Alt. symbols: IFI4 | G1P1 | ADAR1

Approved name: adenosine deaminase RNA specific
Alt. names: interferon-induced protein 4

Location: 1q21.3: 154581695 - 154628013 (-)
Gene type: protein_coding, 42 transcripts.

Scores: LoFtool: 0.124000 | pLI: 0.90759537 | LOEUF: 0.420

HGNC: 225

NCBI: 103, RefSeq: NG_011844.2

Ensembl: ENSG00000160710.19

LRG_1212 | Status: public

OMIM: 146920

Expression | ProteinAtlas

ADAR encodes RNA-specific adenosine deaminase, the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double-stranded RNA through the conversion of adenosine to inosine. This may affect gene expression and function in many ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins since the translational machinery read the inosine as a guanosine; 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 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).

Biallelic LOF or specific dominant negative heterozygous catalytic domain missense variants in ADAR are responsible for about 7% of known cases of AGS, called Aicardi-Goutieres syndrome type 6 (AGS6) [OMIM: 615010]. The latter may arise de novo or be dominantly inherited - p.Gly1007Arg variant is one example, another recurrent ADAR variant, p.Pro193Ala, is seen in affected persons of European origin (PMID: 23001123, 24262145). No deletions or duplications involving ADAR have been reported to cau se AGS thus far. In general, the early-onset neonatal form of AGS is most frequently seen in association with biallelic RNASEH2A, RNASEH2C, or TREX1 mutations. The later-onset presentation (sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurologic function) is most frequently seen in association with biallelic RNASEH2B, SAMHD1, or ADAR mutations, but may also be seen in individuals monoallelic ADAR or IFIH1 mutations (PMID: 25604658). Atypical, sometimes milder or even clinically asymptomatic cases of AGS exist, so the true extent of the phenotype associated with pathogenic variants in AGS-related genes is not yet known. See GeneReviews for details: https://www.ncbi.nlm.nih.gov/books/NBK1475/ In contrast, highly penetrant heterozygous LOF ADAR mutations (thought to act via haploinsufficiency) have been associated with AD dyschromatosis symmetrica hereditaria (DSH) [OMIM: 127400], characterized by hyperpigmented and hypopigmented macules on the face and dorsal aspects of the extremities that appear in infancy or early childhood and predominantly affecting those of Japanese and Chinese ancestry. However, more recently, reports of DSH and AGS co-occurrence has blurred these boundaries, leading some to suggest that these are simply phenotypic variants of the same condition (PMID: 37770123, 33289110, 26802932, 19017046, 16817193). [Load More]