DHX58 (DExH-box helicase 58)

Gene

• Entrez ID: 79132
• Gene name: DExH-box helicase 58
• Gene symbol: DHX58
• Synonyms (NCBI Gene): D11LGP2, D11lgp2e, LGP2, RLR-3
• Chromosome: 17
• Chromosome location: 17q21.2

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT935733	hsa-miR-3150b-3p	CLIP-seq
MIRT935734	hsa-miR-4689	CLIP-seq
MIRT935735	hsa-miR-4729	CLIP-seq
MIRT935736	hsa-miR-4784	CLIP-seq
MIRT2212395	hsa-miR-1254	CLIP-seq
MIRT2212396	hsa-miR-2861	CLIP-seq
MIRT2212397	hsa-miR-3116	CLIP-seq
MIRT2212398	hsa-miR-4446-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002376	Process	Immune system process	IEA
GO:0002753	Process	Cytoplasmic pattern recognition receptor signaling pathway	IBA
GO:0002753	Process	Cytoplasmic pattern recognition receptor signaling pathway	IMP	19211564
GO:0003677	Function	DNA binding	IEA
GO:0003723	Function	RNA binding	IEA
GO:0003724	Function	RNA helicase activity	IEA
GO:0003724	Function	RNA helicase activity	IMP	19211564
GO:0003725	Function	Double-stranded RNA binding	IBA
GO:0003725	Function	Double-stranded RNA binding	IDA	18411269
GO:0003725	Function	Double-stranded RNA binding	IEA
GO:0003727	Function	Single-stranded RNA binding	IBA
GO:0003727	Function	Single-stranded RNA binding	IDA	18411269
GO:0004386	Function	Helicase activity	IEA
GO:0005515	Function	Protein binding	IPI	17190814, 19403670, 21791617, 21903422, 25340845, 30833792
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0008270	Function	Zinc ion binding	IBA
GO:0008270	Function	Zinc ion binding	IDA	19278996
GO:0009615	Process	Response to virus	IEA
GO:0009615	Process	Response to virus	ISS
GO:0009617	Process	Response to bacterium	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0016887	Function	ATP hydrolysis activity	IMP	19211564
GO:0032480	Process	Negative regulation of type I interferon production	IDA	21525357
GO:0032480	Process	Negative regulation of type I interferon production	IEA
GO:0032481	Process	Positive regulation of type I interferon production	IEA
GO:0032481	Process	Positive regulation of type I interferon production	ISS
GO:0039534	Process	Negative regulation of MDA-5 signaling pathway	IMP	21187438
GO:0039536	Process	Negative regulation of RIG-I signaling pathway	IBA
GO:0039536	Process	Negative regulation of RIG-I signaling pathway	IDA	18411269
GO:0039536	Process	Negative regulation of RIG-I signaling pathway	IEA
GO:0039536	Process	Negative regulation of RIG-I signaling pathway	IMP	21187438
GO:0045087	Process	Innate immune response	IEA
GO:0045088	Process	Regulation of innate immune response	IDA	18411269
GO:0045824	Process	Negative regulation of innate immune response	IDA	21525357
GO:0045824	Process	Negative regulation of innate immune response	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051607	Process	Defense response to virus	IEA
GO:0140374	Process	Antiviral innate immune response	IBA
GO:1900245	Process	Positive regulation of MDA-5 signaling pathway	IEA
GO:1900245	Process	Positive regulation of MDA-5 signaling pathway	ISS
GO:1900246	Process	Positive regulation of RIG-I signaling pathway	IEA
GO:1900246	Process	Positive regulation of RIG-I signaling pathway	ISS

Other IDs

• MIM: 608588
• HGNC: 29517
• e!Ensembl: ENSG00000108771

Protein

• UniProt ID: Q96C10
• Protein name: ATP-dependent RNA helicase DHX58 (EC 3.6.4.13) (ATP-dependent helicase LGP2) (Protein D11Lgp2 homolog) (RIG-I-like receptor 3) (RLR-3) (RIG-I-like receptor LGP2) (RLR)
• Protein 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
• PDB: 2RQA, 2W4R, 3EQT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04851	ResIII	1 → 172	Type III restriction enzyme, res subunit	Family
  PF18119	RIG-I_C	215 → 343	RIG-I receptor C-terminal domain	Domain
  PF00271	Helicase_C	349 → 475	Helicase conserved C-terminal domain	Family
  PF11648	RIG-I_C-RD	552 → 667	C-terminal domain of RIG-I	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in testis, nerve and spleen. Also expressed in the brain. {ECO:0000269|PubMed:31256877}.
• Sequence:

  MELRSYQWEVIMPALEGKNIIIWLPTGAGKTRAAAYVAKRHLETVDGAKVVVLVNRVHLV
  TQHGEEFRRMLDGRWTVTTLSGDMGPRAGFGHLARCHDLLICTAELLQMALTSPEEEEHV
  ELTVFSLIVVDECHHTHKDTVYNVIMSQYLELKLQRAQPLPQVLGLTASPGTGGASKLDG
  AINHVLQLCANLDTWCIMSPQNCCPQLQEHSQQPCKQYNLCHRRSQDPFGDLLKKLMDQI
  HDHLEMPELSRKFGTQMYEQQVVKLSEAAALAGLQEQRVYALHLRRYNDALLIHDTVRAV
  DALAALQDFYHREHVTKTQILCAERRLLALFDDRKNELAHLATHGPENPKLEMLEKILQR
  QFSSSNSPRGIIFTRTRQSAHSLLLWLQQQQGLQTVDIRAQLLIGAGNSSQSTHMTQRDQ
  QEVIQKFQDGTLNLLVATSVAEEGLDIPHCNVVVRYGLLTNEISMVQARGRARADQSVYA
  FVATEGSRELKRELINEALETLMEQAVAAVQKMDQAEYQAKIRDLQQAALTKRAAQAAQR
  ENQRQQFPVEHVQLLCINCMVAVGHGSDLRKVEGTHHVNVNPNFSNYYNVSRDPVVINKV
  FKDWKPGGVISCRNCGEVWGLQMIYKSVKLPVLKVRSMLLETPQGRIQAKKWSRVPFSVP
  DFDFLQHCAENLSDLSLD

• Sequence length: 678

Pathways

KEGG:

RIG-I-like receptor signaling pathway

Reactome:

DDX58/IFIH1-mediated induction of interferon-alpha/beta

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DHX58-associated Neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	40194700	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autoimmune Diseases	Autoimmune Diseases	BEFREE	29032202		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	36076988	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36152765, 39265845	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	28940253		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	GWASCAT_DG	29212778		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	Pubtator	40135555	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	31932636	Associate	★☆☆☆☆ Found in Text Mining only
Encephalitis	Encephalitis	BEFREE	29032202		★☆☆☆☆ Found in Text Mining only
Frontotemporal Dementia	Frontotemporal dementia	Pubtator	30739198	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	29321042, 31790472	Associate	★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29032202, 30179292		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	25288302		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30179292		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	30179292		★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	25205107		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	34897916	Associate	★☆☆☆☆ Found in Text Mining only