
DHX58	EIF6	psi-mi:“MI:0915”(physical association)	0.500
STAU2	DHX58	psi-mi:“MI:0915”(physical association)	0.500
DHX58	DICER1	psi-mi:“MI:0915”(physical association)	0.500
DHX58	AGO2	psi-mi:“MI:0915”(physical association)	0.500
RIGI	DHX58	psi-mi:“MI:0915”(physical association)	0.400
DHX58	IFIH1	psi-mi:“MI:0915”(physical association)	0.400
IFI16	DHX58	psi-mi:“MI:0915”(physical association)	0.400
DHX58	P/V	psi-mi:“MI:0915”(physical association)	0.400
P/V/I	DHX58	psi-mi:“MI:0915”(physical association)	0.400
DHX58	P/V/C	psi-mi:“MI:0915”(physical association)	0.400
P/V/C	DHX58	psi-mi:“MI:0915”(physical association)	0.400
AP2B1	DHX58	psi-mi:“MI:0915”(physical association)	0.370
MYC		psi-mi:“MI:0914”(association)	0.350

BioGRID (41): DHX58 (Two-hybrid), DHX58 (Reconstituted Complex), DHX58 (Affinity Capture-Western), DHX58 (Affinity Capture-Western), DHX58 (Affinity Capture-Western), DHX58 (Affinity Capture-Western), DHX58 (Affinity Capture-MS), IFI16 (Affinity Capture-Western), DHX58 (Affinity Capture-Western), TRIM25 (Affinity Capture-Western), DDX58 (Affinity Capture-Western), DHX58 (Affinity Capture-Western), DHX58 (Reconstituted Complex), TRIM14 (Reconstituted Complex), DHX58 (Co-crystal Structure)

ESM2 similar proteins: A0A023PXF5, A6QSQ0, A6SBT4, A7EY76, F1RCY6, O13559, O18475, O48534, P18708, P40105, P40434, P40889, P43538, P46063, P46459, P46460, P46461, P54351, Q14527, Q1EB85, Q2TBP1, Q2U587, Q3B7N1, Q3E7Y4, Q5R410, Q5RF63, Q6AYJ1, Q6PCN7, Q7ZU90, Q86WJ1, Q8NHQ9, Q8R5F7, Q95216, Q96C10, Q99J87, Q9BYX4, Q9CXF7, Q9DGP9, Q9EPU0, Q9FF61

Diamond homologs: A0A1D5PRR9, A0R8U6, A1CS00, A1D4V5, A2Q8R2, A2QQA8, A3GH78, A3LP87, A3LS22, A4RGD1, A4RN08, A5DLE0, A5DQF1, A5E058, A5E0U9, A6RIS1, A6ZSX1, A6ZT77, A6ZVS0, A7EFH4, A7TK63, A7TS37, A7TSV4, B0XMV6, D0PV95, F0LJX3, I3XHK1, O22907, O27830, P0C2N8, P0CQ78, P0CQ79, P0CQ98, P0CQ99, P0CR00, P0CR01, P21507, P25888, P34580, P34689

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2500 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42101942:CAGAC:C	acceptor_gain	1.0000
17:42101945:ACC:A	acceptor_loss	1.0000
17:42101947:C:CA	acceptor_loss	1.0000
17:42103587:AGCC:A	donor_gain	1.0000
17:42103594:T:TA	donor_gain	1.0000
17:42103606:A:AC	donor_gain	1.0000
17:42103607:C:CC	donor_gain	1.0000
17:42103626:TTG:T	donor_gain	1.0000
17:42103651:T:A	donor_gain	1.0000
17:42104765:C:CG	donor_loss	1.0000
17:42104812:G:GA	donor_gain	1.0000
17:42104923:CTGGC:C	acceptor_gain	1.0000
17:42104924:TGGC:T	acceptor_gain	1.0000
17:42104925:GGC:G	acceptor_gain	1.0000
17:42104926:GC:G	acceptor_gain	1.0000
17:42104927:CC:C	acceptor_gain	1.0000
17:42104928:C:CC	acceptor_gain	1.0000
17:42105163:TCCCT:T	acceptor_gain	1.0000
17:42105164:CCCT:C	acceptor_gain	1.0000
17:42105164:CCCTC:C	acceptor_gain	1.0000
17:42105165:CCT:C	acceptor_gain	1.0000
17:42105165:CCTC:C	acceptor_gain	1.0000
17:42105166:CT:C	acceptor_gain	1.0000
17:42105166:CTC:C	acceptor_gain	1.0000
17:42105167:TCT:T	acceptor_gain	1.0000
17:42105168:C:CC	acceptor_gain	1.0000
17:42105168:CT:C	acceptor_loss	1.0000
17:42105169:T:A	acceptor_loss	1.0000
17:42105171:C:CT	acceptor_gain	1.0000
17:42105172:A:T	acceptor_gain	1.0000

