ADAR

adenosine deaminase RNA specific, the group of Adenosine deaminases acting on RNA

Basic information

Region (hg38): 1:154581694-154628013

Previous symbols: [ "IFI4", "G1P1" ]

Links

ENSG00000160710 ∙ NCBI:103 ∙ OMIM:146920 ∙ HGNC:225 ∙ Uniprot:P55265 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyschromatosis symmetrica hereditaria (Definitive), mode of inheritance: AD
• Aicardi-Goutieres syndrome 6 (Definitive), mode of inheritance: AR
• Aicardi-Goutieres syndrome 6 (Definitive), mode of inheritance: AD
• Aicardi-Goutieres syndrome 6 (Strong), mode of inheritance: AD
• Aicardi-Goutieres syndrome 6 (Strong), mode of inheritance: AR
• Aicardi-Goutieres syndrome 6 (Moderate), mode of inheritance: AR
• Aicardi-Goutieres syndrome (Supportive), mode of inheritance: AD
• dyschromatosis symmetrica hereditaria (Supportive), mode of inheritance: AD
• familial infantile bilateral striatal necrosis (Supportive), mode of inheritance: AD
• Aicardi-Goutieres syndrome 6 (Strong), mode of inheritance: AR
• dyschromatosis symmetrica hereditaria (Strong), mode of inheritance: AD
• Leigh syndrome (Limited), mode of inheritance: AR
• Aicardi-Goutieres syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyschromatosis symmetrica hereditaria; Aicardi-Goutieres syndrome 6	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Hematologic; Neurologic	12916015; 12713580; 23001123; 24262145; 25243380

ClinVar

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

• Symmetrical dyschromatosis of extremities;Aicardi-Goutieres syndrome 6 (558 variants)
• Aicardi-Goutieres syndrome 6;Symmetrical dyschromatosis of extremities (324 variants)
• not provided (144 variants)
• Symmetrical dyschromatosis of extremities (140 variants)
• Aicardi-Goutieres syndrome 6 (83 variants)
• Inborn genetic diseases (42 variants)
• not specified (17 variants)
• ADAR-related condition (7 variants)
• 6 conditions (1 variants)
• Aicardi Goutieres syndrome (1 variants)
• 10 conditions (1 variants)
• ADAR-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAR 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			14	219	5	238
missense		6	464	6	2	478
nonsense	10	3				13
start loss			1			1
frameshift	23	2	1			26
inframe indel			6			6
splice donor/acceptor (+/-2bp)	3	6				9
splice region		1	20	22	1	44
non coding	1		71	114	53	239
Total	37	17	557	339	60

Highest pathogenic variant AF is 0.0000197

Variants in ADAR

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

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

Position	Type	Phenotype	Significance	ClinVar
1-154582078-G-GT		Symmetrical dyschromatosis of extremities	Uncertain significance (Jun 14, 2016)
1-154582163-C-T		Symmetrical dyschromatosis of extremities	Benign (Jan 12, 2018)
1-154582170-C-T		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154582183-G-A		Symmetrical dyschromatosis of extremities	Benign (Jan 12, 2018)
1-154582220-G-A		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 12, 2018)
1-154582475-A-AGGGGCATG		Symmetrical dyschromatosis of extremities	Uncertain significance (Jun 14, 2016)
1-154582489-G-A		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154582490-C-T		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154582607-G-A		Symmetrical dyschromatosis of extremities	Benign (Jan 13, 2018)
1-154582653-A-G		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 12, 2018)
1-154582672-A-G		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154582773-C-T		Symmetrical dyschromatosis of extremities	Benign (Jan 13, 2018)
1-154582887-A-C		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 12, 2018)
1-154582935-T-C		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154583005-TAC-T		Symmetrical dyschromatosis of extremities	Uncertain significance (Jun 14, 2016)
1-154583016-T-C		Symmetrical dyschromatosis of extremities	Benign (Jan 13, 2018)
1-154583055-A-C		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154583078-G-A		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154583094-G-C		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154583192-A-T		Symmetrical dyschromatosis of extremities	Benign (Jan 13, 2018)
1-154583240-A-C		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154583257-A-T		Symmetrical dyschromatosis of extremities	Benign (Jan 13, 2018)
1-154583352-G-C		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 13, 2018)
1-154583370-C-A		Symmetrical dyschromatosis of extremities	Benign (Jan 13, 2018)
1-154583400-T-G		Symmetrical dyschromatosis of extremities	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAR	protein_coding	protein_coding	ENST00000368474	15	45938

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0263	0.974	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	502	667	0.753	0.0000402	8058
Missense in Polyphen		122	247.43	0.49307		2967
Synonymous	-1.62	291	258	1.13	0.0000164	2418
Loss of Function	4.78	13	49.2	0.264	0.00000274	615

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000300	0.000300
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:7972084, PubMed:7565688, PubMed:12618436). This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer- associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing- independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication. {ECO:0000269|PubMed:12618436, ECO:0000269|PubMed:15556947, ECO:0000269|PubMed:15858013, ECO:0000269|PubMed:16120648, ECO:0000269|PubMed:16475990, ECO:0000269|PubMed:17079286, ECO:0000269|PubMed:19605474, ECO:0000269|PubMed:19651874, ECO:0000269|PubMed:19710021, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159, ECO:0000269|PubMed:22278222, ECO:0000269|PubMed:7565688, ECO:0000269|PubMed:7972084}.
• Disease: DISEASE: Dyschromatosis symmetrica hereditaria (DSH) [MIM:127400]: An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the face and the dorsal parts of the hands and feet, that appear in infancy or early childhood. {ECO:0000269|PubMed:12916015, ECO:0000269|PubMed:15146470, ECO:0000269|PubMed:15659327}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Aicardi-Goutieres syndrome 6 (AGS6) [MIM:615010]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269|PubMed:23001123}. 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);Measles - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;antisense pathway;Cytokine Signaling in Immune system;Metabolism of RNA;Formation of editosomes by ADAR proteins;C6 deamination of adenosine;mRNA Editing: A to I Conversion;mRNA Editing;Immune System;Interferon alpha/beta signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.236

Intolerance Scores

• loftool: 0.124
• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.71

Haploinsufficiency Scores

• pHI: 0.123
• hipred: Y
• hipred_score: 0.520
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adar
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; liver/biliary system phenotype; embryo 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype

Gene ontology

• Biological process: adenosine to inosine editing;RNA processing;mRNA processing;response to virus;base conversion or substitution editing;pre-miRNA processing;miRNA loading onto RISC involved in gene silencing by miRNA;response to interferon-alpha;negative regulation of protein kinase activity by regulation of protein phosphorylation;positive regulation of viral genome replication;innate immune response;defense response to virus;type I interferon signaling pathway
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;membrane;supraspliceosomal complex
• Molecular function: DNA binding;RNA binding;double-stranded RNA binding;double-stranded RNA adenosine deaminase activity;protein binding;tRNA-specific adenosine deaminase activity;metal ion binding