DHX58

DExH-box helicase 58, the group of DEAH-box helicases

Basic information

Region (hg38): 17:42101404-42112714

Links

ENSG00000108771

∙ NCBI:79132 ∙ OMIM:608588 ∙ HGNC:29517 ∙ Uniprot:Q96C10 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DHX58 gene.

not_specified (107 variants)
not_provided (2 variants)
DHX58-associated_Neurodevelopmental_disorder (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DHX58 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024119.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			106 clinvar	3 clinvar		109
nonsense				1 clinvar		1
start loss						0
frameshift			1 clinvar	1 clinvar		2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	111	6	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DHX58	protein_coding	protein_coding	ENST00000251642	12	11330

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.20e-13	0.267	125378	0	370	125748	0.00147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.517	389	419	0.929	0.0000255	4444
Missense in Polyphen		144	151.69	0.94927		1645
Synonymous	0.602	165	175	0.942	0.0000107	1354
Loss of Function	1.12	23	29.6	0.778	0.00000136	326

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00604	0.00605
Ashkenazi Jewish	0.00279	0.00278
East Asian	0.000444	0.000435
Finnish	0.000232	0.000231
European (Non-Finnish)	0.00101	0.00101
Middle Eastern	0.000444	0.000435
South Asian	0.00321	0.00321
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

Function: FUNCTION: Acts as a regulator of DDX58/RIG-I 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 DDX58/RIG-I 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 DDX58/RIG-I signaling may involve the following mechanisms: competition with DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I 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 DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses, 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. {ECO:0000269|PubMed:16116171, ECO:0000269|PubMed:17020950, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18411269, ECO:0000269|PubMed:19208642, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19278996, ECO:0000269|PubMed:19380577, ECO:0000269|PubMed:21187438, ECO:0000269|PubMed:21525357}.;
Pathway: RIG-I-like receptor signaling pathway - Homo sapiens (human);RIG-I-like Receptor Signaling;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Innate Immune System;Immune System (Consensus)

Recessive Scores

pRec: 0.118

Intolerance Scores

loftool: 0.933
rvis_EVS: -0.28
rvis_percentile_EVS: 33.56

Haploinsufficiency Scores

pHI: 0.0809
hipred: N
hipred_score: 0.486
ghis: 0.532

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.741

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Dhx58
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype;

Gene ontology

Biological process: response to virus;response to bacterium;viral process;negative regulation of type I interferon production;positive regulation of type I interferon production;negative regulation of MDA-5 signaling pathway;negative regulation of RIG-I signaling pathway;innate immune response;regulation of innate immune response;negative regulation of innate immune response;defense response to virus;positive regulation of MDA-5 signaling pathway;positive regulation of RIG-I signaling pathway
Cellular component: cytoplasm
Molecular function: DNA binding;double-stranded RNA binding;single-stranded RNA binding;helicase activity;protein binding;ATP binding;zinc ion binding