AlphaMissense

4472 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42110893:C:G	D131H	0.990
17:42101844:A:G	W652R	0.989
17:42101844:A:T	W652R	0.989
17:42110891:A:C	D131E	0.989
17:42110891:A:T	D131E	0.989
17:42110892:T:A	D131V	0.989
17:42110892:T:G	D131A	0.988
17:42110885:G:C	C133W	0.987
17:42110887:A:G	C133R	0.987
17:42110889:T:A	E132V	0.986
17:42101943:A:G	W619R	0.984
17:42101943:A:T	W619R	0.984
17:42110904:A:G	L127P	0.984
17:42104813:C:G	A506P	0.983
17:42111836:A:C	N19K	0.982
17:42111836:A:T	N19K	0.982
17:42110884:G:C	H134D	0.980
17:42111792:G:T	A34D	0.980
17:42111793:C:G	A34P	0.980
17:42110781:G:T	A168D	0.979
17:42111805:T:G	K30Q	0.979
17:42103629:A:T	V578D	0.978
17:42105089:C:G	G444R	0.978
17:42105089:C:T	G444R	0.978
17:42101842:C:A	W652C	0.977
17:42101842:C:G	W652C	0.977
17:42110787:A:G	L166P	0.976
17:42105118:A:G	L434P	0.975
17:42105868:G:C	F373L	0.975
17:42105868:G:T	F373L	0.975

dbSNP variants (sampled 300 via entrez): RS1000173934 (17:42106650 A>C,T), RS1000435390 (17:42106424 G>A,C), RS1000765004 (17:42104836 G>A), RS1000784105 (17:42112523 G>A,C), RS1001302965 (17:42107253 C>A,T), RS1001314696 (17:42101481 G>A), RS1001333302 (17:42111068 T>A), RS1002003211 (17:42113525 G>A), RS1003536068 (17:42102710 C>T), RS1003721270 (17:42109068 G>T), RS1004223184 (17:42108709 C>A,T), RS1004545914 (17:42107572 C>A), RS1004617402 (17:42109027 A>G), RS1004669117 (17:42113483 G>A,C), RS1005444201 (17:42109680 G>A,C)

Disease associations

OMIM: gene MIM:608588 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005194_157	Coronary artery disease	3.000000e-07
GCST005195_68	Coronary artery disease	7.000000e-09
GCST005196_24	Coronary artery disease	2.000000e-10
GCST009864_4	Fasting plasma glucose	3.000000e-07
GCST90002397_568	Mean spheric corpuscular volume	2.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — RIG-I-like receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression, affects cotreatment	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
TL8-506	increases expression, affects cotreatment	1
alpha phellandrene	increases expression	1
propionaldehyde	increases expression	1
terbufos	increases methylation	1
butyraldehyde	increases expression	1
cupric oxide	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
pentanal	increases 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, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MRK 003	decreases expression	1
licochalcone B	increases expression	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B2ML	Abcam A-549 DHX58 KO	Cancer cell line	Male
CVCL_D7G9	Ubigene HEK293T DHX58 KO	Transformed cell line	Female
CVCL_D9DE	Ubigene HEK293 DHX58 KO	Transformed cell line	Female
CVCL_F1LY	HyCyte A-549 KO-hDHX58	Cancer cell line	Male
CVCL_SK80	HAP1 DHX58 (-) 1	Cancer cell line	Male
CVCL_SK81	HAP1 DHX58 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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