RIGI

RNA sensor RIG-I, the group of DEAD-box helicases|Caspase recruitment domain containing

Basic information

Region (hg38): 9:32455301-32526208

Previous symbols: [ "DDX58" ]

Links

ENSG00000107201 ∙ NCBI:23586 ∙ OMIM:609631 ∙ HGNC:19102 ∙ Uniprot:O95786 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Singleton-Merten syndrome 1 (Limited), mode of inheritance: AD
• Singleton-Merten dysplasia (Supportive), mode of inheritance: AD
• Singleton-Merten syndrome 2 (Strong), mode of inheritance: AD
• Singleton-Merten syndrome 2 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Singleton-Merten syndrome 2	AD	Cardiovascular; Ophthalmologic	Among other manifestations, the condition can include cardiovascular calcifications, and awareness may allow early management (eg, surgical valvuloplasty has been described); Awareness of the risk of glaucoma can allow surveillance, prompt awareness and treatment	Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic	25620203

ClinVar

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

• not provided (397 variants)
• Singleton-Merten syndrome 2 (16 variants)
• not specified (13 variants)
• Inborn genetic diseases (12 variants)
• RIGI-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIGI gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				50	11	61
missense		3	197	9	8	217
nonsense			16			16
start loss						0
frameshift			12	2		14
inframe indel			3			3
splice donor/acceptor (+/-2bp)			6			6
splice region			17	12	9	38
non coding			2	36	19	57
Total	0	3	236	97	38

Variants in RIGI

This is a list of pathogenic ClinVar variants found in the RIGI region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-32457122-T-C			Uncertain significance (Sep 11, 2023)
9-32457124-A-G			Uncertain significance (Jan 17, 2022)
9-32457153-A-G			Benign (Jan 10, 2024)
9-32457170-G-C			Uncertain significance (Feb 11, 2022)
9-32457170-G-T			Uncertain significance (Sep 02, 2022)
9-32457172-C-A		Singleton-Merten syndrome 2 • Inborn genetic diseases	Uncertain significance (Aug 19, 2022)
9-32457173-C-T			Likely benign (Apr 10, 2023)
9-32457177-C-T			Uncertain significance (Aug 16, 2022)
9-32457182-C-T			Likely benign (Nov 10, 2023)
9-32457191-T-C		not specified • RIGI-related disorder	Benign (Feb 01, 2024)
9-32457202-C-A			Uncertain significance (Mar 18, 2022)
9-32457206-T-G			Likely benign (Jan 12, 2023)
9-32457214-C-T			Uncertain significance (Oct 17, 2022)
9-32457219-A-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
9-32457231-T-C			Uncertain significance (Oct 09, 2023)
9-32457234-A-G			Uncertain significance (Nov 27, 2023)
9-32457234-A-T			Uncertain significance (Dec 14, 2022)
9-32457240-A-G			Conflicting classifications of pathogenicity (Aug 18, 2022)
9-32457241-T-A			Likely benign (Dec 01, 2023)
9-32457247-G-A			Likely benign (Jan 08, 2024)
9-32457260-C-T			Likely benign (Oct 19, 2022)
9-32457279-C-T			Uncertain significance (Jul 23, 2022)
9-32457284-G-C			Uncertain significance (Nov 15, 2023)
9-32457288-T-A			Uncertain significance (Dec 11, 2023)
9-32457297-T-G			Uncertain significance (Nov 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIGI	protein_coding	protein_coding	ENST00000379883	18	71023

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.76e-23	0.0188	125329	1	418	125748	0.00167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.823	419	469	0.893	0.0000220	6163
Missense in Polyphen		101	128.02	0.78891		1728
Synonymous	1.34	141	163	0.867	0.00000798	1616
Loss of Function	1.13	40	48.5	0.825	0.00000241	616

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00120	0.00118
Ashkenazi Jewish	0.000122	0.0000992
East Asian	0.000327	0.000326
Finnish	0.000981	0.000786
European (Non-Finnish)	0.00145	0.00144
Middle Eastern	0.000327	0.000326
South Asian	0.00650	0.00636
Other	0.00134	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'- triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK- related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects rotavirus and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. {ECO:0000269|PubMed:15208624, ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19122199, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19576794, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21742966}.
• Disease: DISEASE: Singleton-Merten syndrome 2 (SGMRT2) [MIM:616298]: A form of Singleton-Merten syndrome, an autosomal dominant disorder characterized by marked aortic calcification, dental anomalies, osteopenia, acro-osteolysis, and to a lesser extent glaucoma, psoriasis, muscle weakness, and joint laxity. Additional clinical manifestations include particular facial characteristics and abnormal joint and muscle ligaments. SGMRT2 is an atypical form characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies. {ECO:0000269|PubMed:25620203}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Influenza A - Homo sapiens (human);Cytosolic DNA-sensing pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);RIG-I-like Receptor Signaling;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Cytokine Signaling in Immune system;NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10;Post-translational protein modification;TRAF6 mediated IRF7 activation;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Metabolism of proteins;Innate Immune System;Immune System;TRAF3-dependent IRF activation pathway;Negative regulators of DDX58/IFIH1 signaling;Ub-specific processing proteases;Ovarian tumor domain proteases;Deubiquitination;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.215

Intolerance Scores

• loftool: 0.983
• rvis_EVS: 0.05
• rvis_percentile_EVS: 57.54

Haploinsufficiency Scores

• pHI: 0.687
• hipred: N
• hipred_score: 0.486
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.932

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ddx58
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; hematopoietic 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); neoplasm; liver/biliary system phenotype; immune system phenotype; digestive/alimentary phenotype

Gene ontology

• Biological process: positive regulation of defense response to virus by host;positive regulation of myeloid dendritic cell cytokine production;detection of virus;response to virus;positive regulation of gene expression;viral process;protein deubiquitination;regulation of cell migration;negative regulation of type I interferon production;positive regulation of granulocyte macrophage colony-stimulating factor production;positive regulation of interferon-alpha production;positive regulation of interferon-beta production;positive regulation of interleukin-6 production;positive regulation of interleukin-8 production;regulation of type III interferon production;positive regulation of interferon-beta secretion;cytoplasmic pattern recognition receptor signaling pathway in response to virus;RIG-I signaling pathway;response to exogenous dsRNA;innate immune response;positive regulation of transcription by RNA polymerase II;positive regulation of DNA-binding transcription factor activity;defense response to virus;positive regulation of response to cytokine stimulus;cellular response to exogenous dsRNA;positive regulation of interferon-alpha secretion;positive regulation of tumor necrosis factor secretion;positive regulation of interleukin-6 secretion
• Cellular component: cytoplasm;cytosol;bicellular tight junction;actin cytoskeleton;ruffle membrane
• Molecular function: double-stranded DNA binding;double-stranded RNA binding;single-stranded RNA binding;helicase activity;protein binding;ATP binding;zinc ion binding;ubiquitin protein ligase binding;identical protein binding